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Background: Immunoglobulin E (IgE) is the most important promoter of allergic inflammation. However, there are few systematic studies on IgE in age range, genders, disease spectrum, and time regularity., Aim: To screen the common allergens, allergen spectrum, and IgE difference between type 2 inflammatory allergic diseases and other allergic diseases in Weifang, China., Methods: A retrospective study was performed by estimating patients' clinical data suffering from allergic diseases (urticaria, pollinosis, allergic rhinitis, atopic dermatitis, and bronchial asthma) between May 2019 and April 2020 using an allergen detection kit of Macro-Union Pharmaceutical., Results: 732 of the 1367 patients showed different antigen positive, and the positive rate was 53.5%. The most common allergens were dust mites, mixed fungi, Artemisia pollen, cat/dog dander, and cockroaches. There were 27.0% (369/1367) of the patients with single positive allergen-specific IgE (sIgE), 26.5% (363/1367) with multiple-positive IgE. The total immunoglobulin E (tIgE) levels varied with gender, age, and type of disease. There was a difference in the distribution of allergens between children and adults. A positive correlation between the serum-specific IgE and the corresponding local inhaled allergen density was observed., Conclusions: In this study, we found that type 2 inflammatory allergic diseases have higher serum IgE and a higher probability of inhaled sIgE positive. According to age, gender, and condition, serological IgE detection of allergens provides new insight into the early diagnosis and prevention of allergic diseases., Competing Interests: All authors have no conflicts of interest to disclose., (Copyright © 2021 Zhang Xu-De et al.)

Introduction . Allergen-specific IgE (sIgE) testing provides an objective assessment of sensitization to an allergen. Goal . To identify the time when serum measurements of sIgE would be most sensitive. Methods . This was a prospective study conducted between September 1, 2015, and February 25, 2019. Subjects ≥5 and ≤18 years of age, seen in the ED or admitted with an asthma exacerbation, were tested for total IgE and 8 perennial sIgE levels. Subjects with elevated sIgE were tested again after symptom resolution. Results . A total of 104 subjects were enrolled; 50 subjects were eligible for inclusion in the analysis. There were statistically significant differences between the visits for all sIgE, except Alternaria alternatum. Conclusions . In pediatric patients, serum sIgE levels measured during an asthma exacerbation were elevated compared with when their asthma was in better control. sIgE testing during an asthma exacerbation may help identify asthma triggers, mitigate exposure, and hence improve asthma control.

Severe equine asthma (sEA), which closely resembles human asthma, is a debilitating and performance-limiting allergic respiratory disorder which affects 14% of horses in the Northern Hemisphere and is associated with increased allergen-specific immunoglobulin E (IgE) against a range of environmental proteins. A comprehensive microarray platform was developed to enable the simultaneous detection of allergen-specific equine IgE in serum against a wide range of putative allergenic proteins. The microarray revealed a plethora of novel pollen, bacteria, mould and arthropod proteins significant in the aetiology of sEA. Moreover, the analyses revealed an association between sEA-affected horses and IgE antibodies specific for proteins derived from latex, which has traditionally been ubiquitous to the horse's environment in the form of riding surfaces and race tracks. Further work is required to establish the involvement of latex proteins in sEA as a potential risk factor. This work demonstrates a novel and rapid approach to sEA diagnosis, providing a platform for tailored management and the development of allergen-specific immunotherapy.

Zinc (Zn) is an essential trace element that plays important roles in the immune system. There is little known about the role of trace elements in allergic diseases, and previous reports have shown conflicting results. The aim of this study was to investigate the relationship between serum Zn levels and total or allergen-specific immunoglobulin E (IgE) levels. The initial candidates for this study were those who participated in the 5 th Korean National Health and Nutrition Examination Survey 2010 (n = 8,958), and 1,867 adults who had serum total and allergen specific-IgE levels measured were included. Upon adjusting for covariates, mean total IgE, Dermatophagoides farinae and dog-specific IgE levels increased significantly as the Zn levels decrease from the highest to the lowest quartile (p = 0.009, 0.004, and < 0.001, respectively). The multiple logistic regression analyses showed significant negative linear correlations between serum Zn levels and total, D. farinae-, cockroach-, and dog-specific IgE levels (p-value for linear trend = 0.004, 0.006, 0.027, and < 0.001, respectively). This study demonstrated that total/allergen specific IgE and Zn levels are significantly inversely related.

Background: Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix., Objective: We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies., Methods: Isolated human ASMC were exposed to serum obtained from: (i) healthy controls, or patients with (ii) allergic asthma, (iii) non-allergic asthma, and (iv) atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days., Results: Serum from patients with allergies significantly stimulated: (i) ASMC proliferation, (ii) deposition of collagen type-I (48 hours) and (iii) of fibronectin (24 hours). One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects., Conclusion and Clinical Relevance: Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC.

Objective: To study the association between serum-specific immunoglobulin E (sIgE) allergens and asthma in children., Methods: The serum sIgE allergens were determined using Western blot in 2239 children aged 1-14 years, consisting of 1415 children with asthma alone and 824 children with non-allergic diseases between December 2004 and April 2013. The case-control models of asthma alone and non-allergic diseases were established. The association between allergens and asthma was investigated using multivariate logistic regression analysis., Results: In the 2239 children, 1028 children (45.91%) were serum sIgE-positive, and the allergen with the highest positive rate was house-dust mite (15.68%), followed by house dust (14.29%) and moulds (13.40%). The results of the case-control analysis showed that house-dust mite, moulds, house dust, and cashew nut/peanut/soybean were significantly associated with the development of asthma. House dust was associated with the development of asthma in the 1-2 years old group (P<0.05). House dust and house-dust mite as allergens were identified as the risk factors for the development of asthma in the 3-14 years old group (P<0.05). In the 6-14 years old group, moulds as allergens were identified as the risk factors for the development of asthma (P<0.05). House dust and house-dust mite as allergens increased the risk of asthma in boys and girls, while moulds and cashew nuts/peanuts/soybeans as allergens increased the risk of asthma in boys., Conclusions: House-dust mite, house dust, and moulds are the most common allergens in children with asthma, and they are closely associated with the development of asthma.

The CD14 receptor is expressed on the surfaces of monocytes, macrophages, and, to a lesser extent, of activated granulocytes and B lymphocytes (mCD14). It also exists in soluble form in the serum (sCD14), in which it binds microbial compounds and indoor allergens. The objectives of this study were to see whether serum sCD14 concentrations could be used as a marker of atopic disorders and to estimate the effects of environmental factors (tobacco smoke exposure, childhood residence in urban or rural areas, and having a pet) on sCD14 and IgE values. Mass fraction of sCD14 and total IgE were determined in the sera of atopic (N=53) and non-atopic (N=35) participants using the standard enzyme-linked immunosorbent assay. Exposure to pets and environmental tobacco smoke was estimated based on the International Study of Asthma and Allergies in Childhood questionnaire (ISAAC). Median sCD14 concentration was significantly lower in atopic than in non-atopic girls (3.49 vs. 3.83 μg mL(-1); p<0.010). The number of smokers at home positively correlated with the sCD14 level in atopics, and urban atopics had significantly lower sCD14 levels than rural atopics (3.47 vs. 3.92 μg mL(-1), p=0.028). Median total IgE concentration was significantly lower in atopic pet owners than in atopics with no pets (161 vs. 252 kIU L(-1); p=0.021). In conclusion, while sex and environmental factors might be involved in sCD14 expression, particularly in atopics, we found no correlation between sCD14 and total IgE concentrations. The usefulness of sCD14 as a marker of atopic disorders should be investigated further, particularly in relation to the severity of allergic disorders.

Background: A free running asthma screening test is usually used for screening exercise-induced bronchoconstriction. The total serum allergen IgE level can reveal the patient's atopy characteristics. Our study is to evaluate the diagnostic values of the combination of the two tests in asthmatic children and compare this new diagnostic method with the International Study of Asthma and Allergies in Childhood (ISSAC) questionnaires and the bronchial provocation test, which are popular diagnostic tool for pediatric asthma., Methods: A total of 773 school children were recruited in this study. The children's asthma was diagnosed by means of a combination of the free running asthma screening test and total serum allergen IgE level. The new diagnostic method value was assessed using receiver operating characteristic (ROC) curves and compared with other diagnostic tools such as ISSAC questionnaires and the bronchial provocation test., Results: The AUC of this new diagnostic method was higher than 0.9. When the cut-off value of total serum allergen IgE level was ≥ 47 KU/L, the sensitivity and the specificity were 71.4% and 85.1%, respectively, which were better than those of either the ISSAC questionnaires or bronchial provocation test., Conclusion: The combination of the free running asthma screening test and total serum allergen IgE level may be an effective diagnostic tool for children's asthma.

Airborne fungal spores bearing allergens are the causative agent for inducing immediate hypersensitive reaction in sensitive individuals. In this study the potential aeroallergens have been reported for the first time from Rhizopus oryzae a common airborne mold. Clinical data based on SPT was further confirmed by ELISA. IgE reactive bands were revealed by one-dimensional immunoblotting. A 44 kDa major reactive band was found in all immunoblots. For precise identification of allergens, an immuno-proteomic approach was taken with a combination of 2-Dimensional gel electrophoresis and Mass-spectrometry. 2D map of spore-mycelial protein was confronted with pooled sera and several IgE reactive spots were detected, most of which were glycoproteins and except for one, which has no antigenic determinacy after metaperiodate modification. Each of those spots was identified by MALDI-TOF-TOF. Some bioinformatic approaches were taken to predict the signal peptide and subcellular localization of each protein. Major 44 kDa allergen was identified as Aspartyl endopeptidase. Sequence information was extracted from MS/MS spectra of two tryptic peptides generated from the 44 kDa endopeptidase. Multiple alignments with other reported aspartyl protease allergens showed significant homology. Allergenicity assessment of this protein was performed in silico and identified as a potential putative allergen., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: MicroRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level. While they have been implicated in various diseases, the profile changes in allergen inhalation challenge are not clarified in human. We aimed to evaluate changes in the microRNA profiles in the peripheral blood of asthmatic subjects undergoing allergen inhalation challenge., Results: Seven mild asthmatic subjects participated in the allergen inhalation challenge. In addition, four healthy control subjects (HCs) were recruited. MicroRNA profiles in peripheral blood samples (pre-challenge and 2 hours post-challenge) were measured by the NanoString nCounter assay to determine changes in miRNA levels as these asthmatic subjects underwent an allergen inhalation challenge. One common miRNA, miR-192, was significantly expressed in both comparisons; HCs vs. pre-challenge and pre- vs. post-challenge, showing that miR-192 was significantly under-expressed in asthmatics compared to HCs and decreased in post-challenge at an FDR of 1%. Cell-specific statistical deconvolution attributed miR-192 expression in whole blood to PBMCs. MiR-192 was technically validated using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) showing that the level in asthmatics (pre-challenge) was significantly lower than HCs and that post-challenge was significantly lower than pre-challenge. The normalized relative miR-192 expression quantified using RT-qPCR specific to PBMCs was also validated. Ontology enrichment and canonical pathway analyses for target genes suggested several functions and pathways involved in immune response and cell cycle., Conclusions: The miRNA profile in peripheral blood was altered after allergen inhalation challenge. Change in miR-192 levels may be implicated in asthma mechanisms. These results suggest that allergen inhalation challenge is a suitable method to characterize peripheral miRNA profiles and potentially elucidate the mechanism of human asthma.

Vitamin D has been linked in some studies with atopy- and asthma-associated phenotypes in children with established disease, but its role in disease inception at the community level is less clear. The aim of the present study was to investigate associations between vitamin D status and biological signatures indicative of allergy and asthma development in children aged 6 and 14 years in Perth, WA, Australia (latitude 32° S). Serum vitamin D was assayed in 989 6-yr-olds and 1,380 14-yr-olds from an unselected community birth cohort; 689 subjects were assessed at both ages. Vitamin D levels were assessed as a risk modifier for respiratory and allergic outcomes at both ages, using previously ascertained phenotypic data. The predictive value of vitamin D levels at age 6 yrs for development of clinical phenotypes at age 14 yrs was also examined. Serum vitamin D levels in children of both ages were negatively associated with concurrent allergic phenotypes; sex stratification revealed that this association was restricted mainly to males. Furthermore, vitamin D levels at age 6 yrs were significant predictors of subsequent atopy/asthma-associated phenotypes at age 14 yrs. In an unselected community setting, children (particularly males) with inadequate vitamin D are at increased risk of developing atopy, and subsequently bronchial hyperresponsiveness (BHR) and asthma. In a large unselected cohort, males with inadequate vitamin D at 6 and 14 yrs of age had increased atopy and BHR. Low vitamin D at age 6 yrs was a predictor of atopy and asthma at 14 yrs of age.

Background: Mould-induced atopic respiratory diseases are a worldwide problem. Characterization of fungal allergens is of major clinical importance., Objective: We identified a novel transaldolase family allergen of Cladosporium and Penicillium species., Methods: Fungal allergens were identified by immunoblotting, peptide mass mapping and partial sequencing, cDNA cloning and IgE epitope mapping., Results: A 36.5 kDa IgE-binding component in a partially purified C. cladosporioides preparation was identified. Mass spectrometric analyses suggest that this novel IgE-reacting allergen is a transaldolase. A corresponding full-length 1246 bp cDNA encoding a polypeptide of 325 residues was isolated. The newly identified transaldolase allergen has been designated as Cla c 14.0101. The cDNA encoding the Pencillium chrysogenum transaldolase was isolated by RT-PCR according to the cDNA sequence encoding a P. chrysogenum Wisconsin 54-1255 hypothetical protein. The purified rCla c 14.0101 protein reacted with IgE antibodies in 10 (38%) of 26 Cladosporium cladosporioides-sensitized asthmatic patients. Nine of the 10 rCla c 14.0101-positive sera have IgE binding against the recombinant Penicillium transaldolase (rPen ch 35.0101). Among the eight fungal transaldolase-positive sera tested, three showed IgE binding against the recombinant human transaldolase. To determine cross-reactivity between the Cladosporium and Penicillium fungi, IgE cross-reactivity was detected between these two fungal transaldolase allergens by inhibition assays. Both the N- and the C-terminal fragments of Cla c 14.0101 were recognized by IgE antibodies. The C-terminal IgE-reacting determinant was narrowed down to a region encompassing Thr257 to Ser278 of Cla c 14.0101. It was mapped onto a loop-like structure of a 3D model constructed for Cla c 14.0101., Conclusion and Clinical Relevance: We identified transaldolase as a novel and IgE cross-reactive allergen family of C. cladosporioides and P. chrysogenum. In addition, an IgE-reacting fragment (Thr257 to Ser278) was pinpointed to a loop-like structure on Cla c 14.0101. Results obtained provide important information in clinical mould allergy., (© 2011 Blackwell Publishing Ltd.)

Background: Baker's asthma is an important occupational allergic disease. Wheat lipid transfer protein (LTP) Tri a 14 is a major allergen associated with wheat allergy. No panel of wheat recombinant allergens for component-resolved diagnosis of baker's asthma is currently available., Objective: To evaluate the potential role of recombinant Tri a 14 as a novel tool for the diagnosis of baker's asthma, and to test the heat and proteolytic resistance of the wheat LTP allergen., Methods: A cDNA encoding Tri a 14 was isolated and sequenced, the recombinant allergen produced in Pichia pastoris and purified by chromatographic methods. Physicochemical and immunological comparison of the natural and recombinant forms of Tri a 14 was carried out by N-terminal amino acid sequencing, matrix-assisted laser desorption/ionization mass spectrometry, circular dichroism (CD) analysis, IgE immunodetection, and specific IgE determination and ELISA-inhibition assays using a pool or individual sera from 26 patients with baker's asthma. Thermal denaturation and simulated gastrointestinal digestion of both Tri a 14 forms were checked by spectroscopic and electrophoretic methods, respectively, and biological activity by basophil activation test (BAT)., Results: Natural and recombinant Tri a 14 were similarly folded, as indicated by their nearly identical CD spectra and heat denaturation profiles. A high interclass correlation coefficient (0.882) was found between specific IgE levels to both Tri a 14 proteins in individual sera from baker's asthma patients, but a slightly lower IgE-binding potency of rTri a 14 was detected by ELISA-inhibition assays. Natural and recombinant Tri a 14 elicited positive BAT in two and one out of three patients, respectively. Heat denaturation profiles and simulated gastrointestinal digestion assays indicated that Tri a 14 displayed a high heat and digestive proteolytic resistance, comparable to those of peach Pru p 3, the model food allergen of the LTP family., Conclusions: Recombinant Tri a 14 is a potential tool for baker's asthma diagnosis, based on its physicochemical and immunological similarity with its natural counterpart. Wheat Tri a 14 shows a high thermal stability and resistance to gastrointestinal digestion.

Background: Adiponectin is associated with asthma. The direction of this association is not known in humans. In mice, this association is bidirectional: allergen inhalation affects serum adiponectin, and exogenous adiponectin administration affects asthma. We sought to evaluate whether allergen inhalation affects serum adiponectin in human asthma., Methods: This study included eight sensitized subjects with mild asthma and six healthy control subjects. Asthmatic subjects were challenged with inhaled specific allergen (positive allergen skin test), methacholine, and irrelevant allergen (negative allergen skin test). Control subjects were challenged with irrelevant allergen. Sequential serum samples were obtained before and nine times after each challenge. Serum adiponectin- (primary outcome), leptin-, adiponectin-to-leptin ratio-, eotaxin-, and tumor necrosis factor-alpha-response curves, area under the curves, and baseline and peak concentrations were evaluated. Statistical analysis used repeated-measures analysis of variance and paired t tests., Results: There were no significant differences in outcome measures among the challenges in asthmatic subjects or when compared to control subjects. Type II error is an unlikely explanation for these findings because the study was adequately powered to detect changes in serum adiponectin, as reported in the literature. Further, pooled data showed that serum adiponectin diurnal variation curves were lower in asthmatic subjects than in control subjects., Conclusions: Serum adiponectin concentrations are lower in asthmatic subjects than in control subjects. Specific allergen inhalation in asthmatic subjects does not acutely affect serum adiponectin concentrations. The reverse association (ie, effect of adiponectin on asthma) needs further study. If future studies prove adiponectin to be a protective factor for asthma, modulating adiponectin may open a new approach toward managing asthma.

Objective: To analyze the diagnostic significance of serum total IgE, specific IgE (SIgE), Phadiatop, and eosinophil cationic protein (ECP) in allergic rhinitis and bronchial asthma., Methods: The serum total IgE, SIgE , and Phadiatop were tested in 122 patients with allergic rhinitis. The ECP, SIgE, and Phadiatop were tested in 135 patients with bronchial asthma. Forty healthy persons were used as controls. The serum total IgE were tested by electrochemiluminescence. The serum Phadiatop, ECP, and SIgE were tested by fluorescent-enzyme linked immunosorbent assay., Results: The serum total IgE positive rate of the 122 allergic rhinitis patients was 37.7%, significantly higher than that of the healthy controls (2.5%, chi2 = 18.13, P < 0.01). The specificity of total IgE of the allergic rhinitis patients were 97.5%. The serum ECP positive rate of the bronchial asthma patients was 65.9%, significantly higher than that of the healthy controls (20.0%, chi2 = 26.34, P < 0.01). The sensitivity and specificity of the bronchial asthma patients were 65.9% and 80.0%. The Phadiatop positive rates of the allergic rhinitis and the bronchial asthma patients were 50.0% and 31.9% respectively, both significantly higher than that of the control (0, chi2 = 32.08, 16.89, both P < 0.01). Most kinds of SIgE were from the allergens, such as dust mite, dust, and Artemisia etc., Conclusion: Increase of serum ECP level is an important indicator of airway inflammation activity and inflammation serious degree in the bronchial asthma patients. The increase of serum total IgE has an important diagnostic significance in allergic rhinitis. It is important to detect SIgE and Phadiatop in diagnosis and monitoring of allergic rhinitis and bronchial asthma.

Although rabbits are common domestic pets, severe respiratory allergic reactions to rabbits in households are unusual. Ory c 1, a 17-kDa glycoprotein found in saliva and fur, has previously been identified as a major rabbit allergen. In this report, we describe the cases of three patients with rabbit allergy who presented with asthma and/or rhinitis while living in households with detectable levels of serum-specific IgE and major IgE binding components. Three patients with rabbit allergy and 18 unexposed nonatopic healthy controls were enrolled. Enzyme-linked immunosorbent assays (ELISA) for serum-specific IgE and IgG(4) to rabbit epithelium and inhibition ELISA were performed followed by sodium dodecye sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and IgE immunoblotting. All three patients with rabbit allergy had high serum-specific IgE antibody levels compared with controls. The results of the inhibition ELISA showed significant inhibition with the addition of rabbit epithelium, whereas no significant inhibition was noted with the addition of cat and dog epithelia. Two IgE-binding components with molecular weights of 16 kDa and 67.5 kDa were identified by IgE immunoblotting. In conclusion, rabbit exposure may induce IgE-mediated bronchial asthma and/or rhinitis in domestic settings.

Background: Allergen-specific T(H)2-like cytokine responses are considered to be important in sensitization and allergic diseases., Objective: To examine the profile of house dust mite (HDM) stimulated T-cell cytokines and their relationship to allergic disease in children over the period of the first 5 years of life., Methods: Subjects with a family history of asthma who were enrolled antenatally in the Childhood Asthma Prevention Study and had skin prick tests, clinical evaluation for asthma and eczema, and in vitro assessment of lymphocyte cytokine responses to HDM extract performed at ages 18 months (n = 281), 3 years (n = 349), and 5 years (n = 370). IL-13 at 3 and 5 years and IL-5, IL-10, and IFN- gamma at 18 months, 3 years, and 5 years were measured by ELISA., Results: House dust mite-specific cytokine responses increased with age for all cytokines except IFN-gamma. HDM-specific IL-5 responses at 3 years and 5 years were significantly positively related to skin prick test positivity at 5 years. IL-5 responses at 5 years were also significantly related to asthma at 5 years. Other HDM-specific cytokine responses were not related to asthma or eczema at 5 years. Responses were not altered by a HDM avoidance intervention., Conclusion: IL-5 responses to HDM, the dominant local inhalant allergen, are related to the expression of clinical illness at age 5 years., Clinical Implications: The T-cell response to HDM, as reflected in IL-5 production, is acquired over the first years of life and may play a role in the expression of allergic airways disease.

Background: Exposure to allergen may induce a modified T(H)2 response characterized by high IgG(4) levels, absence of IgE sensitization, and a decreased risk of allergic respiratory symptoms., Objective: To assess the association of IgG(4) level with allergic respiratory symptoms in a community-based sample of adults., Methods: Information on exposure to cats, respiratory symptoms, and mattress allergen levels was obtained from 2780 adults. Levels of cat and house dust mite (HDM) specific IgE, IgG, and IgG(4) were measured. The association of exposure to allergen with IgG(4) and of IgG(4) with symptoms was assessed., Results: Geometric mean (GM) cat specific IgG and IgG(4) was higher in subjects who had a cat that was allowed in the bedroom than in subjects without a cat (adjusted ratio of GM IgG(4), 1.41; 95% CI, 1.25-1.57). Levels of HDM specific IgG and IgG(4) were similar in subjects with undetectable and high (>20.22 microg/g) mattress Der 1 levels (adjusted ratio of GM IgG(4), 1.02; 95% CI, 0.89-1.17). There was no evidence that high cat or HDM specific IgG(4) levels were associated with less IgE sensitization or with fewer symptoms., Conclusion: In this community-based sample of adults, high IgG(4) levels to cat or HDM were not associated with a lower risk of allergic respiratory symptoms., Clinical Implications: In adults, high cat allergen exposure does not protect against respiratory symptoms.

Background: Reduced lung function is a feature of chronic asthma, which becomes apparent at school age. Unknown factors between birth and school age determine the progressive loss of pulmonary function in children with persistent asthma. We investigated the role of allergic sensitisation and allergen exposure early in life., Methods: The German Multicentre Allergy Study followed 1314 children from birth to 13 years of age. We regularly interviewed parents about their child's asthma and measured IgE levels. Allergen exposure was assessed at age 6 months, 18 months, and at 3, 4, and 5 years; lung function was assessed at 7, 10, and 13 years; post-bronchodilator response at 10 and 13 years; and a bronchial histamine challenge was done at 7 years., Results: 90% of children with wheeze but no atopy lost their symptoms at school age and retained normal lung function at puberty. By contrast, sensitisation to perennial allergens (eg, house dust mite, cat and dog hair) developing in the first 3 years of life was associated with a loss of lung function at school age. Concomitant exposure to high levels of perennial allergens early in life aggravated this process: forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio was 87.4 (SD 7.4) for those sensitised and with high exposure compared with 92.6 (6.0) for those not sensitised, p<0.0001; and maximal expiratory flow at 50% (MEF50) 86.4 (25.1) for sensitised and with high exposure compared with 101.5 (23.2; p=0.0031) for those not sensitised. Such exposure also enhanced the development of airway hyper-responsiveness in sensitised children with wheeze. Sensitisation and exposure later in life had much weaker effects and sensitisation to seasonal allergens did not play a part., Interpretation: The chronic course of asthma characterised by airway hyper-responsiveness and impairment of lung function at school age is determined by continuing allergic airway inflammation beginning in the first 3 years of life. However, children with a non-atopic wheezing phenotype lose their symptoms over school age and retain normal lung function at puberty.

Objective: To compare the prevalence of allergy to cockroaches (Blattella germanica and Periplaneta americana) in asthmatic and non-asthmatic children and to determine the degree of agreement between the skin prick test and serum specific IgE levels, as well as to establish the relationship between cockroach allergy and total IgE levels., Methods: A case-control study involving 76 asthmatic and 42 non-asthmatic children aged between 6 and 14 years was conducted in Recife, Brazil. All individuals were submitted to the skin prick test and to the measurement of specific IgE for B. germanica and P. americana, as well as to the determination of total IgE concentration., Results: Asthmatic children showed a higher frequency of positive skin reactions to B. germanica (27.6 vs. 4.8%) and P. americana (27.6 vs. 2.4%) than non-asthmatic ones. The agreement between the skin prick test and the specific IgE results was reasonable for B. germanica (kappa = 0.25) and weak for P. americana (kappa = 0.17). Those patients who tested positive for cockroaches had a significantly higher geometric mean for total IgE than those who tested negative. The agreement between specific IgE and the skin prick test increased as total IgE levels rose, although some skin tests were negative even when total IgE levels were as high as 5000 kU/l. All determinations of cockroach-specific IgE were positive for total IgE levels greater than 2500 kU/l, even among asymptomatic patients., Conclusion: Allergic sensitivity to cockroaches was a predictive factor for asthma severity. The skin prick test is more appropriate for the detection of clinically relevant sensitivity to cockroaches than specific IgE determination.

Background: Genetic studies of atopy rely upon evidence of abnormal IgE production, usually elevated total IgE or skin prick test (SPT) reactions. However, these measures may change with subject age., Methods: We screened 1,099 members of atopic families (aged 6-87 years) by serum total IgE and SPT for 14 allergens. For those SPT negative, we screened for Amb a 1- and Der p 1-specific IgE. Der p 1 IgE-Der p 1 allergen binding affinities were done on randomly selected subjects., Results: There were significantly fewer atopics 10 years old (75.8%) based upon any SPT-positive result. Children 10 years old = 82.3%). Among those SPT-positive for house dust mite extract, there was a positive correlation between Der p 1 binding affinity and the wheal area of the house dust mite extract. There was a positive correlation between the number of SPT-positive reactions and total IgE for both age groups. However, there was only a significant relationship between SPT-positive wheal area and total IgE for those >10 years old and no apparent relationship between wheal area and total IgE for those

Although elevated levels of serum immunoglobulin E (IgE) are considered the hallmark of atopic diseases, their clinical value in evaluating subjects with allergic disorders is under debate. To evaluate possible relationships between serum IgE levels and a variety of clinical parameters, 83 mild asthmatic children [10.98-year-old (2.95)], sensitized to house dust mites (HDM) Dermatophagoides pteronyssinus (Dp) or D. farinae (Df), were enrolled. As compared with normal control reference values detected in our laboratory, children with allergic asthma had higher blood eosinophil counts (expressed both as percentage and as absolute number) and higher fractional exhaled nitric oxide (FeNO) levels but similar values in pulmonary function parameters. In the allergic asthmatic population, serum levels of total, Dp-specific or Df-specific IgE correlated positively with eosinophil counts (Rho > or = 0.30, p < 0.01, each correlation) and FeNO levels (Rho > or = 0.33, p < 0.01, each correlation) but not with pulmonary function parameters (p > 0.1, each correlation). Finally, significant correlations, although moderate, were found in the allergic asthmatic population between eosinophil counts and FeNO levels (Rho > or = 0.42, p < 0.001, each correlation). Thus, in atopic children sensitized to HDM with mild intermittent asthma, IgE levels in blood appear to reflect systemic (blood eosinophils) and organ-specific (FeNO) markers of allergic inflammation but not pulmonary volumes or the degree of airflow limitation.

Eighty-eight patients' sera with allergen-specific IgE levels elevated only to food allergens were collected between October 1997 and March 2002 at the National Taiwan University Hospital. Thirty-three of the patients fulfilled the diagnostic criteria of asthma and were included. Most (72.7%) patients had elevated serum allergen-specific IgE levels only to one food allergen. The most common food allergens were milk and egg white. The patients with elevated soy bean-specific IgE levels had significantly higher levels of serum food allergen-specific IgE than those with either elevated milk or egg white-specific IgE levels. This study investigated some food allergen responses of asthmatic patients whose serum allergen-specific IgE levels were elevated only to food allergens. The results suggested that the allergic asthmatic response in our patients was most likely related to food rather than aeroallergens or fungal allergens.

Background: IgE plays a central role in allergic diseases. Recent studies have postulated an association between serum IgE levels and bronchial asthma., Objective: To examine the differences of atopic phenotypes in a group of individuals with extraordinarily high serum IgE levels (>10,000 kU/L) compared with children with moderately elevated IgE levels (400-1,000 kU/L)., Methods: We investigated 20 children with serum IgE levels greater than 10,000 kU/L and compared them with 56 age-matched children with serum IgE levels of 400 to 1,000 kU/L regarding prevalences of atopic dermatitis, bronchial asthma, allergic rhinoconjunctivitis, allergic sensitization, and history of anaphylaxis., Results: The mean eczema severity score as determined by the Severity Scoring of Atopic Dermatitis Index was 56 vs 18 (P < 0.003), and anaphylactic reactions were reported in 20% of the group with very high serum IgE levels vs 7% in the group with moderate levels (P < 0.02). Sensitization to both aeroallergens and food allergens was detected in 80% of the group with very high serum IgE levels vs 32% of the group with moderate levels (P < 0.001)., Conclusions: Our results indicate that children with very high serum IgE levels are at risk for anaphylactic reactions and more severe atopic dermatitis.

Background: Alcohol-induced asthma, a phenomenon characteristic of Asians, is due to differences in alcohol metabolism, particularly acetaldehyde metabolism. We investigated the effect of polymorphism in acetylaldehyde dehydrogenase 2 (ALDH2) gene on the response to alcohol challenge testing in a group of Japanese asthmatic subjects and normal subjects., Methods: Subjects were 32 asthmatic subjects and 30 healthy individuals. We measured the change in FEV1 after ingestion of 30 gm of ethanol. Blood ethanol, acetylaldehyde, and histamine concentrations were determined. ALDH2 gene type was established by polymerase chain reaction., Results: Ethanol provocation test results were positive in 15 (47% responders) asthmatic subjects. The blood ethanol concentration was similar in responders and nonresponders. The fall in FEV1 was associated with a rise in blood acetaldehyde and histamine concentrations. The response to oral ethanol challenge was positive in three (19%) of 16 patients with normal homozygote ALDH2 genotype, 10 (71%) of 14 patients with type mutant heterozygote, and two (100%) of two patients with type mutant homozygote ALDH2 genotype., Conclusions: Alcohol-induced asthma is probably caused by increased blood acetaldehyde concentration resulting from abnormalities of ALDH2 enzyme activity based on ALDH2 genotype differences.

Endotoxins (ET) are pro-inflammatory substances present in house dust which may increase non-specific bronchial reactivity in asthmatic patients. Endotoxins (EU/g) and Der p 1 levels were compared in the homes of ten asthmatic and ten control children, aged 6-16 years, living in São Paulo, Brazil. The houses were visited once a month from February 1993 to February 1994 and dust samples were collected from the bedding and floor of each subject's house. No significant differences were observed in ET and Der p 1 levels in the homes of asthmatics and controls. The highest ET levels were detected in January and November, whereas the lowest levels were detected in April and August (p < 0.05), demonstrating a distinct seasonal distribution. The highest Der p 1 levels in bedding were observed in July and the lowest in February (p < 0.05), while Der p 1 levels in floor did not show significant differences throughout the year. Symptom and medication scores were evaluated monthly in the group of asthmatic children. There was a significant correlation (p < 0.05, r = 0.63) between clinical symptom scores and ET exposure, however no significant correlation was found for mite exposure (p > 0.05, r = 0.19). The results suggest that ET exposure exacerbates asthmatic symptoms in mite allergic, asthmatic children.

Background: In allergic asthma, CD4+ T lymphocytes are a fundamental component of local chronic inflammation. Their cytokine profile is oriented toward a TH2 phenotype, characterized by production of IL-4, IL-5, IL-10, and IL-13. Egress of T cells from blood to airways after allergen challenge has been described., Objective: We have studied a cohort of six patients with asthma who had multiple allergies to investigate how exposure to allergen affects the proliferation of peripheral CD4+ T lymphocytes with different allergen specificities and lymphokine profiles., Methods: For each patient, CD4+ T-cell lines were generated by in vitro stimulation with sensitizing and with nonsensitizing allergens, and IL-4 and interferon-gamma production by these lines was assessed. Proliferation of peripheral blood CD4+ T lymphocytes in response to the same allergens was measured before and 24 hours after inhalation challenge with a sensitizing allergen., Results: We found that each single sensitizing allergen can deplete peripheral blood of TH2-type CD4+ T lymphocytes specific for all sensitizing allergens, but not of TH1-type CD4+ T lymphocytes., Conclusions: Our results suggest the existence of mechanisms capable of sorting disease-associated antigen specificities together with defined lymphokine patterns into T lymphocytes that can migrate to target organs, in allergic asthma.

Background: The role of Pyroglyphid mites in IgE-mediated sensitization has been well established. Although mites belonging to the genus Dermatophagoides dominate in the acarofauna of domestic dust, non-pyroglyphid mites might also be of clinical importance. In Cuba, Dermatophagoides siboney is found in dust coexisting with D. pteronyssinus and Blomia tropicalis. Dermatophagoides farinae is not found. Storage mites, such as Acarus siro, Lepidoglyphus destructor and Tyrophagus putrescentiae, might also be present., Objectives: The aim of this study was to investigate the allergenic relationships among the mites present in the environment of allergic patients in Cuba., Methods: The crossreactivity between an extract of D. siboney and the above mentioned six mites was studied by specific IgE inhibition, using sera of mite-sensitive patients after incubation with serial dilutions of D. siboney., Results: The inhibitory effect of D. siboney extract was more pronounced against D. farinae, 91%, than against D. pteronyssinus, 62%. Specific IgE to B. tropicalis, A. siro, L. destructor and T. putrescentiae were inhibited to a much lesser extent, i.e. between 47 and 58%. The correlation between IgE to D. siboney and IgE to D. pteronyssinus and D. farinae was of 0.92 and 0.90, respectively. A weaker correlation was found between D. siboney and L. destructor (0.7), A. siro (0.67), B. tropicalis (0.54) and T. putrescentiae (0.51)., Conclusion: Thus, D. siboney seems to be most closely related to D. farinae.

House dust mites have been known as the most important allergen in respiratory allergic diseases. Among several mite allergens, group I and group II antigens were recognized as major allergens. We measured specific IgE and IgG subclass antibodies against whole body antigen (WBA) and two major allergens of Dermatophagoides farinae (Der fI and Der fII) in sera from 66 adults with asthma (asthma group) and 34 normal subjects (healthy group) by ELISA. The mean O.D. values of WBA-specific IgE and IgG subclass antibodies in 100 studied sera were significantly higher than those of the two major allergens (p < 0.001) and the level of Der fII- IgG1, IgG4 and IgE were higher than those of Der fI but IgG2 of Der fI was higher than that of Der fII (p < 0.001). The level of IgG4 of WBA were significantly higher in the atopic group than in the nonatopic group (1.280 +/- 0.634 v.s. 0.8290 +/- 0.388, p < 0.001), but the WBA- IgG1, IgG2, IgG3 were not different between the two groups. Among IgG subclass antibodies of Der fI, IgG2 was significantly higher in the nonatopic group than in the atopic group (1.7770 +/- 0.255 v.s. 1.636 +/- 0.390, p < 0.05) but there were no differences in IgG1, IgG3, and IgG4. Among IgG subclass antibodies of Der fII, IgG2 (1.534 +/- 0.380 v.s. 1.3010 +/- .431, p < 0.05) and IgG4 (1.09650 +/- .567 v.s. 0.708 +/- 0.146, p < 0.001) were significantly higher in the atopic group than in the nonatopic group. IgE antibodies to WBA, Der fI and Der fII were significantly higher in the atopic group (p < 0.001). There were significant correlationships between the levels of IgE and IgG4 of WBA (r = 0.60), Der fI (r = 0.33) and Der fII (r = 0.72). Even though there were no differences in the levels of allergen specific IgE and IgG subclass antibodies between nonatopic healthy and nonatopic asthmatic groups, the number of sera with prominent level of IgG2 of WBA were more common in the nonatopic asthmatic group (69% in nonatopic asthma group v.s. 28% in nonatopic healthy group, X2-test, p < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Seven IgG-binding components in crude mite allergen extracted from Dermatophagoides pteronyssinus (Der p) were identified by immunoblotting analysis. Of these components, the 15-kDa protein was strongly recognized by IgG from patients with bronchial asthma, whereas it was less recognized by IgG from healthy individuals. Then, the 15-kDa protein was purified by reverse-phase high performance liquid chromatography and the protein was demonstrated to induce immediate positive skin reactions in patients with bronchial asthma. The N-terminal amino acid sequence of the 15-kDa protein was also determined and was in agreement with that of Der p II. In an attempt to understand the role of IgG subclass antibody of patients with bronchial asthma, we quantitated the antibodies of IgG subclass to Der p II. The levels of antibodies of total IgG and of all IgG subclasses in patients with bronchial asthma who had never received immunotherapy were higher than those of nonatopic healthy individuals. The levels of Der p II-specific IgG1 and IgG4 in asthmatic patients were 1.97 times and 2.20 times higher, respectively, than those in the control group. The present study demonstrates that patients with bronchial asthma are able to produce antibodies of all IgG subclasses specific to Der p II in response to natural exposure to mite antigen.