ALLERGY

 

Diagnosis, Diagnostics, Immunodiagnosis & Immunodiagnostics:

 

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January 2003

5880.      Adamek-Guzik T, Guzik TJ, Czerniawska-Mysik G, Korpanty G, Mastalerz L, Radwan J, Szczeklik A. Urinary leukotriene levels are increased during exacerbation of atopic eczema/dermatitis syndrome. Relation to clinical status. Allergy. 2002 Aug;57(8):732-6.

 

BACKGROUND: Leukotrienes are potent mediators of allergic inflammation and their role in the pathogenesis of allergic disorders, particularly asthma, is well established. Their importance in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS) is still unclear. We aimed to compare urinary cysteinyl leukotriene (Cys-LT) levels during exacerbation and remission of AEDS in relation to clinical status, IgE levels, and eosinophil counts. METHODS: Urinary Cys-LTs were measured by direct enzyme immunoassay in 17 adult patients with AEDS and in 17 healthy controls in whom atopy had been excluded. Cys-LTs were compared during exacerbation and remission of AEDS in relation to the clinical status measured by SCORAD. Total IgE levels were measured by enzyme-linked immunoassay (ELISA). RESULTS: Mean clinical score during the exacerbation was 64.3 +/- 3.1 and during remission 22.4 +/- 4 (P < 0.01). Cys-LTs levels were significantly higher during the exacerbation of AEDS than in the control group (230.9 +/- 20.8 vs 123.2 +/- 9.9 pg/mg creatinine; P < 0.005). During the remission, the difference between AEDS patients and the control group was not significant (96.3 +/- 8.7 vs 123.2 +/- 9.9 pg/mg creatinine; P = 0.8). During AEDS exacerbation Cys-LTs levels were significantly correlated with the clinical status (rS = 0.73, P < 0.01) and with eosinophil counts (r = 0.86; P < 0.01) but not with the duration of the disease, age of patients, or IgE levels. CONCLUSIONS: Our results point to enhanced biosynthesis of Cys-LTs during the AEDS exacerbations. Inflammatory cells, e.g. eosinophils are the most probable source of Cys-LTs. A strong correlation between Cys-LT levels and clinical status may in part explain preliminary clinical observations of efficacy of leukotriene antagonists in alleviating symptoms of AEDS.

5881.      Alonso-Llamazares A, Martinez-Cocera C, Dominguez-Ortega J, Robledo-Echarren T, Cimarra-Alvarez M, Mesa del Castillo M. Nasal provocation test (NPT) with aspirin: a sensitive and safe method to diagnose aspirin-induced asthma (AIA). Allergy. 2002 Jul;57(7):632-5.

 

BACKGROUND: We have aimed to determine the sensitivity and specificity of a

simpler technique with less risk than oral provocation to diagnose aspirin-induced asthma (AIA). METHODS: We studied a group of 20 AIA patients compared to a control group with 40 aspirin-tolerant patients (confirmed by oral provocation test): 10 asthmatic patients and 30 healthy subjects. A nasal provocation test (NPT) with lysine acetylsalicylic acid (L-ASA) was carried out. Nasal and pulmonary functions were monitored with anterior active rhinomanometry (AAR) and spirometry. An L-ASA solution (900 mg/ml L-ASA, equivalent to 500 mg/ml acetylsalicylic acid) was diluted with saline solution. We administered four increasing doses: 5, 25, 50 and 100 mg/ml acetylsalicylic acid (ASA) with saline solution control. Nasal and pulmonary functions were monitored with rhinomanometry and spirometry. The patients were controlled for nasal inspiratory peak flow and expiratory peak flow. RESULTS: The results showed high sensitivity and specificity: 80% and 92.5%, respectively, with an 84.2% positive predictive value and an 89.2% negative predictive value. The patients had no bronchial or systemic symptoms, and no decreases over 20% were recorded in the FEV1. CONCLUSION: NPT has a high sensitivity and specificity in the diagnosis of AIA. An oral provocation should be performed to confirm the result whenever the clinical situation of the patient permits it.

 

5882.      Baldo BA, Pham NH.  Immunoglobulin E binding determinants on beta-lactam drugs. Curr Opin Allergy Clin Immunol. 2002 Aug;2(4):297-300. Review.

 

PURPOSE OF REVIEW: Allergies to penicillins and cephalosporins remain an important clinical problem, but structural and immunochemical knowledge of the allergenic structures involved has tended to lag behind the heavy usage, consequent adverse reactions and introduction of new therapeutic members of these two families of antibiotics. Evidence of the increasing incidence of reactions to cephalosporins and to "minor" determinants of the beta-lactams is accumulating. Also, although numerous reports detail unique allergic recognitions of individual members of the two families, particularly the cephalosporins, information remains predominantly clinical. The present review summarizes the most recent advances in studies of structural aspects of beta-lactams as allergens. RECENT FINDINGS: For the cephalosporins, a pyrazinone allergenic degradation product of cefaclor and cephalexin has been identified and characterized. The widely used cephalosporin cephalothin was shown to cross-react allergenically with benzylpenicillin and the common cross-reacting structure was identified. The fine structural features on the amoxicillin molecule recognized by antibodies that distinguish "major" and "minor" determinants were identified, and steric factors were used to explain antibody recognition of the amoxicillin determinants. A recent study elucidated the molecular basis of some cases of the multiple drug allergy syndrome and its relationship to beta-lactam allergy. SUMMARY: Findings of the type described in the present review provide fundamental insights into the nature and size of antigenic determinants on "small" molecules such as drugs and other chemicals. At the clinical level, such structure/activity findings have implications for our understanding of drug allergenic cross-reactions, for selection for therapy

of an appropriate member from a family of structurally related drugs and, ultimately, for desensitization of drug-allergic patients.

5883.      Ballmer-Weber BK, Scheurer S, Fritsche P, Enrique E, Cistero-Bahima A, Haase T, Wuthrich B. Component-resolved diagnosis with recombinant allergens in patients with cherry allergy. J Allergy Clin Immunol. 2002 Jul;110(1):167-73.

 

BACKGROUND: In pollen-related food allergy, extracts for skin prick tests (SPTs) are often not standardized, and the test reliability is affected by false-negative reactions. OBJECTIVE: We sought to evaluate a panel of recombinant allergens (RAs) derived from one allergenic food for use in component-resolved in vivo diagnosis, taking cherry as a model food. METHODS: Seventy-nine subjects were included in the study: 24 Swiss patients (group 1) with a positive double-blind placebo-controlled food challenge result to cherries, 23 patients with birch pollen allergy but without cherry allergy (group 2), 23 nonatopic subjects (group 3), and 9 Spanish patients with a history of a cherry allergy (group 4). SPTs were performed in duplicate by using recombinant cherry allergens (Bet v 1-related allergen: recombinant (r) Pru av 1; profilin: rPru av 4; and lipid transfer protein: rPru av 3) in concentrations of 10, 50, and 100 microg/mL. Furthermore, IgE reactivity to rPru av 1, rPru av 4, and rPru av 3 was assessed by means of immunoblot analysis. RESULTS: SPT responses with rPru av 1, rPru av 4, and rPru av 3 were positive in 92%, 17%, and 4% of the patients in group 1; in 74%, 30%, and 0% of the patients in group 2; in 0%, 22%, and 89% of the patients in group 4; and negative for all nonatopic subjects (group 3). Thus the sensitivity of a positive SPT response to at least one of the 3 RAs was 96%. The specificities, negative predictive values, and positive predictive values with the 3 RAs were 100%, 96%, and 100% if calculated in relation to the nonatopic control group but 17%, 79%, and 60% when calculated in relation to the control group with birch pollen allergy. The correlation between SPT and immunoblotting results was excellent. Sensitization to rPru av 3 was associated with more severe symptoms than sensitization to rPru av 1. CONCLUSIONS: SPTs with RAs proved to be highly sensitive for diagnosis of cherry allergy. Component-resolved in vivo diagnosis with standardized amounts of stable RAs allows us to determine sensitization patterns directly, to correlate them with severity of clinical symptoms, and to analyze geographic differences.

 

5884.      Bernstein DI, Cartier A, Cote J, Malo JL, Boulet LP, Wanner M, Milot J, L'Archeveque J, Trudeau C, Lummus Z.  Diisocyanate antigen-stimulated monocyte chemoattractant protein-1 synthesis has greater test efficiency than specific antibodies for identification of diisocyanate asthma. Am J Respir Crit Care Med. 2002 Aug 15;166(4):445-50.

We previously reported that diisocyanate-human serum albumin (DIISO-HSA) stimulated production of monocyte chemoattractant protein-1 (MCP-1) by peripheral blood mononuclear cells is significantly associated with a clinical diagnosis of diisocyanate asthma (DA). Others have reported that antibodies for DIISO-HSA are specific but insensitive markers of DA. This study was performed to evaluate test characteristics of the in vitro MCP-1 assay compared with DIISO-HSA-specific immunoglobulin (Ig) G and IgE in identifying workers with DA. MCP-1 was quantitated in peripheral blood mononuclear cell supernatants 48 hours after incubation with DIISO-HSA antigens. Assay results were compared with outcomes of specific inhalation challenge (SIC) testing. Nineteen of 54 (35%) workers assayed for antibodies and MCP-1 stimulation had SIC-confirmed DA. Mean MCP-1 produced by SIC-positive workers was greater than SIC-negative workers (p < or = 0.001). Diagnostic sensitivity, specificity, and test efficiency for specific IgG were 47%, 74%, and 65%, respectively, and for specific IgE were 21%, 89%, and 65%, respectively. Sensitivity, specificity, and test efficiency of the MCP-1 test were 79%, 91%, and 87%, respectively. This study indicates that the MCP-1 stimulation assay has greater sensitivity and specificity than the specific antibody assays in correctly identifying DA.

5885.      Bernstein JA. Material safety data sheets: are they reliable in identifying human hazards? J Allergy Clin Immunol. 2002 Jul;110(1):35-8. Review.

 

The material safety data sheet (MSDS) is an integral part of a worker's evaluation for suspected occupational asthma and dermatitis. However, established US federal guidelines for creating an MSDS do not require that certain key information relevant to the diagnosis of these disorders be included. This rostrum is intended to highlight the limitations of MSDSs as they pertain to the diagnosis of occupational asthma and occupational dermatitis so that future consideration can be given to modification of the existing MSDS guidelines. This article summarizes the origins of MSDS documents, provides an overview of their format, and discusses some of their inherent limitations, which at times impede proper medical evaluation by physicians and other health care professionals. MSDSs are an essential part of making the workplace a safer environment. More complete disclosure about both irritation and sensitization risks in these documents would facilitate the evaluation of workers for OA and OD. Their current ambiguity often delays the diagnosis of these occupational diseases and places the worker at further risk for development of occupational-related long-term disorders. Health care professionals have an obligation to better educate themselves regarding the interpretation of MSDSs and to recognize that they sometimes provide incomplete data.

5886.      Beyer K, Grishina G, Bardina L, Grishin A, Sampson HA. Identification of an 11S globulin as a major hazelnut food allergen in hazelnut-induced systemic reactions. J Allergy Clin Immunol. 2002 Sep;110(3):517-23.

 

BACKGROUND: Hazelnuts are a common cause of food allergy. Allergic reactions to hazelnuts range from oral allergy syndrome caused by cross-reactivity between tree pollen and hazelnut proteins to severe anaphylactic reactions. Little information is available regarding the identification of pollen-independent hazelnut allergens. OBJECTIVE: The aim of the study was to identify these pollen-independent allergens in patients with hazelnut allergy with systemic reactions. METHODS: Extracted hazelnut proteins were separated by means of 2-dimensional PAGE, and immunolabeling was performed with individual sera from 14 patients with hazelnut-induced systemic reactions. Edman sequencing was performed on a 40-kd protein identified as an allergen. In parallel, RNA isolated from hazelnuts was used to construct a cDNA library. By using the peptide sequence data, oligonucleotide primers were synthesized and used to screen the library. Full-length cDNA clones were isolated, sequenced, expressed, and screened with patient sera. RESULTS: By using 2-dimensional proteomics, a protein fraction at 40 kd was recognized by serum IgE from 86% (12/14) of the patients with hazelnut allergy with systemic reactions. Two internal amino acid sequences were determined by means of Edman sequencing. Screening of the prepared hazelnut cDNA library with oligonucleotides based on these internal peptide sequences resulted in isolation of a novel protein cDNA. The new protein, named Cor a 9, belongs to the 11S globulin seed storage protein family. This family comprises known food allergens in peanut (Ara h 3) and soybean

(glycine max). The pairwise homology among these 3 proteins ranges from 45% to 50%. Interestingly, one known IgE-binding epitope of Ara h 3 shares 67% of homologous amino acid residues with the corresponding area of Cor a 9. The amino acids that differ were previously shown not to be critical for IgE binding in Ara h 3. CONCLUSION: Cor a 9 is the first tree pollen unrelated hazelnut allergen isolated, sequenced, and cloned. The identification of food allergens is the first step toward generating recombinant allergens for use in future immunotherapeutic approaches. In addition, the detection of conserved IgE epitopes in common food allergens, such as seed storage proteins, might be a useful tool for predicting cross-reactivity to certain foods.

5887.      Bickel A, Axelrod FB, Schmelz M, Marthol H, Hilz MJ. Dermal microdialysis provides evidence for hypersensitivity to noradrenaline in patients with familial dysautonomia. J Neurol Neurosurg Psychiatry. 2002 Sep;73(3):299-302.

 

OBJECTIVES: To use the technique of dermal microdialysis to examine sensitivity of skin vessels to noradrenaline (NA) in patients with familial dysautonomia (FD) and in healthy controls. METHODS: In 14 patients with FD and 12 healthy controls, plasma extravasation, local laser Doppler blood flow, and skin blanching were observed before, during, and after application of 10(-6) M NA through a microdialysis membrane, located intradermally in the skin of the lower leg. RESULTS: Maximum local vasoconstriction measured by laser Doppler blood flow did not differ between patients with FD and controls. In contrast, patients with FD had an earlier onset of vasoconstriction (p = 0.02). Moreover, reaction to NA was more prominent and prolonged in FD, shown by a larger zone of skin blanching around the microdialysis membrane (p < 0.001) and delayed reduction of the protein content in the dialysate after termination of NA application (p = 0.03). CONCLUSION: These data support the hypothesis that peripheral blood vessels of patients with FD show a denervation hypersensitivity to catecholamines. This may be one mechanism contributing to the major hypertension that frequently occurs during "dysautonomic crises" in FD.

5888. Bochenek G, Niz Ankowska E, Szczeklik A. Testing for aspirin hypersensitivity. Allergy. 2002 Jul;57(7):562-5. Review.  No abstract.

5889.Bokulic RE. Screening for exercise-induced asthma. J Pediatr. 2002 Sep;141(3):306-8. No abstract.

5890.Caballero ML, Moneo I. Specific IgE determination to Ani s 1, a major allergen from Anisakis simplex, is a useful tool for diagnosis. Ann Allergy Asthma Immunol. 2002 Jul;89(1):74-7.

 

BACKGROUND: The most serious limitation of the serodiagnosis of parasitoses is the occurrence of cross-reactions. OBJECTIVE: The possible use of Anisakis simplex major allergen Ani s 1 for diagnosis. PATIENTS AND METHODS: Forty-nine non-fish-allergic patients with Anisakis simplex hypersensitivity, 21 patients without allergic episodes suffering intestinal anisakiasis with obstruction of the intestinal lumen, and 10 unrelated sera as a control were included in this study to determine specific immunoglobulin (Ig)E and IgG to Anisakis simplex major allergen Ani s 1 by immunoblotting. RESULTS: Eighty-six percent of patients with Anisakis simplex hypersensitivity showed specific IgE directed to Ani s 1. Identical result was obtained for IgG detection in this group. Among patients with intestinal anisakiasis, 86% showed specific IgE, but only 29% had specific IgG (P < 0.001, two-tailed Fisher exact test). One of the 10 control subjects was positive both for IgE and IgG (P < 0.001). CONCLUSIONS: Determination of specific IgE directed to Anisakis simplex major allergen Ani s 1 is a useful tool for the diagnosis of hypersensitivity and intestinal anisakiasis. Further, measurement of specific IgG directed to Anisakis simplex major allergen Ani s 1 is only valid for Anisakis simplex allergy.

5891.      Carroll NG, Mutavdzic S, James AL. Increased mast cells and neutrophils in submucosal mucous glands and mucus plugging in patients with asthma. Thorax. 2002 Aug;57(8):677-82.

 

BACKGROUND: Mucus plugging of the airways is invariably seen in cases of fatal asthma, mucus production is associated with asthma attacks, and the area of submucosal glands is increased in asthma. Mediators secreted from mast cells and neutrophils can stimulate mucous gland secretion. A study was undertaken to count the mast cells and neutrophils in submucosal glands and to relate cell numbers to the presence of mucus in the airway lumen. METHODS: Cartilaginous airways obtained at necropsy from cases of fatal asthma (n=8), non-fatal asthma (n=8), and control cases (n=8) were examined. Contiguous transverse sections were stained for mast cell tryptase and neutrophil elastase, and with Periodic Acid Schiff solution to identify mucus. Mucous gland area, lumen area, and the percentage of the relaxed lumen area occupied by mucus (mucus occupying ratio, MOR) were measured. Mast cells (intact and degranulated) and neutrophils per area of submucosal gland were calculated. RESULTS: Compared with controls, the cases of fatal asthma had increased mucous gland area, MOR, percentage of degranulated mast cells, and numbers of neutrophils in the submucosal glands (p<0.05). In cases of non-fatal asthma the MOR and the numbers of mast cells and neutrophils in the submucosal glands were increased (p<0.05). When all cases were pooled together, the MOR correlated with the total number of mast cells (r=0.55, p=0.005) and with the number of degranulated mast cells in the submucosal glands (r=0.51, p=0.013), but not with the number of neutrophils (r=0.21, p=0.121). CONCLUSION: These results show that mucous gland area, MOR, and mucous gland inflammation are increased in asthma and that degranulation of mast cells may contribute to secretion of mucus into the lumen in cases of fatal asthma.

 

5892.      Cavallo GP, Elia M, Giordano D, Baldi C, Cammarota R. Decrease of specific and total IgE levels in allergic patients after BCG vaccination: preliminary report. Arch Otolaryngol Head Neck Surg. 2002 Sep;128(9):1058-60.

 

BACKGROUND: A systemic reaction to mycobacteria biases the balance of T helper cell types 1 and 2 toward T helper cell type 1. BCG vaccination mimics some characteristics of mycobacterial infection. Children who have undergone tuberculin conversion after BCG vaccination seem to be more likely to lose their atopic symptoms. Inhibition of both allergic response and airway hyperreactivity after vaccination for mycobacteria has been observed in animal experiments. OBJECTIVE: To evaluate the effects that BCG vaccination has on the serological status of allergic people. PARTICIPANTS AND METHODS: This study included 20 volunteers with a history of allergic rhinitis who were required to undergo BCG vaccination by Italian law. Epicutaneous allergy testing with a panel of common seasonal and perennial inhalational allergens and 2 blood withdrawals were performed. The serum total IgE levels and the serum allergen-specific IgE levels of each individual were measured just before BCG vaccination and again 4 months later. Total IgE levels were determined using the paper radioimmunosorbent test, and allergen-specific IgE levels were determined using the radioallergosorbent test. RESULTS: Total IgE and allergen-specific IgE levels were significantly decreased after BCG vaccination (P =.004 and P<.001, respectively). CONCLUSION: BCG, an effective stimulus for cell-mediated immunity, deserves further study to evaluate its ability to modulate the immune response associated with allergic rhinitis.

 

5893.      Chardin H, Raulf-Heimsoth M, Chen Z, Rihs HP, Mayer C, Desvaux FX, Senechal H, Peltre G. Interest of two-dimensional electrophoretic analysis for the characterization of the individual sensitization to latex allergens. Int Arch Allergy Immunol. 2002 Jul;128(3):195-203.

 

BACKGROUND/OBJECTIVE: Latex allergy is a type 1 hypersensitivity reaction that mainly affects high-risk populations such as health care workers, spina bifida-affected or multiply-operated children. Ten molecules have so far been identified and registered as latex allergens (Hev b 1 to Hev b 10). The aim of the present investigation was to identify the major latex allergens by an individual analysis of the IgE response of latex-allergic patients to latex proteins separated by two-dimensional (2-D) gel electrophoresis. MATERIALS AND METHODS: Latex proteins from a sap or a glove extract were separated by 2-D electrophoresis and transferred to a nitrocellulose membrane. Each membrane was incubated with the serum of one latex-allergic patient. The most frequently recognized latex allergens were characterized in sap and glove extracts using monoclonal antibodies or amino acid microsequencing. RESULTS: The one-dimensional screening of 54 patient sera revealed 4 major bands recognized by IgE. The 2-D analysis of the sensitization to latex allergens allows the identification of allergen isoforms and the characterization of an individual response diversity. Hev b 6.01 was recognized by 88.9% of the patients. Protein spots around 14 kD were recognized by 48.1% of the patients and corresponded to Hev b 6.03 as well as other proteins. A not yet characterized doublet of acidic proteins with molecular masses of 43 and 94 kD was recognized by 20.4% of the sera. Only 5.5% of the sera did not recognize any of these 4 major allergens. Hev b 1 is the main protein from the glove extract but was not constantly found in sap extracts. CONCLUSIONS: One-dimensional electrophoretic analysis of the allergen is usually not sufficient to characterize the individual specificity of the IgE response to latex allergens. Latex-glove proteins which are allergens can be absent from the sap extracts and the sensitization to these allergens could be underestimated. Individual 2-D analysis of the sensitization to latex allergens is useful to define the best allergen mixture required for diagnosis and needed for individual therapy monitoring. Copyright 2002 S. Karger AG, Basel

5894.      Cloutier MM. Neutrophils or eosinophils in young children with wheezing: which comes first? Chest. 2002 Sep;122(3):761-3.  No abstract.

5895.      Duarte I, Lazzarini R, Buense R. Interference of the position of substances in an epicutaneous patch test battery with the occurrence of false-positive results. Am J Contact Dermat. 2002 Sep;13(3):125-32.

 

BACKGROUND: Epicutaneous patch tests represent a practical and objective method that help in the etiologic diagnosis of allergic contact dermatitis. The technique of patch test application is an important factor in obtaining good results. OBJECTIVES: The aims of this study were (1) to determine whether the substances that form the test battery interfere with the patch test result and (2) to establish a rule for positioning the substances during patch test application. METHODS: Two hundred patients were studied. The standard patch test battery was applied in 3 versions. The original, with the substances applied in alphabetical order was called version 1 (V1) and tested on the left back in all patients In 100 patients, on the right side, the same substances were tested but applied at different positions, avoiding the proximity of elements with a tendency to cross reaction and/or cosensitizing. This version of the battery was named version 2 (V2). Another 100 patients had V1 applied to the left back, and, on the right side, the version 3 of the battery (V3) was applied, consisting of the same allergens but placed close to those with a tendency for cross reaction and/or cosensitization. RESULTS: In the group V1-V2, 163 results were positive in V1 and 124 in V2, with the difference being statistically significant (P <.05). In the group V1-V3, 134 results were positive in V1 and 207 in V3, with the difference also being significant (P <.005). The substances with the largest number of positive results, when tested close to other elements with a tendency for chemical affinity, were parabens, fragrance-mix, thimerosal, balsam of Peru, potassium dichromate, cobalt chloride, mercapto mix, and propylene glycol. CONCLUSIONS: (1) The substances of a patch test battery eliciting positive responses may interfere with test positivity to neighboring substances. (2) In addition to the already established techniques, the position of the substances forming the test battery needs to be determined; substances with a tendency to cross reaction or cosensitizing substances should be tested distant from one another, thus preventing the occurrence of false-positive results. Copyright 2002, Elsevier Science (USA). All rights reserved.

 

5896.      Ebo DG, Lechkar B, Schuerwegh AJ, Bridts CH, De Clerck LS, Stevens WJ. Validation of a two-color flow cytometric assay detecting in vitro basophil activation for the diagnosis of IgE-mediated natural rubber latex allergy. Allergy. 2002 Aug;57(8):706-12.

 

BACKGROUND: IgE-dependent triggering of basophils not only elicits the release of different mediators but also the up-regulation of certain markers, e.g. CD63, which can be detected by flow cytometry. We intended to investigate if flow cytometric analysis of basophil activation could be a valuable tool in the diagnosis of latex allergy, and to evaluate if the basophil activation test (BAT) could be helpful in determining the clinical significance of a positive latex IgE in individuals with negative history and negative latex skin test. Additionally we aimed to determine the role of cross-reactive carbohydrate determinants (CCDs) in causing positive latex IgE without apparent clinical significance. METHODS: Twelve healthy controls without a history of latex hypersensitivity with a negative latex IgE and skin test (group 1), 24 individuals without a history of latex hypersensitivity with a negative latex IgE and skin test but with other inhalant allergies (group 2), and 29 latex allergic patients with a compelling history of latex allergy with a positive latex IgE and prick test (group 3) were enrolled. The diagnostic performances of the BAT were further evaluated in 13 individuals with a history of latex allergy but with negative specific IgE and/or skin test (group 4). Twenty-four individuals with positive latex IgE without apparent clinical relevance, i.e. without history of latex hypersensitivity and negative latex skin tests, were also analyzed (group 5). The putative role of CCDs causing positive latex IgE results without apparent clinical significance was evaluated by quantification of IgE for bromelain. RESULTS: According, to the receiver operating characteristics(ROC)-generated threshold value of 17% between latex allergic patients and the pooled group of nonlatex allergic individuals, the sensitivity and specificity of the basophil activation test was 93.1% and 91.7%, respectively. In healthy controls, allergic patients without latex hypersensitivity and latex allergic patients the number of positive BATs was 0/12, 3/24 and 27/29, respectively. In the individuals with an evocative history of latex allergy but with negative latex IgE and/or skin test the BAT was positive in all 13 cases. Twenty of 24 individuals without apparent latex allergy but with positive latex IgE had a negative BAT. IgE for bromelain was positive in 1/19 sera from group 2, 1/24 sera from group 3, none of the 8 sera from group 4, but in 16/18 sera from group 5, respectively. CONCLUSION: Flow cytometric analysis of activated basophils seems a highly sensitive and specific tool for diagnosing latex allergy. In addition, the technique might help to determine the clinical relevance of positive IgE quantification in the absence of overt latex allergy. CCDs of natural rubber latex allergens were confirmed to mimic latex sensitization.

 

5897.      Fremeaux-Bacchi V, Guinnepain MT, Cacoub P, Dragon-Durey MA, Mouthon L, Blouin J, Cherin P, Laurent J, Piette JC, Fridman WH, Weiss L, Kazatchkine MO. Prevalence of monoclonal gammopathy in patients presenting with acquired angioedema type 2. Am J Med. 2002 Aug 15;113(3):194-9.

 

PURPOSE: Acquired angioedema type 1 is characterized by a C1 inhibitor deficiency in patients with lymphoproliferative disorders, whereas acquired angioedema type 2 is characterized by anti-C1 inhibitor antibodies, and has not been thought to be associated with lymphoproliferative disease. We studied the clinical features, complement profiles, and associated diseases in 19 new patients with diagnosed acquired angioedema type 2. SUBJECTS AND METHODS: Plasma concentrations and functional activity of complement components were measured by conventional techniques. Functional C1 inhibitor activity was assessed by a chromogenic assay. Autoantibodies to C1 inhibitor were detected using an enzyme-linked immunosorbent assay. RESULTS: The 11 men and 8 women (median age, 60 years) presented with recurrent attacks of angioedema. All patients had detectable anti-C1 inhibitor antibodies in serum. A monoclonal gammopathy was detected in 12 patients (63%) at the time of diagnosis, 11 of whom had an immunoglobulin peak of the same heavy- and light-chain isotypes as the acquired anti-C1 inhibitor antibody. Three of these 12 patients developed a malignant lymphoproliferative disease. CONCLUSION: As with type 1 disease, a large proportion of patients with acquired angioedema type 2 have a lymphoproliferative disorder.

5898.      Ghobrial G, Naser SA, Sweeney M, White R. Identification and characterization of the allergenic proteins of Bahia grass (Paspalum notatum) pollen. Int Arch Allergy Immunol. 2002 Aug;128(4):304-9.

 

BACKGROUND: Pollen of Bahia grass (Paspalum notatum) represents a major cause of type I allergy in diverse geographical areas, particularly in the southeastern coastal plain area of the United States. The aqueous protein extract of Bahia grass pollen contains the allergenically active components that produce skin-test-positive reactions in sensitive patients. OBJECTIVE: The emphasis of this study included the identification and characterization of the allergenic proteins present in the crude protein aqueous extract of Bahia grass pollen. METHODS: The crude extract of Bahia grass pollen, partially purified by isoelectric focusing and fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was electroblotted onto nitrocellulose membranes, probed with sera from patients skin test positive to Bahia grass and detected using anti-human IgE conjugated peroxidase. RESULTS: Four allergenic proteins of Bahia grass pollen with estimated molecular weights of 45, 33, 31 and 28 kD were identified and characterized. Following treatments with deglycosylation enzymes, the 4 allergens retained their antigenic reactivity with Bahia-grass-allergic patient sera containing polyclonal IgE antibodies. CONCLUSION: The crude extract of Bahia grass pollen contains many proteins but only 4 have allergenic reactivity. Following deglycosylation treatment, Bahia grass allergenic proteins have retained their antigenic reactivity with Bahia-grass-allergic patient sera containing polyclonal IgE antibodies. Four proteins reactive with IgE were detected, but the 33-kD protein (pI of 6.59) was the most reactive. Copyright 2002 S. Karger AG, Basel

5899.      Graif Y, Yigla M, Tov N, Kramer MR.  Value of a negative aeroallergen skin-prick test result in the diagnosis of asthma in young adults: correlative study with methacholine challenge testing. Chest. 2002 Sep;122(3):821-5.

 

BACKGROUND: None of the existing tests for the diagnosis of asthma are considered to be definitive. Certain circumstances require prompt diagnosis, and a test able to predict the absence of asthma would be very useful. OBJECTIVE: To evaluate the contribution of a skin-prick test (SPT) to the diagnostic workup of subjects with suspected asthma. PATIENTS AND METHODS: The study included three groups of subjects aged 18 to 24 years: group A, asthmatic patients (n = 175); group B, control subjects (n = 100); and group C, subjects with suspected asthma (n = 150) with normal spirometry findings and a negative exercise challenge test result. All underwent an SPT to a battery of common aeroallergens, and group C underwent a methacholine challenge test (MCT) in addition. The sensitivity,

specificity, positive predictive value, and negative predictive values (NPV) of the SPT were calculated using provocative concentrations of methacholine causing a 20% fall in FEV(1) (PC(20)) of < 4 mg/mL and < 8 mg/mL as diagnostic cutoff values for asthma in the MCT. Bayes' formula was used to determine posttest probabilities of having asthma, both for positive and negative SPT results. RESULTS: A positive SPT result to at least one allergen was found in 95.5%, 54%, and 69% of patients in the three groups, respectively. The sensitivity, specificity, and NPV of the SPT were 90.7%, 52.0%, and 84.8%, respectively, with a cutoff value of PC(20) < 8 mg/mL. The lower cutoff, PC(20) < 4 mg/mL, increased the sensitivity and NPV to 98.2% and 97.8%, respectively. A negative SPT result decreased the probability of having asthma by 10-fold to 20-fold in subjects whose pretest probability was low to moderate. CONCLUSIONS: Incorporating an SPT into the workup of subjects with suspected asthma can reduce the cost of this process significantly. The SPT may be used as a simple, fast, safe, inexpensive, and reliable method to predict the absence of asthma in young adults.

5900.      Hallstrand TS, Curtis JR, Koepsell TD, Martin DP, Schoene RB, Sullivan SD, Yorioka GN, Aitken ML.  Effectiveness of screening examinations to detect unrecognized exercise-induced bronchoconstriction. J Pediatr. 2002 Sep;141(3):343-8.

 

OBJECTIVE: To determine if a physician-administered physical examination and screening questionnaire accurately detects exercise-induced bronchoconstriction (EIB) in adolescent athletes.Study design: Cross-sectional study of 256 adolescents participating in organized sports from 3 suburban high schools. The number of persons screened positive for EIB by physical examination and questionnaire was compared with the number of persons with EIB diagnosed by a "gold standard" test that consisted of a 7-minute exercise challenge followed by serial spirometry. RESULTS: We diagnosed EIB in 9.4% of adolescent athletes. The screening history identified persons with symptoms or a previous diagnosis suggestive of EIB in 39.5% of the participants, but only 12.9% of these persons actually had EIB. Among adolescents with a negative review of symptoms of asthma or EIB, 7.8% had EIB. Among adolescents with no previous diagnosis of asthma, allergic rhinitis, or EIB, 7.2% had EIB diagnosed by exercise challenge. Persons who screened negative on all questions about symptoms or history of asthma, EIB, and allergic rhinitis accounted for 45.8% of the adolescents with EIB. CONCLUSIONS: EIB occurs frequently in adolescent athletes, and screening by physical examination and medical history does not accurately detect it.

5901.      Hamilton RG, Peterson EL, Ownby DR.  Clinical and laboratory-based methods in the diagnosis of natural rubber latex allergy. J Allergy Clin Immunol. 2002 Aug;110(2 Suppl):S47-56. Review.

 

The accurate diagnosis of hypersensitivity to natural rubber latex is the initial step in the effective management of individuals with latex allergy and in ensuring the quality of epidemiologic studies. The diagnostic algorithm used in the evaluation of an individual with suspected latex allergy begins with a comprehensive clinical history during which risk factors (atopy, food allergies, hand dermatitis) and temporal relationships between symptoms and natural rubber product exposure are identified. If type IV hypersensitivity is suspected because of the delayed nature (hours to days) and confinement of symptoms to the skin-latex product contact areas, patch testing can be conducted to confirm the presence of activated T cells with specificity for rubber chemicals. If type I hypersensitivity is suspected because of ocular, upper and lower airway, and/or systemic symptoms that have rapid onset (minutes) after a definable latex exposure, a confirmatory skin or blood test for IgE antibody may be conducted to verify a state of sensitization within the individual. The definitive diagnosis would then be made only after consideration of the individual's clinical history and confirmatory in vivo and/or in vitro laboratory test results. If discordance remains between highly convincing latex-associated symptoms as identified in the history and repetitively negative confirmatory IgE antibody test results, then one of several types of in vivo provocation tests may be performed for adjudication. This overview examines the current state of the art in both in vivo and in vitro diagnostic methods for latex-specific IgE antibody detection in skin and blood. The performance, advantages, and limitations of each diagnostic method are compared.

5902.Hendrick DJ.  Diagnostic tests for occupational asthma. Am J Respir Crit Care Med. 2002 Aug 15;166(4):436-7.  No abstract.

5903. Homa DM, Mannino DM, Redd SC. Regional differences in hospitalizations for asthma in the United States, 1988-1996. J Asthma. 2002 Aug;39(5):449-55.

 

Hospitalization rates for asthma are higher in the Northeast United States than in other regions, despite similar regional prevalence rates. Whether these higher rates reflect differences in asthma presentation or severity or else general differences in hospitalizations is unclear. We examined regional differences in asthma hospitalizations for the United States from 1988 through 1996 using data from the National Hospital Discharge Survey. We classified asthma hospitalizations into those in which asthma was either the primary diagnosis or any listed diagnosis. From 1988 through 1996, the rate of hospitalizations for asthma as the primary diagnosis, per 10,000 population, increased in the Northeast, but declined in other regions. By 1996, these rates were 24.5 in the Northeast, 18.4 in the Midwest, 15.8 in the South, and 14.2 in the West. The Northeast also had the highest absolute rate and the highest rate of increase for asthma as any listed diagnosis during the study period. These higher rates of asthma hospitalizations in the Northeast occurred despite a 9.3% decline in the age-adjusted rate for all hospitalizations in the region. These results indicate a greater rate of hospitalization for asthma in the Northeast than in other regions, suggesting that asthma there may be more severe.

5904.      Jogi R, Bjorksten B, Boman G, Janson C. Serum eosinophil cationic protein (S-ECP) in a population with low prevalence of atopy. Respir Med. 2002 Jul;96(7):525-9.

 

The study is a part of the European Community Respiratory Health Survey. A random sample (n = 351) of 20-44-year olds and persons of the same age with asthma-like symptoms or current asthma medication according to a postal questionnaire (n = 95) were studied. Interview was taken, methacholine challenge was done and ECP, total and specific IgE were measured from serum. The median S-ECP value was 8.0 micrograms/l in the random sample. The geometric mean of S-ECP was higher in subjects with, than without atopy (10.2 vs 8.9 micrograms/l, P < 0.01) and in subjects with bronchial hyperresponsiveness (BHR) than in subjects without BHR (9.9 vs 8.0 micrograms/l, P < 0.01). The levels correlated weakly to forced expiratory volume in one second (FEV1) (r = 0.13, P < 0.01) and were not independently correlated with respiratory symptoms, asthma or FEV1 after adjusting for BHR, IgE, sensitisation and smoking. Our results indicate that the level of eosinophil activation is low in a population with a low prevalence of atopy, even when BHR is common.

5905.      Leon AD, Tellez Araiza M, Arellano Garcia J, Martinez-Cordero E. Interference by rheumatoid factor activity in the detection of antiavian antibodies in pigeon breeders disease. Clin Exp Med. 2002 Jul;2(2):59-67.

 

The assessment of antiavian antibodies is relevant for the study of pigeon

breeder's disease; nevertheless, different factors may hamper their accurate detection. The objective of this study was to determine whether an endogenous interfering effect in pigeon breeder's disease might explain the simultaneous presence of IgM, IgG, and IgA antiavian antibodies in high titers as assessed by ELISA. Fifty-nine patients with pigeon breeder's disease, 80 healthy controls, and 47 asymptomatic breeders were studied. To assess possible interfering effects by endogenous immunoglobulins, serum IgG was separated through protein A-Sepharose CL-4B chromatography. Antiavian antibodies were measured in whole and separated samples by ELISA. Since a decline of IgM antiavian antibodies following IgG removal was consistent with a false-positive effect, the causes were studied. High values of IgM, IgG, and IgA antiavian antibodies were found in 47.4% [corrected] of patients with pigeon breeder's disease. An IgM rheumatoid factor activity against IgG was found through ELISA in sera with false-positive IgM antiavian antibodies. Rheumatoid factor binding was confirmed by Western blot. Experimental addition of purified rheumatoid factor to sera with IgG antiavian antibodies replicated the interfering effect. A control group of rheumatoid arthritis with high rheumatoid factor values did not show positive antiavian antibodies tests. No IgG with anti-IgM or anti-IgA activity was found, and the detection of IgA against IgM and IgG was negative. In conclusion, the study of antiavian antibodies might be affected by different immunoassay conditions. An endogenous rheumatoid factor activity produced false-positive IgM results. Other similar interferences warrant a careful evaluation during the serological assessment of pigeon breeder's disease.

5906.      Li JT.  Allergy testing. Am Fam Physician. 2002 Aug 15;66(4):621-4. Review.

 

Percutaneous and intradermal skin tests and laboratory assays of specific IgE antibodies may be useful in selected cases of allergy management. Percutaneous testing kits are available from various manufacturers. A number of common allergens are available in standardized preparations. Positive and negative skin controls are important in establishing reliable results. Antihistamine medications can interfere with skin testing and should be stopped beforehand. Serious reactions to skin testing are rare. Establishing the sensitivity and specificity of percutaneous testing is difficult because there is no widely accepted gold standard for defining a true allergic reaction. Intradermal testing is more sensitive than percutaneous methods but much less specific. Its use is restricted to testing for allergy to insect stings or penicillin. In cases where skin testing is not available or desirable, laboratory assays for IgE antibodies to specific allergens may be used. These assays are generally less sensitive than skin testing methods. Selected patients with allergic rhinitis or asthma that is not controlled with standard therapy may benefit from allergy testing, especially when it can target allergen avoidance measures or guide immunotherapy.

 

5907.      Niggemann B, Ziegert M, Reibel S. Importance of chamber size for the outcome of atopy patch testing in children with atopic dermatitis and food allergy. J Allergy Clin Immunol. 2002 Sep;110(3):515-6.

 

Because the small backs of young children offer little space for atopy patch testing, it would be helpful to use smaller chambers. We therefore compared 6-mm chambers with the 12-mm chambers used in previous studies. We performed 55 double-blind, placebo-controlled food challenges in 30 children (17 boys, 13 girls) aged 3 to 58 months (median, 13 months). Sensitivity, specificity, positive predictive value, negative predictive value, and efficiency results show that the 12-mm chamber size yields much better results than the 6-mm chamber size. Therefore, 12-mm cups should be used for atopy patch tests with food, even in infants and small children.

 

5908.      Perkins DN, Keith PK. Food- and exercise-induced anaphylaxis: importance of history in diagnosis. Ann Allergy Asthma Immunol. 2002 Jul;89(1):15-23.  No abstract.

5909.      Seidenari S, Giusti F, Massone F, Mantovani L. Sensitization to disperse dyes in a patch test population over a five-year period. Am J Contact Dermat. 2002 Sep;13(3):101-7.

 

BACKGROUND: In spite of sporadic data pointing at the role of textile dyes as important contact allergens, only few studies have addressed the issue of the frequency of sensitization to textile dyes in populations of consecutive patients. OBJECTIVE: The purpose of this study was to evaluate the prevalence of sensitization to disperse dyes, to investigate cross reactivity between azo dyes and para-amino compounds, to describe azo-dye-positive patients, and to study the correlation between clinical aspects and sensitization to different disperse dyes. METHODS: From January 1996 to December 2000, 6,478 consecutive patients were tested with 7 textile dyes: Disperse Blue 124, Disperse Blue 106, Disperse Red 1, Disperse Yellow 3, Disperse Orange 3 (DO3), para-aminoazobenzene (PAAB), and para-dimethylaminoazobenzene (PDAAB). RESULTS: Of the above, 437 patients were allergic. The most common sensitizers were Disperse Blue (DB) dyes and Disperse Orange 3. Both the clinical aspect and the localization of the lesions were unusual in a fair percentage of cases, especially in DB-positive subjects. Involvement of skin folds was observed in 27% of disperse dye-positive patients, mainly comprising DB-sensitive women. Cross-reactivity between azo-dyes and paraphenylenediamine (PPD) was frequent in DO3-, PAAB-, and PDAAB-positive subjects, but not in DB-allergic ones. Moreover, cross reactions between DB106 and DB124 were observed in 59% of DB106- and/or DB124-positive patients. CONCLUSIONS: The frequency of disperse dye allergy is higher than generally estimated. Further studies, using routine diagnostic testing with disperse dyes, are needed to investigate whether this increasing trend is present outside of Europe. Copyright 2002, Elsevier Science (USA). All rights reserved.

5910.      Sterk PJ. Airway hyperresponsiveness: using bronchial challenge tests in research and management of asthma. J Aerosol Med. 2002 Summer;15(2):123-9. Review.

 

Bronchial challenge tests have been standardized in detail during the past two decades. They are providing relevant pathophysiological and clinical information about patients with asthma or chronic obstructive pulmonary disease (COPD), by allowing the measurement of the degree of airway hyperresponsiveness, which includes an increased sensitivity as well as increased maximal response to bronchoconstrictor stimuli. There are various types of challenges, to which the responses are not interchangeable. Responses to so-called "indirect" challenges are largely dependent on the state of activation of inflammatory or resident cells within the airways, and the state of activation can vary rapidly, either spontaneously or through intervention. Responses to "direct" challenges are dependent on less variable, rather chronic features of airways inflammation or remodeling. Bronchoprovocation tests provide integrated information about

multiple pathophysiological pathways within the airway. This is in contrast to the measurements of cells, mediators, or cytokines in biological fluids, which provide only very specific information on selected inflammatory pathways. It has recently been shown that the outcome of asthma can substantially be improved when long-term treatment is not only guided by symptoms and lung function, but also by the degree of airway hyperresponsiveness to direct stimuli. Taken together, current data warrant a broader usage of bronchoprovocation tests in the research as well as clinical management of asthma and COPD. In asthma, it allows selective, individually targeted therapy of the patient as opposed to the currently recommended regimens that are (increasingly) unselective in their approach. The potential benefits of monitoring other phenotypic disease markers is currently under investigation.

5911.      Tan RA, Spector SL. Exercise-induced asthma: diagnosis and management. Ann Allergy Asthma Immunol. 2002 Sep;89(3):226-35; quiz 235-7, 297. Review.

 

OBJECTIVE: To review the diagnosis and management of exercise-induced asthma (EIA). DATA SOURCES: Computer-assisted literature searches on MEDLINE for articles, abstracts, and other relevant data on exercise-induced asthma STUDY SELECTION: Published articles, abstracts, and conference proceedings were selected. RESULTS: EIA is seen in 40 to 90% of asthmatic patients. Exercise can be the sole trigger or be one of multiple triggers of asthma exacerbations. A good history and physical examination can diagnose most cases of EIA. Spirometry can confirm the diagnosis. Exercise testing may be necessary in certain cases. Prevention through both pharmacologic and nonpharmacologic measures is the key to EIA management. Inhaled beta-agonists remain the medications of choice for EIA prophylaxis. Inhaled cromolyn and antileukotrienes are alternatives. Good long-term control of asthma with anti-inflammatory medications such as inhaled steroids will also decrease the incidence of EIA. CONCLUSIONS: Early diagnosis and proper preventive and maintenance therapy can reduce episodes of EIA and enable patients to continue to engage in sports and lead an active life.

 

5912. Xu X, Weiss ST. Asthma, rhinitis, and skin test reactivity to aeroallergens in families of asthmatic subjects in Anqing, China. Am J Respir Crit Care Med. 2002 Sep 1;166(5):774-5.  No abstract.

Pathogenesis:

5913. Crane J, Wickens K, Beasley R, Fitzharris P. Asthma and allergy: a worldwide problem of meanings and management? Allergy. 2002 Aug;57(8):663-72. Review.  No abstract.

5914. Fujisawa T, Fujisawa R, Kato Y, Nakayama T, Morita A, Katsumata H, Nishimori H, Iguchi K, Kamiya H, Gray PW, Chantry D, Suzuki R, Yoshie O. Presence of high contents of thymus and activation-regulated chemokine in platelets and elevated plasma levels of thymus and activation-regulated chemokine and macrophage-derived chemokine in patients with atopic dermatitis. J Allergy Clin Immunol. 2002 Jul;110(1):139-46.

 

BACKGROUND: T(H)2 cells and eosinophils selectively express CC chemokine receptor 4 and CCR3, respectively, and their chemokine ligands are likely to play important roles in the pathogenesis of atopic dermatitis (AD). OBJECTIVE: The purpose of this study was to demonstrate the presence of thymus and activation-regulated chemokine (TARC) in platelets and its release during clotting and to evaluate the circulating levels of TARC, macrophage-derived chemokine (MDC), and eotaxin in control subjects and patients with AD. METHODS: We compared plasma and serum contents of TARC, MDC, and eotaxin. We measured TARC contents in platelet lysates. We analyzed the correlation of plasma levels of TARC, MDC, and eotaxin with various clinicolaboratory parameters in patients with AD. RESULTS: Serum contents of TARC rapidly increased during clotting, whereas those of MDC and eotaxin increased only slightly. We demonstrated that platelets contained TARC, and its levels were dramatically elevated in patients with AD. Platelets also released TARC on stimulation with thrombin. We therefore evaluated circulating levels of these chemokines in control subjects and patients with AD by using plasma samples. Plasma TARC levels were significantly increased in patients with AD (P <.0001) and showed significant correlations with severity scoring of atopic dermatitis (SCORAD) index (r = 0.665, P <.00001), serum lactate dehydrogenese levels (r = 0.696, P =.00001), eosinophil counts (r = 0.381, P =.007), and platelet counts (r = 0.562, P <.0001). Similarly, plasma MDC levels were significantly increased in patients with AD (P <.0001) and showed significant correlations with SCORAD index (r = 0.727, P <.0001), serum lactate dehydrogenese levels (r = 0.861, P <.0001), eosinophil counts (r = 0.505, P =.005), and platelet counts (r = 0.370, P =.01). On treatment, plasma TARC and MDC levels were dramatically decreased in accordance with improved SCORAD scores (P =.0012 and P =.0007, respectively). On the other hand, plasma eotaxin levels did not show any significant increase or correlation with any of the clinical parameters in patients with AD. CONCLUSION: Platelets from patients with AD contain high levels of TARC. Thus platelets might play an important role in AD pathogenesis by releasing T(H)2-attracting TARC on activation. Furthermore, circulating levels of TARC and MDC, but not those of eotaxin, correlate well with the disease activity of AD.

5915.      Hunt LW, Kelkar P, Reed CE, Yunginger JW. Management of occupational allergy to natural rubber latex in a medical center:  the importance of quantitative latex allergen measurement and objective follow-up. J Allergy Clin Immunol. 2002 Aug;110(2 Suppl):S96-106. Review.

 

When our employees began coming to the Occupational Health Service, Dermatology, and Allergy Clinics with symptoms of allergy to rubber gloves 12 years ago, the Mayo Clinic initiated 3 responses. (1) The Allergic Disease Research Laboratory adapted well-established technology to measure both the IgE antibody specific to natural rubber allergens, and by use of this IgE antibody, the allergens in rubber products and in the air of the workplace. (2) The Division of Allergic Diseases and Internal Medicine reviewed the prevalence and severity of the problem. (3) The Clinical Practice Committee appointed a multidisciplinary task force to implement measures to reduce exposure. The 3 sections of this article describe the Mayo Clinic's experience of successful control of this occupational health problem. Use of only gloves with low or undetectable allergen content greatly reduced the concentration of allergen in the work site, reduced the number of new cases of occupational allergy to rubber, and allowed individuals with latex allergy to work at their usual jobs.

5916.      Kumagai N, Yamamoto K, Fukuda K, Nakamura Y, Fujitsu Y, Nuno Y, Nishida T. Active matrix metalloproteinases in the tear fluid of individuals with vernal keratoconjunctivitis. J Allergy Clin Immunol. 2002 Sep;110(3):489-91.

 

Corneal epithelial lesions distinguish vernal keratoconjunctivitis (VKC) from other ocular allergic diseases. Such lesions result from degradation of the corneal epithelial basement membrane, which comprises mostly type IV collagen and laminin. Matrix metalloproteinase 2 (MMP-2) and MMP-9 catalyze the degradation of these 2 extracellular matrix proteins. The possible role of MMP-2 and MMP-9 in the pathogenesis of corneal lesions associated with VKC was investigated by assaying tear fluid for the presence of these enzymes. Tear fluid was collected from 6 eyes of 6 patients with active VKC, 14 eyes of 14 patients with active allergic conjunctivitis, and 6 eyes of 6 nonallergic healthy volunteers. Gelatin zymography revealed that the tear fluid of healthy volunteers contained inactive proforms of both MMP-2 and MMP-9 but not the active forms of these enzymes. Active forms of MMP-2 or MMP-9 were detected in a minority of patients with allergic conjunctivitis. However, with the exception of one individual for whom active MMP-9 was not detected, tear fluid from all patients with VKC contained both proforms and active forms of MMP-2 and MMP-9. These results implicate MMP-2 and MMP-9 in the pathogenesis of corneal epithelial disorders associated with VKC.

 

5917.  Martin S, Weiss JM, Simon JC. Advances in allergy research -- basic and clinical science make progress. Trends Immunol. 2002 Jul;23(7):329-30.  No abstract.

5918. Raivio T, Palvimo JJ, Kannisto S, Voutilainen R, Janne OA. Transactivation assay for determination of glucocorticoid bioactivity in human serum. J Clin Endocrinol Metab. 2002 Aug;87(8):3740-4.

 

We have developed a mammalian cell (COS-1) bioassay, which measures glucocorticoid bioactivity (GBA) directly from a small amount of human serum. The assay is based on the expression of human glucocorticoid receptor (GR) together with a coactivator protein and reporter plasmid containing GR response elements upstream of the luciferase gene. Ten microliters of human serum, in duplicate, are added directly to the cell culture medium, and GBA is derived from reporter gene activity. The assay differentiates between biopotencies of synthetic steroids, and importantly, mifepristone (RU486) is able to block glucocorticoid-induced response. The assay is sensitive (<15.6 nM cortisol in fetal calf serum) and precise, with the within- and between-assay coefficients of variation less than 8% and 10%, respectively. We measured serum GBA (bioassay) and cortisol (RIA) levels in 34 asthmatic children (age range, 5.7-14.2 yr) at baseline and after treatment with either inhaled budesonide (800 microg/d, n = 14), fluticasone propionate (500 microg/d, n = 14), or cromones (control group, n = 6). Pretreatment serum GBA and cortisol levels correlated strongly (r = 0.90, P < 0.0001, n = 34). Two months of treatment with inhaled budesonide resulted in excess GBA in circulation, which was not attributable to endogenous cortisol (P < 0.001). In the fluticasone propionate group, the presence of serum excess GBA was at the borderline of statistical significance (P < 0.08) after 2 months of inhalation therapy, and no excess GBA was detected in the cromone group. In conclusion, our bioassay enables measurement of mammalian cell response to bioactive glucocorticoids in circulation and provides a novel means to investigate patients receiving drugs acting through the GR.

5919. Stratakos G, Kalomenidis J, Routsi C, Papiris S, Roussos C. Transient lactic acidosis as a side effect of inhaled salbutamol. Chest. 2002 Jul;122(1):385-6.  No abstract.

5920. Toyoda M, Nakamura M, Makino T, Hino T, Kagoura M, Morohashi M. Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis. Br J Dermatol. 2002 Jul;147(1):71-9.

 

BACKGROUND: Neurogenic components, such as neurotrophic factors and neuropeptides, are probably involved in the pathogenesis of atopic dermatitis (AD) via the neuroimmunocutaneous system. Numerous in vitro and in vivo studies have shown that nerve growth factor (NGF), the best-characterized member of the neurotrophin family, modulates the synthesis of the neuropeptide substance P (SP), both of which may be associated with the pathogenesis of human allergic diseases. OBJECTIVES: To evaluate the levels of NGF and SP in the plasma of patients with AD and to examine their possible correlation with disease activity. METHODS: We measured plasma levels of NGF by an immunoenzymatic assay and of SP by aradioimmunoassay in 52 patients with AD, and compared them with 35 normal non-atopic controls. The severity of the disease in AD patients was evaluated using validated clinical scoring systems. RESULTS: Patients with AD had significant increases in plasma levels of NGF and SP compared with controls (P < 0.0005 and P < 0.0001, respectively). A positive correlation between the plasma levels of NGF and SP was found in AD patients (correlation coefficient, Cc = 0.920, P < 0.0001). There was a significant correlation of plasma NGF and SP levels with disease activity evaluated using three different scoring systems: the grading system of Rajka and Langeland (P < 0.001 and P < 0.01, respectively), the objective Severity Scoring of AD (Cc = 0.656, P < 0.005 and Cc = 0.752, P < 0.0005, respectively) and the Eczema Area and Severity Index (Cc = 0.740, P < 0.001 and Cc = 0.765, P < 0.005, respectively). CONCLUSIONS: These data represent the first reported evidence of increased plasma levels of NGF and SP in an allergic human skin disease. They suggest that these neurogenic factors systemically modulate the allergic response in AD, probably through interactions with cells of the immune-inflammatory component. In addition, NGF and SP may be useful markers of disease activity in patients with AD.

5921. Weisel CP. Assessing exposure to air toxics relative to asthma. Environ Health Perspect. 2002 Aug;110 Suppl 4:527-37. Review.

 

Asthma is a respiratory disease whose prevalence has been increasing since the mid 1970s and that affects more than 14.6 million residents of the United States. Environmental triggers of asthma include air pollutants that are respiratory irritants. Air toxics emitted into the ambient air are listed in the 1990 Clean Air Act Amendments as hazardous air pollutants (HAPs) if they can adversely affect human health, including the respiratory tract. HAPs include particulate and gaseous-phase pollutants, individual organic compounds and metals, and mixtures. Associations between asthma exacerbation and both particles and indoor volatile organic compounds (VOCs), often referred to as indoor air quality, have been reported. Studies conducted in the United States, Canada, and Europe over the past two decades have shown that most people living in the developed countries spend the majority of their time indoors and that the air concentrations of many air toxics or HAPs are higher indoors than in the ambient air in urban, suburban, and rural settings. Elevated indoor air concentrations result from emissions of air toxics from consumer products, household furnishings, and personal activities. The Relationship of Indoor, Outdoor and Personal Air (RIOPA) study was designed to oversample homes in close proximity to ambient sources, excluding residences where smokers lived, to determine the contribution of ambient emissions to air toxics exposure. The ratios of indoor to outdoor air concentrations of some VOCs in homes measured during RIOPA were much greater than one, and for most other VOCs that had indoor-to-outdoor ratios close to unity in the majority of homes, elevated ratios were found in the paired samples with the highest concentration. Thus, although ambient emissions contribute to exposure of some air toxics indoors as well as outdoors, this was not true for all of the air toxics and especially for the higher end of exposures to most volatile organic air toxics examined. It is therefore critical, when evaluating potential effects of air toxics on asthma or other adverse health end points, to determine where the exposure occurs and the source contributions for each air toxic and target population separately and not to rely solely on ambient air concentration measurements.

5922.  Yang Y, Li L, Wong GW, Krilis SA, Madhusudhan MS, Sali A, Stevens RL. RasGRP4, a new mast cell-restricted Ras guanine nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs. Identification of defective variants of this signaling protein in asthma, mastocytosis, and mast cell leukemia patients and demonstration of the importance of RasGRP4 in mast cell development and function. J Biol Chem. 2002 Jul 12;277(28):25756-74.

 

A cDNA was isolated from interleukin 3-developed, mouse bone marrow-derived mast cells (MCs) that contained an insert (designated mRasGRP4) that had not been identified in any species at the gene, mRNA, or protein level. By using a homology-based cloning approach, the approximately 2.6-kb hRasGRP4 transcript was also isolated from the mononuclear progenitors residing in the peripheral blood of normal individuals. This transcript information was then used to locate the RasGRP4 gene in the mouse and human genomes, to deduce its exon/intron organization, and then to identify 10 single nucleotide polymorphisms in the human gene that result in 5 amino acid differences. The >15-kb hRasGRP4 gene consists of 18 exons and resides on a region of chromosome 19q13.1 that had not been sequenced by the Human Genome Project. Human and mouse MCs and their progenitors selectively express RasGRP4, and this new intracellular protein contains all of the domains present in the RasGRP family of guanine nucleotide exchange factors even though it is <50% identical to its closest homolog. Recombinant RasGRP4 can activate H-Ras in a cation-dependent manner. Transfection experiments also suggest that RasGRP4 is a diacylglycerol/phorbol ester receptor. Transcript analysis of an asthma patient, a mastocytosis patient, and the HMC-1 cell line derived from a MC leukemia patient revealed the presence of substantial amounts of non-functional forms of hRasGRP4 due to an inability to remove intron 5 in the precursor transcript. Because only abnormal forms of hRasGRP4 were identified in the HMC-1 cell line, this immature MC progenitor was used to address the function of RasGRP4 in MCs. HMC-1 leukemia cells differentiated and underwent granule maturation when induced to express a normal form of RasGRP4. Thus, RasGRP4 plays an important role in the final stages of MC development.

 

Therapy:

5923. Heffler LC, Kastman AL, Jacobsson Ekman G, Scheynius A, Fransson J. Langerhans cells that express matrix metalloproteinase 9 increase in human dermis during sensitization to diphenylcyclopropenone in patients with alopecia areata. Br J Dermatol. 2002 Aug;147(2):222-9. No abstract.

5924. Murphy LA, Atherton D. A retrospective evaluation of azathioprine in severe childhood atopic eczema, using thiopurine methyltransferase levels to exclude patients at high risk of myelosuppression. Br J Dermatol. 2002 Aug;147(2):308-15. No abstract.

 

April 2003

6448.       Abraham D, Saltoun CA. Facial swelling and eosinophilia in a 44-year-old woman. Ann Allergy Asthma Immunol. 2002 Dec;89(6):561-5. No abstract.

6449.      Ahlstedt S, Holmquist I, Kober A, Perborn H. Accuracy of specific IgE antibody assays for diagnosis of cow's milk allergy. Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl 1):21-5.

OBJECTIVE: The primary objective of this report was to discuss the accuracy of specific immunoglobulin (Ig)E antibody determinations in the diagnosis and prognosis of reactions to allergens, especially cow's milk, in the context of other relevant clinical information. DATA SOURCES: A review was undertaken of the relevant literature on IgE antibody assays in conjunction with some unpublished information from the authors' investigations. STUDY SELECTION: The pertinent data for this article were selected on the basis of the expert opinion of the authors. RESULTS: IgE antibody formation and allergy commence early in life, which can be reflected by specific IgE antibody determinations in serum samples with use of particular systems developed for commercial use. After the first such system was introduced in 1974, development of the technology has ensued. Some systems using excess of allergen extracts of good quality have proven to yield highly accurate results over time. Assays that detect all antibodies present in the serum sample and that demonstrate parallelism between dilutions of specific IgE antibodies and total IgE concentration allow quantitative determinations of specific IgE antibodies. Such specific IgE antibody data can be used not only for a dichotomized evaluation of the presence or absence of sensitization in an individual patient, but also for an evaluation of the relative risk for a clinical reaction to an allergen such as cow's milk.Thus, the specific IgE antibody information can be used in the diagnosis, prediction of the course, and followup management of allergic disease, particularly when sensitization to multiple allergens is present. CONCLUSIONS: Specific IgE antibodies can be accurately determined with certain technologic systems. Such determinations provide information, not available by other means, for the diagnosis, prognosis, and followup of patients with allergy-like symptoms.

6450.      Anderson SD, Brannan JD, Chan HK. Use of aerosols for bronchial provocation testing in the laboratory: where we have been and where we are going. J Aerosol Med. 2002 Fall;15(3):313-24. Review.

Bronchial provocation testing with pharmacological agents that act directly on airway smooth muscle has important limitations. These include the inability to identify exercise-induced asthma (EIA), to differentiate the airway hyperresponsiveness (AHR) of airway remodelling from the AHR of active inflammation and to differentiate between doses of steroids. Recent studies show that tests that act indirectly to narrow airways are more sensitive than pharmacological agents for identifying airway inflammation and response to treatment. Adenosine monophosphate (AMP) is an indirect challenge that acts on mast cells to cause release of mediators. Hypertonic saline is another and, since its development in the 1980s, has become widely used in Australia. Hypertonic (4.5%) saline is used to identify those with active asthma, those with EIA and those who wish to enter certain occupations or sports (e.g., diving). The recent development, again in Australia, of a test that uses dry powder mannitol has promise for use in the laboratory, the office, or for testing in the field. AHR to mannitol identifies people with EIA and is an estimate of its severity. The mannitol response is modified by drugs used to prevent EIA, implying that similar mediators are involved. A mannitol test can be used to monitor response to steroids and is more sensitive than histamine for identifying persistent airway hyperresponsiveness in asthmatics well controlled on steroids. These findings suggest that indirect challenges give more useful clinical information about currently active asthma  and the response to treatment than direct challenge and they will become more widely used.

6451.      Bag R, Bandi V, Fromm RE Jr, Guntupalli KK. The effect of heliox-driven bronchodilator aerosol therapy on pulmonary function tests in patients with asthma. J Asthma. 2002 Oct;39(7):659-65.

To compare the effects of heliox-driven (He 80:O2 20) to air-driven (N 79:O2 21) beta2-agonist aerosol therapy on pulmonary function tests (PFTs) in patients with asthma, a prospective randomized crossover study was undertaken in the asthma clinic of the university-affiliated county hospital in Houston, TX. Thirty-one patients (22 female, age range 18-44) with clinically stable asthma consented. All patients were studied on two different days with both heliox and air as driving gas, therefore serving as their own controls. The PFTs including forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), maximal mid-expiratory flow rate (FEF(25-75)), and maximal expiratory flow rate (FEFmax) were obtained while breathing ambient air at baseline and 30 min after the bronchodilator treatment. Albuterol sulfate 2.5 mg was nebulized with either heliox or compressed air at 8 L/min for 8 min. When heliox was used as driving agent, additional heliox was delivered via a closed system and no entrainment of external air was allowed. Primary outcome measure was absolute change in FEV1 (deltaFEV1). There were no statistically significant differences in baseline PFTs on the two days of the study. All patients had good bronchodilator response (> or = 12% improvement in FEV1) with either driving gas. The deltaFEV1 after heliox-driven bronchodilator (HDBD) and air-driven bronchodilator (ADBD) were 0.68+/-0.38 L/sec (CI: 0.54-0.82) vs. 0.51+/-0.26 L/sec (CI: 0.42-0.60), respectively (p=0.004). The deltaFEV1 with HDBD was 49+/-90% (range -36% to 433%) more than ADBD. A subgroup analysis showed this was largely due to better response rates in patients with moderate to severe obstruction. There was more improvement in both FVC and FEFmax with HDBD than ADBD (p<0.05). The changes in FEF (25-75) were similar. We conclude that HDBD therapy improves FEV1, FVC, and FEFmax significantly more than ADBD in patients with asthma. Further large randomized studies are needed to better characterize responders and the impact on clinical outcomes.

6452.      Bahna SL. Cow's milk allergy versus cow milk intolerance. Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl 1):56-60. Review.

BACKGROUND: Although cow's milk allergy (CMA) and cow's milk intolerance (CMI) are two different terms, they are often used interchangeably, resulting in confusion both in clinical practice and in research reports. OBJECTIVE: To promote the appropriate differential use of the terms CMA and CMI. METHODS: Highlighting the differences in clinical and laboratory findings between CMA and CMI. Information was derived from reviewing the literature on these two topics, supplemented by the clinical experience of the author. RESULTS: CMA is an immunologically mediated reaction to cow's milk proteins that may involve the gastro-intestinal tract, skin, respiratory tract, or multiple systems, ie, systemic anaphylaxis. Its prevalence in the general population is probably 1 to 3%, being highest in infants and lowest in adults. Even though it can cause severe morbidity and even fatality, dietary elimination is associated with good prognosis. However, CMI should refer to nonimmunologic reactions to cow's milk (CM), such as disorders of digestion, absorption, or metabolism of certain CM components. The most common cause of CMI is lactase deficiency, which is mostly acquired during late childhood or adulthood. It has high racial predilection, being highest in dark-skinned populations and lowest in northern Europeans. Lactose intolerance is generally a benign condition, with symptoms limited to the gastro-intestinal tract, yet the primary acquired type lasts for a lifetime.Symptoms can be well ameliorated by reducing the intake of CM or using lactose-hydrolyzing agents. CONCLUSIONS: Adverse reactions to CM should be differentiated into immunologic (CMA) and nonimmunologic (CMI). The latter is still a general term that comprises several conditions and requires further differentiation.

6453.      Bernsen RM, van der Wouden JC. Does the sibling effect have its origin in utero? Investigating birth order, cord blood immunoglobulin E concentration, and allergic sensitization at age 4 years. Am J Epidemiol. 2002 Nov 1;156(9):882. No abstract.

6454.      Blaisdell CJ, Weiss SR, Kimes DS, Levine ER, Myers M, Timmins S, Bollinger ME.  Using seasonal variations in asthma hospitalizations in children to predict hospitalization frequency. J Asthma. 2002 Oct;39(7):567-75.

Asthma hospitalization rates have increased in the United States since 1980. The exposure risk of many environmental factors, which contribute to respiratory disease, vary throughout the year. The objective of this study was to investigate the seasonal variation of pediatric asthma hospitalizations and predict hospitalization frequency. This was a longitudinal analysis of all pediatric asthma hospitalizations in the state of Maryland by age, gender, race, and residence using non-confidential discharge data sets from 1986 to 1999. Of the 631,422 pediatric hospitalizations in the state of Maryland during the years 1986-1999, 45,924 (7%) had a primary admission diagnosis of asthma. Frequency of hospitalization for asthma was lowest in the summer in all age groups, and highest in the fall. Seasonal variation in severe asthma episodes was least striking in children aged 15-18. This was in contrast to non-asthma admissions, which were highest in winter in preschool children, but relatively flat in school- and teenaged children. Using neural network modeling, weekly asthma hospitalizations could be predicted with an R2 between 0.71 and 0.8. Temporal trends in asthma hospitalizations were seen in each age group, gender, race, and location. The seasonal variability in asthma hospitalizations suggests that acute asthma is influenced by variables beyond socioeconomic factors and adherence to medical regimens. Strategies to combat exacerbations of asthma should take into consideration seasonal effects on a population. In addition, temporal trends examined over many years can be used to predict frequency of severe asthma episodes in a population.

6455.      Budde IK, Lopuhaa CE, de Heer PG, Langdon JM, MacDonald SM, van der Zee JS, Aalberse RC.  Lack of correlation between bronchial late allergic reaction to Dermatophagoides pteronyssinus and in vitro immunoglobulin E reactivity to histamine-releasing factor derived from mononuclear cells. Ann Allergy Asthma Immunol. 2002 Dec;89(6):606-12.

BACKGROUND: Activity of immunoglobulin (Ig)E-dependent histamine-releasing factor (HRF) is dependent on the IgE molecules bound to the surface of basophils. Sera capable of passively sensitizing basophils to release histamine to HRF were designated IgE+ sera. IgE+ and HRF have been suggested to play a role in late allergic reaction (LAR). OBJECTIVE: The working hypothesis was tested that IgE+ induces a LAR. Further, activity of HRF produced by mononuclear cells (HRF(mn)) was compared with that of recombinant HRF p23. METHODS: Atopic patients (n = 82) were bronchially provoked with Dermatophagoides pteronyssinus extract and the change in forced expiratory volume in 1 second was monitored. A LAR was defined as forced expiratory volume in 1 second as percentage of baseline < 80% 4 to 10 hours after allergen challenge. The presence of HRF-responsive IgE in serum was determined using basophils sensitized in vitro by serum. RESULTS: The presence of HRF(mn)-responsive IgE (IgE(mn+)) in serum was shown not be essential for a LAR: 63% of the patients with a LAR had no IgE(mn+) in their serum. Further, 71% of patients with IgE(mn+) did not have a LAR. HRF(mn) and recombinant HRF p23 were not equivalent in the bioassay: serum of 38 of 82 atopic patients sensitized basophils to release histamine to HRF(mn), whereas this was found with serum of 1 of 82 patients to HRF p23. CONCLUSIONS: The results do not support the hypothesis that IgE(mn+) induces a LAR, but do not exclude the alternative hypothesis that HRFs are released during a LAR and contribute to asthma severity. PMID: 12487227 [PubMed - indexed for MEDLINE]

6456.      Burgdorff T, Venemalm L, Vogt T, Landthaler M, Stolz W. IgE-mediated anaphylactic reaction induced by succinate ester of methylprednisolone. Ann Allergy Asthma Immunol. 2002 Oct;89(4):425-8.

BACKGROUND: In systemic administration the prevalence of anaphylactic reactions attributable to corticosteroids is approximately 0.3%. Positive prick tests with different corticosteroids have been reported suggesting an immunoglobulin (Ig)E-mediated mechanism. OBJECTIVE: A 42-year-old man with multiple sclerosis developed flush, erythema, and itching a few minutes after the begin of an intravenous infusion of methylprednisolone-21-sodium succinate. DIAGNOSTIC AND RESULTS: Prick tests were found to be positive with methylprednisolone-21-sodium succinate and prednisolone-21-sodium succinate, whereas prick tests with prednisolone without ester and betamethasone-21-dihydrogen phosphate showed negative results. Oral challenge with prednisolone without ester and intravenous challenge with betamethasone-21-dihydrogen phosphate were well tolerated. Specific IgE-antibodies against methylprednisolone-21-sodium succinate were found in the serum of the patient. Because of the positive prick test and specific IgE antibodies against methylprednisolone-21-sodium succinate, the diagnosis of IgE-mediated anaphylactic reaction could be proven. Succinate ester was suspected to be immunogenic, as other corticosteroids without this particular ester or with other substitutions at the C21 remained negative both in the prick and the challenge tests. CONCLUSIONS: This patient showed an adverse reaction caused by methylprednisolone-21-sodium succinate. The uniqueness in this case was the presence of specific IgE antibodies against this esterified corticosteroid in the patient's serum proving that this reaction was based upon a true IgE-mediated mechanism. PMID: 12392389 [PubMed - indexed for MEDLINE]

 

6457.      Busse PJ, Nowak-Wegrzyn AH, Noone SA, Sampson HA, Sicherer SH. Recurrent peanut allergy. N Engl J Med. 2002 Nov 7;347(19):1535-6. No abstract.

6458.      Butani L. Corticosteroid-induced hypersensitivity reactions. Ann Allergy Asthma Immunol. 2002 Nov;89(5):439-45; quiz 445-6, 502. Review.

OBJECTIVE: To review and present data on the prevalence, clinical manifestations, diagnostic techniques, and management options in patients with hypersensitivity reactions to corticosteroid preparations. DATA SOURCES: All English language articles pertaining to human subjects were reviewed using the Pubmed database from 1964 to June 2002. Indexing terms used were anaphylaxis OR allergic OR anaphylactoid OR hypersensitivity AND steroid OR corticosteroid. Further cross-references were obtained after reviewing articles from the aforementioned search. STUDY SELECTION: A total of 11,493 articles were identified with the above search terms. Only those articles, including letters and editorials, describing systemic reactions to steroids were included in the review. Excluded from our review were articles dealing with contact dermatitis to topical steroid preparations. This resulted in a total of 80 articles which were reviewed. RESULTS: Although rare, steroid-induced hypersensitivity reactions do occur. They range from minor rashes to the more serious cardiovascular collapse. The mechanisms of steroid-induced adverse events vary from patient to patient, some being classic immunoglobulin E-mediated whereas others are pseudoallergic in nature. Skin testing and provocative challenges offer two ways to diagnose such reactions. Treatment consists of substituting the steroid with an alternative preparation, which can be tolerated by the patient. CONCLUSIONS: Although little is known about the epidemiology of steroid-induced hypersensitivity, because most data are derived from case reports, it is clear that steroid-induced hypersensitivity is a heterogeneous entity, with no single uniform mechanism. A great deal of work still needs to be done so that the pathogenesis of such adverse events can be clearly determined and effective therapeutic interventions devised.

6459.      Csoma Z, Kharitonov SA, Balint B, Bush A, Wilson NM, Barnes PJ. Increased leukotrienes in exhaled breath condensate in childhood asthma. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1345-9

Cysteinyl leukotrienes (cys-LTs; LTC4, LTD4, and LTE4) are generated predominantly by mast cells and eosinophils and induce airway smooth muscle contraction, microvascular leakage, and mucous hypersecretion whereas leukotriene B4 (LTB4) is a potent chemoattractant of neutrophils. We measured cys-LTs and LTB4 in exhaled breath condensate from children aged 7-14 years including healthy nonatopic children (n = 11) and children with mild intermittent asthma (steroid naive, n = 11), mild persistent asthma (low-dose inhaled steroid treatment, n = 13), or moderate to severe persistent asthma (high-dose inhaled steroid treatment, n = 13). Exhaled LTB4 levels were increased in patients with mild and moderate to severe persistent asthma compared with patients with mild intermittent asthma (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 52.7 +/- 3.8 pg/ml, p < 0.001 and p < 0.0001) and normal subjects (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 47.9 +/- 4.1 pg/ml, p < 0.0001). Elevated exhaled cys-LT levels were found in patients with mild and moderate to severe persistent asthma compared with normal subjects (27.9 +/- 2.8 and 31.5 +/- 4.5 versus 18.5 +/- 0.5 pg/ml, p < 0.01 and p < 0.05). There was an inverse correlation between exhaled cys-LTs and LTB4 in patients with mild persistent asthma. We conclude that exhaled cys-LTs and LTB4 may be noninvasive markers of airway inflammation in pediatric asthma.

6460.      Deramo M. Food challenges vs. skin antigen testing. Am Fam Physician. 2002 Dec 1;66(11):2048. No abstract.

6461.      Desai PR, Babu M. Scimitar syndrome as a differential diagnosis in a child with recurrent wheeze. Arch Dis Child. 2002 Oct;87(4):357. No abstract.

6462.      Diaz-Perales A, Tabar AI, Sanchez-Monge R, Garcia BE, Gomez B, Barber D, Salcedo G.  Characterization of asparagus allergens: a relevant role of lipid transfer proteins. J Allergy Clin Immunol. 2002 Nov;110(5):790-6.

BACKGROUND: No asparagus allergen has been characterized to date. Lipid transfer proteins (LTPs) have an ubiquitous distribution in plant foods and have been identified as relevant allergens in some fruits, seeds, and pollens. OBJECTIVE: We sought to identify asparagus allergens and to evaluate the potential involvement of the panallergen LTP family in asparagus allergy. METHODS: Eighteen patients with asthma, anaphylaxis, and/or contact urticaria after asparagus ingestion or exposure and positive skin prick test (SPT) responses and serum-specific IgE levels to asparagus were selected. Two LTPs were isolated from crude asparagus extract by using chromatographic methods and characterized by means of N-terminal amino acid sequencing. Both isolated proteins were tested by means of immunodetection, CAP inhibition assays, and SPTs. Additional aspara gus allergens were located by using immunodetection with a pool of sera from patients allergic to asparagus and with rabbit polyclonal antibodies to sunflower pollen profilin and anti-complex asparagine-linked glycans antibodies. RESULTS: The purified LTPs showed an N-terminal amino acid sequence similar to that of Pru p 3 and a strong reaction to anti-Pru p 3 antibodies. Each isolated protein reached inhibition values of up to 60% in CAP inhibition assays against asparagus extracts and elicited positive SPT responses in 9 of 18 patients with asparagus allergy. Immunodetection assays allowed us to identify profilin and cross-reacting carbohydrate determinants as asparagus IgE-binding components. CONCLUSION: Asparagus LTPs are relevant allergens. In addition, profilin and glycoproteins harboring complex asparagine-linked glycans can also be involved in asparagus allergy.

6463.      Eishi K, Lee JB, Bae SJ, Takenaka M, Katayama I. Impaired sweating function in adult atopic dermatitis: results of the quantitative sudomotor axon reflex test. Br J Dermatol. 2002 Oct;147(4):683-8.

BACKGROUND: Impaired sweating is thought to be a cause of barrier dysfunction in atopic dermatitis (AD). OBJECTIVES: To examine the sweating function in AD in a quantitative manner. METHODS: We investigated the sweating response of lesional and non-lesional skin of adult patients with AD by a quantitative sudomotor axon reflex test in which the axon reflex is stimulated by acetylcholine iontophoresis. Sweat volume on the volar aspect of the forearm was measured in 18 adult patients with AD and in 40 non-atopic controls; five patients with Sjogren's syndrome were also studied as disease comparators. We also evaluated the sweating function in four AD patients after topical corticosteroid therapy. Latency time, direct (DIR) sweat volume and axon reflex-mediated indirect (AXR) sweat volumes were the variables studied. RESULTS: The latency time in AD patients was significantly prolonged and AXR sweat volume significantly reduced compared with those in non-atopic control subjects. The latency time and AXR sweat volume of lesional AD skin were significantly more prolonged and reduced, respectively, than those of non-lesional skin. In contrast, the DIR sweat volume of lesional or non-lesional AD skin induced by direct stimulation with acetylcholine was only slightly reduced when compared with that in non-atopic controls. Latency time and sweat volumes of lesional and non-lesional AD skin improved after topical corticosteroid therapy. CONCLUSIONS: These results suggest that the impaired sweat response in AD is attributable to an abnormal sudomotor axon reflex, which is reversed by topical corticosteroid administration.

6464.      El-Asrar AM, Al-Kharashi SA. Full panretinal photocoagulation and early vitrectomy improve prognosis of retinal vasculitis associated with tuberculoprotein hypersensitivity (Eales' disease). Br J Ophthalmol. 2002 Nov;86(11):1248-51.

BACKGROUND/AIMS: Eales' disease is an uncommon vasoproliferative retinal disease affecting otherwise healthy young men that is characterised by obliterative retinal periphlebitis, with sequelae such as recurrent vitreous haemorrhage and traction retinal detachment. This study was undertaken to determine whether visual prognosis of Eales' disease could be improved by appropriate medical and surgical treatment. METHODS: The authors retrospectively studied 30 patients (46 eyes) who were treated from 1992 to 2001. Recorded data included patient age, sex, race, medical history, medications, results of the ophthalmological examination, results of diagnostic laboratory evaluation, and details of systemic and surgical treatments. The mean follow up was 10.6 months. RESULTS: 19 patients (23 eyes) who presented with active periphlebitis received systemic steroids and antituberculous therapy. Extensive full panretinal photocoagulation was performed in 21 eyes that presented with new vessel formation and peripheral capillary closure with or without vitreous haemorrhage. Vitrectomy and endolaser panretinal photocoagulation was necessary in 15 eyes, for severe non-clearing vitreous haemorrhage in 11 eyes and vitreous haemorrhage with traction retinal detachment in four eyes. Complete regression of the disease was achieved in all eyes. Vitrectomy resulted in a significant visual improvement with 14 of the 15 eyes (93.3%) achieving > or =20/200 visual acuity. Overall, the distribution of visual acuities among eyes improved from presentation to final follow up, with 36.4% of eyes having 20/40 or better acuity at presentation compared with 63.6% of eyes by final follow up. CONCLUSIONS: These results suggest that aggressive treatment of Eales' disease with systemic steroids and antituberculous therapy, full panretinal photocoagulation and early vitrectomy, when necessary, may result in improving the anatomic and visual outcome.

6465.      El-Azhary RA, Yiannias JA. Allergic contact dermatitis to epoxy resin in immersion oil for light microscopy. J Am Acad Dermatol. 2002 Dec;47(6):954-5.

Allergic contact dermatitis caused by immersion oil used for microscopy is a recently recognized phenomenon. We report a case with characteristic findings of periorbital erythema and edema in a cytogenetics technician. Positive patch test responses to epoxy resin, epoxy acrylate, and the immersion oil were noted. This case represents yet another contact allergic reaction, possibly airborne, to epoxy resin present in immersion oil used for microscopy.

6466.      Fiocchi A, Bouygue GR, Restani P, Bonvini G, Startari R, Terracciano L. Accuracy of skin prick tests in IgE-mediated adverse reactions to bovine proteins. Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl 1):26-32. Review.

OBJECTIVES: To review the recent literature on the diagnostic accuracy of skin prick tests (SPTs) in pediatric food allergy, focusing on adverse reactions to milk and beef. To present data about the test performance characteristics of beef extracts used in SPTs among children with atopic dermatitis (AD) reporting immediate hypersensitivity to beef. DATA SOURCES: MEDLINE search using the following algorithm ["skin prick test" AND "food allergy" OR allergen; 1997-2002; English; all children]. Prospective sensitivity study of SPTs in 34 patients. STUDY SELECTION: Thirty-four children with AD (median age 2.29 years) were consecutively recruited between 1992 and 2000 because of immediate reactions to beef. On double-blind, placebo-controlled food challenges (entry criterion), 20 of the patients reacted to beef and 14 did not. Cut-off points for skin prick test wheal positivity was selected by receiving-operator characteristic analysis for fresh and commercial beef allergens. Sensitivity and specificity of skin tests and indices of reproducibility were calculated. RESULTS: In the literature, the positive predictive accuracies of skin prick tests vary between 69 and 100% and the negative predictive accuracies between 20 to 86% for cow's milk. In our series, SPTs with commercial beef extracts were highly diagnostic (100% sensitivity; 10% false positive rate) and SPTs with fresh beef were highly specific (100%), albeit with a false-positive rate of 21.42%. CONCLUSIONS: From the literature, we conclude that the diagnostic accuracy of SPTs with milk should be reappraised in the workup of cow's milk allergy. Carrying out commercial and fresh food SPTs at the same time substantially reduces costs and diagnostic work. Oral provocation is necessary in 20.68% of children with AD who have immediate symptoms to beef. Greater allergen standardization and streamlining of the workup of cow's milk allergy are desirable future goals.

6467.      Friedmann PS. The pathogenesis of atopic eczema. Hosp Med. 2002 Nov;63(11):653-6.

Atopic eczema is associated with a genetic predisposition to dysregulation of the immune system. T lymphocytes differentiate towards the Th2 type with promotion of immunoglobulin E antibodies. Allergic responses to environmental allergens develop and microbes, including staphylococci and pityrosporum yeasts, may contribute to the inflammatory process.

6468.      Fung MA. The clinical and histopathologic spectrum of "dermal hypersensitivity reactions," a nonspecific histologic diagnosis that is not very useful in clinical practice, and the concept of a "dermal hypersensitivity reaction pattern". J Am Acad Dermatol. 2002 Dec;47(6):898-907.

BACKGROUND: "Dermal hypersensitivity reaction" (DHR) is diagnosed by dermatopathologists but is not an accepted clinical disease entity. There are no clear guidelines for its diagnosis, differential diagnosis, or management. 

OBJECTIVES: The objectives were to define the histologic criteria for cases histologically diagnosed as DHR and identify corresponding clinical disorders. METHODS: Skin biopsy specimens from 130 patients diagnosed as "consistent with DHR" were reviewed. Additional information was obtained from patients, their dermatologists, and medical records. RESULTS: Follow-up in 74 of 110 patients (median, 26.6 mo) revealed, most commonly, diagnoses of urticaria, drug reactions, and spongiotic (eczematous) dermatitis. Among the remaining cases, 37 of 59 reported persistence of disease, some exhibiting a uniform phenotype characterized by excoriated, edematous papules on the trunk. Histopathologic features present in more than 90% of 143 biopsy specimens included superficial and mid-perivascular lymphocytic infiltrates with eosinophils. CONCLUSION: DHR is a perivascular lymphocytic dermatitis with eosinophils involving the papillary and upper reticular dermis and minimal, if any, primary epidermal alteration. The term DHR does not represent any known clinical disorder; rather, it corresponds to many clinical disorders. The use of the phrase "dermal hypersensitivity reaction pattern" may be helpful in conveying the idea that a particular histologic pattern may be seen in a number of clinical disorders.

 

6469.      Gavrovic-Jankulovic M, cIrkovic T, Vuckovic O, Atanaskovic-Markovic M, Petersen A, Gojgic G, Burazer L, Jankov RM. Isolation and biochemical characterization of a thaumatin-like kiwi allergen. J Allergy Clin Immunol. 2002 Nov;110(5):805-10.

BACKGROUND: Kiwi fruit allergy, as well as its association with hypersensitivity to other foods and to pollen, has been extensively reported in the last few years. Several IgE-binding components have been detected in kiwi extract, but only one 30- kd allergen has been isolated; it was identified as actinidin (Act  c 1). Recently, we have reported a 24-kd kiwi protein to be a potential major allergen in a group of patients with oral allergy syndrome (OAS).

OBJECTIVE: The aim of this study was to purify and characterize the 24-kd kiwi allergen biochemically. METHODS: Seven polysensitized patients with OAS to kiwi were used in this study. The kiwi allergen was isolated by using a combination of gel permeation, ion exchange, and immobilized metal ion affinity chromatography. Its biochemical characterization included determination of its isoelectric point, molecular weight, N-terminal sequencing, concanavalin A -binding ability, digestibility in simulated gastric fluid, and antifungal activity. Western blotting, 2-dimensional PAGE immunoblotting, and skin prick tests were performed to characterize the isolated protein immunochemically. RESULTS: All 7 patients recognized the isolated 24-kd kiwi protein as an allergen. The isolated protein consisted of 2 isoforms with isoelectric points of 9.4 and 9.5 migrated as one protein band of 20 kd after SDS-PAGE under nonreducing conditions or at 24 kd under reducing conditions. The partial N-terminal sequence revealed that it is a thaumatin-like protein (TLP) with concanavalin A -binding ability. The protein showed antifungal activity toward Saccharomyces carlsbergensis, and Candida albicans. The protein was degraded by the simulated gastric fluid within 1 minute. Both isoforms bound IgE from a pool of sera in a 2-dimensional PAGE immunoblot. The TLP elicited positive skin prick test responses in 4 (80 %) of 5 patients with OAS. CONCLUSION: This study reported isolation and full characterization of a new kiwi allergen, TLP (isoelectric points of 9.4 and 9.5 and molecular weight of 24 kd), which belongs to the family of pathogenesis-related proteins. The isolated protein expressed antifungal activity toward S carlsbergensis and C albicans.

 

 

6470.      Gehring U, Bischof W, Fahlbusch B, Wichmann HE, Heinrich J. House dust endotoxin and allergic sensitization in children. Am J Respir Crit Care Med. 2002 Oct 1;166(7):939-44.

A higher exposure to endotoxin was hypothesized to contribute to lower prevalence of allergic sensitization and hay fever in children growing up on a farm. We studied the association between house dust endotoxin and allergic sensitization. We randomly selected 740 children, aged between 5 and 10 years, from a group of children who participated in two cross-sectional surveys performed in Saxony-Anhalt, Germany, from 1992 to 1993 and from 1995 to 1996, such that 50% of the children were atopic or had a diagnosis of asthma. From 1996 to 1998, we collected living-room floor dust in the homes of 454 of these children (61%). The content of endotoxin in house dust was quantified using a chromogenic kinetic limulus amoebocyte lysate test and was related with health outcomes measured in the preceding cross-sectional surveys. Multiple logistic regression analyses adjusted for place of residence, sex, age, parental education, parental atopy, and pet ownership showed a negative association between exposure to endotoxin and sensitization to one or more allergens (aOR [95% CI] 0.95 [0.83; 1.10]) and two or more allergens (aOR [95% CI] 0.80 [0.67; 0.97]) using 0.35 kU/L as the cutoff value for sensitization. The protective effect was strengthened with increasing degree of sensitization. In conclusion, exposure to higher levels of house dust endotoxin is associated with lower prevalence of allergic sensitization in children.

6471.      Gorelick MH, Stevens MW, Schultz TR. Comparability of acute asthma severity assessments by parents and respiratory therapists. Arch Pediatr Adolesc Med. 2002 Dec;156(12):1199-202.

OBJECTIVE: To compare the assessments of parents and respiratory therapists (RTs) of acute asthma severity in children discharged after emergency department (ED) treatment. DESIGN: Prospective cohort study. SETTING: Home care visit within 24 hours of discharge from an urban children's hospital ED. PARTICIPANTS: Children aged 2 to 17 years discharged to home after treatment in the ED (at least 1 inhaled bronchodilator treatment administered) were randomly selected to have a home care visit. MAIN OUTCOME MEASURES: Registered RTs went to the child's home and asked the parent questions about his or her perception of the child's symptoms. The RT performed a clinical assessment including pulse oximetry. RESULTS: Ninety children were selected for home care, and 51 patients (57%) successfully completed the home care visit; 48 (53%) underwent a complete assessment by both raters. There were no differences in demographic features or ED clinical variables between those successfully contacted and those not reached. Of those evaluated, 43 parents (84%) reported their child's asthma was improved, and the rest reported no change. Parents underestimated the degree of wheezing or work of breathing relative to the RT in 3 of 48 patients (6%), but only 1 of these was considered substantial (>1 point discrepancy). Findings were overestimated in 14 (29%) of 48 cases, but only 5 (10%) were substantial. CONCLUSIONS: Parents and RTs provide comparable assessments of acute asthma severity in children within 24 hours of discharge from the ED. Clinically important discrepancies are uncommon, and underestimation of severity by parents is rare.

 

6472.      Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, Wardlaw AJ, Pavord ID. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002 Nov 30;360(9347):1715-21.

BACKGROUND: Treatment decisions in asthma are based on assessments of symptoms

and simple measures of lung function, which do not relate closely to underlying eosinophilic airway inflammation. We aimed to assess whether a management strategy that minimises eosinophilic inflammation reduces asthma exacerbations compared with a standard management strategy. METHODS: We recruited 74 patients with moderate to severe asthma from hospital clinics and randomly allocated them to management either by standard British Thoracic Society asthma guidelines (BTS management group) or by normalisation of the induced sputum eosinophil count and reduction of symptoms (sputum management group). We assessed patients nine times over 12 months. The results were used to manage those in the sputum management group, but were not disclosed in the BTS group. The primary outcomes were the number of severe exacerbations and control of eosinophilic inflammation, measured by induced sputum eosinophil count. Analyses were by intention to treat. FINDINGS: The sputum eosinophil count was 63% (95% CI 24-100) lower over 12 months in the sputum management group than in the BTS management group (p=0.002). Patients in the sputum management group had significantly fewer severe asthma exacerbations than did patients in the BTS management group (35 vs 109; p=0.01) and significantly fewer patients were admitted to hospital with asthma (one vs six, p=0.047). The average daily dose of inhaled or oral corticosteroids did not differ between the two groups. INTERPRETATION: A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment.

6473.      Greenberger PA. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol. 2002 Nov;110(5):685-92. Review.

Allergic bronchopulmonary aspergillosis (ABPA) complicates asthma and cystic fibrosis. The survival factors in Aspergillus fumigatus that support saprophytic growth in bronchial mucus are not understood. Prednisone remains the most definitive treatment but need not be administered indefinitely. MHC II -restricted CD4(+) T( H)2 clones have been derived from patients with ABPA. The total serum IgE concentration is elevated sharply but is "nonspecific. " IgE serum isotypic antibodies to A fumigatus are useful in diagnosis; this is in contrast to the situation for patients with asthma without ABPA. High-resolution computed tomography of the chest demonstrates multiple areas of bronchiectasis in most patients with ABPA and is a useful radiologic tool. Some asthma control patients might have a few bronchiectatic airways, but not to the extent seen in or of the same character as those in ABPA. This review discusses clinical, radiologic, investigational, pathogenetic, and treatment issues of ABPA.

6474.      Greenberger PA. Corresponding patterns of rhinitis and asthma during pregnancy. Ann Allergy Asthma Immunol. 2002 Nov;89(5):437-8. No abstract.

6475.      Grob M, Reindl J, Vieths S, Wuthrich B, Ballmer-Weber BK. Heterogeneity of banana allergy: characterization of allergens in banana-allergic patients. Ann Allergy Asthma Immunol. 2002 Nov;89(5):513-6.

BACKGROUND: Banana is a frequent cause of food allergy, particularly in latex-sensitized patients.

OBJECTIVE: The aim of the study was to get insights in immunoglobulin (Ig)E antibody responses of patients with a history of allergic reaction to banana but not to latex. METHODS: In four patients who complained about symptoms after banana consumption, skin prick tests (SPTs) with aeroallergens, latex, banana, avocado, and kiwi were performed. Total and specific serum IgE to birch pollen, rBet v 1 and rBet v 2, latex, banana, avocado, and kiwi were determined by the CAP method (Pharmacia Diagnostics, Uppsala, Sweden). Allergens were identified by immunoblotting with banana extract and recombinant banana profilin. Two patients underwent double-blind, placebo-controlled food challenges (DBPCFC) with banana. RESULTS: All patients showed a positive SPT to banana, and three were IgE-CAP positive (> or = class 2). Two patients were also sensitized (SPT and CAP) to latex, avocado, kiwi, and birch pollen. In the immunoblot these two patients' sera reacted to 32- to 34-kDa proteins, which had already been described as major banana allergens. In both patients banana allergy was confirmed by DBPCFC. The third patient also had a sensitization to avocado, but not to latex or pollen. Immunoblot analysis detected a single band at 70 kDa. The fourth patient was sensitized to birch pollen, rBet v 1 and rBet v 2, but not to latex. Immunoblot analysis in this patient's serum was positive with recombinant banana profilin. CONCLUSIONS: The relevance of banana as a source of food allergy was confirmed in two patients by DBPCFC. In 1 of 2 patients, in whom banana allergy was not a consequence of latex sensitization, a 70-kDa protein was identified as a banana allergen, and in the other patient profilin was detected as a putative cross-reactive allergen.

6476.      Hall SW. Idiopathic environmental intolerances. Minn Med. 2002 Oct;85(10):33-6.

Health concerns related to the quality of the environment in offices, schools, homes, and residences have increased dramatically over the past 2 decades. One health problem frequently confronting medical practitioners and often attributed to environmental quality problems is idiopathic environmental intolerances (IEI). Formerly known as multiple chemical sensitivities, IEI is an acquired disorder characterized by adverse reactions attributed to exposure to a variety of substances under ordinary conditions. Alleged precipitants include solvents, pesticides, detergents, dusts, and fragrances. Symptoms include fatigue, malaise, headache, concentration and memory difficulties, lightheadedness, cough, hoarseness, and rhinitis without objective physical signs or consistent laboratory abnormalities. The role of the environment in precipitating these complaints continues to be controversial, and no intervention or treatment has thus far been proven to be effective. While not progressive or life threatening, IEI is often functionally disabling and very distressing to affected individuals. The investigation of IEI should involve, at a minimum, a clinical evaluation of the affected person and in most cases an environmental evaluation as well. IEI should be managed without overutilization of diagnostic tests or prescription of unnecessary environmental, occupational, or dietary restrictions.

6477.      Howard TD, Postma DS, Koppelman GA, Koppelman GH, Zheng SL, Wysong AK, Xu J, Meyers DA, Bleecker ER.  Fine mapping of an IgE-controlling gene on chromosome 2q: Analysis of CTLA4 and CD28. J Allergy Clin Immunol. 2002 Nov;110(5):743-51.

BACKGROUND: Several genomic regions have been identified that might contain genes contributing to the development of asthma and atopy. These include chromosome 2q33, where we have observed evidence for linkage for variation in total serum IgE levels in a Dutch asthma population. Two candidate genes, CTLA4 and CD28, important homeostatic regulators of T-cell activation and subsequent IgE production, map within this candidate region.

OBJECTIVE: We sought to fine-map the chromosome 2q33 region and evaluate CTLA4 and CD28 as candidate genes for the regulation of total serum IgE levels and related phenotypes. METHODS: The coding regions of CTLA4 and CD28 were resequenced in 96 individuals; 4 novel SNPs in CTLA4 and 10 in CD28 were identified. Polymorphisms in both genes were analyzed in 200 asthmatic probands and their spouses (n = 201). RESULTS: Subsequent fine- mapping in this region has resulted in an increased log of the odds (lod) score (1.96 to 3.16) for total serum IgE levels. For CTLA4, the +49 A/G single nucleotide polymorphism (SNP) in exon 1 and the 3 ' untranslated region microsatellite were significantly associated with total serum IgE levels (P =.0005 and.006, respectively). For the combined +49 A/G and 3 'untranslated region genotypes, individuals homozygous for the risk allele for both polymorphisms (AA and 86/86) had the highest total serum IgE values (87.1 IU/mL), whereas those individuals with the GG and XX/XX genotypes (anything but the 86-bp allele) had the lowest IgE values (29.3 IU/mL). Significant association was also observed for the CTLA4 -1147 C/T SNP with bronchial hyperresponsiveness (BHR) and asthma (P =.008 and.012, respectively), but not for allergy-related phenotypes. Promoter luciferase assays examining the –1147 polymorphism suggested that the T allele, which was associated with increased BHR susceptibility, was expressed at half the level of the C allele. Individuals with the risk genotypes for both BHR (-1147 CT or TT) and elevated IgE levels (+49 AA) were 4.5 times more likely to have asthma than individuals with both nonrisk genotypes (P =.0009). No significant associations were observed for SNPs in CD28. CONCLUSION: These data suggest that the costimulatory pathway, specifically CTLA4, is important in the development of atopy and asthma.

 

6478.      Kanazawa H, Hirata K, Yoshikawa J. Involvement of vascular endothelial growth factor in exercise induced bronchoconstriction in asthmatic patients. Thorax. 2002 Oct;57(10):885-8.

BACKGROUND: There is evidence that the bronchial microcirculation has the potential to contribute to the pathophysiological mechanisms of exercise induced bronchoconstriction (EIB) in asthmatic subjects. Vascular endothelial growth factor (VEGF), which is highly expressed in asthmatic airways, increases vascular permeability. The relationship between VEGF levels in induced sputum and the severity of EIB in asthmatic subjects was studied. METHODS: The concentration of VEGF in induced sputum was examined in 23 asthmatic subjects and 11 normal controls. The asthmatic subjects performed an exercise test and the % maximal fall in forced expiratory volume in 1 second (FEV(1)) was measured. Beclomethasone dipropionate (BDP) 400 micro g twice daily was administered to the asthmatic subjects for 8 weeks and the exercise test and sputum induction were repeated. RESULTS: The concentration of VEGF in induced sputum was significantly higher in asthmatic subjects than in normal controls. There was a significant correlation between the concentration of VEGF and the % maximal fall in FEV(1) (r=0.826, p=0.0001) and between the concentration of VEGF and airway vascular permeability index (r=0.621, p=0.0037). After treatment with inhaled BDP there was a significant decrease in the concentration of VEGF in the asthmatic subjects (before treatment: 7051 (2361) pg/ml, after treatment: 4498 (2135) pg/ml, p<0.0001). The change in the concentration of VEGF was significantly correlated with the change in the % maximal fall in FEV(1) (r=0.463, p=0.031). CONCLUSIONS: Excessive production of VEGF in asthmatic airways may contribute to the pathogenesis of EIB via increased airway vascular permeability.

 

6479.      Kim HK, Shin BK, Cho SJ, Moon JS, Kim MK, Kim CY, Park SH, Kim KT, In KH, Oh YH, Kang EY, Park SH, Kim I.  Transthoracic fine needle aspiration and core biopsy of pulmonary lesions. A study of 296 patients. Acta Cytol. 2002 Nov-Dec;46(6):1061-8.

OBJECTIVE: To retrospectively investigate and compare the usefulness of transthoracic fine needle aspiration (FNA), core biopsy and a combination of the two in the diagnosis of pulmonary lesions. STUDY DESIGN: Two hundred ninety-six patients who had undergone FNA, core biopsy or both for lung lesions were divided into malignant and benign groups according to the final diagnoses, which were based on the cytologic and histopathologic findings combined with clinical features. In each group, the diagnostic usefulness of FNA, core biopsy and a combination of the two were evaluated by comparing the results of each with the final diagnoses. RESULTS: In the malignant group, FNA was diagnostically helpful in 188 of 205 patients (91.7%) and core biopsy in 158 of 180 patients (87.8%). The combination of the two methods improved the result to 172 of 178 patients (96.6%). The sensitivities were 94.6%, 88.3% and 97.2%, respectively, for each result. In the benign group, 71.1% (64/90), 70.1% (47/67) and 74.2% (49/66) of cases received specific or nonspecific diagnoses by FNA, core biopsy and their combination, respectively. The rates of specific diagnoses were 20.1%, 21.0% and 31.8%, respectively. CONCLUSION: The combination of FNA and core biopsy markedly improved the diagnostic yields in the malignant group and, to a lesser degree, also in the benign group.

6480.      Kleine-Tebbe J, Vogel L, Crowell DN, Haustein UF, Vieths S. Severe oral allergy syndrome and anaphylactic reactions caused by a Bet v 1-related PR-10 protein in soybean, SAM22. J Allergy Clin Immunol. 2002 Nov;110(5):797-804.

BACKGROUND: Anaphylactic reactions to soy products have been attributed to stable class 1 food allergens. OBJECTIVE: IgE- mediated reactions to a soy-containing dietary food product in patients allergic to birch pollen were investigated. METHODS: Detailed case histories were taken from 20 patients. Their sera were analyzed for IgE (UniCAP) specific for birch, grass, mugwort, the recombinant birch allergens rBet v 1 and rBet v2, and soy protein. Extracts from birch pollen, soy isolate, rBet v 1, and the recombinant PR-10 soy protein rSAM22 were coupled to paper disks or nitrocellulose for IgE measurements (enzyme allergosorbent test) or Western blot analysis. Enzyme allergosorbent testing, Western blot inhibition, and histamine release studies were performed with the same allergens. RESULTS: Most patients (17/20) experienced facial, oropharyngeal, and/or systemic allergic symptoms within 20 minutes after ingesting the soy product for the first time. Birch pollen allergy (16/20) was common, along with oral allergy syndrome to apple (12/20) or hazelnut (11/20). IgE levels to birch and Bet v 1 but not to other inhalants were high in 18 of 20 patients. Significant IgE binding to rSAM22 occurred in 17 of 20 patients. Blot experiments with the soy isolate revealed IgE-binding bands at 17 kd (15/20), 22 kd (1/20), and 35 to 38 kd (2/20); the former was inhibited by preincubation of the sera with rBet v 1 or rSAM22. Birch extract and soy isolate, rBet v 1, and rSAM22 induced dose-dependent histamine release in the nanomolar range. CONCLUSION: Immediate-type allergic symptoms in patients with birch pollen allergy after ingestion of soy protein-containing food items can result from cross-reactivity of Bet v 1 -specific IgE to homologous pathogenesis-related proteins, particularly the PR-10 protein SAM22.

6481.      Kopp MV, Brauburger J, Riedinger F, Beischer D, Ihorst G, Kamin W, Zielen S, Bez, Friedrichs F, Von Berg A, Gerhold K, Hamelmann E, Hultsch, Kuehr J. The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis. J Allergy Clin Immunol. 2002 Nov;110(5):728-35.

BACKGROUND: Binding of allergens with IgE to the IgE receptors on mast cells and basophils results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs), triggering allergic cascades that result in allergic symptoms, such as asthma and rhinitis. OBJECTIVE: We sought to investigate whether anti-IgE (Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy (SIT) affects the leukotriene pathway. METHODS: Ninety-two children (age range, 6-17 years) with sensitization to birch and grass pollens and with seasonal allergic rhinitis were included in a phase III, placebo- controlled, multicenter clinical study. All subjects were randomized to one of 4 treatment groups. Two groups subcutaneously received birch SIT and 2 groups received grass SIT for at least 14 weeks before the start of the birch pollen season. After 12 weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical efficacy variable was symptom load (ie, the sum of daily symptom severity score and rescue medication score during pollen season). Blood samples taken at baseline and at the end of study treatment after the grass pollen season were used for separation of leukocytes in this substudy. After in vitro stimulation of the blood cells with grass and birch pollen allergens, SLT release (LTC4, LTD4, and LTE4) was quantified by using the ELISA technique. RESULTS: Before the study treatment, SLT release to birch and grass pollen exposure did not differ significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n = 23), a lower symptom load occurred during the pollen season compared to placebo + SIT-grass (n = 24, P =.012). The same applied to both groups receiving birch SIT (n = 23 and n = 22, respectively; P =.03). At the end of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT, resulted in significantly lower SLT release after stimulation with the corresponding allergen (416 ng/L [5th-95th percentile, 1-1168] and 207 ng/L [1-860 ng/L], respectively) compared with placebo plus SIT (2490 ng/L [384-6587 ng/L], P =.001; 2489 ng/L [1-5670 ng/L], P =.001). In addition, treatment with anti-IgE was also followed by significantly lower SLT releases to the allergens unrelated to SIT (grass SIT 300 ng/L [1-2432 ng/L] in response to birch allergen; birch SIT: 1478 ng/L [1-4593 ng/L] in response to grass pollen) in comparison with placebo (grass SIT: 1850 ng/L [1-5499 ng/L], P =.001; birch SIT: 2792 ng/L [154-5839 ng/L], P =.04]. CONCLUSION: Anti-IgE therapy reduces leukotriene release of peripheral leukocytes stimulated with allergen in children with allergic rhinitis undergoing allergen immunotherapy independent of the type of SIT allergen used.

 

6482.      Krumbiegel P, Denk E, Russow R, Rolle-Kampczyk U, Metzner G, Herbarth O. (15)N(2)]arginine as a first potential inhaled diagnostic agent to characterize respiratory diseases. Exp Lung Res. 2002 Oct-Nov;28(7):535-42.

Conventional diagnosis of the pulmonary tract uses physical methods such as spirometry and oscillometry. However, the inhalation of a chemical diagnostic agent ought to provide novel ways of more specific diagnosis, for instance of inflammatory states of the bronchial and lung mucosa. The stable isotope technique using a (15)N-labeled substrate appears to be a suitable tool for this application. In a pilot study, defined amounts of the amino acid L-[guanidino-(15)N(2)]arginine monohydrochloride (aqueous solution, 20 atom % (15)N) were inhaled as a diagnostic agent by healthy volunteers and pulmonary patients suffering from asthma bronchiale. The amino acid is resorbed and partly metabolized to (15)NO. The exhaled air was collected under defined conditions in 10-L breath bags and analyzed for NO using chemiluminescence. Under standardized test conditions, healthy persons (n = 6) exhaled 0.97 +/- 0.08 micromol NO/m(3) and asthmatic patients (n = 7) 1.17 +/- 0.14 micromol NO/m(3). A better distinction was expected comparing the (15)NO exhalation. The (15)N abundance of NO was determined using a Cryotrap gas chromatography - mass spectrometry set-up. Between 30 and 80 minutes after inhaling 700 mg [(15)N]arginine, a maximum with a plateau of the (15)NO abundance was found in the exhaled air. At this time, healthy and asthmatic subjects exhibited clear differences in their exhaled (15)NO amounts. Under standardized test conditions, the healthy persons (n = 6) exhaled 102.3 +/- 6.7 nmol (15)NO/m(3), whereas asthmatic patients (n =7) exhaled only 76.1 +/- 10.9 nmol (15)NO/m(3). It is concluded that (15)NO yielded after the inhalation of (15)N-labeled arginine could be a potential marker for demonstrating pathophysiological changes in the lung epithelium. This method could pave a new diagnostic principle of "inhalative breath test."

 

6483.      Kukurin GW. Chronic pediatric asthma and chiropractic spinal manipulation: a prospective clinical series and randomized clinical pilot study. J Manipulative Physiol Ther. 2002 Oct;25(8):540-1. No abstract.

6484.      Lai DS, Lue KH, Hsieh JC, Lin KL, Lee HS. The comparison of the efficacy and safety of cetirizine, oxatomide, ketotifen, and a placebo for the treatment of childhood perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2002 Dec;89(6):589-98.

BACKGROUND: There has been no study comparing the long-term effects of ketotifen, oxatomide, and cetirizine for the treatment of perennial allergic rhinitis among children. OBJECTIVE: We conducted a study to compare the efficacy of the three agents for the treatment of perennial allergic rhinitis among children. METHODS: The study consisted of a double-blind, placebo-controlled, randomized design, comprising 69 perennial allergic rhinitis patients with mite allergy, aged 6 to 12 years, randomly assigned to 1 of 4 test treatment groups for 3 months: 19 in the cetirizine group (10 mg daily), 18 in the ketotifen group (1 mg, twice daily), 16 in the oxatomide group (1 mg/kg, twice daily), and 16 in the placebo group. We used the nasal symptom score of diary card and the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire and eosinophil cation protein peripheral blood total eosinophil count and immunoglobulin E level, eosinophil proportion from a nasal smear, and nasal peak expiratory flow rate to evaluate the effect of the four agents. RESULTS: Cetirizine was significantly more effective at reducing the mean rhinorrhea score compared with oxatomide for both weeks 8 and 12 (P < 0.01). Before the end of week 12, cetirizine was significantly more effective than ketotifen (P < 0.01). Cetirizine and oxatomide significantly decreased the mean Pediatric Rhinoconjunctivitis Quality of Life Questionnaire score compared with the placebo for week 12 (P < 0.05). CONCLUSIONS: Cetirizine was more effective than oxatomide and ketotifen for the relief of nasal congestion and rhinorrhea, and was responsible for significantly decreasing the eosinophil representation of a posttreatment nasal smear.

 

6485.      Lapid-Gortzak R, Rosen S, Weitzman S, Lifshitz T. Videokeratography findings in children with vernal keratoconjunctivitis versus those of healthy children. Ophthalmology. 2002 Nov;109(11):2018-23.

PURPOSE: To determine videokeratographic topography of eyes with vernal keratoconjunctivitis (VKC) and to assess whether the severity of the VKC is related to the presence of changes compatible with keratoconus. PARTICIPANTS: Seventy-six persons aged 6 to 21 years: 40 patients with VKC and 36 healthy controls. DESIGN: A comparative, observational case series. METHODS: We examined 76 persons, of whom 40 were patients with VKC and 36 were control subjects, and compared the outcomes of videokeratography (VKG) patterns (EyeSys Laboratories, Houston, TX), numerical corneal indices, and spherical equivalent refraction. MAIN OUTCOME MEASURES: Corneal topographic patterns, corneal numeric indices, and corneal mirror imagery. RESULTS: We found many more abnormal patterns on VKG among the VKC patients than expected when compared with 'normal' eyes (P = 0.02 for the right eye and P = 0.001 for the left eye). Videokeratography allowed us to define a subgroup of patients with infraclinical keratoconus. A trend of superior corneal steepening ('superior keratoconus') was also found.

CONCLUSIONS: Vernal keratoconjunctivitis patients have more abnormal corneal topographic patterns than non VKC controls. Videokeratography may help decide how to follow-up and treat a presumed self-limiting disease.

 

6486.      Laube BL, Curbow BA, Costello RW, Fitzgerald ST. A pilot study examining the relationship between stress and serum cortisol concentrations in women with asthma. Respir Med. 2002 Oct;96(10):823-8.

The mechanism (s) by which stress exacerbates asthma is unknown. One explanation could be a reduction in endogenous serum cortisol concentrations as a result of stress. Our objective was to determine if a reduction in morning serum cortisol concentrations is associated with higher levels of stress in women with asthma. In this pilot study, seven women with a history of allergic-asthma were prospectively assigned to either low, moderate, or high stress groups based on a combination of their level of current stress and their resources to cope with the stress. After stress group assignment, women donated a morning blood sample, which was analyzed for serum cortisol concentration by an independent laboratory whose personnel were blinded to the subjects' stress status. Three women were assigned to the low stress group, two to the moderate stress group and two to the high stress group. Serum cortisol concentrations ranged from 8 to 23 microg/dl, averaging 14 +/- 6 microg/dl. A Spearman rank correlation indicated that serum cortisol concentrations were significantly inversely related to the stress groupings (r(s) = -0.915; P = 0.025). These results suggest that a reduction in morning serum cortisol concentration may be associated with higher levels of stress and lower resources to cope with the stress in women with allergic-asthma.

6487.      Lewith GT, Hyland ME, Shaw S. Do attitudes toward and beliefs about complementary medicine affect treatment outcomes? Am J Public Health. 2002 Oct;92(10):1604-6. No abstract.

6488.      Litonjua AA, Milton DK, Celedon JC, Ryan L, Weiss ST, Gold DR. A longitudinal analysis of wheezing in young children: the independent effects of early life exposure to house dust endotoxin, allergens, and pets. J Allergy Clin Immunol. 2002 Nov;110(5):736-42.

BACKGROUND: It has been postulated that exposure to bacterial endotoxins and animals early in life might confer protection against the development of asthma and allergies. OBJECTIVE: We investigated the longitudinal effects of exposure to house dust endotoxin (HDE), allergen levels, and the presence of a dog in the home on wheezing in young children over a 4-year period. METHODS: Two hundred twenty-six children younger than 5 years were followed for 4 years. Endotoxin and allergen levels were measured from house dust collected at baseline. Longitudinal associations were investigated by using a proportional hazards technique that allowed for multiple outcomes per subject. RESULTS: Exposure to high concentrations of HDE of greater than the median level was associated with an increased risk for wheezing over the period of observation (multivariate relative risk, 1.52; 95 % CI, 1.07-2.14), but this risk rapidly decreased over time (P for trend =.005). Exposure to cockroach allergen was associated with increased risk for wheezing, whereas exposure to cat allergen and the presence of a dog in the home were both associated with decreased risk for wheezing. The risks associated with cockroach allergen, cat allergen, and dog did not change over the period of observation. CONCLUSION: The negative associations between exposures to dogs and cat allergen and wheeze appear to be independent of the effects of endotoxin and suggest that separate mechanisms might mediate the effects of HDE exposure and pet exposure on the developing immune system.

6489.      Mattos W, Lim S, Russell R, Jatakanon A, Chung KF, Barnes PJ. Matrix metalloproteinase-9 expression in asthma: effect of asthma severity, allergen challenge, and inhaled corticosteroids. Chest. 2002 Nov;122(5):1543-52.

BACKGROUND: Asthma is associated with remodeling of the extracellular matrix (ECM) and increased airway obstruction, and the mechanisms of this process are unknown. Matrix metalloproteinases (MMPs) are a group of enzymes capable of degrading the ECM. They are released along with their inhibitors, tissue inhibitor of MMP (TIMP). STUDY OBJECTIVE:s: To determine whether severe, persistent asthma is associated with increased levels of MMP-9 in the airway compared with mild asthma, and to assess the effect of both allergen exposure and steroid treatment on MMP-9 and TIMP-1 levels. DESIGN: Prospective analysis of levels and activity of MMP-9 and TIMP-1 in BAL fluid (BALF) and induced sputum obtained from asthmatics of differing disease severity. In patients with mild asthma, MMP-9 and TIMP-1 levels were studied in induced sputum following allergen challenge and in BALF after inhaled steroid therapy. PATIENTS: Eighteen patients with mild asthma, 10 patients with severe asthma, and 10 nonsmoking, atopic subjects had their sputum studied. Fourteen of the patients with mild

asthma underwent allergen challenge. BAL was collected from 16 patients with mild asthma before and after 4 weeks treatment with inhaled budesonide, 800 micro g bid, or placebo. RESULTS: Patients with severe asthma had increased levels and activity of sputum MMP-9 in their sputum compared with patients with mild asthma and normal subjects. Allergen challenge increased the MMP-9/TIMP-1 ratio and MMP-9 activity. Inhaled budesonide had no effect on MMP-9 or TIMP-1 in patients with mild asthma. CONCLUSIONS: MMP-9 may play a role in chronic airway inflammation and remodeling in asthma, as concentrations are increased in severe, persistent asthma and following allergen challenge. Inhaled steroids may not affect MMP-9 and TIMP in patients with mild asthma, and additional studies in patients with more severe asthma are needed.

6490.      Maziak W. Does the sibling effect have its origin in utero? Investigating birth order, cord blood immunoglobulin E concentration, and allergic sensitization at age 4 years. Am J Epidemiol. 2002 Nov 1;156(9):882;  No abstract.

6491.      McCann WA, Ownby DR. The reproducibility of the allergy skin test scoring and interpretation by board-certified/board-eligible allergists. Ann Allergy Asthma Immunol. 2002 Oct;89(4):368-71.

BACKGROUND: Allergy skin testing is a cornerstone in the evaluation of the allergic patient. This seemingly simple test is subject to multiple variables that can affect the result. OBJECTIVE: To evaluate the degree of variability among board-certified/board-eligible allergists in the scoring and interpretation of allergen skin tests. MATERIALS AND METHODS: A series of allergen prick skin tests were digitally photographed and a questionnaire generated. Approximately 70 board-certified/board-eligible allergists were asked to grade each test item and to interpret them as positive, negative, or indeterminate or if they desired a followup intradermal test. RESULTS: Thirty-three interpretable responses were obtained. The majority of respondents (24) used a grading scale of 0 to 4. Agreement among physicians using a 0 to 4+ scale ranged from a standard deviation of 0.26 to 1.35, with greatest agreement on items with median/mode scores of 4+. The largest standard deviations were found on test items with median/mode scores of 1+ to 2+. Interpretation of the test items also showed greatest variation for those items with median/mode scores of 1+ to 2+. The number of intradermal tests requested ranged from 0 to 11 (of 22 test items). CONCLUSIONS: The results demonstrate interphysician variation in the scoring and interpretation of epicutaneous skin tests. A questionnaire such as the one used here may serve a useful quality control instrument to ensure reproducible scoring of skin tests. In addition, the results highlight the need for greater study on the clinical utility of intradermal skin testing when epicutaneous tests are negative or equivocal.

6492.      Morell F, Roger A, Cruz MJ. Usefulness of specific skin tests in the diagnosis of hypersensitivity pneumonitis. J Allergy Clin Immunol. 2002 Dec;110(6):939. No abstract.

6493.      Naimer SA, Cohen AD, Mumcuoglu KY, Vardy DA. Household papular urticaria. Isr Med Assoc J. 2002 Nov;4(11 Suppl):911-3.

BACKGROUND: Papular urticaria often occurs after bites of insects such as mosquitoes, sandflies, bed bugs and fleas. Multiple bites and local pruritus are characteristic symptoms. Treatment is usually symptomatic and includes antihistamines and corticosteroids. The reappearance of the symptoms can be prevented by successful control of the parasite. OBJECTIVES: To find the causative agent of papular urticaria in afflicted households with involvement of numerous family members, all in a narrow geographic area. PATIENTS: We describe the cases of 20 patients belonging to seven families, who presented to the local primary clinic, suffering from papular urticaria. RESULTS: The cat flea, Ctenocephalides felis, was the hematophagous insect responsible for all infestations. The pruritus and the papular urticaria were treated symptomatically with calamine lotion, topical corticosteroids or oral antihistamines. All clinical symptoms disappeared within a few weeks after effective control of the parasites by spraying and fumigating the infested locations. CONCLUSIONS: Thorough investigation--including, at times, environmental inspection--is necessary to reach the rewarding discovery of the etiology of household papular urticaria. This condition may arise in other environments of similar character.

6494.      Nakayama K, Shinkawa M, Ohrui T, Hirai H, Sasaki H. Interferon-gamma responses to mycobacterial antigens in Heaf-positive children. Lancet. 2002 Oct 26;360(9342):1335. No abstract.

6495.      Paredi P, Kharitonov SA, Barnes PJ. Analysis of expired air for oxidation products. Am J Respir Crit Care Med. 2002 Dec 15;166(12 Pt 2):S31-7. Review.

Chronic inflammation is a critical feature of chronic obstructive pulmonary disease, cystic fibrosis, and asthma. This inflammation is associated with the increased production of reactive oxygen species or oxidative stress in the lungs. Oxidative stress may have several adverse effects and may amplify the inflammatory process; however, monitoring oxidative stress is difficult and may not be reflected by changes in blood markers. We have therefore developed several noninvasive markers in the exhaled breath that may indicate oxidative stress in the lungs, and we studied these in relationship to the severity of chronic inflammatory lung diseases. We analyzed the exhaled breath for the  content of nitric oxide as a marker of inflammation, carbon monoxide as a  marker of oxidative stress, and ethane, which is one of the end products of lipid peroxidation. In addition, we measured the concentration of markers of oxidative stress such as isoprostanes in exhaled breath condensate. Our results confirm that there are increased inflammation, oxidative stress, and lipid peroxidation in lung disease, as shown by elevated levels of nitric oxide, carbon monoxide, and ethane, respectively. The finding of lower levels of these gases in patients on steroid treatment and of higher levels in those with more severe lung disease, as assessed by lung function tests and clinical symptoms, reinforces the hypothesis that the noninvasive measurement of exhaled gases maybe useful in monitoring the underlying pathologic pathways of lung disease. Longitudinal studies are required to assess the clinical usefulness of these measurements in the monitoring of chronic inflammatory lung disease.

6496.      Peng Z, Rasic N, Liu Y, Simons FE. Mosquito saliva-specific IgE and IgG antibodies in 1059 blood donors. J Allergy Clin Immunol. 2002 Nov;110(5):816-7. No abstract.

6497.      Platts-Mills TA. The future of allergy and clinical immunology lies in evaluation, treatment, and research on allergic disease. J Allergy Clin Immunol. 2002 Oct;110(4):565-6. Review. No abstract.

6498.      Roller C, Namjou K, Jeffers JD, Camp M, Mock A, McCann PJ, Grego J. Nitric oxide breath testing by tunable-diode laser absorption spectroscopy: application in monitoring respiratory inflammation. Appl Opt. 2002 Oct 1;41(28):6018-29.

We used a high-resolution mid-IR tunable-laser absorption spectroscopy (TLAS) system with a single IV-VI laser operating near 5.2 microm to measure the level of exhaled nitric oxide (eNO) in human breath. A method of internal calibration using simultaneous eNO and exhaled CO2 measurements eliminated the need for system calibration with gas standards. The results observed from internally calibrating the instrument for eNO measurements were compared with measurements of eNO calibrated to gas standards and were found to be similar. Various parameters of the TLAS system for eNO breath testing were examined and include gas cell pressure, exhalation time, and ambient NO concentrations. A reduction in eNO from elevated concentrations (approximately 44 parts in 10(9)) to near-normal levels (<20 parts in 10(9)) from an asthmatic patient was observed after the patient had received treatment with an inhaled glucocorticoid anti-inflammatory medication. Such measurements can help in evaluating airway inflammation and in monitoring the effectiveness of anti-inflammatory therapies.

6499.      Romano A, Viola M, Mondino C, Pettinato R, Di Fonso M, Papa G, Venuti A, Montuschi P.  Diagnosing nonimmediate reactions to penicillins by in vivo tests. Int Arch Allergy Immunol. 2002 Oct;129(2):169-74.

BACKGROUND: Maculopapular and urticarial rashes are nonimmediate manifestations common during penicillin treatment; the former often represent cell-mediated hypersensitivity. Our objectives were to assess the incidence of allergy in adults reporting nonimmediate manifestations during penicillin therapy and to evaluate the diagnostic potential of patch tests, delayed-reading skin tests and challenges in such cases. METHODS: We used prick and intradermal tests as well as patch tests with penicillin determinants, ampicillin, amoxicillin and any other suspect penicillins. We also performed challenges with the suspect antibiotics. RESULTS: Such antibiotics were aminopenicillins in 93.1% of 259 patients, most of whom had suffered from maculopapular rashes followed by piperacillin (4.2%). Three subjects displayed immediate skin test positivity. Ninety-four subjects showed patch test and delayed intradermal test positivity to the culprit penicillin (90 to aminopenicillins and 4 to piperacillin) and were considered as having had delayed hypersensitivity reactions. Five of the 8 subjects who displayed delayed intradermal test positivity and patch test negativity to the suspect penicillin underwent challenges, 2 reacted positively to the responsible aminopenicillin. Among the remaining 154 with negative results in allergologic tests, 125 agreed to undergo challenges; only 3 reacted. In all, 98 patients -- 93 of whom had experienced maculopapular rashes -- displayed delayed hypersensitivity (94 to aminopenicillins and 4 to piperacillin).

CONCLUSIONS: Both patch and intradermal tests are useful in evaluating nonimmediate reactions to penicillins, particularly maculopapular rashes. Patch test and delayed intradermal positivity together indicate delayed hypersensitivity. Intradermal testing appears to be slightly more sensitive than patch testing. Copyright 2002 S. Karger AG, Basel.

6500.      Schmidt MH, Raulf-Heimsoth M, Posch A. Evaluation of patatin as a major cross-reactive allergen in latex-induced potato allergy. Ann Allergy Asthma Immunol. 2002 Dec;89(6):613-8.

BACKGROUND: Potential cross-reactions between natural rubber latex and fruit/vegetable specific immunoglobulin (Ig)E antibodies have been reported for many years. This study was designed to investigate the molecular basis of acquired food sensitization focusing on the storage protein patatin and the patatin-like latex protein Hev b 7. OBJECTIVE: The amount of potato-specific IgE in the serum of latex-allergic health care workers and children with atopic dermatitis was determined to evaluate cross-reactivity between Hev b 7 and patatin. Additionally, the stability of potato patatin to digestion was investigated. METHODS: Human serum was tested on its reactivity to latex and potato proteins by IgE immunoblotting after one-dimensional (1-D) and 2-D electrophoresis. Latex- and potato-specific IgE concentrations were measured in fluorescence enzyme immunoassays (CAP, Pharmacia, Uppsala, Sweden). Further, potato patatin was chromatographically isolated to perform auto-inhibition tests. Stability of patatin to degradation was determined by digestion in vitro.

RESULTS: Patatin was identified as major cross-reactive potato allergen by N-terminal sequencing. Seventy-five percent of the potato-sensitized people reacted with patatin in 1-D immunoblots, and 25% of the positive reactions to Hev b 7 could be blocked by preincubation of the patients' sera with purified potato patatin. Examination of children with atopic dermatitis showed that most sera contained patatin-specific IgE, whereas no Hev b 7-specific IgE was detected. Finally, patatin has been found partially stable to digestion in vitro.

CONCLUSIONS: Patatin was identified as a major cross-reactive protein in latex-associated potato allergy and appears to be relevant for atopic dermatitis. Therefore, patatin could be a suitable marker for the determination of potato sensitization, and it may also constitute an important food allergen. Cross-reactivity between Hev b 7 and patatin was restricted to primarily latex-sensitized adults, suggesting a different mechanism of sensitization in children with atopic dermatitis.

6501.      Sousa AR, Parikh A, Scadding G, Corrigan CJ, Lee TH. Leukotriene-receptor expression on nasal mucosal inflammatory cells in aspirin-sensitive rhinosinusitis. N Engl J Med. 2002 Nov 7;347(19):1493-9.

BACKGROUND: Patients with asthma who have aspirin sensitivity have greater cysteinyl leukotriene production and greater airway hyperresponsiveness to the effects of inhaled cysteinyl leukotrienes than their aspirin-tolerant counterparts. We hypothesized that the latter effect reflects elevated expression of the cysteinyl leukotriene receptor CysLT1 on inflammatory cells in the target organ and that its expression is down-regulated by aspirin desensitization. METHODS: We obtained nasal-biopsy specimens from 22 aspirin-sensitive and 12 non-aspirin-sensitive patients with chronic rhinosinusitis and nasal polyps. Additional specimens were then obtained from subgroups of the aspirin-sensitive patients after intranasal application of lysine aspirin or placebo for two weeks (five and four patients, respectively) or for six months (five and four patients, respectively). The numbers of leukocytes expressing the CysLT1 and leukotriene B4 (LTB4) receptors per unit area of sections of the nasal submucosa were determined by immunohistochemistry.

RESULTS: The absolute number of cells expressing the CysLT1 receptor was significantly higher in the aspirin-sensitive patients than in the non-aspirin-sensitive patients (median, 542 cells per square millimeter [range,148 to 1390] vs. 116 cells per square millimeter [range, 40 to 259]; P<0.001). The percentage of CD45+ leukocytes expressing the CysLT1 receptor was also higher in the aspirin-sensitive subjects (25 percent of CD45+ leukocytes [range, 4 to 50] vs. 5 percent of CD45+ leukocytes [range, 2 to 11]; P<0.001); the percentage of CD45+ leukocytes expressing the LTB4 receptor did not differ significantly between these two groups. Desensitization was associated with a decrease in the numbers of inflammatory cells expressing CysLT1.

CONCLUSIONS: The elevated numbers of nasal inflammatory leukocytes expressing the CysLT1 receptor in aspirin-sensitive patients with chronic rhinosinusitis as compared with their non-aspirin-sensitive counterparts and the down-regulation of receptor expression after desensitization to aspirin are probably fundamental in the pathogenesis of aspirin sensitivity and in the mechanism of aspirindesensitization. Copyright 2002 Massachusetts Medical Society

6502.      Stablein JJ, Bucholtz GA, Lockey RF. Melaleuca tree and respiratory disease. Ann Allergy Asthma Immunol. 2002 Nov;89(5):523-30.

BACKGROUND: The role of Melaleuca quinquenervia tree as a source of allergen(s) and respiratory irritant(s) is controversial. OBJECTIVE: Determine whether Melaleuca tree pollen or odor is medically important. METHODS: A 2-year aeroallergen survey and skin test (ST) results of 1,017 subjects were reviewed. Sixteen subjects were selected based on positive Melaleuca pollen extract (MPE) STs. Double-blind nasal challenges with MPE were performed on six subjects. Single-blind bronchial challenges with MPE were performed on four. To evaluate the irritant effect, 11 subjects received 34 different Melaleuca odor challenges (blossoms, bark, and leaves) through a closed system for up to 30 minutes. Four inhaled an odor from cajeput oil (derived from Melaleuca leaves) for 1 hour. Spirometry was performed before and after odor challenges. Radioallergosorbent test using MPE was compared with MPE STs in 15 subjects. RESULTS: The aeroallergens survey revealed insignificant numbers of Melaleuca pollen. Ninety-seven of 1,017 subjects were a 2+ or greater intradermal MPE ST. One of 6 double-blind nasal challenges and 1 of 4 single-blind bronchial challenges using MPE were positive in subjects with positive MPE STs. All 38 odor challenges with blossoms, bark, leaves, and cajeput oil were nonreactive. The MPE radioallergosorbent test correlated with MPE ST results. CONCLUSIONS: The Melaleuca tree is not a significant source  of aeroallergen. The Melaleuca odor is not a respiratory irritant. MPE antigen(s) has been shown to cross-react with pollen extracts from a proven aeroallergen (Bahia grass pollen) possibly explaining the few cases of positive MPE STs with positive nasal/bronchial challenges.

6503.      Stewart AE, Hunsaker DH. Fungus-specific IgG and IgE in allergic fungal rhinosinusitis. Otolaryngol Head Neck Surg. 2002 Oct;127(4):324-32.

OBJECTIVE: Our study goal was to study fungus-specific immunoglobulins G (sIgG) and E (sIgE) in polypoid rhinosinusitis with and without evidence of allergic fungal rhinosinusitis (AFS). STUDY DESIGN AND SETTING: A prospective analysis was conducted of fungal sIgG and sIgE using a 9-mold RAST panel in 13 AFS, 11 AFS-like, and 27 non-AFS polypoid rhinosinusitis patients. Nonpolyp controls included 17 volunteers with allergic rhinitis and 11 with no atopic history. RESULTS: All groups had elevated fungal sIgG levels. Polyps, increasing polyp severity, and AFS were associated with elevated fungal sIgG to a greater number of molds. The AFS group had sIgE elevations (>or=class II) to an average of 5 molds versus only 0.1 in the non-AFS polyp group. Total IgE was 971 U/mL versus 64 U/mL, respectively. CONCLUSIONS: Multiple elevations of fungal sIgE are adequate diagnostic evidence of these fungi when fungal cultures and histologic examinations are negative in diagnosing AFS. The significance of increased fungal sIgG remains unclear. SIGNIFICANCE: Early recognition of AFS may be facilitated by screening polypoid rhinosinusitis patients with total serum IgE and RAST testing.

6504.      Strunk RC, Korenblat PE. Choice of a medication to treat asthma: is an improvement in symptoms sufficient for deciding? J Allergy Clin Immunol. 2002 Dec;110(6):832-3. No abstract.

6505.      Suissa S, Ernst P, Kezouh A. Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma. Thorax. 2002 Oct;57(10):880-4.

BACKGROUND: Inhaled corticosteroids are effective at preventing asthma morbidity and mortality. Most studies, however, have focused on short term effects, raising uncertainty about their effectiveness in the long term. METHODS: The Saskatchewan Health databases were used to form two population based cohorts of asthma patients aged 5-44 between 1975 and 1991. The first cohort included all subjects from the start of asthma treatment, while the second included subjects hospitalised for asthma from the date of discharge. Subjects were followed up,starting 1 year after cohort entry and continuing until 1997, 54 years of age, or death. The outcome was the first asthma hospital admission and readmission, respectively, to occur during follow up. A nested case-control design was used by which all cases were matched on calendar time and several markers of asthma severity to all available controls within the cohort. RESULTS: The full cohort included 30 569 asthmatic subjects of which 3894 were admitted to hospital for asthma and 1886 were readmitted. The overall rate of asthma hospitalisation was 42.4 per 1000 asthma patients per year. Regular use of inhaled corticosteroids was associated with reductions of 31% in the rate of hospital admissions for asthma (95% confidence interval (CI) 17 to 43) and 39% in the rate of readmission (95% CI 25 to 50). The rate reduction found during the first 4 years of follow up was sustained over the longer term. Regular use of inhaled corticosteroids can potentially prevent between five hospital admissions and 27 readmissions per 1000 asthma patients per year. CONCLUSION: Regular use of low dose inhaled corticosteroids prevents a large proportion of hospital admissions with asthma, both early and later on in the course of the disease.

6506.      Tomimori Y, Tsuruoka N, Fukami H, Saito K, Horikawa C, Saito M, Muto T, Sugiura N, Yamashiro K, Sumida M, Kakutani S, Fukuda Y. Role of mast cell chymase in allergen-induced biphasic skin reaction. Biochem Pharmacol. 2002 Oct 1;64(7):1187.

Intradermal injection of human chymase (EC 3.4.21.39) into the mouse ear elicited an edematous skin reaction in a biphasic manner, with a transient reaction peaking at 1 hr, followed by a delayed response persisting for at least 24hr. The kinetics of this reaction was analogous to the biphasic skin reaction induced by ascaris extract in actively sensitized mice. A similarity between the two dermatitis models was also shown by histological analysis, i.e. accumulation of inflammatory cells was observed exclusively in the later phases of the skin reaction. A chymase inhibitor, SUN-C8077 [3-(3-aminophenylsulfonyl)-7-chloroquinazorine 2,4(1H, 3H)-dione], significantly inhibited both the early- and late-phase responses of the skin reaction induced by ascaris extract. These findings suggest that chymase may play an important role in the allergen-induced biphasic skin reaction. A histamine receptor antagonist, homochlorcyclizine, inhibited the early-phase but not the late-phase of the chymase-induced skin reaction. In addition, human chymase showed chemotactic activity to human polymorphonuclear leukocytes in vitro. Mast cell chymase may participate in the two phases of allergic skin inflammation by two distinct mechanisms, i.e. histamine- and leukocyte-dependent mechanisms, respectively.

6507.      Tripathi DM. Role of allergy testing and immunotherapy in the management of respiratory allergic disease.  Bombay Hospital Journal. 2002 Jul; 44(3): 419-

ABSTRACT: The central point of allergy diagnosis remains the skin testing even- to-day, when the test results can be better guaranteed and differentiated through modern process like provocation test or RAST. In the diagnosis of allergic conditions such as bronchial asthma, allergic rhinitis in which allergy may be a pathogenic factor has been substantially facilitated by allergy skin testing. Skin testing demonstrates the presence of IgE directed against the specific allergen tested. Although, there are a variety of in-vivo and in-vitro methods for assessing the presence of specific IgE antibodies, the skin testing is preferred because it is simple, inexpensive, specific and results are immediately available. Allergy skin tests correlate well with clinical history, provocative challenge and in-vitro allergy assays such as RAST, modified RAST, QUIDEL, allergen screens, histamine release and immunocap system.

6508.      Turner SW, Young S, Landau LI, Le Souef PN. Reduced lung function both before bronchiolitis and at 11 years. Arch Dis Child. 2002 Nov;87(5):417-20.

BACKGROUND AND AIMS: We have previously shown an association between reduced premorbid lung function (V'maxFRC) and bronchiolitis. We hypothesised that individuals with bronchiolitis will go on to have reduced lung function and increased respiratory symptoms in childhood. METHODS: V'maxFRC was measured at 1 month of age; individuals with bronchiolitis were prospectively identified. Annual symptom questionnaires were completed from 3 to 6 years. At 11 years of age, children underwent an assessment including questionnaire, lung function, airway response to histamine (AR), and skin prick testing. RESULTS: Eighteen individuals with bronchiolitis were ascertained from 253 cohort members. Children with bronchiolitis had increased viral induced wheeze at 3 (OR 5.8, 95% CI 1.4 to 25.2; n = 103) and 5 years (OR 5.3, 95% CI 1.1 to 25.5; n = 101). At 11 years of age, 194 children were assessed including 16 with past bronchiolitis. These 16 individuals had reduced mean z scores for % V'maxFRC compared with other children (-0.56 and 0.06 respectively) and mean z scores for % FEF(25-75) at 11 years (-0.53 and 0.06 respectively). At 11 years, FEV(1), FVC PEF, AR, atopy, wheeze, and diagnosed asthma were not different between groups. CONCLUSIONS: Reduced lung function is present before and after bronchiolitis; the level of reduction is comparable. The mechanism for wheeze and reduced lung function after bronchiolitis appears to be related to premorbid lung function and not bronchiolitis per se.

6509.      Wenzel SE, Trudeau JB, Barnes S, Zhou X, Cundall M, Westcott JY, McCord K, Chu HW.  TGF-beta and IL-13 synergistically increase eotaxin-1 production in human airway fibroblasts. J Immunol. 2002 Oct 15;169(8):4613-9.

Chronic diseases may involve an "innate" response followed by an adaptive immune response, of a Th1 or Th2 variety. Little is known regarding the interactions of these responses. We hypothesized that TGF-beta1 (innate response factor associated with wound repair) in combination with IL-13 (Th2 factor) might augment inflammatory processes associated with asthma. Airway fibroblasts were cultured from asthmatic subjects and normal controls. These fibroblasts were exposed to TGF-beta1 and IL-13 alone or in combination, and eotaxin-1 expression and production were evaluated. At 48 h, eotaxin-1 production was markedly increased with the combination of TGF-beta1 and I L-13 (p < 0.0001) compared with either stimulus alone. mRNA increased slightly at 1 h with IL-13 or TGF-beta1 plus IL13, peaked, and became significantly increased over IL-13 alone at 24 h. Protein was measurable from 6 h with IL-13 and TGF-beta1 plus IL-13, but greater levels were measured over time with the combination. Actinomycin ablated the increase in mRNA and protein seen with IL-13 alone and with TGF-beta1 plus IL-13. Cycloheximide blocked the increase in mRNA at 6 h in both conditions, but also blocked the increase at 24 h with TGF-beta1 plus IL-13. STAT-6 was rapidly activated with both IL-13 and the combination, without difference. Finally, eotaxin-1-positive fibroblasts were identified in severe asthma biopsies in greater numbers than in normals. These results support the concept that interactions of innate and adaptive immune systems may be important in promoting the tissue eosinophilia of asthma, particularly in those with more severe disease.

6510.      Yang YH, Wang SJ, Chuang YH, Lin YT, Chiang BL. The level of IgA antibodies to human umbilical vein endothelial cells can be enhanced by TNF-alpha treatment in children with Henoch-Schonlein purpura. Clin Exp Immunol. 2002 Nov;130(2):352-7.

Anti-endothelial cell antibodies (AECA) have been found to play an important role in many vascular disorders. In order to determine the presence of AECA in children with Henoch-Schonlein purpura (HSP), and to elucidate the pathogenic and clinical value of their measurement in this disease, AECA were detected by immunofluorescence staining and a human umbilical vein endothelial cell (HUVEC)-based enzyme-linked immunosorbent assay (ELISA) in 20 children with HSP, 10 children with juvenile rheumatoid arthritis (JRA) without vasculitis and 10 normal healthy children. Antibodies against another endothelial cells, human dermal microvascular endothelial cells (HMVEC-d) were also detected by cell-based ELISA. In some experiments, we compared the binding activity of antibodies to HUVEC with and without tumour necrosis factor-alpha (TNF-alpha) or interleukin-1 (IL-1) pretreatment. Patients with acute onset of HSP had higher serum levels of IgA antibodies, both against HUVEC and against HMVEC-d, than healthy controls (P = 0.001, P = 0.008, respectively). Forty-five per cent of patients had positive IgA AECA to HUVEC, and 35% had positive IgA AECA to HMVEC-d. The titres of IgA antibodies to HUVEC paralleled the disease activity. After TNF-alpha treatment, the values of IgA AECA to HUVEC in HSP patients were significantly increased (P = 0.02). For IgG and IgM AECA, there was no difference between HSP patients and controls (P = 0.51, P = 0.91). Ten JRA children without vasculitis had no detectable IgG, IgM or IgA AECA activity. The results of this study showed that children with HSP had IgA AECA, which were enhanced by TNF-alpha treatment. Although the role of these antibodies is not clear, IgA AECA provide another immunological clue for the understanding of HSP.

Pathogenesis:

6511.      Arm JP, Austen KF. Leukotriene receptors and aspirin sensitivity. N Engl J Med. 2002 Nov 7;347(19):1524-6. No abstract.

6512.      Banerjee B, Kurup VP, Greenberger PA, Kelly KJ, Fink JN. C-terminal cysteine residues determine the IgE binding of Aspergillus fumigatus allergen Asp f 2. J Immunol. 2002 Nov 1;169(9):5137-44.

The knowledge of the structure function relationship of the allergen is essential to design allergenic variants with reduced IgE binding capacity but intact T cell reactivity. Asp f 2 is a major allergen from the fungus Aspergillus fumigatus and >90% of A. fumigatus-sensitized individuals displayed IgE binding to Asp f 2. In the present study, we evaluated the involvement of C-terminal cysteine residues in IgE binding conformation of Asp f 2. The deletion mutants were constructed by adding three C-terminal cysteines of the native Asp f 2 one at a time to the non-IgE binding Asp f 2 (68-203). The point mutants of Asp f 2 (68-268) with C204A and C257A substitutions were constructed to study the role of C-terminal cysteines in IgE binding. Immunological evaluation of reduced and alkylated Asp f 2 and its mutants were conducted to determine the contribution of free sulfhydryl groups as well as the disulfide bonds in allergen Ab interaction. Four-fold increase in IgE Ab binding of Asp f2 (68-267) compared with Asp f 2 (68-266) and complete loss in IgE binding of C204A mutant of Asp f 2 (68-268) indicate the involvement of C(204) and C(267) in IgE binding conformation of Asp f 2. A significant reduction in IgE binding of wild and mutated Asp f 2 after reduction and alkylation emphasizes the importance of cysteine disulfide bonds in epitope Ab interaction. The hypoallergenic variants may be explored further to develop safe immunotherapeutic strategy for allergic disorders.

6513.      Borger P, Black JL, Roth M. Asthma and the CCAAT-enhancer binding proteins: a holistic view on airway inflammation and remodeling. J Allergy Clin Immunol. 2002 Dec;110(6):841-6. Review.

Asthma is an airway disease with increasing prevalence characterized by intermittent reversible airway obstruction, airway inflammation, and airway wall remodeling. The disease is generally triggered by inhalation of allergens, but nonallergic asthma triggers are quite common. The pathogenesis of asthma is well documented, and a great deal of research has been carried out to elucidate the underlying mechanisms. A multitude of articles have focused on cells alleged to be involved in the pathogenesis, including circulating cells from the immunologic compartment (ie, eosinophils and T lymphocytes) and resident cells, such as fibroblasts, airway smooth muscle cells, and, more recently, the airway epithelium. Despite the enormous amount of research, it is still unclear what exactly causes asthma. A general feature of most studies is an enhanced activation status of asthmatic cells, suggesting a general defect with respect to regulation of cellular responses. Here we discuss the ubiquitous transcription factor family of CCAAT-enhancer binding proteins (C/EBPs) and its involvement in inflammation and proliferation. We propose that an imbalance of C/EBP isoform expression might lead to an enhanced activity of asthmatic cells and provide an overall hypothesis that both airway inflammation and remodeling can be conceived as the result of an imbalance of C/EBP isoform expression.

6514.      Budde IK, de Heer PG, Natter S, Mahler V, van der Zee JS, Valenta R, Aalberse RC. Studies on the association between immunoglobulin E autoreactivity and immunoglobulin E-dependent histamine-releasing factors. Immunology. 2002 Oct;107(2):243-51.

It has been reported that serum immunoglobulin E (IgE) from certain atopic patients can sensitize basophils to release histamine in response to IgE-dependent histamine-releasing factors (HRFs). It has also been shown that patients suffering from severe forms of atopy may contain IgE autoantibodies. It was investigated whether HRF-responsive sera contained IgE autoantibodies and if there was an association between IgE autoreactivity and IgE-dependent responsiveness to HRF. The presence of HRF-responsive IgE (IgE+) in serum of patients with respiratory atopy was determined by stimulating stripped human basophils sensitized by serum with peripheral blood mononuclear cell (PBMC)-derived HRF, and measuring the release of histamine. In parallel, these sera were screened for the presence of IgE autoantibodies to nitrocellulose-blotted human cellular extracts. The capacity of IgE autoantigen-containing preparations to induce histamine release was tested in the stripped basophil assay. Eleven out of 52 sera contained IgE autoantibodies to blotted cellular extracts of human PBMCs or of the human epithelial cell line A431. No significant association was found between IgE autoreactivity and IgE-dependent responsiveness to HRF: 7/26 IgE+ sera contained IgE to human cellular extracts, and 4/26 of the sera without IgE+ did also. IgE autoantigen-containing extracts did not induce histamine release of appropriately sensitized basophils. By size-exclusion chromatography it was shown that a 32 000 MW autoantigen eluted in the >55 000 MW fraction, which indicates that this protein forms polymers or complexes with other  macromolecules. This might explain the discrepancy between binding and histamine-releasing activity. A 20 000 MW IgE-defined autoantigen cross-reacted with a shrimp allergen. Our results indicate that IgE-reactivity to immunoblotted human protein and IgE-dependent HRF activity are distinct entities that may co-occur in atopic patients.

6515.      Choi IS. Disappearance of aspirin intolerance with antiasthma treatment. J Allergy Clin Immunol. 2002 Oct;110(4):665-6. No abstract.

6516.      Cloutier MM, Wakefield DB, Hall CB, Bailit HL. Childhood asthma in an urban community: prevalence, care system, and treatment. Chest. 2002 Nov;122(5):1571-9.

OBJECTIVES: We describe the system of asthma care in Hartford, CT, an urban,minority community. METHODS: The health field concept was used to organize factors influencing asthma prevalence and severity. Data were obtained from national, state, and municipal reports, and from surveys of children in Hartford seeking medical care in an asthma program called Easy Breathing. RESULTS: Between June 1, 1998, and May 1, 2000, 21% of children receiving Medicaid in Hartford did not file a medical claim. Between 1998 and 2000, the number of providers in Hartford decreased by 37% while the number of outpatient visits increased by 8%. Using claims data, we found the following: 19.0% of Hartford children had asthma (data from the International Classification of Disease, ninth revision, and the National Drug Code); and 12% of children with asthma filled a prescription for inhaled corticosteroid therapy, 83% for a bronchodilator, and 36% for an oral corticosteroid. Children with asthma were more likely to be hospitalized (10% vs 5%, respectively) and to visit an emergency department (45% vs 29%, respectively), and, on average, they had more hospital days (0.603 vs 0.415 days per child, respectively) and more outpatient visits per year (4.7 vs 2.5 visits, respectively) compared to children without asthma. Asthma prevalence in the 6,643 children surveyed in the Easy Breathing program was 41%. Persistent asthma was diagnosed in 50% of the children with asthma. Asthma prevalence varied by ethnic origin, age, and gender, and was highest in Hispanic/Puerto Rican children, in children 5 to 10 years of age, in boys up to 10 years of age, and in girls after 15 years of age. CONCLUSION: Improved personal behaviors and medical care will have a limited sustained impact on childhood asthma until basic environmental issues are modified. The health field concept provides a mechanism with which to address the issues surrounding asthma in urban communities.

6517.      Dreskin SC, Dale SN, Foster SM, Martin D, Buchmeier A, Nelson HS. Measurement of changes in mRNA for IL-5 in noninvasive scrapings of nasal epithelium taken from patients undergoing nasal allergen challenge. J Immunol Methods. 2002 Oct 15;268(2):189-95.

Nasal allergen challenge of patients with allergic rhinitis results in increased numbers of inflammatory cells and increased production of pro-inflammatory cytokines including interleukin 5 (IL-5). We report a sensitive, noninvasive method to measure changes in the amount of mRNA for IL-5 in nasal epithelium and have used this method to detect alterations of IL-5 mRNA from patients undergoing a nasal allergen challenge. Ten grass or ragweed allergic adults were challenged out of season with appropriate pollen extracts at sufficient dose to give a rhinitis total symptom score of 5 on a scale of 12. After allergen exposure, symptoms were recorded hourly. At 0, 3, and 6 h after allergen exposure, secreted proteins were collected on filter paper strips and two superficial scrapings of nasal epithelium were obtained. The scrapings of epithelium were immediately immersed in 100 microl of RNAlater (Ambion, Austin, TX) and stored at 4 degrees C for up to 1 month without loss of RNA quality. Total RNA was isolated and RT-PCR was performed. cDNA for IL-5 was then measured by real-time fluorescence quantitative PCR with Pre-Developed TaqMan Assay Reagents (PE Biosystems, Foster City, CA). Sufficient RNA was isolated from eight subjects to measure IL-5 mRNA. Data were normalized for content of ribosomal RNA. The relative amount of cDNA for IL-5 was calculated by comparison with internal standards prepared from phytohemagluttinin-stimulated peripheral blood mononuclear cells. Messenger RNA for IL-5 was increased 8.7+/-2.7-fold at 3 h (p<0.01) and 39.5+/-20.9-fold at 6 h (p<0.01). Increased IL-5 mRNA levels at 6 h closely correlate with total symptom scores at 6 h (r=0.88; p=0.007). IL-5 protein was measured by ELISA in eluates from the filter papers. At 6 h, there was increased IL-5 protein (7.7+/-2.8 ng/ml) compared with time zero (1.8+/-0.5 ng/ml) (p=0.02). The levels of IL-5 protein did not correlate significantly with the symptoms score or with changes in the levels of IL-5 protein with IL-5 mRNA. These data show that changes in IL-5 mRNA in patients with allergic rhinitis undergoing an allergen challenge correlate with total symptom scores better than changes in IL-5 protein eluted from filter paper. Furthermore, these changes can be measured quantitatively in very small amounts of tissue.

6518.      Guilbert T, Morgan W. Increased asthma symptoms and healthcare utilization during the fall and winter seasons in children with asthma living in the inner city: opportunity for school-based intervention. J Pediatr. 2002 Nov;141(5):604-5. No abstract.

6519.      Jousilahti P, Salomaa V, Hakala K, Rasi V, Vahtera E, Palosuo T. The association of sensitive systemic inflammation markers with bronchial asthma. Ann Allergy Asthma Immunol. 2002 Oct;89(4):381-5.

BACKGROUND: Airway inflammation is a characteristic feature of bronchial asthma. Previous studies have shown an increased local inflammatory activity in the airway mucosa of asthma patients. OBJECTIVES: To analyze the association of asthma with three sensitive markers of systemic inflammation, C-reactive protein, serum amyloid-A (SAA), and plasma fibrinogen. METHODS: A cross-sectional, population-based study including 1,513 Finnish men aged 45 to 74 years, who participated in a chronic disease risk factor survey in 1997. Of the participating men, 97 were classified as asthma patients. The odds ratios of asthma were analyzed by quartile of each inflammation marker. RESULTS: In logistic regression models the age-adjusted odds ratios (second, third, and fourth quartile as compared with the first quartile) of asthma increased gradually with increasing quartile of C-reactive protein (1.28, 1.19, 1.96, P for trend = 0.039), SAA (1.20, 3.00, 3.49, P for trend < 0.001), and fibrinogen (1.22, 1.79, 3.16, P for trend < 0.001). The associations were independent of smoking. Further adjustment for waist-to-hip ratio, a marker of central obesity, and symptoms of chronic bronchitis weakened the observed association, but the increasing trend in the association of SAA and fibrinogen with asthma remained highly significant. CONCLUSIONS: Sensitive markers of systemic inflammation, particularly SAA and fibrinogen, were positively and significantly associated with asthma prevalence. These findings support the hypothesis that not only local, but also systemic, inflammation exist in bronchial asthma.

6520.      Karlsson H, Hessle C, Rudin A. Innate immune responses of human neonatal cells to bacteria from the normal gastrointestinal flora. Infect Immun. 2002 Dec;70(12):6688-96.

The hygiene hypothesis postulates that the prevalence of allergy has increased due to decreased microbial stimulation early in life, leading to delayed maturation of the immune system. The aim of this study was to examine the cytokine pattern produced from cord blood mononuclear cells relative to adult cells after stimulation with bacterial strains from the normal flora. Mononuclear cells from cord and adult blood samples were stimulated with the following bacteria: Bifidobacterium adolescentis, Enterococcus faecalis, Lactobacillus plantarum, Streptococcus mitis, Corynebacterium minutissimum, Clostridium perfringens, Bacteroides vulgatus, Escherichia coli, Pseudomonas aeruginosa, Veillonella parvula, and Neisseria sicca. The levels of interleukin 12 (IL-12), tumor necrosis factor alpha (TNF-alpha), IL-10, and IL-6 were measured by enzyme-linked immunosorbent assay. The TNF-alpha production was also analyzed after blocking CD14, Toll-like receptor 2 (TLR-2), and TLR-4 prior to stimulation with bacteria. The levels of IL-12 and TNF-alpha were similar in cord and adult cells. Gram-positive bacteria induced considerably higher levels of IL-12 and TNF-alpha than gram-negative bacteria in both cord and adult cells. The levels of IL-6 were significantly higher in newborns than in adults, whereas the levels of IL-10 were similar in newborns and adults. Gram-negative and gram-positive bacteria induced similar levels of IL-6 and IL-10 in cord cells. L. plantarum bound or signaled through CD14, TLR-2, and TLR-4, whereas E. coli acted mainly through CD14 and TLR-4. These results indicate that the innate immune response in newborns to commensal bacteria is strong and also suggest that different bacterial strains may have differential effects on the maturation of the immune system of infants.

6521.      Levinson AI. Novel immunomodulatory therapies for immunoglobulin E-mediated diseases. Isr Med Assoc J. 2002 Nov;4(11 Suppl):881-3. Review.  No abstract.

6522.      Lipworth BJ. Adrenal insufficiency after treatment with fluticasone. Second line controller treatment might have been tried. BMJ. 2002 Oct 12;325(7368):836. No abstract.

6523.      Liu LY, Sedgwick JB, Bates ME, Vrtis RF, Gern JE, Kita H, Jarjour NN, Busse WW, Kelly EA. Decreased expression of membrane IL-5 receptor alpha on human eosinophils: II. IL-5 down-modulates its receptor via a proteinase-mediated process. J Immunol. 2002 Dec 1;169(11):6459-66.

In the accompanying study, we demonstrated that following Ag challenge, membrane (m)IL-5Ralpha expression is attenuated on bronchoalveolar lavage eosinophils, soluble (s)IL-5Ralpha is detectable in BAL fluid in the absence of increased steady state levels of sIL-5Ralpha mRNA, and BAL eosinophils become refractory to IL-5 for ex vivo degranulation. We hypothesized that IL-5 regulates its receptor through proteolytic release of mIL-5Ralpha, which in turn contributes to the presence of sIL-5Ralpha. Purified human peripheral blood eosinophils were incubated with IL-5 under various conditions and in the presence of different pharmacological agents. A dose-dependent decrease in mIL-5Ralpha was accompanied by an increase in sIL-5Ralpha in the supernatant. IL-5 had no ligand-specific effect on mIL-5Ralpha or sIL-5Ralpha mRNA levels. The matrix metalloproteinase-specific inhibitors BB-94 and GM6001 and tissue inhibitor of metalloproteinase-3 partially inhibited IL-5-mediated loss of mIL-5Ralpha, suggesting that sIL-5Ralpha may be produced by proteolytic cleavage of mIL-5Ralpha. IL-5 transiently reduced surface expression of beta-chain, but had no effect on the expression of GM-CSFRalpha. Pretreatment of eosinophils with a dose of IL-5 that down-modulated mIL-5Ralpha rendered these cells unable to degranulate in response to further IL-5 stimulation, but they were fully responsive to GM-CSF. These findings suggest that IL-5-activated eosinophils may lose mIL-5Ralpha and release sIL-5Ralpha in vivo, which may limit IL-5-dependent inflammatory events in diseases such as asthma.

6524.      Narasimhan R, Lakshman R, Amos RS, Williams LH, Egner W, Finn A. Juvenile dermatomyositis associated with hereditary angioneurotic oedema. Arch Dis Child. 2002 Dec;87(6):563. No abstract.

6525.      Ostergaard MS, Stauning JA, Andersen JS, Jorgensen M. The PAT study's methods, asthma classification, and results are questionable. J Allergy Clin Immunol. 2002 Oct;110(4):671; author reply, 671-2. No abstract.

6526.      Peroni DG, Chatzimichail A, Boner AL. Food allergy: what can be done to prevent progression to asthma? Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl 1):44-51. Review.

OBJECTIVES: The primary objective of this review is to discuss risk factors for asthma development in food allergen-sensitized children. In the paper we discuss the possible measures to prevent progression to asthma by allergen and other adjuvant factor avoidance. DATA SOURCES: A review from literature of articles on these topics was performed. STUDY SELECTION: Relevant publications on asthma risk factors and implementation of protective factors were critically evaluated. RESULTS: Children with familiar history of atopy and sensitization to food proteins in early infancy are at high risk of subsequent respiratory allergic diseases and require specific prevention. Because early allergic sensitization is a significant risk factor for later development of asthma, prevention of asthma by early allergen avoidance is mandatory in high-risk children. Adjuvant factors such as tobacco smoke and mold exposure may act as nonspecific triggers for the development of atopy. The role of protective factors such as infections in early life, breast-feeding, a "healthy" diet needs to be evaluated in prospective studies. Pharmacologic intervention with antihistamines led to significant reduction in incidence of asthma in high-risk children, but confirmatory longitudinal studies in large populations are necessary. CONCLUSIONS: There is now accumulating evidence that preventing exposure to house-dust mite may significantly reduce the prevalence of childhood asthma.

However, allergen avoidance can not be recommended as the only strategy. Avoidance of adjuvant factors and implementation of potential protective factors aimed to reduce the risk to progression to asthma need to be evaluated in prospective studies.

6527.      Phanish MK, Owen A, Parry DH. Spontaneous regression of acquired C1 esterase inhibitor deficiency associated with splenic marginal zone lymphoma presenting with recurrent angio-oedema. J Clin Pathol. 2002 Oct;55(10):789-90.

A 52 year old woman with marginal zone lymphoma developed recurrent episodes of angio-oedema and was found to have C1 esterase inhibitor deficiency. She declined chemotherapy for the lymphoma. Fourteen months after her initial presentation she was found to be in partial remission, and this was confirmed by peripheral blood film and bone marrow examinations. This was associated with normalisation of C1 esterase inhibitor, C1q, and C4 values. Regression of acquired C1 esterase inhibitor deficiency associated with spontaneous partial remission of lymphoma has not been reported previously.

6528.      Riegert-Johnson DL, Volcheck GW. The incidence of anaphylaxis following intravenous phytonadione (vitamin K1): a 5-year retrospective review. Ann Allergy Asthma Immunol. 2002 Oct;89(4):400-6. Review.

BACKGROUND: Phytonadione (vitamin K1) administered intravenously (i.v.) has been associated with anaphylaxis, although the incidence is not known. The anaphylaxis is thought to be attributable to the solubilizing vehicle, polyethoxylated castor oil (Cremophor EL, BASF AG, Ludwingshafen, Germany). OBJECTIVE: To estimate the incidence of anaphylaxis after i.v. administration of phytonadione. METHODS: A retrospective review of anaphylaxis after i.v. phytonadione over a 58-month period at a large academic center was performed. During the period of the study a protocol for the administration of i.v. phytonadione was in place. A review of computerized records and survey of staff identified cases of anaphylaxis meeting predefined inclusion criteria. Inaddition, a literature review was performed for articles concerning anaphylaxis after i.v. phytonadione. RESULTS: Over the 58 months of the study, a total of 6,572 doses of i.v. phytonadione were administered. Two cases of anaphylaxis after i.v. phytonadione were identified. The incidence of anaphylaxis was 3 per 10,000 doses with 95% confidence intervals of 0.04 to 11 per 10,000 doses. The literature review identified 14 cases meeting inclusion criteria with no reviews of the literature or estimates of incidence. CONCLUSIONS: The incidence of anaphylaxis after i.v. phytonadione is overall comparable or slightly less than other drugs known to cause anaphylaxis. We do not recommend routine pretreatment with antihistamines or corticosteroids before administration of phytonadione.

6529.      Sanklecha MU. Cefaclor induced serum sickness like reaction. Indian J Pediatr. 2002 Oct;69(10):921. No abstract.

6530.      Schott M, Feldkamp J, Klucken M, Kobbe G, Scherbaum WA, Seissler J. Calcitonin-specific antitumor immunity in medullary thyroid carcinoma following dendritic cell vaccination. Cancer Immunol Immunother. 2002 Dec;51(11-12):663-8.

In this study, we investigated the immune response following immunotherapy with calcitonin-pulsed dendritic cells (DC) in 7 patients with metastasized medullary thyroid carcinoma. After immunization with 1-5 x 10(6) autologous DC, significant calcitonin-specific T cell proliferation was detectable in 3 patients. Measurement of cytokine release from T lymphocytes demonstrated high post-treatment interferon-gamma (IFN-gamma) secretion after stimulation with calcitonin in 5 patients, one of whom experienced significant tumor regression. In contrast, antigen-specific interleukin-4 (IL-4) production was only slightly increased in 4 patients. All 7 patients developed a strong delayed-type hypersensitivity (DTH) skin reaction, which was confirmed to be mediated by infiltrating CD4+ T-helper cells and CD8+ cytotoxic T cells in all 3 patients who underwent skin biopsy. This is the first study to show that a polypeptide hormone can be used to develop a DC vaccination strategy for the immunotherapy of highly malignant endocrine cancers.

6531.      Siltanen M, Kajosaari M, Savilahti EM, Pohjavuori M, Savilahti E. IgG and IgA antibody levels to cow's milk are low at age 10 years in children born preterm. J Allergy Clin Immunol. 2002 Oct;110(4):658-63.

BACKGROUND: Both innate and specific defenses of the preterm infant are even less developed than those of term infants, and the immune systems of preterm infants might be skewed differently at birth. Their immune responses to food antigens started early in life might therefore differ from those of term infants. OBJECTIVE: We sought to compare antibody levels to cow's milk, ovalbumin, and gliadin at age 10 years in children who had been born either preterm or at term. METHODS: IgG and IgA isotype antibodies to whole cow's milk, beta-lactoglobulin, alpha-casein, and ovalbumin, as well as IgG antibody levels to gliadin and to tetanus and diphtheria toxoids, were measured for a group of 62 children born preterm and 61 control subjects born at term. These children were studied at the same time for atopy. RESULTS: Children born preterm had markedly lower levels of antibodies to cow's milk and to its protein fractions (P <.0001 for IgA and IgG antibodies to cow's milk and alpha-casein and IgG beta-lactoglobulin antibodies). IgG gliadin antibodies were also significantly lower in the preterm group (P =.03), although the difference was not significant for IgG ovalbumin antibodies. In the preterm group both those born before gestational week 30 and those given cow's milk-based formula early (before day 50) had the lowest levels of cow's milk antibodies. In the preterm group atopy was associated with low levels of IgG cow's milk antibodies but with high levelsof IgG ovalbumin antibodies. CONCLUSIONS: Early introduction of food antigens into the immature gastrointestinal tract of preterm infants might result in tolerance. The presence of less atopy in these children might also be a result of tolerance development.

6532.      Terashima T, Amakawa K, Matsumaru A, Yamaguchi K. Correlation between cysteinyl leukotriene release from leukocytes and clinical response to a leukotriene inhibitor. Chest. 2002 Nov;122(5):1566-70.

STUDY OBJECTIVES: Antileukotriene drugs are widely used in patients with bronchial asthma, but not all patients show significant clinical improvements, and no factors have been identified that are correlated with the clinical response to these drugs. This study was designed to examine the factors correlated with a response to a leukotriene receptor antagonist, pranlukast, in patients with asthma. DESIGN: WBC counts, IgE, and ex vivo leukotriene release from leukocytes were measured, and 31 patients with asthma were treated with pranlukast, a leukotriene receptor antagonist, for 4 weeks. MEASUREMENTS: Outcome measurements included twice-daily peak expiratory flow rate (PEFR), daytime and nocturnal symptoms, and frequency of beta(2)-agonist use. Subjects with a reduction of > 20% in symptom scores or beta(2)-agonist use, or an improvement of PEFR of > 10% were designated as responders; others were designated as nonresponders. Logistic regression analysis assessed the efficacy of models using various allergic markers correlated with the response to pranlukast. RESULTS: There were 16 responders and 15 nonresponders. The release of cysteinyl leukotrienes from the leukocytes of the responders was higher than that of the nonresponders (p < 0.05). There was a significant correlation between the clinical response and the release of cysteinyl leukotrienes, but not demographic features, WBC counts, percentage of eosinophils, or serum IgE levels (p < 0.05). Subjects with a release of cysteinyl leukotrienes of > 3,500 pg/mL were 11.0 times more likely to respond to pranlukast than those with < 3,500 pg/mL (95% confidence interval, 2.0 to 60.5). CONCLUSION: Cysteinyl leukotriene release from leukocytes is correlated with leukotriene receptor antagonist response.

6533.      Tousi P, Rahmati M, Korshid SM. Urticaria and hepatitis C infection: is there a relationship? Int J Dermatol. 2002 Oct;41(10):712-3. No abstract.

6534.      Wagner CW. The ongoing evaluation of the impact of depression on asthma. Ann Allergy Asthma Immunol. 2002 Dec;89(6):540-1. No abstract.

6535.      Ward KM, Celebi JT, Gmyrek R, Grossman ME. Acute infectious purpura fulminans associated with asplenism or hyposplenism. J Am Acad Dermatol. 2002 Oct;47(4):493-6.

Acute infectious purpura fulminans is a rapidly progressive syndrome of hemorrhagic skin necrosis associated with acute infection and disseminated intravascular coagulation. We report 5 cases of purpura fulminans and briefly review the literature. All cases were associated with encapsulated organisms (Streptococcus pneumoniae or Group A streptococcus), and 4 of the 5 patients had asplenism or functional hyposplenism.

6536.      Wentworth P Jr, McDunn JE, Wentworth AD, Takeuchi C, Nieva J, Jones T, Bautista C, Ruedi JM, Gutierrez A, Janda KD, Babior BM, Eschenmoser A, Lerner RA.  Evidence for antibody-catalyzed ozone formation in bacterial killing and inflammation. Science. 2002 Dec 13;298(5601):2195-9.

Recently, we showed that antibodies catalyze the generation of hydrogen peroxide (H2O2) from singlet molecular oxygen (1O2*) and water. Here, we show that this process can lead to efficient killing of bacteria, regardless of the antigen specificity of the antibody. H2O2 production by antibodies alone was found to be not sufficient for bacterial killing. Our studies suggested that the antibody-catalyzed water-oxidation pathway produced an additional molecular species with a chemical signature similar to that of ozone. This species is also generated during the oxidative burst of activated human neutrophils and during inflammation. These observations suggest that alternative pathways may exist for biological killing of bacteria that are mediated by potent oxidants previously unknown to biology.

6537.      Yousef E, McGeady SJ. Lactic acidosis and status asthmaticus: how common in pediatrics? Ann Allergy Asthma Immunol. 2002 Dec;89(6):585-8. Review.

BACKGROUND: Lactic acidosis is a well described phenomenon in adult patients with severe asthma. However, this entity is rarely reported in children with status asthmaticus. OBJECTIVE: To report our experience in a 13-year-old girl who developed lactic acidosis as a complication of status asthmaticus and to investigate the prevalence of this complication of severe asthma. We sought to determine the frequency of lactic acidosis in such patients and to review etiologies of lactic acidosis. METHODS: 1) Observations on the clinical and laboratory findings in an adolescent girl with status asthmaticus who developed lactic acidosis were recorded. 2) The medical records of 100 children and adolescents with status asthmaticus admitted to an intensive care unit were reviewed for laboratory evidence of lactic acidosis. 3) We also reviewed our own previous experience of status asthmaticus with respiratory failure. RESULTS: Among 100 patients admitted to a pediatric intensive care unit for status asthmaticus, a single case of isolated metabolic acidosis was identified. This proved to be attributable to lactic acidosis. When records of patients with severe respiratory failure were examined, no cases of metabolic acidosis were found. CONCLUSIONS: Although rare, lactic acidosis does occur in pediatric-aged

patients during status asthmaticus. It is important that this complication be recognized and treated because acidosis may inhibit the effectiveness of bronchodilator therapy, produce electrolyte disturbances, and cause serious adverse effects on the patient's cardiovascular system.

6538.      Zerbib F, Guisset O, Lamouliatte H, Quinton A, Galmiche JP, Tunon-De-Lara JM.  Effects of bronchial obstruction on lower esophageal sphincter motility and gastroesophageal reflux in patients with asthma. Am J Respir Crit Care Med. 2002 Nov 1;166(9):1206-11.

The relationship between gastroesophageal reflux and asthma remains unclear. The aim of this study was to analyze the effect of bronchial obstruction on lower esophageal sphincter (LES) motility and reflux in patients with asthma. LES motility and esophageal pH were assessed in eight subjects with intermittent asthma and eight healthy volunteers during three consecutive 30-minute periods: baseline, methacholine-induced bronchospasm, and after inhalation of the beta2-agonist salbutamol. Healthy subjects inhaled 2 mg of methacholine, whereas subjects with asthma inhaled the dose of methacholine causing a 15% fall in FEV(1), as determined by a previous methacholine challenge. LES motility, esophageal pH, and FEV(1) were not significantly different between the three periods in healthy subjects. In patients with asthma, methacholine induced a 21.9 +/- 2.6% decrease in FEV(1) and a concomitant increase in the rate of transient LES relaxation (TLESR) and reflux episodes. Inhalation of salbutamol decreased the rate of TLESRs but not the number of reflux episodes. We conclude that in patients with asthma, methacholine-induced bronchospasm increases the rate of TLESR and the number of reflux episodes. These results support the belief that, in asthma, bronchial obstruction may be responsible for reflux or may aggravate reflux through a mechanism that remains to be further clarified.

 

Therapy:

6539.      Busse WW, Lenfant C, Lemanske RF Jr. Asthma guidelines: a changing paradigm to improve asthma care. J Allergy Clin Immunol. 2002 Nov;110(5):703-5. No abstract.

6540.      Kawashima M, Harada S, Tango T. Review of fexofenadine in the treatment of chronic idiopathic urticaria. Int J Dermatol. 2002 Oct;41(10):701-6.

Chronic idiopathic urticaria (CIU), characterized by the appearance of itchy wheals of unknown etiology, can be extremely debilitating and can significantly reduce a patient's quality of life (QOL). Fexofenadine, a non-sedating, H1-receptor selective, long-acting antihistamine, is licensed worldwide for the treatment of CIU. A number of dose-ranging studies have evaluated the efficacy and safety of fexofenadine for the the treatment of CIU. In two similar North American studies, patients received either fexofenadine HCI (20, 60, 120, or 240 mg bid) or placebo. All four doses of fexofendine were statistically superior to placebo at reducing pruritus and reducing the number of wheals (P < or = 0.0238). A dose-finding study undertaken in Japanese patients confirmed that fexofenadine HCI (60 mg and 120 mg bid) is an effective treatment for CIU. A similar dose response was shown in all three studies when the results were compared. Furthermore, health outcome analyses of the North American studies indicated that fexofenadine HCI 60 mg bid significantly improved patient's QOL. In these studies, fexofenadine had a consistently comparable safety profile to placebo, with no dose-related trends in the incidence of adverse events. In conclusion, fexofenadine is an effective and well-tolerated treatment for CIU, with a wide therapeutic window. Importantly, the lack of ethnic differences between the studies from North America and Asia indicate that the efficacy and safety of fexofenadine demonstrated in these studies are cross-culturally applicable.

6541.      Kull I, Wickman M, Lilja G, Nordvall SL, Pershagen G. Breast feeding and allergic diseases in infants-a prospective birth cohort study. Arch Dis Child. 2002 Dec;87(6):478-81.

AIMS: To investigate the effect of breast feeding on allergic disease in infants up to 2 years of age. METHODS: A birth cohort of 4089 infants was followed prospectively in Stockholm, Sweden. Information about various exposures was obtained by parental questionnaires when the infants were 2 months old, and about allergic symptoms and feeding at 1 and 2 years of age. Duration of exclusive and partial breast feeding was assessed separately. Symptom related definitions of various allergic diseases were used. Odds ratios (OR) and 95% confidence intervals (CI) were estimated in a multiple logistic regression model. Adjustments were made for potential confounders. RESULTS: Children exclusively breast fed during four months or more exhibited less asthma (7.7% v

12%, OR(adj) = 0.7, 95% CI 0.5 to 0.8), less atopic dermatitis (24% v 27%, OR(adj) = 0.8, 95% CI 0.7 to 1.0), and less suspected allergic rhinitis (6.5% v 9%, OR(adj) = 0.7, 95% CI 0.5 to 1.0) by 2 years of age. There was a significant risk reduction for asthma related to partial breast feeding during six months or more (OR(adj) = 0.7, 95% CI 0.5 to 0.9). Three or more of five possible allergic disorders-asthma, suspected allergic rhinitis, atopic dermatitis, food allergy related symptoms, and suspected allergic respiratory symptoms after exposure to pets or pollen-were found in 6.5% of the children. Exclusive breast feeding prevented children from having multiple allergic disease (OR(adj) = 0.7, 95% CI 0.5 to 0.9) during the first two years of life. CONCLUSION: Exclusive breast feeding seems to have a preventive effect on the early development of allergic disease-that is, asthma, atopic dermatitis, and suspected allergic rhinitis, up to 2 years of age. This protective effect was also evident for multiple allergic disease.

6542.      McDonald E, Cook D, Newman T, Griffith L, Cox G, Guyatt G. Effect of air filtration systems on asthma: a systematic review of randomized trials. Chest. 2002 Nov;122(5):1535-42.

STUDY OBJECTIVES: To systematically review the evidence of randomized trials evaluating the effects of residential air filtration systems on patients with asthma. DATA SOURCES: We searched for published and unpublished studies using MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Collaboration. We reviewed all reference lists for additional articles of relevance, and contacted experts in the field and air filter manufacturers. STUDY SELECTION: We identified 10 relevant randomized controlled trials that examined the influence of a residential air filtration system on patients with asthma. DATA EXTRACTION: In duplicate and independently, we abstracted data on the methodologic quality, population, intervention, and outcomes. DATA SYNTHESIS: Five of 10 studies enrolled adults only. One study included children only. The sample size ranged from 9 to 45 participants in each study, for a total of 216 patients across all studies. Two studies reported a statistically significant decrease in airway responsiveness associated with air filter utilization. Air filters were associated with significantly lower total symptom scores (weighted mean difference of 0.47; 95% confidence interval [CI], 0.69 to 0.25) on a 10-point scale, and lower sleep disturbance score (weighted mean difference of 0.93; 95% CI, 1.44 to 0.42); however, heterogeneity of results weakens the inferences from these trials. Air filtration systems were not associated with any differences in medication use or morning peak expiratory flow values. None of these trials employed validated scales to measure clinical symptoms or quality of life. CONCLUSIONS: Among patients with allergies and asthma, use of air filters is associated with fewer symptoms. Rigorous sufficiently powered randomized clinical trials are

6543.      Rapoport D. Overdrugged patients: enough is enough needed to more precisely define the influence of air filtration on health-related quality of life and symptom control for asthmatic patients.. Can Fam Physician. 2002 Nov;48:1764. No abstract.

6544.      Sampson HA. Food allergy: from biology toward therapy. IJCP. 2002 Aug; 13(3): 17-27

ABSTRACT: Studies confirm that food allergies affect as much as 2.5 percent of the adult population. Emerging knowledge of the mechanisms is opening avenues for specific immunologic interventions, some of which have now entered clinical trials. At present, physicians can help patients to avoid allergens and can address the risk of anaphylaxis.

 

July 2003

7057.      Aguilar Leon DE, Novelo Retana V, Martinez-Cordero E. Anti-avian antibodies and rheumatoid factor in pigeon hypersensitivity pneumonitis. Clin Exp Allergy. 2003 Feb;33(2):226-32.

BACKGROUND: Although several immunological abnormalities may be present in pigeon hypersensitivity pneumonitis (HP), few specific hallmarks have been described. OBJECTIVE: To determine whether the presence of rheumatoid factor (RF) could be useful to discriminate pigeon HP from asymptomatic breeders (AB) and other interstitial lung diseases. METHODS: Fifty-three patients with pigeon HP, 47 AB, 31 idiopathic pulmonary fibrosis (IPF) patients and a rheumatoid arthritis (RA) group were studied. IgM RF was determined through enzyme-linked immunosorbent assay (ELISA) and western blot using human IgG and IgG Fc fragment as antigens. IgG and IgA anti-avian antibodies (AA) against pigeon serum antigen were also measured. The use of F(ab')2 fraction of peroxidase-labelled anti-human immunoglobulins prevented endogenous interferences. Possible cross-binding of RF with avian antigens and the reactivity against human IgG by AA were studied. RESULTS: RF tests were frequently positive in HP (52.8%) in comparison to AB (4.2%) and IPF (12.9%; P = 2.6 x 10-10 and 4.1 x 10-5). Therefore, the presence of RF in pigeon HP showed a sensitivity of 52% and was highly specific considering the results of AB and IPF (95 and 87%, respectively). The RA group revealed positive RF but negative AA tests. RF activity was confirmed through western blot using purified IgG Fc fragment. Overlapping levels of IgG and IgA AA were found in HP and AB. The frequency of AA was low in IPF. The cross-reaction of RF with avian antigens was excluded, and no reactivity against human IgG by AA was detected. Other endogenous interferences were ruled out. CONCLUSION: No single immunological test may definitively distinguish pigeon HP from AB and other interstitial lung disorders; however, positive RF, together with high AA levels, seems to be useful in differentiating the diagnosis.

7058.      Alvarez-Puebla MJ, Garcia-Figueroa BE, Tabar-Purroy AI, Olaguibel-Rivera JM.   Discriminant analysis in allergic rhinitis and asthma: methacholine dose-response slope allows a good differentiation between mild asthma and rhinitis. Respir Med. 2003 Jan;97(1):30-6.

Asthma and rhinitis frequently coexist in allergic patients, but nasal symptoms may predominate, leading to asthma underdiagnosis and undertreatment. Discriminant analysis obtains the best differentiation between groups using one or one set of variables. Our aim was to identify the laboratory test [allergen exposure, total and specific serum IgE, lung function, blood eosinophils and, bronchial response and sensitivity to methacholine (Mth) and allergen] or combination of them that allowed the best differentiation between mild asthma and allergic rhinitis. A cross-sectional analysis was performed in 86 Dermatophogoides pteronyssinus allergic rhinitis patients, who were classified according to clinical data as rhinitis plus mild asthma (n = 62) or "pure" rhinitis (n = 24). Bronchial symptoms had been exhaustively evaluated during a 2-years pre-inclusion period. Patients underwent skin tests and bronchial challenge with Mth and allergen. The exposure to D. pteronyssinus allergen (Der pl) was quantified in dust samples. Dose-response curves with Mth [until the FEV1 fell by 40% or the maximal dose (200 mg/ml) was inhaled] were attained. We developed multiple models of discriminant analysis in order to evaluate the capacity of the above variables to differentiate groups. Asthma patients had higher total and specific IgE levels and a greater sensitivity (PD20 values) and response [dose-response slope (DRS)] to both Mth and allergen. The model entering these variables was the one that correctly classified more patients (79.2%). The discriminative power of the model that only included Mth-DRS values was similar to the above (78.8%). Bronchial response to Mth is quantitatively different in allergic rhinitis patients who display mild asthma symptoms when compared to those that only report rhinitis, suggesting a distinct bronchial intrinsic behavior. The utilization of complete dose-response curves with Mth allows a good separation between mild asthma and "pure" rhinitis patients and might be useful in the diagnosis of mild asthma. Whether the early detection and treatment of these patients prevents the development of symptomatic asthma needs further evaluation.

7059.      Andre F, Cavagna S, Andre C. Gelatin prepared from tuna skin: a risk factor for fish allergy or sensitization? Int Arch Allergy Immunol. 2003 Jan;130(1):17-24.

BACKGROUND: Although fish gelatin may represent a useful alternative to bovine or porcine gelatin, the clearly recognized high prevalence of fish allergy could increase the risk of anaphylaxis to gelatin. The rationale for investigating tuna gelatin rather than gelatin from more allergenic fishes is the availability of an industrial gelatin under development. The infrequent occurrence of tuna allergy should influence the safety of a derived product. The present study investigated IgE antibodies to tuna-skin-derived gelatin in adults and children with documented fish allergy or sensitization. METHODS: Serum samples were taken from 100 consecutive patients with fish allergy or sensitization and tested for IgE antibodies against hydrolyzed or nonhydrolyzed gelatin extracted from tuna skin as compared to extracts from tuna flesh, tuna skin as well as bovine or porcine gelatin. Patients with tuna allergies or sensitization were sensitive to the same tuna species (yellowfin) as that from which the gelatin was obtained. IgE antibodies to these various extracts were analyzed using SDS-PAGE and immunoblotting. RESULTS: Only 3 of the 100 serum samples tested gave evidence of reactivity to gelatin extracted from tuna skin. Cross-reactivity between bovine/porcine and fish gelatin was not observed. CONCLUSION: The risk of adverse reactions to tuna skin gelatin seems to be significantly lower than the risk of fish allergy. Fish gelatin may represent a valuable alternative to bovine or porcine gelatin. Copyright 2003 S. Karger AG, Basel

7060.      Aoyagi M, Shimojo N, Sekine K, Nishimuta T, Kohno Y. Respiratory syncytial virus infection suppresses IFN-gamma production of gammadelta T cells. Clin Exp Immunol. 2003 Feb;131(2):312-7.

The immunological mechanisms by which respiratory syncytial virus (RSV) contributes to the development of asthma are poorly understood. gammadelta T cells are important in mucosal defence, and may contribute to the establishment of primary immune responses by producing cytokines early during respiratory infections. Thus, we used flow cytometry and intracellular cytokine staining to investigate the expression of interferon (IFN)-gamma and interleukin (IL)-4 by mitogen-stimulated gammadelta T cells from the peripheral blood of 15 hospitalized infants with RSV bronchiolitis, seven rotavirus-infected infants and eight normal controls. gammadelta T cells from RSV-infected infants had a lower proportion of IFN-gamma-producing cells (median, 4.00%; range, 0.58-6.60%) and a slightly but significantly higher proportion of IL-4-producing cells (median, 0.40%; range, 0.13-2.76%) than rotavirus-infected infants (median, 32.10%; range, 14.43-61.21%; P < 0.01, median, 0.00%; range, 0.00-0.00%; P < 0.05) in the acute phase. By contrast, differences in cytokine production by total CD3+ T cells did not differ significantly between patient groups. Thus, reduced IFN-gamma-production by gammadelta T cells in the peripheral blood of RSV-infected infants is accompanied by increased Th2 cytokine production during the acute phase of disease. At follow-up, eight children had recurrent episodes of wheezing. The frequencies of IFN-gamma-producing gammadelta T cells were significantly lower in patients who developed recurrent wheezing (median, 0.65%; range, 0.02-1.75%) than in patients without recurrent wheezing (median, 6.90%; range, 5.25-10.98%; P < 0.005). Cytokine production by gammadelta T cells may therefore be important in the pathogenesis of acute RSV disease, and play a part in the development of recurrent childhood wheezing after bronchilolitis.

7061.      Bender BG, Leung SB, Leung DY. Actigraphy assessment of sleep disturbance in patients with atopic dermatitis: an objective life quality measure. J Allergy Clin Immunol. 2003 Mar;111(3):598-602.

BACKGROUND: Patients with atopic dermatitis (AD) frequently report compromised quality of life because of disturbed sleep and daytime fatigue secondary to their skin disease, but few studies provide objective measurement of sleep change in this population. OBJECTIVE: The purpose of this investigation was to contrast subjective and objective measures of sleep quality in patients with AD. METHODS: Fourteen adult patients with AD and 14 adult control subjects with no skin disease wore actigraphs for 1 week and completed questionnaires about sleep, itch, and quality of life. RESULTS: As measured by self-report and actigraphy, the AD group slept more poorly and reported more daytime fatigue than the control group. Actigraphy alone was correlated with itch and quality of life and was able to discriminate movement during sleep, number of awakenings, minutes asleep, and minutes awake. CONCLUSIONS: Results from this study demonstrate that sleep is significantly compromised in patients with AD. Patients' perception of their sleep provides less detail and accuracy than actigraphy. The actigraph is an objective, unobtrusive measure of sleep at home in patients with skin disease and can provide an important outcome measure in clinical trials.

7062.      Boumiza R, Monneret G, Forissier MF, Savoye J, Gutowski MC, Powell WS, Bienvenu J. Marked improvement of the basophil activation test by detecting CD203c instead of CD63. Clin Exp Allergy. 2003 Feb;33(2):259-65.

BACKGROUND: The flow cytometric basophil activation test by detection of CD63 expression has been developed as an alternative method for in vitro diagnosis of IgE-mediated reactions to various allergens. Despite promising initial studies, the test remains disappointing in terms of sensitivity. CD203c has recently been demonstrated as a specific activation marker of basophils that is rapidly up-regulated after allergen challenge in sensitized patients. OBJECTIVE: The goal of the present study was to compare basophil activation tests by using either CD203c or CD63 in the diagnosis of immediate-type allergy to latex. METHODS: Twenty-seven patients (health care workers of our institution) who developed clinical features evocative of allergy after contact with latex were included and classified into two groups. Group 1 (n = 16) comprised true allergic patients who presented with typical signs of immediate allergic reaction associated with a positive skin test (prick test). Group 2 (n = 11) consisted of patients whose clinical history was not typical and had negative skin test. Twelve healthy subjects were also studied as controls. We compared the sensitivity of two triple-staining flow cytometric protocols measuring basophil activation after latex stimulation: CD45-IgE-CD63 and CD45-IgE-CD203c. RESULTS: The CD203c protocol showed a higher sensitivity than the CD63 protocol (75% vs. 50%). In comparison, latex-specific IgE sensitivity was found to be 69%. Furthermore, the magnitude of the basophil response was significantly higher with CD203c in comparison with CD63. Specificity was 100% for both protocols. CONCLUSION: Due to superior gating of basophils and a higher range of activation in response to allergen, the basophil activation test is markedly improved by use of CD203c instead of CD63.

7063.      Chou H, Chang CY, Tsai JJ, Tang RB, Lee SS, Wang SR, Peng HJ, Shen HD.  The prevalence of IgE antibody reactivity against the alkaline serine protease major allergen of Penicillium chrysogenum increases with the age of asthmatic patients. Ann Allergy Asthma Immunol. 2003 Feb;90(2):248-53.

BACKGROUND: Penicillium species are prevalent airborne fungi. However, the prevalence of allergic sensitization to Penicillium antigens and the true impact of these ubiquitous fungi on atopic respiratory disorders remain to be determined. OBJECTIVE: The purpose of this study was to analyze the prevalence of immunoglobulin (Ig)E and IgG antibodies against Penicillium chrysogenum (Pen ch 13), the alkaline serine protease major allergen of P. chrysogenum, in asthmatic patients of different age groups. METHODS: Pen ch 13 was purified from a culture medium of P. chrysogenum. The reactivity of IgE and IgG antibodies to Pen ch 13 in the serum samples of 212 asthmatic patients was analyzed by immunoblotting methods. RESULTS: Sixty-nine (33%) of the 212 sera analyzed showed IgE and/or IgG immunoblot reactivity to Pen ch 13. Significant differences in the prevalence of IgE and/or IgG antibody reactivity to Pen ch 13 were found among eight different age groups of 212 asthmatic patients. The frequency of IgE-binding reactivity to Pen ch 13 increased significantly with the age of the patients. It was 7% for the group less than 10 years old and 42% for the group older than 70 years old. In addition, a significant difference between the prevalence of IgE (7%) and IgG (33%) antibodies against Pen ch 13 in the group aged 10 or less was also found. CONCLUSIONS: Our study demonstrates that IgE and IgG antibodies specific for Pen ch 13 were detected in approximately one-third of the 212 asthmatic patients analyzed. Our results suggest that allergic sensitization to Pen ch 13, and possibly to other airborne Penicillium species, is more common in older asthmatic patients. PMID: 12602675 [PubMed - indexed for MEDLINE]

7064.      Corradi M, Folesani G, Andreoli R, Manini P, Bodini A, Piacentini G, Carraro S, Zanconato S, Baraldi E. Aldehydes and glutathione in exhaled breath condensate of children with asthma exacerbation. Am J Respir Crit Care Med. 2003 Feb 1;167(3):395-9.

Oxidative stress is implicated in the pathogenesis of asthma, and clinical studies show an imbalance in the level of oxidants to the level of antioxidants in subjects with asthma. Aldehydes and glutathione are examples of biomarkers of oxidant-induced damage and antioxidant status in asthma, respectively. In the study, we applied analytical techniques based on liquid chromatography for the assessment of aldehydes and glutathione in the exhaled breath condensate of children with asthma and in control subjects without asthma. Twelve subjects with asthma were evaluated at exacerbation and after 5 days of therapy with prednisone. At exacerbation, malondialdehyde levels were higher in patients with asthma (30.2 +/- 2.4 nM) than in control subjects (19.4 +/- 1.9 nM, p = 0.002) and were reduced after steroid therapy (18.5 +/- 1.6 nM, p = 0.001). At exacerbation, glutathione levels were lower in subjects with asthma (5.96 +/- 0.6 nM) than in control subjects (14.1 +/- 0.8 nM, p < 0.0001) and were increased after the therapy (8.44 +/- 1.2 nM, p = 0.04). Malondialdehyde and glutathione both in subjects with asthma and control subjects were negatively correlated (r = -0.5, p = 0.001). The study shows that aldehydes and glutathione are detectable in the exhaled breath condensate of children with asthma and healthy children and that their levels are modified during asthma exacerbation and after a 5-day course of therapy with oral prednisone. PMID: 12411284 [PubMed - indexed for MEDLINE]

7065.      De Boissieu D, Waguet JC, Dupont C. The atopy patch tests for detection of cow's milk allergy with digestive symptoms. J Pediatr. 2003 Feb;142(2):203-5.

Infants (n = 35) with digestive symptom were investigated for diagnosis of cow's milk allergy (CMA). Milk atopy patch tests (APTs) were positive in 19 of 24 CMA versus 1 of 11 in non-CMA patients (P <.001). This sensitivity (79%) and specificity (91%) suggest that the APT could improve the detection of conditions related to CMA. Publication Types: Validation Studies PMID: 12584547 [PubMed - indexed for MEDLINE]

7066.      Eaton DA, Roland PS, Mabry RL, Shoup AG. Electrocochleography and intranasal allergen challenge as investigational tools in patients with inhalant allergy and Meniere's disease. Laryngoscope. 2003 Jan;113(1):33-6.

OBJECTIVES: To expand on a prior study investigating the relation between inhalant allergy and Meniere's disease using electrocochleography and to present data from five patients heretofore unmentioned in previous reports. STUDY DESIGN: Prospective study of five patients identified with Meniere's disease and inhalant allergy in the practices of two faculty otolaryngologists. METHODS: Patients were tested twice using electrocochleography: once as a baseline and again 20 minutes following intranasal challenge with the allergen to which they were most sensitive. RESULTS: Three patients had no prior history of immunotherapy, and all were found to have a >15% increase in summating potential (SP)/action potential (AP) ratio after antigen challenge. However, only one of these patients developed audiovestibular symptoms. Two patients had a history of immunotherapy. One of these patients was tested using three different antigens to which she was highly sensitive on skin testing, one of which provoked audiovestibular symptoms on environmental exposure. Postchallenge electrocochleography, however, demonstrated normal SP/AP ratios with only one antigen causing a >15% increase. The other patient had elevated SP/AP ratios both before and after challenge and developed no audiovestibular symptoms despite a >15% increase. CONCLUSIONS: Previous work using this investigational tool has identified that all patients with a normal electrocochleography were asymptomatic from an audiovestibular standpoint at the time of postchallenge testing. An elevated SP/AP was not reliably correlated with audiovestibular symptoms in this group of patients. Further investigation in this area will examine the utility of using the variability of the SP and AP to predict audiovestibular symptoms.PMID: 12514378 [PubMed - indexed for MEDLINE]

7067.      Gonzalez-Quintela A, Gude F, Boquete O, Rey J, Meijide LM, Suarez F, Fernandez-Merino MC, Perez LF, Vidal C. Association of alcohol consumption with total serum immunoglobulin E levels and allergic sensitization in an adult population-based survey. Clin Exp Allergy. 2003 Feb;33(2):199-205.

BACKGROUND: Chronic alcoholism is associated with increased total serum IgE levels. OBJECTIVE: The study aimed to investigate the relationship between alcohol intake and both total serum IgE levels and allergic sensitization in a general adult population. MATERIALS AND METHODS: A total of 720 subjects was randomly selected (stratified by age) from the population older than 18 years of A-Estrada (Spain) and invited to participate in the study. From 697 eligible subjects, 469 (67%, median age 54 years, range 18 to 92 years, 44% males, 75% of cases from a rural environment) agreed to participate. A battery of 13 skin prick tests to common aeroallergens was performed in all subjects. Cases with at least one positive test (n = 121, 26%) were considered to have allergic sensitization. The most frequent sensitisers were mites and pollens (24% and 10% of subjects, respectively). Total serum IgE was measured in 465 subjects (99%). Alcohol consumption was registered as the number of standard (approximately 10 g) drinking units habitually consumed per week. A total of 244 subjects (52%) were alcohol consumers (median intake, 14 units/week, range 1 to 147 units/week). Abstainers (n = 225, 48%) constituted the reference category. RESULTS: Alcohol consumption of more than 14 units/week was associated with an increase in serum IgE levels after adjusting for age, gender, allergic sensitization and smoking (P = 0.02). Alcohol consumption was not significantly associated with either overall allergic sensitization or mite sensitization after adjusting for age, gender and smoking. However, alcohol consumption of more than 14 units/week was associated with an increased prevalence of pollen sensitization (adjusted OR 3.15, 95% CI 1.19 to 8.34, P = 0.02). CONCLUSION: Alcohol consumption above a certain threshold is associated with an increase in total serum IgE levels. Alcohol consumption may also be associated with an increased prevalence of pollen sensitization. PMID: 12580912 [PubMed - indexed for MEDLINE]

7068.      Hamilton RG, Adkinson NF Jr. Clinical laboratory assessment of IgE-dependent hypersensitivity. J Allergy Clin Immunol. 2003 Feb;111(2 Suppl):S687-701. Review.

This chapter reviews clinical and laboratory analyses that aid in the diagnosis and management of human allergic (IgE-dependent) diseases. The diagnostic algorithm for immediate-type hypersensitivity begins with a thorough clinical history and physical examination. Once signs and symptoms compatible with an allergic disorder have been identified, a skin test and/or blood test for allergen-specific IgE antibodies may serve as primary confirmation to strengthen the diagnosis. Puncture and intradermal skin testing provide a biologically relevant immediate-type hypersensitivity response in the skin, with resultant wheal and flare reactions within 15 minutes of allergen application. Bleeding, dermatographism, and antihistamines may confound the quality of the skin test. Allergen-specific IgE antibody may also be detected in the blood using a radioallergosorbent test (RAST). Nonisotopic "second-generation" RAST-type assays have evolved to provide more quantitative, sensitive, precise IgE antibody results. In vivo provocation tests may serve as secondary confirmatory tests when the clinical history is discordant with a primary IgE antibody test result. The multiallergen screen is a qualitative RAST-type assay that detects specific IgE antibody to approximately 15 allergens that evoke a large majority of aeroallergen or food-related allergic disorders. Other useful serological assays performed in the diagnostic allergy laboratory include total serum IgE, Hymenoptera venom-specific IgG antibody, IgG precipitins for organic dusts, mast cell tryptases, and the venom RAST inhibition test. Above all, in vivo or laboratory confirmatory test results that are inconsistent with the clinical history should be repeated as for any laboratory assessment. Publication Types:    Review     Review, Tutorial PMID: 12592314 [PubMed - indexed for MEDLINE]

7069.      Holgate ST, Peters-Golden M. Introduction: the anti-inflammatory role of cysteinyl leukotriene receptor antagonists in asthma. J Allergy Clin Immunol. 2003 Jan;111(1 Suppl):S1-4. No abstract availabe.

7070.      Jin GB, Nakayama H, Shmyhlo M, Inoue S, Kondo M, Ikezawa Z, Ouchi Y, Cyong JC.  High positive frequency of antibodies to metallothionein and heat shock protein 70 in sera of patients with metal allergy. Clin Exp Immunol. 2003 Feb;131(2):275-9.

Two principal types of stress protein, heat shock proteins (hsps) and metallothionein (MT), are induced in cells responding to a variety of stresses. They play an important role in protecting cells from these stresses. However, many reports indicate that antibodies to hsps are present in human serum and are associated with several autoimmunity diseases. Metals, which are commonly allergenic to humans, induce both MT and hsp70 (one of the hsps family). Until now, there has been no report of any antibody to MT in human serum. In the present study, serum samples from healthy controls (Group I), and patients suffering from atopic dermatitis without (Group II) or with (Group III) metal allergy, were measured for antibodies to MT and hsp70, using an enzyme-linked immunosorbent assay (ELISA). Metal allergy was confirmed by patch testing. We first found that antibody to MT exists in human serum. We also found a high positive frequency of antibody to MT (51.3%) and to hsp70 (43.6%) in the sera of Group III, compared to those of Group I (3.8% and 5.1%) or Group II (6.4% and 5.1%). Furthermore, there was a strong positive correlation between antibody to MT and antibody to hsp70 in Group III (P = 0.0013), but not in Group I and Group II. Our results indicate that antibody to MT exists in human serum, as do antibodies to hsps, and suggest that elevated levels of MT and hsp70 antibodies are associated with metal allergy in atopic patients. PMID: 12562388 [PubMed - indexed for MEDLINE]

7071.      Kaito K, Otsubo H, Ogasawara Y, Kimura H, Kurihara E, Koike M, Aiso M, Kobayashi M. Serum soluble interleukin-2 receptor in eosinophilia. Acta Haematol. 2003;109(1):23-8.

The relationship between soluble interleukin-2 receptor (sIL-2R) levels and clinical characteristics was evaluated in patients with eosinophilia. Thirty-eight out of 60 patients showed sIL-2R levels of more than 800 U/ml. In these patients, sIL-2R was closely related to the eosinophil count, but not the IgE level. Their underlying diseases were heterogeneous, including neoplasms and collagen diseases. In patients with lower sIL-2R levels, there was no relationship to the eosinophil count, but sIL-2R was correlated with the IgE level. These findings indicate that patients with eosinophilia and higher sIL-2R levels tend to have underlying diseases other than allergy, and might be more severely ill than patients with lower sIL-2R levels. sIL-2R may be a good marker for evaluating patients with eosinophilia, as an indicator of the probable etiology and severity of their diseases. Copyright 2003 S. Karger AG, Basel PMID: 12486319 [PubMed - indexed for MEDLINE]

7072.      Linneberg A, Petersen J, Nielsen NH, Madsen F, Frolund L, Dirksen A, Jorgensen T. The relationship of alcohol consumption to total immunoglobulin E and the development of immunoglobulin E sensitization: the Copenhagen Allergy Study. Clin Exp Allergy. 2003 Feb;33(2):192-8.

BACKGROUND: Several studies in patient populations have reported a positive association between alcohol consumption and serum total IgE. Furthermore, we have previously reported a positive association between alcohol consumption and the prevalence of skin prick test (SPT positivity) to inhalant allergens in a population-based cross-sectional study. OBJECTIVE: To investigate the relationship of alcohol consumption to levels of serum total IgE and the development of IgE sensitization to inhalant allergens. METHODS: In 1990, self-reported consumption of alcohol, serum total IgE, SPT positivity and specific IgE positivity to inhalant allergens were assessed in 1112 subjects, aged 15-69 years, participating in a population-based cross-sectional study in Copenhagen, Denmark. In 1998, they were invited to a follow-up and 734 were re-examined (participation rate 69.0%). Adjustment for potential confounders was performed by using multivariable regression analyses. RESULTS: In non-atopic (specific IgE negative) subjects there was a positive association between alcohol consumption and the concentration of total IgE (P = 0.001). During the follow-up period, 45 and 33 subjects developed SPT positivity and specific IgE positivity, respectively. There was no significant association between alcohol consumption and the development of SPT positivity or specific IgE positivity. However, the risk of developing SPT positivity tended to increase with increasing consumption of alcohol (P = 0.055). CONCLUSIONS: This epidemiological study confirms that alcohol consumption has an influence on levels of serum total IgE. A significant association between alcohol consumption and the development of IgE sensitization was not established. However, there seems to be a lack epidemiological data on this issue. PMID: 12580911 [PubMed - indexed for MEDLINE]

7073.      Mayorga C, Torres MJ, Corzo JL, Alvarez J, Garcia JA, Rodriguez CA, Blanca M, Jurado A. Immediate allergy to tetanus toxoid vaccine: determination of immunoglobulin E and immunoglobulin G antibodies to allergenic proteins. Ann Allergy Asthma Immunol. 2003 Feb;90(2):238-43.

BACKGROUND: Adverse reactions to tetanus toxoid (TT) vaccine are mostly mild and limited to the injection site. However, immunoglobulin (Ig)E-mediated reactions may occur, and the incidence of anaphylactic responses to TT immunization is 0.001%. When TT induces an allergic reaction, the potential causative agents can be TT antigens, thimerosal or aluminum phosphate. OBJECTIVE: We studied four children who developed immediate urticaria after TT vaccine, soon after the reaction and 5 years later. METHODS: Skin tests were performed separately with TT vaccine and two vaccine components, thimerosal and aluminum phosphate, and the diagnosis was confirmed by provocation test. IgE and IgG antibodies to TT and their specificities were determined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting were performed to characterize the antigenic proteins. RESULTS: All four children were immediate skin test-positive to TT, but negative to thimerosal and aluminum phosphate; 3 developed a reaction after intramuscular provocation using increasing doses of TT vaccine; and 1 refused to be tested. All these tests were negative in five controls, all of whom received TT vaccine and developed only local swelling at the site of application 24 hours after vaccine administration. After 5 years the IgG antibodies were still high in all cases and the IgE antibody values fell by 50%. Patients allergic to TT vaccine produced IgE and IgG antibodies, which decreased at different rates but remained for at least 5 years. The pattern of antibody decrease was confirmed by radioallergosorbent test, enzyme-linked immunoadsorbent assay, or immunoblotting assay. IgE and IgG antibodies recognized two proteins derived from TT, of 150 and 50 kDa, corresponding to the intracellular form and to a chain of the extracellular form of the tetanus neurotoxin. CONCLUSIONS: In children with immediate allergic reactions to TT vaccine, antibodies may persist for at least 5 years, requiring evaluation by skin and/or in vitro tests before subsequent treatment.PMID: 12602673 [PubMed - indexed for MEDLINE]

7074.      Oura H, Bertoncini J, Velasco P, Brown LF, Carmeliet P, Detmar M. A critical role of placental growth factor in the induction of inflammation and edema formation. Blood. 2003 Jan 15;101(2):560-7.

Angiogenesis is a prominent feature of a number of inflammatory human diseases, including rheumatoid arthritis, psoriasis, and cutaneous delayed-type hypersensitivity (DTH) reactions. Up-regulation of placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, has been found in several conditions associated with pathologic angiogenesis; however, its distinct role in the control of angiogenesis has remained unclear. To directly investigate the biologic function of PlGF in cutaneous inflammation and angiogenesis, DTH reactions were investigated in the ear skin of wild-type mice, of PlGF-deficient mice, and of transgenic mice with targeted overexpression of human PlGF-2 in epidermal keratinocytes, driven by a keratin 14 promoter expression construct. Chronic transgenic delivery of PlGF-2 to murine epidermis resulted in a significantly increased inflammatory response, associated with more pronounced vascular enlargement, edema, and inflammatory cell infiltration than seen in wild-type mice. Conversely, PlGF deficiency resulted in a diminished and abbreviated inflammatory response, together with a reduction of inflammatory angiogenesis and edema formation. VEGF expression was up-regulated at a comparable level in the inflamed skin of all genotypes. These findings reveal that placental growth factor plays a critical role in the control of cutaneous inflammation, and they suggest inhibition of PlGF bioactivity as a potential new approach for anti-inflammatory therapy. PMID: 12393422 [PubMed - indexed for MEDLINE]

7075.      Pham DN, Chu HW, Martin RJ, Kraft M. Increased matrix metalloproteinase-9 with elastolysis in nocturnal asthma. Ann Allergy Asthma Immunol. 2003 Jan;90(1):72-8.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is capable of degrading elastin, whereas tissue inhibitor of metalloproteinase-1 (TIMP-1) can inhibit MMP-9 activity. We observed reduced airway tissue elastin volume density in six subjects with nocturnal asthma (NA) as compared with seven subjects with nonnocturnal asthma (NNA) and seven normal controls (NL) when endobronchial biopsies were evaluated morphometrically at 4:00 PM and 4:00 AM. OBJECTIVE: We hypothesized that increased metalloproteinases and decreased tissue inhibitors of metalloproteinases in the airways of subjects with NA may be responsible for reduced elastin volume density. METHODS: Ten additional subjects with NA, 10 subjects with NNA, and 7 normal control subjects underwent bronchoscopy with bronchoalveolar lavage at 4:00 PM and 4:00 AM. Levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined in bronchoalveolar lavage by enzyme-linked immunosorbent assay. RESULTS: There was a fourfold circadian increase in bronchoalveolar lavage levels of MMP-9, and there was a twofold increase in MMP-9:TIMP-1 ratio in NA subjects from 4:00 PM to 4:00 AM. There were no circadian changes in the NNA and NL subjects. At 4:00 AM, MMP-9 levels and the MMP-9:TIMP-1 ratio were highest in NA subjects. At 4:00 PM, no significant group differences were observed. The MMP-9 levels positively correlated with the overnight fall in forced expiratory volume in 1 second and the MMP-9/TIMP-1 ratio negatively correlated with the 4:00 AM % predicted forced expiratory volume in 1 second. CONCLUSIONS: Our results from these two pilot studies suggest that increased MMP-9 and decreased TIMP-1 at night in NA may lead to reduced elastin density. PMID: 12546341 [PubMed - indexed for MEDLINE]

7076.      Silkoff P.  Exhaled nitric oxide as a diagnostic tool. Am J Respir Crit Care Med. 2003 Feb 15;167(4):665-6. No abstract available.

7077.      Skowron M, Perret E, Marano F, Caput D, Tournier F. Interleukin-13 alters mucociliary differentiation of human nasal epithelial cells. Chest. 2003 Mar;123(3 Suppl):373S-4S. Review. No abstract available.

7078.      Tamura Y, Kawaguchi J, Serizawa N, Hirahara K, Shiraishi A, Nigi H, Taniguchi Y, Toda M, Inouye S, Takemori T, Sakaguchi M. Analysis of sequential immunoglobulin E-binding epitope of Japanese cedar pollen allergen (Cry j 2) in humans, monkeys and mice. Clin Exp Allergy. 2003 Feb;33(2):211-7.

BACKGROUND: Japanese cedar (Cryptomeria japonica; CJ) pollinosis has been reported to occur naturally in Japanese monkeys (Macaca fuscata) as well as in humans. Most human patients and monkeys with pollinosis have specific IgE for Cry j 2, a major allergen of CJ pollen. OBJECTIVE: The main purpose of this study was to identify IgE B cell epitopes of Cry j 2 using a synthetic peptide in humans, monkeys and mice. METHODS: We synthesized 38 overlapping peptides that span the entire length of Cry j 2. We examined the B cell epitopes of Cry j 2 that are recognized by IgE in the sera of human patients and monkeys with pollinosis and immunized mice using synthetic peptides of Cry j 2. We also examined the reaction of Cry j 2-specific mouse monoclonal IgG antibodies to the peptides. Furthermore, we conducted a histamine release assay with leucocytes from a pollinosis patient using human serum albumin (HSA) conjugated with the peptides as a B cell epitope. RESULTS: We found that 16 of the 20 pollinosis patients who had specific IgE to Cry j 2 also exhibited IgE reaction with some Cry j 2 peptides. Of these 16 patients, 10 exhibited IgE reaction with Cry j 2 peptide no. 13 (121GQCKWVNGREICNDRDRPTA140). Five of the seven monkeys with CJ pollinosis exhibited a reaction with peptide no. 13. Furthermore, IgE in mice immunized with Cry j 2 and two mouse monoclonal IgG antibodies reacted with peptide no. 13. Peptide no. 13-conjugated HSA showed the release of histamine from basophils. Furthermore, to determine the minimum epitope in peptide no. 13, we conducted an enzyme-linked immunosorbent assay inhibition test. The core of the epitope in humans, monkeys and mice was 124KWVNGREI131. CONCLUSION: We found that 124KWVNGREI131 is an important B cell epitope recognized by IgE in humans, monkeys and mice. PMID: 12580914 [PubMed - indexed for MEDLINE]

7079.      Wang CL, Wu YT, Liu CA, Lin MW, Lee CJ, Huang LT, Yang KD. Expression of CD40 ligand on CD4+ T-cells and platelets correlated to the coronary artery lesion and disease progress in Kawasaki disease. Pediatrics. 2003 Feb;111(2):E140-7.

OBJECTIVE: Kawasaki disease (KD) is an acute febrile vasculitic syndrome in children. CD40 ligand (CD40L) has been implicated in certain types of vasculitis. We proposed that CD40L expression might be correlated with coronary artery lesions in KD. METHODS: Blood samples were collected from 43 patients with KD before intravenous immunoglobulin (IVIG) treatment and 3 days afterward. Forty-three age-matched febrile children with various diseases were studied in parallel as controls. CD40L expression on T-cells and platelets were detected by flow cytometry, and soluble CD40L (sCD40L) levels were measured by enzyme-linked immunosorbent assay. RESULTS: We found that CD40L expression on CD4(+) T-cells was significantly higher in patients with KD than in the febrile control (FC) group (28.69 +/- 1.17% vs 4.37 +/- 0.36%). CD40L expression decreased significantly 3 days after IVIG administration (28.69 +/- 1.17% vs 13.53 +/- 0.55%). CD40L expression on platelets from patients with KD was also significantly higher than in the FC group (8.20 +/- 0.41% vs 1.26 +/- 0.12%) and decreased after IVIG therapy. sCD40L levels were also significantly higher in KD patients with those of FC (9.69 +/- 0.45 ng/mL vs 2.25 +/- 0.19 ng/mL) but were not affected by IVIG treatment 3 days afterward (9.69 +/- 0.45 ng/mL vs 9.03 +/- 0.32 ng/mL). More interesting, we found that in KD patients, CD40L expression on CD4(+) T-cells and platelets but not on CD8(+) T-cells or sCD40L was correlated with the occurrence of coronary artery lesions. CONCLUSIONS: CD40L might play a role in the immunopathogenesis of KD. IVIG therapy might downregulate CD40L expression, resulting in decrease of CD40L-mediated vascular damage in KD. This implicates that modulation of CD40L expression may benefit to treat KD vasculitis. PMID: 12563087 [PubMed - indexed for MEDLINE]

7080.      Wang L, McParland BE, Pare PD. The functional consequences of structural changes in the airways: implications for airway hyperresponsiveness in asthma. Chest. 2003 Mar;123(3 Suppl):356S-62S. Review. No abstract available.

7081.      Wessler I, Reinheimer T, Kilbinger H, Bittinger F, Kirkpatrick CJ, Saloga J, Knop J. Increased acetylcholine levels in skin biopsies of patients with atopic dermatitis. Life Sci. 2003 Mar 28;72(18-19):2169-72.

Recent experimental evidence indicates that non-neuronal acetylcholine is involved in the regulation of basic cell functions. Here we investigated the cholinergic system in the skin of healthy volunteers and patients with atopic dermatitis (AD). The synthesizing enzyme, choline-acetyltransferase (ChAT), was studied by anti-ChAT immunohistochemistry and enzyme assay. Skin biopsies taken from healthy volunteers and from AD patients were separated into the 2 mm superfical (epidermis and upper dermis) and 3 mm underlying portion (deeper dermis and subcutis). ChAT enzyme activity was detected in homogenized skin and subcutaneous fat (about 13 nmol/mg protein/h). ChAT immunoreactivity was expressed in keratinocytes, hair papilla, sebaceous and eccrine sweat glands, endothelial cells and mast cells. In healthy volunteers the superficial and underlying portion of skin biopsies contained 130 +/- 30 and 550 +/- 170 pmol/g acetylcholine (n = 12), respectively. In AD patients (n = 7) acetylcholine was increased 14-fold in the superficial and 3-fold in the underlying biopsy portion. The present study demonstrates the widespread expression of ChAT protein in the vast majority of human skin cells. Tissue levels of acetylcholine are greatly (14-fold) enhanced in the superficial 2 mm skin of AD patients. Copyright 2003 Elsevier Science Inc. Publication Types:    Clinical Trial  PMID: 12628475 [PubMed - indexed for MEDLINE]

7082.      Yu CJ, Lin YF, Chiang BL, Chow LP. Proteomics and immunological analysis of a novel shrimp allergen, Pen m 2. J Immunol. 2003 Jan 1;170(1):445-53.

Shellfish are a common cause of adverse food reactions in hypersensitive individuals and shrimp is one of the most frequently reported causes of allergic reactions. A novel allergen from Penaeus monodon, designated Pen m 2, was identified by two-dimensional immunoblotting using sera from subjects with shrimp allergy, followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis of the peptide digest. This novel allergen was then cloned and the amino acid sequence deduced from the cDNA sequence. The cloned cDNA encoded a 356-aa protein with an acetylated N terminus at Ala2, identified by postsource decay analysis. Comparison of the Pen m 2 sequence with known protein sequences revealed extensive similarity with arginine kinase (EC 2.7.3.3) from crustaceans. Pen m 2 was purified by anion exchange chromatography and shown to have arginine kinase activity and to react with serum IgE from shrimp allergic patients and induce immediate type skin reactions in sensitized patients. Using Pen m 2-specific antisera and polyclonal sera from shrimp-sensitive subjects in a competitive ELISA inhibition assay, Pen m 2 was identified as a novel cross-reactive Crustacea allergen. This novel allergen could be useful in allergy diagnosis and in the treatment of Crustacea-derived allergic disorders. PMID: 12496430 [PubMed - indexed for MEDLINE]

7083.      Zheng X, Nakamura K, Furukawa H, Nishibu A, Takahashi M, Tojo M, Kaneko F, Kakinuma T, Tamaki K. Demonstration of TARC and CCR4 mRNA expression and distribution using in situ RT-PCR in the lesional skin of atopic dermatitis. J Dermatol. 2003 Jan;30(1):26-32.

Thymus- and activation-regulated chemokine (TARC/CCL17) and its receptor, CC chemokine receptor 4 (CCR4), have been proven to be involved in a number of allergic diseases, especially atopic dermatitis (AD). The purpose of this study was to examine the expression and distribution of TARC and CCR4 mRNAs in samples of AD (n=15, acute lesions 8, chronic lesions 7) and normal skin (n=6). The expression and distribution of TARC and CCR4 mRNAs were detected with the in situ reverse transcription (RT) -polymerase chain reaction (PCR) technique. TARC mRNA was expressed in epidermal keratinocytes, dermal endothelial cells and infiltrating cells. CCR4 mRNA was expressed in dermal endothelial cells and infiltrating cells. In acute AD lesional skin, there were more positive cells, and the staining intensity was stronger than in chronic lesions (p<0.05). The distribution of positive cells was as follows: In the epidermis, keratinocytes in the basal layer showed the strongest staining, and keratinocytes in the spinous layer showed moderate staining; the superficial area showed faint staining. In the dermis, infiltrating cells located in the superficial area of the dermis showed the strongest staining, positive staining intensity became weaker and the percentage of positive cells became less as the location became deeper. There were no positive cells in normal skin. These data further substantiate the role of TARC/CCR4 in the pathogenesis of AD. PMID: 12598706 [PubMed - indexed for MEDLINE]

 

Pathogenesis:

 

7084.      Bergeron C, Page N, Barbeau B, Chakir J. Interleukin-4 promotes airway remodeling in asthma: regulation of procollagen I (alpha1) gene by interleukin-4. Chest. 2003 Mar;123(3 Suppl):424S. Review. No abstract available.

7085.      Dibbern DA Jr, Palmer GW, Williams PB, Bock SA, Dreskin SC. RBL cells expressing human Fc epsilon RI are a sensitive tool for exploring functional IgE-allergen interactions: studies with sera from peanut-sensitive patients. J Immunol Methods. 2003 Mar 1;274(1-2):37-45.

Rat basophilic leukemia cells (RBL SX-38) express the alpha, beta, and gamma chains of human Fc varepsilon RI. Following sensitization with IgE from a subset of allergic human donors, these cells can be triggered by exposure to anti-IgE or to very low concentrations of specific allergens. We examined 18 sera from patients who were highly sensitive to peanuts by history and had anti-peanut IgE by in vitro testing. The ability of these sera to sensitize the RBL SX-38 cells for degranulation with peanut allergens correlates very well with the absolute amount of anti-peanut IgE (r=0.95; p<0.001). The most effective sera contained at least 50 kU/l of total IgE and at least 15 kU/l of peanut-specific IgE. RBL SX-38 cells sensitized with these sera degranulated optimally upon exposure to anti-IgE (net degranulation of 40+/-8%, means+/-S.D.; n=8) and to a 10(5)-10(6) dilution of crude peanut extract (CPE) (37+/-7% net degranulation; 93+/-13% of that seen with anti-IgE). This assay is quite sensitive. Cells sensitized with selected sera are activated by exposure to a 1:10(7) dilution of the CPE containing picogram amounts of peanut allergens. This assay is also quite specific. Cells sensitized with sera from patients with anti-peanut IgE and no detectable IgE against soybean, walnut or grass pollen did not degranulate following exposure to these latter antigens. The converse was also true; cells sensitized with sera from patients without anti-peanut IgE did not react to peanut. These data demonstrate that RBL cells expressing human Fc varepsilon RI form the basis of a useful model system for the detection of allergens and for the study of IgE-allergen interactions.

7086.      El Bahlawan L, Christensen M, Binaei S, Murphy C, Zhang Q, Quasney M.  Lack of association between the tumor necrosis factor-alpha regulatory region genetic polymorphisms associated with elevated tumor necrosis factor-alpha levels and children with asthma. Chest. 2003 Mar;123(3 Suppl):374S-5S. No abstract available

7087.      Lobos E, Nutman TB, Hothersall JS, Moncada S. Elevated immunoglobulin E against recombinant Brugia malayi gamma-glutamyl transpeptidase in patients with bancroftian filariasis: association with tropical pulmonary eosinophilia or putative immunity. Infect Immun. 2003 Feb;71(2):747-53.

A major allergen of the lymphatic filarial nematode Brugia malayi, a homologue of gamma-glutamyl transpeptidase (gamma-GT), is involved in the pathology of tropical pulmonary eosinophilia (TPE) through its potent allergenicity and the induction of antibodies against the host pulmonary epithelium. To investigate the immunoglobulin G (IgG) subclass and IgE responses to recombinant B. malayi gamma-GT, we analyzed the results obtained from 51 patients with differing clinical manifestations of bancroftian filariasis. gamma-GT-specific IgG1, rather than IgG4, was the predominant IgG subclass, particularly in patients with TPE (geomean, 6,321 ng/ml; range, 78 to 354,867 ng/ml) and was 75 times higher than in patients with elephantiasis (CP) (P < 0.003) and 185 times higher than in endemic normal individuals (ENL) (P < 0.010). IgG2 responses were low and IgG3 was almost absent, with no significant differences among the groups. gamma-GT-specific IgG4 responses were significantly elevated in those with subclinical microfilaremia (MF) compared to the CP and ENL groups and correlated with the presence of circulating filarial antigen (CAg). More significantly, gamma-GT-specific IgE antibody levels were strikingly elevated in patients with TPE (geomean, 681 ng/ml; range, 61 to 23,841 ng/ml) and in the ENL group (geomean, 106 ng/ml; range, 13 to 1,405 ng/ml) whereas the gamma-GT-specific IgE level was 44 and 61 times lower in those with MF and CP, respectively (P < 0.001). Elevated gamma-GT-specific IgE/IgG4 ratios were demonstrated in patients with TPE (ratio, 45) and ENL (ratio, 107). Because expression of gamma-GT in Brugia infective third-stage larvae (L3) was demonstrated by immunoblot analysis, the elevated gamma-GT-specific IgE antibodies appear to be associated not only with pulmonary pathology but also with possible resistance to infection in lymphatic filariasis.

7088.      Roche N, Stirling RG, Lim S, Oliver BG, Oates T, Jazrawi E, Caramori G, Chung KF. Effect of acute and chronic inflammatory stimuli on expression of protease-activated receptors 1 and 2 in alveolar macrophages. J Allergy Clin Immunol. 2003 Feb;111(2):367-73.

BACKGROUND: Protease-activated receptors 1 and 2 (PAR-1 and PAR-2) are 7-transmembrane G protein-coupled receptors activated by serine proteases in many cell types, including monocytes-macrophages, leading to the production of pro-inflammatory mediators, cytokines, and growth factors. OBJECTIVE: We determined the influence of chronic smoking and asthma on the expression of PAR-1 and PAR-2 receptors on alveolar macrophages (AMs). METHODS: We used RT-PCR and immunocytochemistry with confocal microscopy to determine mRNA and protein expression of PAR-1 and PAR-2 in AMs obtained from healthy smokers, asthmatic patients, and healthy subjects. In addition, we examined the effect of IL-1beta and LPS. RESULTS: PAR1 mRNA was decreased, whereas PAR2 mRNA was increased in 24-hour cultured AMs from smokers when compared with values in AMs from healthy subjects. Paradoxically, there was a higher degree of PAR-1 protein staining in AMs from smokers, whereas PAR-2 staining was similar in smokers and healthy subjects. PAR-1 and PAR-2 mRNA and protein expression were similar in asthmatic patients and control subjects. IL-1beta and LPS had no effect on PAR1 and PAR2 gene expression by AMs. CONCLUSIONS: There is a dissociation between gene and protein expression of PAR-1 and PAR-2. PAR-1 protein overexpression in AMs from smokers might be important in the pathophysiology of chronic airways disease.

7089.      Sekiya T, Tsunemi Y, Miyamasu M, Ohta K, Morita A, Saeki H, Matsushima K, Yoshie O, Tsuchiya N, Yamaguchi M, Yamamoto K, Tamaki K, Hirai K.  Variations in the human Th2-specific chemokine TARC gene. Immunogenetics. 2003 Jan;54(10):742-5.

Th2-specific chemokine thymus and activation-regulated chemokine (TARC)/CC chemokine ligand (CCL)17 is highly implicated in the pathogenesis of Th-2-dominated allergic diseases such as bronchial asthma (BA) and atopic dermatitis (AD). We performed polymorphism screening of the coding and promoter regions of the TARC gene. We found two rare variations in the coding region of exon 3 (2134C>T and 2037G>A) and a single nucleotide polymorphism (SNP) in the 5'-flanking region (-431C>T). Individuals carrying the 431T allele showed significantly increased serum levels of TARC compared with those not carrying the 431T allele, suggesting that this SNP has functional significance. However, when the genotypes at the SNP site were determined for 158 healthy individuals, 105 patients with BA and 148 patients with AD, we observed no significant association of the SNP with susceptibility to BA or AD.

7090.      Vercelli D. Learning from discrepancies: CD14 polymorphisms, atopy and the endotoxin switch. Clin Exp Allergy. 2003 Feb;33(2):153-5. No abstract available.

 

Vaccines:

7091.      Himly M, Jahn-Schmid B, Dedic A, Kelemen P, Wopfner N, Altmann F, van Ree R, Briza P, Richter K, Ebner C, Ferreira F. Art v 1, the major allergen of mugwort pollen, is a modular glycoprotein with a defensin-like and a hydroxyproline-rich domain. FASEB J. 2003 Jan;17(1):106-8.

In late summer, pollen grains originating from Compositae weeds (e.g., mugwort, ragweed) are a major source of allergens worldwide. Here, we report the isolation of a cDNA clone coding for Art v 1, the major allergen of mugwort pollen. Sequence analysis showed that Art v 1 is a secreted allergen with an N-terminal cysteine-rich domain homologous to plant defensins and a C-terminal proline-rich region containing several (Ser/Ala)(Pro)2-4 repeats. Structural analysis showed that some of the proline residues in the C-terminal domain of Art v 1 are posttranslationally modified by hydroxylation and O-glycosylation. The O-glycans are composed of 3 galactoses and 9-16 arabinoses linked to a hydroxyproline and represent a new type of plant O-glycan. A 3-D structural model of Art v 1 was generated showing a characteristic "head and tail" structure. Evaluation of the antibody binding properties of natural and recombinant Art v 1 produced in Escherichia coli revealed the involvement of the defensin fold and posttranslational modifications in the formation of epitopes recognized by IgE antibodies from allergic patients. However, posttranslational modifications did not influence T-cell recognition. Thus, recombinant nonglycosylated Art v 1 is a good starting template for engineering hypoallergenic vaccines for weed-pollen therapy.

7092.      Smithers M, O'Connell K, MacFadyen S, Chambers M, Greenwood K, Boyce A, Abdul-Jabbar I, Barker K, Grimmett K, Walpole E, Thomas R. Clinical response after intradermal immature dendritic cell vaccination in metastatic melanoma is associated with immune response to particulate antigen. Cancer Immunol Immunother. 2003 Jan;52(1):41-52.

Metastatic melanoma is poorly responsive to treatment, and immunotherapeutic approaches are potentially beneficial. Predictors of clinical response are needed to identify suitable patients. We sought factors associated with melanoma-specific clinical response following intradermal vaccination with autologous melanoma peptide and particulate hepatitis B antigen (HBsAg)-exposed immature monocyte-derived dendritic cells (MDDC). Nineteen patients with metastatic melanoma received a maximum of 8, 2-weekly vaccinations of DC, exposed to HBsAg in addition to autologous melanoma peptides. A further 3 patients received an otherwise identical vaccine that did not include HBsAg. Patients were assessed 1-2 monthly for safety, disease volume, and cellular responses to HBsAg and melanoma peptide. There was no significant toxicity. Of 19 patients receiving HBsAg-exposed DC, 9 primed or boosted a cellular response to HBsAg, and 10 showed no HBsAg response. HBsAg-specific responses were associated with in vitro T cell responses to melanoma peptides and to phytohemagglutinin (PHA). Zero out of 10 non-HBsAg-responding and 4/9 HBsAg-responding patients achieved objective melanoma-specific clinical responses or disease stabilization - 1 complete and 2 partial responses and 1 case of stable disease ( P=0.018). Development of melanoma-specific cellular immunity and T cell responsiveness to mitogen were greater in the group of patients responding to HBsAg. Therefore stimulation of an immune response to nominal particulate antigen was necessary when presented by melanoma peptide-exposed immature DC, to achieve clinical responses in metastatic melanoma. Since general immune competence may be a determinant of treatment response, it should be assessed in future trials on DC immunotherapy.

 

October 2003

7691.   Adams BK, Cydulka RK.  Asthma evaluation and management. Emerg Med Clin North Am. 2003 May;21(2):315-30.

Asthma is a chronic inflammatory illness with acute exacerbations, which often is encountered in the ED setting. Knowledge of the presentation and treatment of asthma is crucial for any physician treating patients with this disease. Beta-agonist, anticholinergic, and corticosteroid therapy continue to be the mainstay of emergency therapy despite advances in newer medications. Proper attention to long-term treatment of asthma and aggressive treatment of acute exacerbations should help reduce morbidity and mortality.

7692.   Akdis M, Trautmann A, Klunker S, Daigle I, Kucuksezer UC, Deglmann W, Disch R, Blaser K, Akdis CA. T helper (Th) 2 predominance in atopic diseases is due to preferential apoptosis of circulating memory/effector Th1 cells. FASEB J. 2003 Jun;17(9):1026-35.

T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated, Th2-biased peripheral immune response appears to be an important pathogenetic factor. In atopic dermatitis, circulating cutaneous lymphocyte-associated antigen-bearing (CLA+) CD45RO+ T cells with skin-specific homing property represent an activated memory/effector T cell subset. They express high levels of Fas and Fas ligand and undergo activation-induced apoptosis. The freshly purified CLA+ CD45RO+ T cells of atopic individuals display distinct features of in vivo-triggered apoptosis such as pro-caspase degradation and active caspase-8 formation. In particular, the Th1 compartment of activated memory/effector T cells selectively undergoes activation-induced cell death, skewing the immune response toward surviving Th2 cells in atopic dermatitis patients. The apoptosis of circulating memory/effector T cells was confined to atopic individuals whereas non-atopic patients such as psoriasis, intrinsic-type asthma, contact dermatitis, intrinsic type of atopic dermatitis, bee venom allergic patients, and healthy controls showed no evidence for enhanced T cell apoptosis in vivo. These results define a novel mechanism for peripheral Th2 response in atopic diseases.

7693.   Anees W.  Use of pulmonary function tests in the diagnosis of occupational asthma. Ann Allergy Asthma Immunol. 2003 May;90(5 Suppl 2):47-51.

OBJECTIVE: To discuss the different methods of assessing lung function measurements for the diagnosis of occupational asthma, focusing in particular on serial peak expiratory flow rate (PEFR) monitoring, including details on how PEFR records should be kept, plotted, and analyzed and limitations of the method. DATA SOURCES: Published studies on the use of diagnostic methods in occupational asthma, expert opinion, and recently obtained data from studies performed at a large occupational lung disease clinic. STUDY SOURCES: The expert opinion of the author was used to select the relevant data for review. RESULTS: Objective methods are necessary for the diagnosis of occupational asthma, since clinical history alone is not a satisfactory means of diagnosis. Serial PEFR monitoring has a high diagnostic sensitivity and specificity for occupational asthma and is more useful than evaluation of cross-shift change in forced expiratory volume in 1 second or change in nonspecific bronchial hyperresponsiveness. Interpretation is best performed by expert visual evaluation of plots of maximum, mean, and minimum daily PEFR readings. CONCLUSIONS: Despite some limitations of the method, serial PEFR monitoring is usually the most appropriate first-line investigation in workers suspected of having occupational asthma.

7694.   Baraldi E, Carraro S, Alinovi R, Pesci A, Ghiro L, Bodini A, Piacentini G, Zacchello F, Zanconato S.  Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations. Thorax. 2003 Jun;58(6):505-9.

BACKGROUND: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory      metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific      for lipid peroxidation, which makes them potentially reliable biomarkers for      oxidative stress. A study was undertaken to evaluate the effect of a course of      oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. METHODS: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FE(NO)) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FE(NO) was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children. RESULTS: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4-15.6); 8-isoprostane, 12.0 pg/ml (9.4-29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0-5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1-3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9-8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4-11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FE(NO) levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations. CONCLUSION: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.

7695.   Barczyk A, Pierzchala W, Sozanska E.  Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine. Respir Med. 2003 Jun;97(6):726-33.

 

BACKGROUND: Interleukin-17 (IL-17) is a novel cytokine secreted by activated human memory CD4+ T cells. In vivo IL-17 recruits neutrophils into the airways via the release of CXC chemokines (interleukin-8) from bronchial epithelial cells. Since neutrophils are implicated in pathogenesis of chronic obstructive pulmonary disease (COPD) chronic bronchitis (CB) and asthma, we hypothesized that there would be increased concentration of IL-17 in the airways of these patients. To test this hypothesis, we measured levels of IL-17 in induced sputum of COPD patients, chronic bronchitis and asthmatics and compared them with healthy controls. METHODS: Levels of IL-17 in induced sputum were measured via ELISA method in 19 COPD, 16 CB, 10 asthma and 11 control subjects. Airway responsiveness to methacholine was performed in people with FEV1 higher than 70% of predicted. RESULTS: There were no significant differences in IL-17 levels between control group and the other groups. However, levels of IL-17 in sputum of COPD patients were significantly lower than in asthma (P=0.004) and in CB (P=0.01) groups. Medians and (ranges) were as follows: asthma--37.6 pg/ml (18.8-55.7 pg/ml), CB 293 pg/ml (18.8-49.7 pg/ml) and COPD 24.6 pg/ml (0-34.1 pg/ml). Comparison of healthy control subjects (PC20 > 8 mg/ml) to a group with bronchial hyperreactivity, which consisted of asthmatics and CB patients, whose PC20 was less than 8 mg/ml, revealed that levels of IL-17 were significantly increased in the second group (P=0.02). Also, levels of IL-17 were significantly increased (P=0.02) in the asthmatic patients with bronchial hyperreactivity compared to healthy subjects. Moreover levels of IL-17 in sputum of all studied subjects correlated negatively with PC20 (r=-0.51, P=0.002). CONCLUSIONS: According to our results IL-17 is probably not involved in pathogenesis of stable COPD, but it may play a role in people with airway hyperresponsiveness.

7696.   Baroody FM.  Allergic rhinitis: broader disease effects and implications for management.Otolaryngol Head Neck Surg. 2003 May;128(5):616-31.

 

Allergic rhinitis is a burdensome disease for a significant part of the population in both adults and children. Poorly controlled allergic rhinitis can trigger exacerbations of asthma, sinusitis, and otitis media, diseases with which it shares common pathophysiologic elements. Consequently, early diagnosis and treatment should be a priority for patients and physicians, not only to control the symptoms of allergic rhinitis but also to improve the management of associated diseases. Several pharmacologic therapies can be considered in an armamentarium that includes antihistamines (intranasal and systemic), intranasal cromolyn, intranasal anticholinergic agents, intranasal steroids, systemic steroids, immunotherapy, and, most recently, leukotriene receptor antagonists. Often, combinations of these treatments are used to maximize control of refractory symptoms.

7697.   Bellia V, Battaglia S, Catalano F, Scichilone N, Incalzi RA, Imperiale C, Rengo F.  Aging and disability affect misdiagnosis of COPD in elderly asthmatics: the SARA study. Chest. 2003 Apr;123(4):1066-72.

STUDY OBJECTIVES: This study investigated to what extent a diagnosis of COPD is erroneously made or the disease remains unrecognized in elderly asthmatic patients, and identified factors leading to misdiagnosis and underdiagnosis of asthma in such patients. DESIGN: A multicenter study involving 24 Italian pulmonary or geriatric institutions. PATIENTS: One hundred twenty-eight asthmatic patients (98 women, 76.6%) aged 73 +/- 6.4 years (mean +/- SD) were selected from the cohort of the Salute Respiratoria nell'Anziano (respiratory health in the elderly) study. METHODS: All patients underwent a clinical evaluation that included clinical history and spirometry with a bronchodilator test. A diagnosis of asthma was based on criteria proposed by international guidelines adapted to the elderly population. A multidimensional geriatric assessment was performed to estimate physical and cognitive impairments and 1mood state. Finally, the diagnosis of respiratory disease previously made by a doctor, if any, was recorded. RESULTS: Of asthmatic patients, COPD had been improperly diagnosed in 19.5%, whereas 27.3% of asthmatic patients did not report any previous diagnosis of asthma. The main correlates of misdiagnosis were older age and disability. Conversely, underdiagnosis was associated with better functional conditions, expressed by spirometry, even when wheezing or a significant response to the bronchodilator test occurred. CONCLUSIONS: Asthma in the elderly is frequently confused with COPD. Misdiagnosis can be related to older age and to greater degree of disability. Asthma in patients with mild functional impairment may be underdiagnosed in spite of overt respiratory symptoms suggestive of asthma.

7698.   Bhattarai MD.  Asthma mistaken for chronic obstructive pulmonary disease. Lancet. 2003 May 31;361(9372):1914-5. No abstract

7699.   Burks W.  Peanut allergy: a growing phenomenon. J Clin Invest. 2003 Apr;111(7):950-2. No abstract

7700.   Cameron HL, Yang PC, Perdue MH.  Glucagon-like peptide-2-enhanced barrier function reduces pathophysiology in a model of food allergy. Am J Physiol Gastrointest Liver Physiol. 2003 Jun;284(6):G905-12. Epub 2003 Jan 29.

Penetration of the gut epithelial barrier by intact luminal antigen is necessary for immunologically mediated pathophysiology in the context of food allergy. We investigated if glucagon-like peptide-2 (GLP-2) could affect immediate hypersensitivity and late-phase allergic inflammation in a murine model. Mice were sensitized to horseradish peroxidase (HRP); studies were conducted 14 days later. Mice were treated with 5 microg GLP-2 subcutaneously 4 h before antigen challenge. For immediate hypersensitivity, jejunal segments in Ussing chambers were challenged by luminal HRP antigen. GLP-2 treatment reduced the uptake of HRP and the antigen-induced secretory response after luminal challenge. GLP-2 appears to reduce macromolecular uptake independent of the CD23-mediated

enhanced antigen uptake pathway. For the late phase, mice were gavaged with antigen, and 48 h later the function and histology of the jejunum were examined. GLP-2 prevented the usual prolonged permeability defect and reduced the number of inflammatory cells in the mucosa. Our studies demonstrate that a single treatment of sensitized mice with GLP diminishes both immediate and late-phase hypersensitivity reactions characteristic of food allergy by inhibiting transepithelial uptake of antigen.

7701.   Chakir J, Shannon J, Molet S, Fukakusa M, Elias J, Laviolette M, Boulet LP, Hamid Q.  Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-beta, IL-11, IL-17, and type I and type III collagen expression. J Allergy Clin Immunol. 2003 Jun;111(6):1293-8.

BACKGROUND: Important features of airway remodeling in asthma include the formation of subepithelial fibrosis and increased deposition of types I and III collagen. TGF-beta, IL-11, and IL-17 are profibrotic cytokines involved in the formation of subepithelial fibrosis and are increased in patients with asthma, particularly in those with severe disease. OBJECTIVE: The purpose of this study was to investigate the effect of corticosteroids on the expression of these profibrotic cytokines and on extracellular matrix deposition. METHODS: We used immunocytochemistry to measure the expression of TGF-beta, IL-11, IL-17, and collagen types I and III in the airways of patients with mild asthma (n = 9), patients with moderate-to-severe asthma (n = 10), and control subjects without asthma (n = 6). Baseline bronchial biopsy specimens were obtained in all groups. In addition, repeat biopsies were obtained in the patients with moderate-to-severe asthma after a 2-week course of oral corticosteroids. RESULTS: TGF-beta expression was significantly higher in all groups with asthma, and it did not decrease after treatment with oral corticosteroids. Levels of IL-11 and IL-17 were increased in patients with moderate-to-severe asthma compared with patients with mild asthma and normal controls (P <.05). The expression of these cytokines decreased with oral corticosteroids in the moderate-to-severe group to levels that were comparable to those seen in the patients with mild asthma and in the normal controls (P <.005). Expression of types I and III collagens was higher in the patients with moderate-to-severe asthma than in the patients with mild asthma and the controls (P <.05; P <.001). Treatment with corticosteroids did not decrease the expression of types I and III collagens. CONCLUSIONS: These results confirm the association of increased levels of TGF-beta, IL-11, IL-17, and types I and III collagens with severe disease and suggest that the failure of cortico-steroids to decrease collagen deposition might be due to persistently elevated TGF-beta expression.

7702.   Chetta A, Castagnaro A, Foresi A, Del Donno M, Pisi G, Malorgio R, Olivieri D.  Assessment of breathlessness perception by Borg scale in asthmatic patients: reproducibility and applicability to different stimuli. J Asthma. 2003 May;40(3):323-9.

In asthmatics, the score of bronchoconstriction-associated breathlessness at 20% fall in forced expiratory volume at first second FEV1) evaluated on a Borg scale (PS20) is a tool successfully used to measure the perception of symptoms. This prospective laboratory study evaluated the applicability of PS20 to assess the breathlessness induced by ultrasonically nebulized distilled water (UNDW) and methacholine (M) and its reproducibility. Twenty-two mild and clinically stable asthmatic patients performed UNDW and M challenge tests. The PS20 was calculated by linear interpolation of the last two points of the perception/fall in FEV1 curve of the UNDW and M tests. The reproducibility of PS20 M was assessed by repeating measurements on 2 separate days by 3 weeks. PS20 UNDW and PS20 M did not differ and were respectively 1.82 +/- 1.85 and 2.03 +/- 1.86. They were significantly related (rs=0.63; p<0.01) and the bias between PS20 UNDW and PS20 M was -0.21 with the limits of agreement ranging from -3.2 to 3.6. The intraclass correlation coefficient for repeated measurement of PS20 M was 0.82; the bias between the two measurements was 0.2 with the limits of agreement ranging from -2.8 to 3.2. All patients had a measurable breathlessness perception degree on a Borg scale during both distilled water challenges and methacholine. Asthmatic patients with normal, exaggerated or poor breathlessness perception were also similar for both stimuli. In addition, PS20 showed a good reproducibility and this allows the serial evaluation of patient's breathlessness perception by this technique in clinical settings and in the physiology laboratory.

7703.   Cisternas MG, Blanc PD, Yen IH, Katz PP, Earnest G, Eisner MD, Shiboski S, Yelin EH.  A comprehensive study of the direct and indirect costs of adult asthma. J Allergy Clin Immunol. 2003 Jun;111(6):1212-8.

BACKGROUND: Asthma is a common and costly health condition, but most estimates of its economic effect have relied on secondary sources with limited condition-specific detail. OBJECTIVE: We sought to estimate the magnitude of direct and indirect costs of adult asthma from the perspective of society. METHODS: We used cross-sectional survey data from an ongoing community-based panel study of 401 adults with asthma originally derived from random samples of northern California pulmonologists, allergist-immunologists, and family practitioners to assess health care use for asthma, to assess purchase of items to assist with asthma care, and to measure work and other productivity losses. Unit costs derived from public-use and proprietary data sources were then assigned to the survey items. RESULTS: Total per-person annual costs of asthma averaged $4912 US dollars, with direct and indirect costs accounting for $3180 US dollars (65%) and $1732 US dollars (35%), respectively. The largest components within direct costs were pharmaceuticals ($1605 US dollars [50%]), hospital admissions ($463 US dollars[15%]), and non-emergency department ambulatory visits ($342 US dollars [11%]). Within indirect costs, total cessation of work accounted for $1062 US dollars (61%), and the loss of entire work days among those remaining employed accounted for another $486 US dollars (28%). Total per-person costs were $2646, $4530, and $12,813 US dollars for persons self-reporting mild, moderate, and severe asthma, respectively (P <.0001, 1-way ANOVA). CONCLUSION: Asthma-related costs are substantial and are driven largely by pharmaceuticals and work loss.

7704.   Cooper PJ, Chico ME, Rodrigues LC, Ordonez M, Strachan D, Griffin GE, Nutman TB.  Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics. J Allergy Clin Immunol. 2003 May;111(5):995-1000.

 

BACKGROUND: Childhood infections might protect against the expression of atopy. Geohelminths are among the most prevalent infections of childhood and might contribute to the low prevalence of allergic disease reported from rural areas of the tropics. OBJECTIVE: We sought to establish whether geohelminth infections protect against atopy and to explore whether this protection is dependent on infection chronicity. METHODS: The risk of atopy (measured by means of allergen skin test reactivity) associated with active geohelminth infections (measured by means of the presence of eggs in stool samples) or with chronic geohelminth infections (measured by means of high levels [>/=3564 IU/mL] of total serum IgE or the presence of detectable anti-Ascaris lumbricoides IgG4 antibodies) was investigated in an analytic cross-sectional study conducted among school-age children attending rural schools in Pichincha Province in Ecuador. RESULTS: A total of 2865 children aged 5 to 19 years from 55 schools was examined. Active infection with any geohelminth and infections with A lumbricoides or Ancylostoma duodenale were associated with significant protective effects against allergen skin test reactivity. Children with the highest levels of total IgE or with anti-A lumbricoides IgG4 antibodies were protected against skin test reactivity also, and the protective effects of high IgE or anti-A lumbricoides IgG4 and or active geohelminth infections were statistically independent. CONCLUSION: Active infections with geohelminth parasites and the presence of serologic markers of chronic infections (high levels of total serum IgE or anti-A lumbricoides IgG4)are independent protective factors against allergen skin test reactivity among school-age children living in an endemic region of the rural tropics.

 

7705.   Covar RA, Szefler SJ, Martin RJ, Sundstrom DA, Silkoff PE, Murphy J, Young DA, Spahn JD. Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma. J Pediatr. 2003 May;142(5):469-75.

 

OBJECTIVE: Exhaled nitric oxide (FE(NO)) was evaluated in children with asthma after 4 to 6 years of treatment with budesonide, nedocromil, or albuterol as needed. STUDY DESIGN: FE(NO), spirometry, total eosinophil count, and serum eosinophil cationic protein levels were obtained from 118 children at the Denver site of the Childhood Asthma Management Program upon completion of treatment and after a 2- to 4-month washout. RESULTS: Budesonide-treated patients had significantly lower median (1st, 3rd quartile) FE(NO) (21.5 [13.2, 84.4] vs 62.5 [26.2, 115.0] ppb, P <.01) and eosinophil cationic protein levels (17.4 [10.1, 24.3] vs 24.0 [15.4, 33.9] mg/dL, P =.05) compared with placebo, whereas no differences were noted between nedocromil and placebo groups. After washout, FE(NO) levels were similar between the three treatments. FE(NO) levels significantly correlated with degree of bronchial hyperresponsiveness, bronchodilator reversibility, allergen skin prick tests, serum IgE, and total eosinophil count. FE(NO) levels were also higher in patients with nocturnal symptoms and in patients requiring beta-agonist use at least once weekly. CONCLUSIONS: Budesonide therapy was more effective than nedocromil in reducing FE(NO). Unfortunately, the effects of long-term budesonide were not sustained after its discontinuation. FE(NO) may be a complementary tool to current practice guidelines in assessing asthma control and medication response.

7706.   Dagoye D, Bekele Z, Woldemichael K, Nida H, Yimam M, Hall A, Venn AJ, Britton JR, Hubbard R, Lewis SA. Wheezing, allergy, and parasite infection in children in urban and rural Ethiopia. Am J Respir Crit Care Med. 2003 May 15;167(10):1369-73. Epub 2003 Jan 24.

 

Epidemiological studies in developing countries suggest that intestinal parasite infection may reduce the risk of asthma. Because this evidence is all derived from adults and older children, we have investigated the relation between parasite infection, wheezing, and allergen skin sensitization in nested case-control studies drawn from a survey of 7,155 children aged 1 to 4 years living in urban and rural areas of Jimma, Ethiopia. Infection with parasites was common, predominantly with Trichuris (54%), Ascaris (38%), and hookworm (10%). Wheezing in the past year was significantly more prevalent in urban (4.4%) than rural children (2.0%), and was less prevalent in those infected with Ascaris (age, sex, and urban/rural adjusted odds ratio, 0.5; 95% confidence interval, 0.3 to 0.9), particularly in relation to high-intensity infection. Similar,although nonsignificant, associations were found for hookworm (adjusted odds ratio, 0.6; 95% confidence interval, 0.2 to 1.8), but there was no suggestion of any relation to Trichuris infection. Dermatophagoides pteronyssinus and cockroach (Blattella germanica) skin sensitization was more prevalent in rural than urban children, and was unrelated to wheeze. We conclude that Ascaris and possibly hookworm infection protects against wheeze in young Ethiopian children, and that this effect is not mediated by inhibition of allergen sensitization.

7707.   Di Franco A, Bartoli ML, Carnevali S, Cianchetti S, Bacci E, Dente FL, Giannini D, Taccola M, Vagaggini B, Paggiaro PL.  Analysis of sputum cell counts during spontaneous moderate exacerbations of asthma in comparison to the stable phase. J Asthma. 2003 Apr;40(2):155-62.

BACKGROUND: Acute airway inflammation is considered to characterize asthma exacerbations, but its specific cellular pattern has not yet been completely evaluated. AIM: To evaluate the prevalence of sputum eosinophilia during acute asthma exacerbations of moderate severity, compared with a stable phase of the disease, and to assess the concordance between changes in pulmonary function and sputum eosinophilia in the period between exacerbation and post exacerbation. METHODS: We compared sputum and blood inflammatory cell counts in 29 asthmatic subjects during a spontaneous moderate exacerbation of asthma (visit 1) with sputum and blood cell counts measured 4 weeks after the resolution of asthma exacerbation (visit 2). At visit 1, all subjects required an appropriate 1 week treatment with oral corticosteroids. RESULTS: At visit 1, all subjects were able to collect spontaneous sputum, whereas at visit 2 sputum was induced by inhalation of hypertonic saline (NaCl 3, 4, and 5%, 10 minutes each) with beta2-agonist pretreatment. Asthma exacerbation was accompanied by a significant increase in sputum eosinophil percentages compared with levels after exacerbation [25% (1-78) versus 4% (0-23), p<0.05). Only four subjects showed low sputum eosinophil percentages during exacerbation, and these showed no differences in main clinical findings with respect to subjects with sputum eosinophilia. At visit 2, the stability of asthma was assessed on the basis of PEF, FEV1, symptoms, and use of rescue beta2-agonist. Asthma was defined as stable in 21 out of 29 subjects. Sputum eosinophil percentages fell significantly between visit 1 and visit 2 in both stable and unstable patients, but at visit 2 sputum eosinophil percentages were still high in subjects with unstable asthma. In patients who proved to be stable at visit 2, there was a significant correlation between the changes recorded in sputum eosinophil percentages and in FEV1 between the two visits (rho: 0.723, p<0.001).

CONCLUSION: Sputum cosinophil but not neutrophil percentages increase in most asthmatic subjects during moderate exacerbation of asthma. Changes in the degree of airway eosinophilic inflammation are related to changes in the severity of airway obstruction during asthma exacerbation.

7708.   Ebo DG, Stevens WJ, Bridts C, De Clerck LS.  Clinical laboratory assessment of IgE. J Allergy Clin Immunol. 2003 Jun;111(6):1414; No abstract

7709.   Ferguson J.  Diagnosis and treatment of the common idiopathic photodermatoses. Australas J Dermatol. 2003 May;44(2):90-6.

The idiopathic photodermatoses are the most common cause of photosensitivity and the commonest of these are polymorphic light eruption, actinic prurigo, chronic actinic dermatitis and solar urticaria. The clinical presentation, investigation and treatment of these four disorders are presented. Spontaneous improvement does occur.

7710.   Foetisch K, Westphal S, Lauer I, Retzek M, Altmann F, Kolarich D, Scheurer S, Vieths S.  Biological activity of IgE specific for cross-reactive carbohydrate determinants. J Allergy Clin Immunol. 2003 Apr;111(4):889-96.

BACKGROUND: The clinical relevance of IgE specific for cross-reactive carbohydrate determinants (CCDs) has been a matter of controversy. Until now, no convincing experiments have been performed to test the biologic significance of individual multivalent allergens that carry multiple carbohydrate epitopes. OBJECTIVE: We sought to contribute to the understanding of the role of CCD-specific IgE antibodies and to study whether CCD-specific IgE antibodies are able to activate basophils using different multivalent glycoproteins as antigens. METHODS: Purified natural tomato beta-fructofuranosidase (nLyc e 2)and rLyc e 2.02 expressed in Escherichia coli were compared by means of histamine release tests. In addition, native and deglycosylated horseradish peroxidase and a neoglycoprotein consisting of a defined glycopeptide (Manalpha1-6[Xylbeta1-2]Manbeta1-4GlcNAcbeta1-4[Fucalpha1-3]GlcNAc) coupled to BSA were used in histamine release assays using stripped basophils from normal donors resensitized with IgE from CCD-reactive patients with food allergy to tomato. RESULTS: Ten CCD-positive and 2 CCD-negative sera from patients with tomato allergy underwent histamine release testing by using the glycoproteins and nonglycosylated controls as antigens, respectively. All sera induced histamine release with tomato extract (up to 100%), confirming the allergic status of the donors. Four of the CCD-positive sera induced releases ranging from 12% to 82% with all of the glycoproteins but not with the nonglycosylated or monovalent controls. All other sera showed no response or only very weak response to the glycoproteins. CONCLUSION: Approximately one third of the CCD-positive sera from patients with tomato allergy have biologically relevant CCD-specific IgE antibodies. Therefore the general claim that CCD-specific IgE is clinically irrelevant has to be reconsidered critically. Hence IgE specific for CCDs should be taken into consideration in the diagnosis and therapy of certain allergies. In the subgroup of patients sensitized to CCDs, the use of natural allergens should be preferred over the use of recombinant allergens expressed in prokaryotic organisms.

7711.   Fritsche R.  Animal models in food allergy: assessment of allergenicity and preventive activity of infant formulas. Toxicol Lett. 2003 Apr 11;140-141:303-9.

 

Food allergies occur in about 5-10% of the overall infant and small-child population. Cow's milk protein allergy (CMPA) is the most common in young infants, with a 2-4% incidence. When breastfeeding is not possible, hypoallergenic (HA) cow's milk based formulas are usually given during the first months of life for prevention of CMPA. Depending on primary (sensitization) or secondary (triggering) prevention, the requested quality of HA formulas may be different. Besides in vitro methods, in vivo and ex vivo animal models are helpful in assessing residual allergenicity and the preventive effect of HA formulas. The sensitizing capacity of a formula can be examined by either the parenteral rat (IgE), the guinea pig (IgG1a mediated) or the oral mouse (IgE)models. The triggering IgE mediated allergenicity is tested by a parenteral rat model with oral gavage for intestinal mast cell protease (RMCPII) release. These animal models are also used for testing the oral tolerance inducing capacities of formulas. Together with cellular in vitro assays, animal models are very helpful in predicting allergenicity and the tolerogenic potential of HA infant formulas.

7712.   Goldrick BA.  Allergic aspergillosis. Am J Nurs. 2003 Apr;103(4):89. No abstract

7713.   Gruchalla RS, Gan V, Roy L, Bokovoy J, McDermott S, Lawrence G, Hynan L, Luckett P.  Results of an inner-city school-based asthma and allergy screening pilot study: a combined approach using written questionnaires and step testing. Ann Allergy Asthma Immunol. 2003 May;90(5):491-9.

 

BACKGROUND: A questionnaire alone may not be an adequate screening tool for asthma. OBJECTIVE: To determine whether an asthma questionnaire used in

combination with an exercise step test is better than a questionnaire alone in screening for asthma in children and to evaluate the validity of a rhinitis questionnaire in determining atopy. METHODS: The International Study of Asthma and Allergies in Childhood (ISAAC) asthma core questionnaire was used to screen for asthma in 307 inner-city first through third graders. All children who had scores consistent with a diagnosis of asthma underwent step testing, as did a subset of children who had negative overall scores. All children who had inconsistent asthma scores and step test results underwent methacholine challenge testing. The same 307 children underwent rhinitis screening and children who had one or more positive responses on the ISAAC rhinitis questionnaire underwent skin testing as did a subset of children who had all negative responses. RESULTS: Three hundred of 307 asthma and rhinitis questionnaires were returned. Twenty-eight children (9%) had global asthma scores that were considered to be positive (5 or above). Twenty-four of these children underwent step testing as did 34 randomly selected children who had negative global asthma scores. Thirty-one (91%) of the 34 children who had negative global asthma scores had negative step tests. Similarly, 20 of 24 children (83%) of the children who had positive global asthma scores had negative step tests. Only 4 children who had positive global asthma scores were step test-positive or had reversible airway obstruction at baseline. Using a positive methacholine challenge as the gold standard for establishing bronchial hyperresponsiveness, the global asthma score derived from the eight-item ISAAC asthma questionnaire yielded a sensitivity of 64%, a specificity of 11%, a positive predictive value of 47%, and a negative predictive value of 20%. Comparing the six-item ISAAC rhinitis questionnaire results to the gold standard, skin test reactivity, the questionnaire yielded a sensitivity of 76%, a specificity of 21%, a positive predictive value of 56%, and a negative predictive value of 40%. CONCLUSIONS: Step testing was not useful as a screening tool for asthma. In addition, the ISAAC asthma questionnaire may not be a good asthma screening tool for inner-city pediatric populations, especially if the form is self-administered. Investigators should first validate both the ISAAC asthma and rhinitis screening questionnaires in the particular population to be studied before widespread asthma and allergy screening efforts are initiated using these tools.

7714.   Halpern MT, Khan ZM, Stanford RH, Spayde KM, Golubiewski M.   Asthma: resource use and costs for inhaled corticosteroid vs leukotriene modifier treatment--a meta-analysis. J Fam Pract. 2003 May;52(5):382-9.

 

OBJECTIVE: To compare the effects of inhaled corticosteroid treatment with leukotriene modifier treatment on medical resource use and costs for asthma patients. STUDY DESIGN: Meta-analysis combining results from published and unpublished studies. DATA SOURCES: Studies were identified from the MEDLINE and EMBASE databases and the GlaxoSmithKline internal database study registers. Two independent reviewers evaluated the identified studies; studies meeting specified inclusion criteria were abstracted and summarized by meta-analysis with a random effects model. OUTCOMES MEASURED: Hospitalization rate, emergency department visit rate, emergency department costs, drug costs, total asthma-related costs, and total medical care costs. RESULTS: Patients taking inhaled corticosteroids had: a significantly lower annual rate of hospitalization than those taking leukotriene modifiers (2.2% vs 4.3%, respectively; P<.05); a greater decline in hospitalization rate (before vs after therapy initiation) than those taking leukotriene modifiers (decline of 2.4% vs 0.55%; P<.01); a lower annual rate of emergency department visits than those taking leukotriene modifiers (6.2% vs 7.7%; P<.005); lower total asthma-related medical costs than those taking leukotriene modifiers (P<.05) and a 17% reduction in overall total medical care costs (P not significant). CONCLUSIONS: Patients with asthma treated with inhaled corticosteroids have significantly fewer asthma-related hospitalizations and emergency department visits and lower total asthma-related health care costs than patients treated with leukotriene modifiers. These meta-analysis findings are consistent with results from randomized controlled trials showing improvements in lung function for patients taking inhaled corticosteroids as opposed to leukotriene modifiers.

7715.   Hammarsten R, Hammarsten J, Jemsby P.  Preoperative skin testing of materials used in surgical procedures. AORN J. 2003 Apr;77(4):762-6, 769-71.

 

Postoperative skin complications increase health care costs and cause patient suffering. In the OR, patients are exposed to materials with adhesive substances that have the potential to cause allergic or toxic effects on the skin. Intraoperatively and postoperatively, these reactions can result in skin complications. The objective of this study was to investigate the incidence of skin reactions in connection with the application of different materials. Skin reactions after preoperative skin testing occurred in 3% to 50% of patients with atopic or contact eczema, allergy, or asthma in their medical history.

7716.   Han Z, Junxu, Zhong N.  Expression of matrix metalloproteinases MMP-9 within the airways in asthma. Respir Med. 2003 May;97(5):563-7.

The matrix metalloproteinase (MMP) enzymes MMP-9, have relevance to chronic structural airway changes in asthma, which can be generated by structural and inflammatory cells, and have the ability to degrade proteoglycans and thus potentially enhance airway fibrosis and smooth muscle proliferation through their ability to release and activate latent, matrix-bound growth factors. Immunostaining for MMP-9 was undertaken in acetone-fixed and glycolmethacrylate-embedded endobronchial biopsy specimens obtained by fibreoptic bronchoscopy under local anaesthesia. The findings from 30 asthmatic subjects were compared with those from 18 chronic obstructive pulmonary disease (COPD) subjects and 10 healthy controls. Meanwhile, pulmonary function test and airway responsiveness were performed. Immunoreactivity for MMP-9 was assessed by an image analysis system. The biopsy specimens from asthmatic subjects contained significantly more eosinophils (P < 0.001) than those from COPD subjects, and healthy control did not contain eosinophils. MMP-9 immunoreactivity could be identified in endobronchial biopsy specimens from all the asthmatic subjects and 40% ofthe COPD subjects, but could not be identified in healthy controls. Gelatinase B (MMP-9) immunoreactivity was located in bronchial epithelium and extracellular matrix in submucosa, prominent in denuded epithelium. The immunohistochemical score for MMP-9 was significantly correlated with eosinophilic number in bronchial mucosa. FEV1% predicted FEV1/FVC (%) (r = 0.52,0.41, 0.37, respectively P < 0.01 did not correlate with PD20 FEV1 from asthmatic subjects. MMP-9 is expressed by bronchial epithelium and may be a important factor for eosinophil infiltraed into airway from asthma subjects.

7717.   Hepner DL, Castells MC.  Latex allergy: an update. Anesth Analg. 2003 Apr;96(4):1219-29. No abstract

7718.   Kalliomaki M, Salminen S, Poussa T, Arvilommi H, Isolauri E.  Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet. 2003 May 31;361(9372):1869-71.

 

Perinatal administration of the probiotic Lactobacillus rhamnosus strain GG(ATCC 53103), reduces incidence of atopic eczema in at-risk children during the first 2 years of life (infancy). We have therefore assessed persistence of the potential to prevent atopic eczema at 4 years. Atopic disease was diagnosed on the basis of a questionnaire and a clinical examination. 14 of 53 children receiving lactobacillus had developed atopic eczema, compared with 25 of 54 receiving placebo (relative risk 0.57, 95% CI 0.33-0.97). Skin prick test reactivity was the same in both groups: ten of 50 children previously given lactobacillus compared with nine of 50 given placebo tested positive. Our results suggest that the preventive effect of lactobacillus GG on atopic eczema extends beyond infancy.

7719.   Kanazawa H, Asai K, Hirata K, Yoshikawa J.  Possible effects of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease. Am J Med. 2003 Apr 1;114(5):354-8.

 

PURPOSE: Expression of vascular endothelial growth factor (VEGF) is reduced in the lungs of patients with emphysema. We examined whether VEGF levels in sputum differed in patients with emphysema, bronchitis, or asthma, as compared with controls. METHODS: Fifty-nine patients with chronic obstructive pulmonary disease (COPD) (25 with emphysema, 19 with chronic bronchitis, and 15 with a mixed type), 20 patients with bronchial asthma, and 11 normal controls were included in the study. The concentration of VEGF in induced sputum and the correlations between VEGF levels and pulmonary function were examined. RESULTS: The mean (+/- SD) concentration of VEGF in induced sputum was significantly higher in patients with asthma (6440 +/- 1820 pg/mL, P <0.0001) or bronchitis (4120 +/- 1100 pg/mL, P <0.0001) than in normal controls (1860 +/- 1220 pg/mL), but significantly lower in patients with emphysema (500 +/- 300 pg/mL, P =0.03). The concentration of VEGF in sputum from patients with bronchitis correlated inversely with forced expiratory volume in 1 second (r = -0.87; P =0.0002); in contrast, there was a positive correlation between these two measurements in patients with emphysema (r = 0.82; P <0.0001). In addition, sputum VEGF concentrations correlated with the diffusing capacity of carbon monoxide in patients with emphysema (r = 0.87; P <0.0001), but not in those with bronchitis (r = -0.22; P =0.36). CONCLUSION: In patients with bronchitis, increased levels of VEGF in induced sputum were associated with airflow limitation. In contrast, decreased levels of VEGF were associated with airflow limitation and alveolar destruction in patients with emphysema. Thus, our findings suggest that VEGF may affect the pathogenesis of these two common types of COPD. Copyright 2003 by Excerpta Medica Inc.

7720.   Kerschenlohr K, Decard S, Przybilla B, Wollenberg A.  Atopy patch test reactions show a rapid influx of inflammatory dendritic epidermal cells in patients with extrinsic atopic dermatitis and patients with intrinsic atopic dermatitis. J Allergy Clin Immunol. 2003 Apr;111(4):869-74.

 

BACKGROUND: Normal human skin harbors a single epidermal dendritic cell (DC) population, the CD1a(+++)CD11b(-) Langerhans cells. In many chronic inflammatory skin diseases, the epidermal DC pool bears a second population, the CD1a(+)CD11b(+++) inflammatory dendritic epidermal cells (IDECs). Immunophenotypic, ultrastructural, and functional aspects of IDECs have been investigated in chronic untreated skin lesions of intrinsic and extrinsic atopic dermatitis (AD), contact dermatitis (CD), and psoriasis, but little is known about freshly induced early skin lesions. OBJECTIVE: We sought to characterize enumerative and immunophenotypic changes in the epidermal DC pool during the development of eczematous skin lesions. METHODS: The atopy patch test with aeroallergens and food-protein allergens and a conventional patch test with standard-series haptens were performed as models for early skin lesions of extrinsic and intrinsic AD and CD, respectively. After 72 hours, epidermal cell suspensions were prepared, analyzed in a standardized flow cytometric technique, and compared with the results obtained from chronic lesions. RESULTS: The migration of IDECs into the epidermis occurs within 72 hours and is thus an early event. It continues in chronic AD, but not in chronic CD, lesions. The specific upregulation of FcepsilonRI, especially on IDECs, occurs later during formation of extrinsic but not intrinsic AD lesions. LCs were negative for Cd36 in patch test lesions, whereas in chronic skin lesions, LCs expressed Cd36. CONCLUSION: The DC alteration during skin lesion formation can be subdivided into early and late events, with the influx of IDECs as an early event and the alteration of the DC phenotype as a late event.

7721.   Lierl MB.  Exhaled nitric oxide: a useful aide in pediatric asthma management? J Pediatr. 2003 May;142(5):461-2. No abstract

7722.   Lieutier-Colas F, Purohit A, Meyer P, Fabries JF, Kopferschmitt MC, Dessanges JF, Pauli G, de Blay F. Bronchial challenge tests in patients with asthma sensitized to cats: the importance of large particles in the immediate response. Am J Respir Crit Care Med. 2003 Apr 15;167(8):1077-82.

 

Our aim was to compare bronchial responses to major cat allergen (Fel d 1) in individuals with intermittent asthma sensitized to cats (19 subjects) according to the droplet particle size. We used three nebulizers, which delivered particles with mass median aerodynamic diameters of 1.4, 4.8, and 10.3 microm. A dosimeter nebulizer was used. The cat allergen was diluted to obtain the same amount of Fel d 1 per puff with each nebulizer. Each patient underwent three methacholine bronchial challenge tests (BCT), each followed 24 hours later by a cat allergen BCT, each performed with a different nebulizer (randomly selected each time, with patient and tester always blinded). Subjects did not differ for methacholine responsiveness, FEV1, mean forced expiratory flow during the middle half of the FVC (FEF25-75), PEF, or dyspnea (Borg scale) before any of the three cat BCTs. Cat allergen PD20 was 271 ng of Fel d 1 with the 1.4 microm nebulizer, 46 ng with the 4.8 microm nebulizer, and 13.5 ng with the 10.3 microm nebulizer (p = 0.00001). Inhalation of small particles (1.4 microm) resulted in significantly lower FEF25-75 24 hours after provocation than large particles did. In conclusion, immediate bronchial response appears to be localized in large airways, and the use of large particles is more appropriate for cat allergen BCTs.

7723.   Lim AY, Chambers DC, Ayres JG, Stableforth DE, Honeybourne D.   Exhaled nitric oxide in cystic fibrosis patients with allergic bronchopulmonary aspergillosis. Respir Med. 2003 Apr;97(4):331-6.

 

Exhaled nitric oxide (NO) is thought to be a marker of asthmatic inflammation. Levels in cystic fibrosis (CF) are generally low. This study aimed to measure exhaled NO in CF patients at high risk of developing ABPA and patients at low risk. We studied nine patients at high risk of developing ABPA and 36 at low risk. The two groups were similar in age and spirometry. All patients in the high-risk group were taking oral or inhaled glucocorticoids, compared to 56% in the low-risk group (P=0.02). The exhaled NO levels were lower in the high-risk group than in the low-risk group (2.0 vs. 3.6 ppb), mean difference (95% CI) 1.6 (-3.6 to 0.4) ppb, P=0.001. On subgroup analysis of patients on oral glucocorticoids, the exhaled NO levels were significantly lower in patients with a high risk of developing ABPA (n=7) than patients with a low risk (n=8) (P=0.011). The number of patients who were on inhaled, but not oral glucocorticoids was too small to analyse usefully. Exhaled NO levels were lower in CF patients with a high risk of developing ABPA and on glucocorticoids. This may be because oral glucocorticoids exert a greater effect on exhaled NO than inhaled glucocorticoids. Alternatively, inducible nitric oxide synthase may be down-regulated by Aspergillus toxin.

7724.   Litonjua AA, Sparrow D, Guevarra L, O'Connor GT, Weiss ST, Tollerud DJ.  Serum interferon-gamma is associated with longitudinal decline in lung function among asthmatic patients: the Normative Aging Study. Ann Allergy Asthma Immunol. 2003 Apr;90(4):422-8.

 

BACKGROUND: Cytokines are important mediators of the asthmatic response. A retrospective pilot study showed that serum levels of interleukin (IL)-5 and interferon (IFN)-gamma were related to lung function decline among asthmatic patients over the preceding 3 years. To confirm these findings, we tested the hypothesis that serum cytokines are associated with longitudinal lung function decline. METHODS: We conducted a prospective, longitudinal study of 25 asthmatic and 50 nonasthmatic men (median age, 63 years; range, 45 to 80 years)participating in the Normative Aging Study. All study subjects completed two consecutive triennial examinations, including spirometry, methacholine challenge testing, allergy skin testing, and phlebotomy. Serum levels were measured for IL-4, IL-5, IL-6, IL-8, IL-10, and IFN-gamma. RESULTS: Among asthmatic patients, a higher initial serum level of IFN-gamma was associated with a greater rate of decline of forced expiratory volume in 1 second (FEV1; beta = -67 mL/year per log increase in serum IFN-gamma, P = 0.04) and, to a lesser extent, of FEV1/forced vital capacity ratio (beta = -0.91%/year per log increase in serum IFN-gamma, P = 0.07) after adjusting for age, smoking status, and baseline level of lung function. Serum IL-5 level was associated with a rate of decline in FEV1 of borderline significance (beta = -61 mL/year per log increase in serum IL-5, P = 0.08) among asthmatic patients. These relationshipswere not observed among nonasthmatic patients. CONCLUSIONS: Serum levels of IFN-gamma are associated with subsequent rate of change in lung function among asthmatic patients in this cohort of middle-aged and older men, and may be useful as biologic markers of risk for accelerated lung function decline in population studies.

7725.   Macy E, Mangat R, Burchette RJ.  Penicillin skin testing in advance of need: multiyear follow-up in 568 test result-negative subjects exposed to oral penicillins. J Allergy Clin Immunol. 2003 May;111(5):1111-5.

 

BACKGROUND: There are few published data on adverse drug reactions and/or resensitization associated with oral penicillin use in penicillin allergy history-positive/penicillin skin test-negative individuals during routine clinical care with multiyear follow-up. OBJECTIVES: We sought to provide long-term follow-up data on the type, severity, and frequency of adverse reactions associated with oral penicillin use in individuals who have histories of penicillin "allergy" yet also have negative results on penicillin skin tests done in advance of need. We also aimed to repeat testing on individuals with penicillin-associated adverse reactions. METHODS: Medical records were reviewed for penicillin use and associated adverse reactions in all 568 penicillin skin test-negative individuals who had received at least 1 course of oral penicillin after testing but before December 31, 2001, during routine care. These individuals were drawn from a group of 1246 penicillin skin test-negative individuals seen initially between November 16, 1994, and August 13, 2001. RESULTS: The mean length of follow-up was 4.26 +/- 1.64 years (range, 0.39-7.12 years). The mean penicillin exposure was 3.94 +/- 3.91 courses (range, 1-22 courses). Only 65 (11.4%) of 568 subjects had any penicillin-associated reactions, and 6 subjects had 2 reactions each. A reaction occurred in 27 subjects (4.8%) with their first penicillin reexposure. There were 71 (3.2%)reactions with 2236 total penicillin courses. There were no serious reactions. Repeated testing was done in 33 subjects older than age 18 years. Only 1 subject was positive on repeated penicillin skin testing. CONCLUSION: Penicillin use after negative penicillin skin testing done in advance of need is safe, and

resensitization is rare.

7726.   Malmberg LP, Pelkonen AS, Haahtela T, Turpeinen M.   Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma. Thorax. 2003 Jun;58(6):494-9.

 

BACKGROUND: Respiratory function and airway inflammation can be evaluated in preschool children with special techniques, but their relative power in identifying young children with asthma has not been studied. This study was undertaken to compare the value of exhaled nitric oxide (FE(NO)), baseline lung function, and bronchodilator responsiveness in identifying children with newly detected probable asthma. METHODS: Ninety six preschool children (age 3.8-7.5 years) with asthmatic symptoms or history and 62 age matched healthy non-atopic controls were studied. FE(NO) was measured with the standard online single exhalation technique, and baseline lung function and bronchodilator responsiveness were measured using impulse oscillometry (IOS). RESULTS: Children with probable asthma (n=21), characterised by recent recurrent wheeze, had a significantly higher mean (SE) concentration of FE(NO) than controls (22.1 (3.4) ppb v 5.3 (0.4) ppb; mean difference 16.8 ppb, 95% CI 12.0 to 21.5) and also had higher baseline respiratory resistance, lower reactance, and larger bronchodilator responses expressed as the change in resistance after inhalation of salbutamol. Children with chronic cough only (n=46) also had significantly raised mean FE(NO) (9.2 (1.5) ppb; mean difference 3.9 ppb, 95% CI 0.8 to 7.0)but their lung function was not significantly reduced. Children on inhaled steroids due to previously diagnosed asthma (n=29) differed from the controls only in their baseline lung function. The analysis of receiver operating characteristics (ROC) showed that FE(NO) provided the best power for discriminating between children with probable asthma and healthy controls, with a sensitivity of 86% and specificity of 92% at the cut off level of 1.5 SD above predicted. CONCLUSIONS: FE(NO) is superior to baseline respiratory function and bronchodilator responsiveness in identifying preschool children with probable asthma. The results emphasise the presence of airway inflammation in the early stages of asthma, even in young children.

7727.   Medeiros M Jr, Figueiredo JP, Almeida MC, Matos MA, Araujo MI, Cruz AA, Atta AM, Rego MA, de Jesus AR, Taketomi EA, Carvalho EM.  Schistosoma mansoni infection is associated with a reduced course of asthma. J Allergy Clin Immunol. 2003 May;111(5):947-51.

 

BACKGROUND: Helminthic infections decrease skin reactivity to indoor allergens, but data on whether they influence asthma severity are lacking. OBJECTIVE: This study evaluated the course of asthma in patients with and without Schistosoma mansoni infection. METHODS: Asthmatic subjects were enrolled from 3 low-socioeconomic areas: a rural area endemic for schistosomiasis (group 1) in addition to a rural area (group 2) and a slum area (group 3), both of which were not endemic for schistosomiasis. A questionnaire on the basis of the International Study of Asthma and Allergies in Childhood study was applied in these 3 areas, and from each area, 21 age- and sex-matched asthmatic subjects were selected for a prospective 1-year study. Pulmonary function tests, skin prick tests with indoor allergens, stool examinations, and serum evaluations were performed in these subjects. Every 3 months, the subjects were evaluated for asthma exacerbation through physical examination, and a questionnaire regarding asthma symptoms and use of antiasthma medicine was administered. RESULTS: The prevalence of S mansoni infection was greater in group 1 compared with in groups 2 and 3 (P <.0001), whereas the frequency of other helminth and protozoa infections was similar among the 3 groups. The frequency of positive skin test responses to indoor allergens was less (19.0%) in group 1 subjects relative to those in group 2 (76.2%) and group 3 (57.1%; P <.001). The frequencies of symptoms, use of antiasthma drugs, and pulmonary abnormal findings at physical examination were less in group 1 subjects than in group 2 and 3 subjects (P =.0001). CONCLUSION: Our results suggest that S mansoni infection is associated with a milder course of asthma.

 

7728.   Moneret-Vautrin DA, Kanny G, Fremont S.  Laboratory tests for diagnosis of food allergy: advantages, disadvantages and future perspectives. Allerg Immunol (Paris). 2003 Apr;35(4):113-9.

 

Numerous biological tests point to the diagnosis of food sensitization: detection of specific IgEs by Rast techniques, multi-detection assays, immunoblotting, screening of basophil activation (BAT or FAST), assays for leukotriene LTC4 release (CAST), measurement of plasma histamine, serum tryptase, serum ECP, urinary EDN, completed by mannitol-lactulose test evaluating intestinal permeability, assay of fecal IgEs, Rast for specific IgG4. Primary screening for anti-food IgEs by multi-detection assays seeks justification from insufficient clinical data and false positive tests are common in patients sensitized to pollens or latex, on account of in vitro cross reactivities (CR). Multiple CR explain positive Rast to vegetal food allergens in such patients. Biological tests should not be performed as the first line of diagnosis. In vivo sensitisation is assessed by positive prick-tests, demonstrating the bivalence of allergens, as well as the affinity of specific IgEs, two conditions necessary to bridge membrane bound specific IgEs, leading to the release of mediators. Prick-tests are closer to clinical symptoms than biological tests. However, the diagnosis of food allergy is based on standardised oral challenges. Exceptions are high levels of specific IgEs to egg (> 6 kUl/l), peanut (> 15 kUl/l), fish (> 20 kUl/l) and milk (> 32 kUl/l), reaching a 95% predictive positive value. Rast inhibition tests are useful to identify masked allergens in foods. Research developments will have impact on the development of new diagnostic tools: allergen mixes reinforcing a food extract by associated recombinant major allergens, multiple combination of recombinant allergens (chips) or tests with synthetic epitopes aimed a the prediction of recovery. Laboratory tests take place in the decision free for the diagnosis for the food allergy and the follow-up of the levels specific IgEs is a tool to assess outcome and contributes to predict recovery or persistent allergy. Up to now the significance of positive laboratory tests showing the implication of IgEs is at the crossroads of the allergist's and biologist's expertise.

 

7729.   Munoz-Furlong A.  Daily coping strategies for patients and their families. Pediatrics. 2003 Jun;111(6 Pt 3):1654-61.

 

The diagnosis of food allergy in a child has an impact on every minute of every day for the child and the child's family. The patient and family must learn how to read labels, adapt recipes, and educate other family members, child care providers, camp counselors, and teachers. They must know how to recognize symptoms of a reaction and what to do during a reaction. Decisions such as which restaurant to go to and where to go on vacation take on new meaning, as family decisions must be centered on avoidance of the child's food allergen. It is possible to manage food allergies successfully while allowing the child to participate in common childhood activities. Education of the family is key. This discussion provides the pediatrician or primary care physician with practical information for educating patients and their families about managing food allergy.

7730.   Noga O, Hanf G, Kunkel G.  Immunological and clinical changes in allergic asthmatics following treatment with omalizumab. Int Arch Allergy Immunol. 2003 May;131(1):46-52.

 

IgE plays a key role in allergic asthma. We investigated whether omalizumab treatment of patients with moderate to severe allergic asthma leads to changes in inflammatory mediators and clinical symptoms. This sub-study was conducted on 35 patients with a positive skin prick test (SPT) requiring daily administration of beclomethasone dipropionate (500-1,000 microg), who participated in a multicentre, randomised, double-blind, placebo-controlled study. Omalizumab or placebo was administered at 0.016 mg/kg/IgE every 4 weeks. Patients recorded peak expiratory flow, asthma symptom score and beta(2)-agonist use in daily diaries and spirometry was performed at each visit. beta(2)-Agonist use and SPT wheal reaction decreased significantly (p < 0.05). Circulating levels of IL-5, IL-6, IL-8, IL-10, IL-13 and s-ICAM were measured before and after 16 weeks of treatment. IL-13 and s-ICAM were measured before and after 16 weeks of treatment. IL-13 decreased significantly (p < 0.01). IL-5 and IL-8 decreased in the omalizumab group compared to baseline. The other circulating mediators did not demonstrate any changes. Histamine release was significantly reduced (p < 0.01). Airway resistance (p < 0.05) and the provocative concentration inducing a 20% decrease in FEV(1) (p < 0.05) were measured before, after 16 weeks, and 3 months after completion of treatment. Both parameters decreased significantly (p < 0.05). Peripheral eosinophil count decreased significantly compared to placebo (p < 0.01). These findings suggest that omalizumab has potential as a novel treatment for allergic asthma.

7731.   Novak N, Tepel C, Koch S, Brix K, Bieber T, Kraft S.  Evidence for a differential expression of the FcepsilonRIgamma chain in dendritic cells of atopic and nonatopic  donors. J Clin Invest. 2003 Apr;111(7):1047-56.

While mast cells and basophils constitutively express the high-affinity IgE receptor (Fc epsilon RI), it is absent or weakly expressed on APCs from normal donors. Fc epsilon RI is strongly upregulated on APCs from atopic donors and involved in the pathophysiology of atopic diseases. Despite its clinical relevance, data about Fc epsilon RI regulation on APCs are scarce. We show that in all donors intracellular alpha chain of the Fc epsilon RI (Fc epsilon RI alpha) accumulates during DC differentiation from monocytes. However, expression of gamma chains of the Fc epsilon RI (Fc epsilon RI gamma), mandatory for surface expression, is downregulated. It is low or negative in DCs from normal donors lacking surface Fc epsilon RI (Fc epsilon RI(neg) DCs). In contrast, DCs from atopics express surface Fc epsilon RI (Fc epsilon RI(pos) DCs) and show significant Fc epsilon RI gamma expression, which can be coprecipitated with Fc epsilon RI alpha. In Fc epsilon RI(neg) DCs lacking Fc epsilon RI gamma, immature and core glycosylated Fc epsilon RI alpha accumulates in the endoplasmic reticulum. In Fc epsilon RI(pos) DCs expressing Fc epsilon RI gamma, an additional mature form of Fc epsilon RI alpha exhibiting complex glycosylation colocalizes with Fc epsilon RI gamma in the Golgi compartment. IgE binding sustains surface-expressed Fc epsilon RI on DCs from atopic donors dependent on baseline protein synthesis and transport and enhances their IgE-dependent APC function. We propose that enhanced Fc epsilon RI on DCs from atopic donors is driven by enhanced expression of otherwise limiting amounts of Fc epsilon RI gamma and is preserved by increased IgE levels.

7732.   Nowak-Wegrzyn A.  Future approaches to food allergy. Pediatrics. 2003 Jun;111(6 Pt 3):1672-80.

 

BACKGROUND: Infantile food protein-induced enterocolitis syndrome (FPIES) is a severe, cell-mediated gastrointestinal food hypersensitivity typically provoked by cow's milk or soy. Solid foods are rarely considered a cause. OBJECTIVE: To describe the clinical characteristics and natural history of FPIES provoked by solid foods. METHODS: Patients with FPIES induced by solid foods were identified and their clinical course compared with a control group with FPIES caused by cow's milk and/or soy evaluated over the same time period. RESULTS: Fourteen infants with FPIES caused by grains (rice, oat, and barley), vegetables (sweet potato, squash, string beans, peas), or poultry (chicken and turkey) were identified. Symptoms were typical of classical FPIES with delayed (median: 2 hours) onset of vomiting, diarrhea, and lethargy/dehydration. Eleven infants (78%) reacted to >1 food protein, including 7 (50%) that reacted to >1 grain. Nine (64%) of all patients with solid food-FPIES also had cow's milk and/or soy-FPIES. Initial presentation was severe in 79% of the patients, prompting sepsis evaluations (57%) and hospitalization (64%) for dehydration or shock. The diagnosis of FPIES was delayed, after a median of 2 reactions (range: 2-5).

Thirty patients with typical cow's milk- and/or soy-FPIES were identified for comparison. Overall, 48% of the 44 infants with FPIES were reactive to >1 food protein, and the risk for multiple food hypersensitivity approached 80% in the infants with solid food or soy-induced FPIES. None of the patients developed FPIES to maternally ingested foods while breastfeeding unless the causal food was fed directly to the infant. CONCLUSIONS: Cereals, vegetables, and poultry meats, typically regarded as of low allergenic potential, must be considered in the evaluation of FPIES, particularly in infants previously diagnosed with FPIES to cow's milk or soy, and as an initial cause in patients who have been exclusively breastfed. Infants with FPIES are at risk for multiple dietary protein hypersensitivities during an apparent period of immunologic susceptibility. Pediatricians should consider FPIES in the differential diagnosis of shock and sepsis.

 

7733.   Nugent JS, Quinn JM, McGrath CM, Hrncir DE, Boleman WT, Freeman TM.  Determination of the incidence of sensitization after penicillin skin testing. Ann Allergy Asthma Immunol. 2003 Apr;90(4):398-403.

 

BACKGROUND: Concerns for sensitization after penicillin skin testing are afactor in limiting the timing and population for whom this testing is offered. The sensitizing potential of the penicillin skin test has never been studied directly. METHODS: A total of 329 volunteers underwent prick and intradermal skin testing with penicillin G, benzylpenicilloyl-polylysine, and a minor determinant mixture. Those with negative skin testing had repeat testing 4 weeks later. Medical history and antibiotic use were determined by interview, questionnaire, and electronic pharmacy records. RESULTS: Seventy-two of the 329 subjects (22%) reported a history of previous beta-lactam reaction, of which 10 (14%) had a positive initial skin test. Overall, the initial skin test was positive in 23 of 329 (7%). Of the subjects with a negative initial skin test, 239 completed the second test 4 weeks later. Of these, 6 subjects (2.5%, 95% confidence interval 0.5% to 4.5%) converted to a positive skin test. None had taken a beta-lactam antibiotic between the two tests, and none had any previous history of beta-lactam reaction. One subject reported having never taken a beta-lactam antibiotic before. In comparison to the 233 subjects who did not convert their skin test, the statistically significant factors favoring sensitization were: f