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The aimof the study was to study the range of substances that cause respiratory sensitization in adults and children living in Dnipro as of 2019. Materials and research methods.Enzyme-linked immunosorbent assay was used to study the serum of venous blood, which determined the specific IgE of up to 9 allergens that are most common in the home. Kits for quantification of allergen-specific IgE from Vitrotest Specific-IgE, Ukraine were used. Conducted allergy diagnosis for 380 people with certain features of allergy history of various types of allergies, who went to the laboratory to specify the etiological root cause of their disease. Research results.As a result of the analysis of the received data the distribution of allergens on their prevalence among the population of Dnipro was established. The degree of hypersensitivity to each specific allergen and their ability to cross-react with each other was determined. Among the allergens of the household panel, the most dangerous were allergens of molds, which caused a sensitization reaction in 292 people, which was 76.8 % of all surveyed. The top three (in prevalence) of household allergens included: cat epithelium, which caused sensitization in 125 people (32.9 %) and Derm mite. Farinae, sensitivity to which was found in 117 patients (30.7 %). The share of inadequately strong allergopathological reactions is one third of all examined and prevails in people with sensitization to allergic agents of the household panel such as cat epithelium, Derm mite. Farinae and Derm. Pteronyssinus. Hyperractivity to fungi of the genus Candida and mold has been found in 9–12 % of people. The lowest severity of sensitization was observed in the epithelium of the dog and house dust, and low sensitivity in the reactivity structure of allergopathological reactions was observed for allergens of the epidermal group (down and feathers of poultry) and cockroaches. The development of cross-reactions took place between allergens of epidermal origin: there was a hypersensitivity to the hair and epithelium of dogs and cats (r=0.94, P˂0.01), poultry feathers and cockroaches (r=0.99, P˂0.01). This association of cross-reactions is possible, given the theory of minor and major proteins, and is due to their similarity: the similarity of the inclusion in the allergen structures of specific forms of molecules inherent in both allergic agents that may have allergy-stimulating effects. Conclusions.Cross-linking between several types of related allergens is the best way to further investigate this issue. It makes sense to include in the laboratory study a molecular method for the determination of major and minor proteins in the case of the greatest relationship to determine not only a specific allergen as an etiological factor, but also a specific sensitizing protein that is part of them. This is of great importance for subsequent immunotherapy when the removal of only one (major) protein agent can reduce the risk of susceptibility reactions to several types of allergens

Identifying allergen distribution is meaningful and significant for effective diagnosis and treatment of allergic diseases. This study compared the allergen sensitivity in four southern China cities. We enrolled 55,432 participants (27,408 male, 28,024 female) between 2007 and 2019. The allergen-specific IgE levels were compared by the χ2 test. The five prevalent sensitivities were for mite mix (10,985, 19.82%), cockroach (4,860, 8.77%), crab (4,450, 8.03%), fish mix (3,874, 6.99%), and house dust (3,486, 6.29%). Almost all allergen sensitivities decreased with age, particularly from infant to middle aged participants (p < 0.05). An exception was Shenzhen, where food allergen positive rates remained constant in all age groups studied. The proportion of male sensitive to at least one food allergen (OR 1.130; 95% CI 1.088-1.174, p < 0.0025) or aeroallergen (OR, 1.117; 95% CI, 1.078-1.158, p < 0.0025) was higher than female in all four cities. Except for dog dander and tree mix, all aeroallergens differed significantly between seasons (p < 0.05). Liuzhou had the highest rates of food allergen- and aeroallergen-positive participants. The allergen-specific IgE distribution differed among the studied cities, with significant seasonal differences. Young age, male sex, and aeroallergens were risk factors for allergic disease.

The aim of the study was to study the range of substances that cause respiratory sensitization in adults and children living in Dnipro as of 2019. Materials and research methods. Enzyme-linked immunosorbent assay was used to study the serum of venous blood, which determined the specific IgE of up to 9 allergens that are most common in the home. Kits for quantification of allergen-specific IgE from Vitrotest Specific-IgE, Ukraine were used. Conducted allergy diagnosis for 380 people with certain features of allergy history of various types of allergies, who went to the laboratory to specify the etiological root cause of their disease. Research results. As a result of the analysis of the received data the distribution of allergens on their prevalence among the population of Dnipro was established. The degree of hypersensitivity to each specific allergen and their ability to cross-react with each other was determined. Among the allergens of the household panel, the most dangerous were allergens of molds, which caused a sensitization reaction in 292 people, which was 76.8 % of all surveyed. The top three (in prevalence) of household allergens included: cat epithelium, which caused sensitization in 125 people (32.9 %) and Derm mite. Farinae, sensitivity to which was found in 117 patients (30.7 %). The share of inadequately strong allergopathological reactions is one third of all examined and prevails in people with sensitization to allergic agents of the household panel such as cat epithelium, Derm mite. Farinae and Derm. Pteronyssinus. Hyperractivity to fungi of the genus Candida and mold has been found in 9–12 % of people. The lowest severity of sensitization was observed in the epithelium of the dog and house dust, and low sensitivity in the reactivity structure of allergopathological reactions was observed for allergens of the epidermal group (down and feathers of poultry) and cockroaches. The development of cross-reactions took place between allergens of epidermal origin: there was a hypersensitivity to the hair and epithelium of dogs and cats (r=0.94, P˂0.01), poultry feathers and cockroaches (r=0.99, P˂0.01). This association of cross-reactions is possible, given the theory of minor and major proteins, and is due to their similarity: the similarity of the inclusion in the allergen structures of specific forms of molecules inherent in both allergic agents that may have allergy-stimulating effects. Conclusions. Cross-linking between several types of related allergens is the best way to further investigate this issue. It makes sense to include in the laboratory study a molecular method for the determination of major and minor proteins in the case of the greatest relationship to determine not only a specific allergen as an etiological factor, but also a specific sensitizing protein that is part of them. This is of great importance for subsequent immunotherapy when the removal of only one (major) protein agent can reduce the risk of susceptibility reactions to several types of allergens, Метою роботи було вивчення спектру речовин, що викликають респіраторну сенсибілізованість у дорослих та дітей, які мешкають на території м. Дніпро станом на 2019-ий рік. Матеріал і методи: методом імуноферментного аналізу було досліджено сироватку венозної крові, в якій визначали специфічний IgE до 9 алергенів, що найчастіше зустрічаються у побуті. Застосовувалися набори для кількісного визначення алерген-специфічних IgE від «Vitrotest Specific-IgE, Україна». Проводили алергологічну діагностику для 380 осіб з певними особливостями алергологічного анамнезу при різних видах алергопатології, що звернулися до лабораторії з метою конкретизації етіологічної першопричини свого недугу. Результати. Визначено ступінь гіперчутливості до алергенів та їх здатність до перехресного реагування між собою. Серед алергенів побутової панелі найбільш небезпечними виявились алергени пліснявих грибів, які викликали реакцію сенсибілізації у 292 осіб, що склало 76,8 % від всіх обстежених. До першої трійки (за поширеністю) алергенів побутового спектру ввійшли: епітелій кота, який викликав сенсибілізацію у 125 осіб (32,9 %) та кліщ Derm. Farinae, чутливість до якого встановлена у 117 пацієнтів (30,7 % осіб). Частка неадекватно сильних алергопатологічних реакцій становить третину від усіх обстежених та превалює у людей з сенсибілізацією до алергічних агентів побутової панелі таких, як епітелій кота, кліщ Derm. Farinae та Derm. Pteronyssinus. У 9-12 % осіб встановлена гіперрактивність до грибків роду Candida та плісняви. Розвиток перехресних реакцій мав місце між алергенами епідермального походження: відмічалась підвищена чутливість до шерсті та епітелію собак і котів (r=0,94, P˂0,01), пір’я сільськогосподарських птахів та звичайного таргана (r=0,99, P˂0,01). Висновки. Встановлення перехресних зв’язків між декількома видами споріднених алергенів якнайкраще сприяє подальшому дослідженню даного питання. Має сенс долучити до лабораторного дослідження молекулярний метод із визначення мажорних та мінорних білків у випадку найбільшого взаємозв’язку з метою визначення не лише конкретного алергену як етіологічного фактору, але й конкретного сенсибілізуючого протеїну, що входить до їх складу. Це має велике значення для проведення наступної імунотерапії, коли за усуненням лише одного (мажорного) білкового агенту можливо зменшити ризики виникнення реакцій чутливості для кількох різновидів алергенів

BACKGROUND: Allergic rhinoconjunctivitis is a public health problem. Allergen Immunotherapy is an effective and safe treatment, that modifies the natural course of allergic disease and induces long-term tolerance.OBJECTIVE: To correlate basophil and antibody biomarkers of subcutaneous immunotherapy to clinical outcomes and cellular changes in target tissue.METHODS: Adults suffering from allergic rhinoconjunctivitis due to grass pollen allergy were randomized to receive subcutaneous immunotherapy (n=18) or to an open control group (n=6). Patients reported daily symptom and medication scores and weekly rhinitis related quality of life scores during four pollen seasons. Biomarkers were measured every 3 months for three years treatment and every 6 months in the follow-up year. Nasal and cutaneous allergen challenge tests were performed annually. Leucocyte subsets were assessed in nasal mucosa biopsies at baseline and after treatment.RESULTS: Subcutaneous immunotherapy led to a 447-fold decrease in basophil sensitivity during the first treatment year. This remained hundredfold lower than baseline during the 3 year-treatment period and tenfold lower during the follow-up year (n=18, p=0.03). Decrease in basophil sensitivity after three weeks of treatment predicted long-term improvement in seasonal combined symptom and medication scores (ῥ=-0.69, p=0.0027) during three years of treatment. AUC of IgE blocking factor correlated to nasal allergen challenge (ῥ =0.63, p=0.0012) and SPT (ῥ =0.45, p=0.03). Plasma cell numbers in the nasal mucosa increased during treatment (p=0.02).CONCLUSION: Decrease in basophil sensitivity after three weeks of subcutaneous allergen immunotherapy predicted the clinical outcome of this treatment.

Introduction The measurement of clinically important specific IgE (sIgE) antibody is pivotal for both diagnosis and management of allergy. Two methods may be distinguished depending on the number of antigens tested simultaneously: singleplex and multiplex. BioIC is a multiplex, advanced, automated microfluidic immunoassay system enabling simultaneous sIgE measurement against multiple allergens. ImmunoCAP is a singleplex assay for sIgE detection and gold standard method for diagnosis of allergy. Aim To compare and validate the diagnostic capability of a multiplex sIgE assay – BioIC assay with a singleplex ImmunoCAP assay. Material and methods Using both BioIC assay and ImmunoCAP assay, the sIgE level in serum samples from 20 allergic disease patients with respect to 33 allergens (16 inhalant allergens, 16 food allergens and 1 contact allergen) was measured. Receiver operating characteristic (ROC) area under the curve (AUC), qualitative and semi-quantitative comparisons were performed to compare both sIgE measurement methods using statistical analyses. Results ROC AUC analysis showed similar sensitivity and specificity of BioIC assay and ImmunoCAP assay. In qualitative analysis, the negative and positive agreements were 100% equal for each allergen. Spearman’s rank correlation coefficients identified very high positive correlations between two assays for all tested allergens (p < 0.001). Conclusions The BioIC showed agreement with ImmunoCAP assay. Sensitivity and specificity of both assays are similar, thus they showed similar diagnostic performance. However, careful interpretation of obtained results is necessary in clinical applications because of methodological differences between these two systems.

Background and Objectives: Different types of food introduced gradually in the diet will expose children to different food allergens, increasing the chance of developing allergic diseases. The aim of our study was to determine if allergen-specific IgE values can influence, depending on the diet, the prediction of remission of urticaria in children. Materials and Methods: This prospective study was conducted in 132 patients diagnosed over two years with urticaria, admitted to “Sf. Maria” Clinical Pediatric Hospital Iaşi. Total IgE assay was performed by ELISA, and determination of specific serum IgE by the CLA System Quanti Scan method (Innogenetics, Heiden, Germany). Data were gathered and statistical analysis was performed using statistical software SPSS, using descriptive and inferential statistics. Results: The determination of specific IgE to food allergens was performed on a total of 132 cases. The values of specific IgE were positive for one or more food allergens in 84 patients (63.64%). The most common allergens involved were: cow’s milk in 33.3% cases, egg white in 22.6% cases, and hazelnuts in 11.9% cases. The specific IgE values for the different types of food included in our study had a predictive value for disease remission. Conclusions: The determination of specific IgE confirms the presence of a particular food allergen and may have predictive value for the future development of an allergic manifestation.

Funding Information: This research was supported by Jane & Aatos Erkko Foundation. Non

Equine skin diseases are common, causing increased costs and reduced welfare of affected horses.Genetic testing, if available, can complement early detection, disease diagnosis, and clinical treatment and offers horse breeders the possibility to rule out carrier status. The mechanisms of complex disease can be investigated by using the latest state-of-the-art genomic technologies. Genome-based strategies may also serve as an efficient and cost-effective strategy for the management of the disease severity levels, with particular interest in complex traits such as insect bite hypersensitivity, chronic progressive lymphedema, and melanoma. ispartof: VETERINARY CLINICS OF NORTH AMERICA-EQUINE PRACTICE vol:36 issue:2 pages:323-+ ispartof: location:United States status: published

Background: Allergic rhinitis (AR) is a common disorder. The diagnosis is based on the concordance between allergy sensitization and history. Serum allergen specific immunoglobulin E (sIgE) assessment allows characterization of the relevant sensitizing allergens. Presently, Allergic Rhinitis and its Impact on Asthma (ARIA) classification subdivides AR based on symptoms severity and duration. However, the relationship between sIgE levels and symptom severity is still a matter of debate. Objective: Therefore, this study aimed at relating sIgE levels with symptom severity assessed by ARIA classification in a group of patients with AR. Methods: We enrolled 217 patients with AR (123 women; median age, 39.5 years). The sIgE levels (expressed in kUA/L) to house-dust mite were detected by the fluorescence enzyme immunoassay in peripheral blood samples. The IgE calibrators were traceable to the second international reference preparation 75/502 of human serum IgE from the World Health Organization. Symptom severity was assessed by ARIA classification. Results: We found a significant difference in sIgE levels in patients with mild intermittent versus mild persistent symptoms (p < 0.05), mild intermittent versus moderate-to-severe persistent symptoms (p < 0.001), moderate-to-severe intermittent versus moderate-to-severe persistent symptoms (p < 0.01), and mild persistent versus moderate-to-severe persistent symptoms (p < 0.05). Conclusion: Analysis of these findings indicated that the sIgE level to house-dust mite might be a reliable biomarker for symptom severity in patients with AR. This outcome might be clinically relevant, particularly in candidates for immunotherapy.

Background: The prevalence of asthma is on the rise in Saudi Arabia. Data regarding the immunological profile of asthma in adults in the Aseer region, in southwestern Saudi Arabia, have not been well studied. Objectives: Our aim was to study the immunological factors associated with sensitization to asthma among adults in the Aseer region. Methods: A cross-sectional study with a nested case control design in a 1:1 ratio was conducted on a sample of adults attending primary health care centers in the Aseer region. The study used a validated Arabic version of the International study of asthma and allergies in childhood (ISAAC) questionnaire. The presence of wheezing in the past 12 months was used as a proxy for bronchial asthma. Matched age and sex controls were selected. Both groups were tested for complete blood count (CBC), total and differential white blood cell (WBC) count including eosinophils, total immunoglobulin E (IgE) measurement, allergen-specific immunoglobulin E (IgE), and cytokine levels. Results: The present study included 110 cases and 157 age- and sex-matched controls. Rye wheat was found to be a significant outdoor sensitizing agent ((odds ratio) OR = 5.23, 95% CI: 1.06&ndash, 25.69). Indoors, house dust mites Dermatophagoides petronyssinus (OR = 2.04, 95% CI: 1.04&ndash, 3.99) and Dermatophagoides farinae (OR = 2.50, 95% CI: 1.09&ndash, 5.75) were significant. Higher total IgE (OR = 1.84, 95% CI: 1.10&ndash, 3.06) and eosinophil levels (OR = 2.85, 95% CI: 1.14&ndash, 7.15) were significantly associated with adult bronchial asthma in Aseer. On the other hand, the role of cytokines was not significant. Conclusions: In the present study, certain environmental agents were found to be important with regards to sensitization to bronchial asthma in adults. Knowledge about these sensitization agents should be disseminated to health providers and treating physicians in order to enhance preventive environmental control measures and asthma management. Asthma-treating physicians in the region should be alerted to the use of targeted biological therapies in selected asthmatics with difficult-to-control courses.

Background The pathogenesis of asthma, which is an allergic lung disease, is associated with a variety of allergens such as house dust mite, pollen, and mould, IgE containing serum IgE and allergen-specific-IgE, and inflammatory cytokines including thymus and activation-regulated chemokine (TARC)/CCL17. Because aging is an essential factor in the pathogenesis of asthma, we examined biomarkers related to asthmatic subjects depending on age. Results Physiological indices such as FEV1(forced expiratory capacity in 1 s), FEV1 (% predicted), and FEV1/FVC(forced vital capacity) (%) in asthmatic subjects were lower than those in normal subjects. Total IgE, Der p1 specific IgE, and Der f1 specific IgE were elevated in serum of asthmatics relative to normal individuals. Regulated on activation, normal T cell expressed and secreted (RANTES)/CCL5 in serum and interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein (MCP)-1/CCL2, RANTES, and macrophage inflammatory protein (MIP)-1α/CCL3 in bronchoalveolar lavage fluid (BALF) of asthmatic subjects were higher than in normal individuals. Upon classification of experimental groups depending on age, physiological indices and Der p1-specific IgE (class) were decreased in middle aged adult and elderly adult groups relative to the young adult group. TARC levels in serum were strongly elevated in the elderly adult group relative to the young adult and the middle aged adult groups. TARC in serum was related to total IgE in serum in the elderly adult group. Conclusions Taken together, although TARC in serum and BALF is not different between normal and asthmatic individuals, TARC increases in serum of elderly asthmatic subjects. The level of TARC has a positive effect on the level of IgE in the elderly adult group. These findings may help us better understand the relationship of pathogenesis of allergic diseases and aging. Electronic supplementary material The online version of this article (10.1186/s12979-018-0118-7) contains supplementary material, which is available to authorized users.

Background: Allergy is characterized by allergen-specific IgE production. Molecular-based allergy diagnostic allows to define the precise sensitization profile. Bet v 1 is the major allergen of the PR-10 family. It has been reported that pan-allergens could affect the sensitization panel in adults. Objective: This study aimed to evaluate the impact of Bet v 1 sensitization on clinical presentation in a sample of children with Bet v 1-sensitization; oral allergy syndrome (OAS) or anaphylaxis (ANA) were considered. Methods: Serum IgE molecular components were assessed by ISAC method. Sera and clinical data from 132 children, 91 males (68.94%) and 41 females (31.06%), mean age 9.08 years (3.45 years), were analyzed. Results: Bet v 1-sensitized children were frequently, but not exclusively, sensitized to other molecules belonging to PR-10 family. However, there was no significant difference concerning IgE levels between children with or without food allergy and between children with OAS and ANA, but hazelnut only for generic food allergy. Conclusions: The present study demonstrates that Bet v 1 sensitization may affect the sensitization pattern in children living in Genoa, a Mediterranean city located in a birch-free area, but it is unable to discriminate patients from a clinical point of view. So, ISAC test should be integrated with more precise IgE assay. (www.actabiomedica.it)

Introduction and objective. The association between airborne pollen counts or duration of pollen season and allergy symptoms is not always distinguished. The purpose of this study was to examine the correlation between pollen exposure (annual total pollen quantity and main pollen season length) of selected allergenic plants in the atmosphere of Bratislava, and concentration of allergen-specific immunoglobulin E (sIgE) in serum of patients with seasonal allergy during 2002–2003. Materials and methods. The concentration of pollen was monitored by a Burkard volumetric pollen trap. At the same time, 198 pollen allergic patients were testing to determine the values of sIgE antibodies against selected pollen allergens; a panel of 8 purified allergens was used. Results. The highest percentages of sensitization were detected for Poaceae and [i]Ambrosia[/i] pollen allergens. The most abundant airborne pollen types were Urticaceae, [i]Betula[/i], [i]Populus[/i], Fraxinus, Pinus and Poaceae. The length of the pollen season varied. The longest pollen season was that of the [i]Plantago[/i] – 105 days, and the shortest, [i]Corylus[/i] – 20 days. A significant correlation was found between annual total pollen quantity and median sIgE values, especially in 2002. Conclusions. A strong and significant positive correlation was observed between pollen counts, excluding [i]Betula[/i], and sIgE levels in both analysed years. The correlation was weaker and negative in the case of length of pollen season and sIgE values.

Background Epidemiological evidence indicates that the age at onset of asthma and allergen sensitization in early life is decreasing in people from Western countries. To explore latent trends, we conducted a retrospective examination of the age at onset of asthma and specific IgE antibodies against inhalant allergens in Japanese asthmatic children. Methods We conducted a case series study of 103 consecutive children with atopic type of asthma (aged 2 years to 16 years, mean age 9.4 ± 3.4 years). Diagnoses of asthma and allergic rhinitis were defined according to Japanese guidelines. The onset of asthma and allergic rhinitis was also defined as any report of asthma and allergic rhinitis confirmed by a physician. Allergen sensitization was evaluated as specific serum IgE levels for 9 common inhalant allergens in peripheral blood. Atopic type of asthma was defined as a being positive for at least one aeroallergen. Results Mean age at asthma onset was 2.3 ± 1.9 years, which is slightly lower than that of previous reports, including those published in Japan. A high prevalence rate of up to 80% was found for perennial antigens including Dermatophagoides spp. and house dust, as reported previously. Notably, some of the children aged at 1 year tested positive for these allergens. Conclusions The age at onset of asthma seems to be decreasing in comparison with previous reports. Furthermore, the age at onset of allergen sensitization against inhalant allergens appears to follow this trend.

Background/PurposeEnvironmental factors, different ages, and detection methods might affect the profiles of allergy sensitization and confound the diagnosis of allergic diseases. The purpose of this study was to investigate the different profiles of allergen sensitization in different ages, geographic areas, and detection methods.MethodsWe analyzed the patients who received allergen sensitization tests by the automated microfluidic-based immunoassay system (BioIC) method at Show Chwan Memorial Hospital in Changhua City and at Chang Bing Show Chwan Hospital in Lu-gang from January 2011 to December 2011. Results were compared in different ages (3–6, 7–18, and ≥19), different geographic areas, and different detection methods and analyzed by Chi-square or Fisher exact test depending on sample size.ResultsA total of 1145 patients were analyzed. The younger the age, the higher the food allergy sensitization rate is found (26.6% vs. 14.7% vs.11.1% p

Background The prevalence of Japanese cedar (JC) pollinosis in Japanese children is increasing. However, few studies have reported the relationship between pollen count levels and the prevalence of pollinosis. To evaluate the relationship between JC pollen count levels and the prevalence of pollinosis in children, we investigated the sensitization and development of symptoms for JC pollen in two areas of Akita in northeast Japan with contrasting levels of exposure to JC pollen. Methods The study population consisted of 339 elementary school students (10–11 years of age) from the coastal and mountainous areas of Akita in 2005–2006. A questionnaire about symptoms of allergic rhinitis was filled out by the students’ parents. A blood sample was taken to determine specific IgE antibodies against five common aeroallergens. Results The mean pollen count in the mountainous areas was two times higher than that in the coastal areas in 1996–2006. The prevalence rates of nasal allergy symptoms and sensitization for mites were almost the same in both areas. On the other hand, the rates of nasal allergy symptoms and sensitization for JC pollen were significantly higher in the mountainous areas than in the coastal areas. The rate of the development of symptoms among children sensitized for JC pollen was almost the same in both areas. Conclusions These results suggest that pollen count levels may correlate with the rate of sensitization for JC pollinosis, but may not affect the rate of onset among sensitized children in northeast Japan.

Objectives The aim of this study was to determine associations between lung function, bronchial hyperresponsiveness (BHR), and atopy with exposure to fire smoke among firefighters.Methods The study was comprised of 402 firefighters, a randomly chosen subset of a previous survey among firefighters in the Netherlands. Subjects underwent spirometry and methacholine provocation, and blood samples were taken to assess atopy. Exposure to fire smoke was registered by a questionnaire.Results Hyperresponsiveness expressed as dose-response slope (DRS) was positively and significantly associated with the number of fires fought in the last 12 months with and without adjustments for smoking, gender, atopy, age, and exposure in the main job held. Limiting the analysis to firefighters without exposure within 7 days of testing did not change any of the associations. The association between the number of fires and the DRS was stronger among atopics, and hyperresponsiveness expressed as PD(20) was also significantly associated, indicating that atopics are at higher risk of developing BHR as a result of smoke exposure. Respiratory protection devices were not optimally used.Conclusions It is recommended that awareness be heightened among firefighters to avoid exposure to all fire smoke and that management be sensitive to the adequate use of sell-contained breathing apparatuses by their personnel.

Background In studies on allergies in mouse models, IgE production is an essential parameter to be evaluated. Here, we examine the effect of commercially available immunoreaction enhancer solutions and different blocking reagents in enzyme-linked immunosorbent assay (ELISA) for total or antigen-specific murine IgE in order to improve the assays. Methods Sera from mice immunized with recombinant house dust mite major allergens, Der f 1 and Der p 1, were used for the assays. Total IgE was measured by sandwich ELISA using monoclonal antibodies against murine IgE. Antigen-specific IgE was assayed using allergen-coated plates. Sensitivity or signal intensity in ELISA was compared among conditions differing in the use of enhancer solutions, blocking reagents, or monoclonal antibodies, and incubation time. Results Use of enhancer solutions improved the sensitivity of ELISA for total IgE by approximately 30-fold of that using a conventional buffer. A blocking reagent caused more unwanted enhancement of the background signal in blank wells in ELISA for total IgE compared with another blocking reagent, however, improved signal intensity in ELISA for antigen-specific ELISA without significant enhancement of the background signal. Optimal assay conditions were determined. Conclusions Enhancer solutions are effective in improving ELISAs for total and antigen-specific murine IgE. Selection of blocking reagents was important to decrease unwanted enhancement of background signals and was effective in enhancing signals for positive samples. The ELISAs improved in this study are useful for the study of allergies in mouse models.

Background An important portion of asthmatics do not respond to current therapies. Thus, the need for new therapeutic drugs is urgent. We have demonstrated a critical role for PARP in experimental asthma. Olaparib, a PARP inhibitor, was recently introduced in clinical trials against cancer. The objective of the present study was to examine the efficacy of olaparib in blocking established allergic airway inflammation and hyperresponsiveness similar to those observed in human asthma in animal models of the disease. Methods We used ovalbumin (OVA)-based mouse models of asthma and primary CD4+ T cells. C57BL/6J WT or PARP-1−/− mice were subjected to OVA sensitization followed by a single or multiple challenges to aerosolized OVA or left unchallenged. WT mice were administered, i.p., 1 mg/kg, 5 or 10 mg/kg of olaparib or saline 30 min after each OVA challenge. Results Administration of olaparib in mice 30 min post-challenge promoted a robust reduction in airway eosinophilia, mucus production and hyperresponsiveness even after repeated challenges with ovalbumin. The protective effects of olaparib were linked to a suppression of Th2 cytokines eotaxin, IL-4, IL-5, IL-6, IL-13, and M-CSF, and ovalbumin-specific IgE with an increase in the Th1 cytokine IFN-γ. These traits were associated with a decrease in splenic CD4+ T cells and concomitant increase in T-regulatory cells. The aforementioned traits conferred by olaparib administration were consistent with those observed in OVA-challenged PARP-1−/− mice. Adoptive transfer of Th2-skewed OT-II-WT CD4+ T cells reversed the Th2 cytokines IL-4, IL-5, and IL-10, the chemokine GM-CSF, the Th1 cytokines IL-2 and IFN-γ, and ovalbumin-specific IgE production in ovalbumin-challenged PARP-1−/−mice suggesting a role for PARP-1 in CD4+ T but not B cells. In ex vivo studies, PARP inhibition by olaparib or PARP-1 gene knockout markedly reduced CD3/CD28-stimulated gata-3 and il4 expression in Th2-skewed CD4+ T cells while causing a moderate elevation in t-bet and ifn-γ expression in Th1-skewed CD4+ T cells. Conclusions Our findings show the potential of PARP inhibition as a viable therapeutic strategy and olaparib as a likely candidate to be tested in human asthma clinical trials.

Many explanations have been put forward for the rapidly increasing prevalence of allergies, asthma and other chronic inflammatory disorders especially in developed countries 1–3, including the influence of the living environment (rural vs urban, farm vs nonfarm) 4–6, change of diet 7, increased air pollution 8, reduced infections 9 and parasite exposure 10, and increased use of antibiotics 11. Several explanations can be regarded as versions of the ‘hygiene hypothesis’ 10,12–14 or the ‘old friends hypothesis’ 3,15: changes of environment and lifestyle in industrialized countries have reduced the infectious/parasitic burden and exposure to environmental microbes, which may now be insufficient to induce a robust anti-inflammatory regulatory network in the developing immune system 16. The immunomodulatory role of saprophytic bacteria in the soil and vegetation is increasingly recognized 3,10,14,17,18, and the disruption of the ancient connection of humankind with soil may have significant consequences 3,16. Based on this observation and considerations of other possible environmental influences, the hygiene and old friends hypotheses have been extended to the ‘biodiversity hypothesis’, with a focus on childhood exposure to diverse natural environments with diverse macrobiota and microbiota 3,17,19. Here, we test the biodiversity hypothesis by analysing the relationship between land use around the homes of study subjects, as a measure of environmental biodiversity, and atopic sensitization (atopy) in four cohorts of children aged 0.5–20 years. We observe a strong relationship between the proportion of forest and agricultural land around the home and atopy in children older than 6 years, with prevalence exceeding 30%. The relative abundance of Proteobacteria increased significantly on the skin of healthy individuals along the gradient from built to green environments, suggesting an influence of the environmental microbiota on the human commensal microbiota, which may be related to or reflects the mechanisms by which the habitat gradient influences atopic sensitization.

We developed an in vitro system to diagnose allergy using an allergen microarray and photo-immobilization technique. Photo-immobilization is useful for preparing the allergen microarray because it does not require specific functional groups of the allergen and because any organic material can be immobilized by a radical reaction induced by photo-irradiation. To prepare the plates, allergen solutions were mixed with polymer and a bis- azidophenyl derivative, a photo-reactive cross-linker, the mixtures were micro-spotted on the plate, and the droplets were dried. The plate was irradiated with an ultraviolet lamp for immobilization. For the assay, human serum was added to the microarray plate. Allergen-specific immunoglobulin E (IgE) adsorbed on the micro- spotted allergen was detected by peroxidase-conjugated anti-IgE antibody. The chemiluminescence intensities of the substrate decomposed by the peroxidase were detected with a sensitive CCD camera. All allergens were immobilized by this method and used to screen allergen-specific IgE.

Paper I, II and III of this thesis are not available in Munin: I. Hansen TE, Evjenth B, Holt J.: ‘Increasing prevalence of asthma, allergic rhinoconjunctivitis and eczema among schoolchildren: Three surveys during the period 1985-2008’. Acta Paediatr 2013;102:47-52. Available at http://dx.doi.org/10.1111/apa.12030 II. Evjenth B, Hansen TE, Holt J.: ‘Exhaled nitric oxide decreases during exercise in non-asthmatic children’. Clin Respir J 2013;7:121-127. Available at http://dx.doi.org/10.1164/ajrccm.161.3.9905043 III. Evjenth B, Hansen TE, Holt J. The effect of exercise on exhaled nitric oxide depends on allergic rhinoconjunctivitis in children. (Manuscript). Astma og allergisk øye- og nesekatarr (rhinokonjunktivitt, AR) er de vanligste kroniske sykdommene blant barn i den vestlige verden. I de siste tiårene har prevalensen (forekomsten) av sykdommene økt betydelig, men i enkelte Europeiske land rapporteres det om en utflating i prevalensen av astma. I klinisk praksis brukes laboratorietester til å understøtte diagnosene astma og AR. Analyser av biologiske markører i utåndingsluften kan gi verdifull informasjon om betennelsesmekanismer i luftveiene. Fraksjonen av ekshalert nitrogenoksid (FENO) er den eneste av disse markørene som er standardisert for bruk innen barnemedisin. FENO er en markør på eosinofil betennelse i nedre luftveier. FENO er omfattende studert, men hvilken effekt anstrengelsestester har på FENO hos barn er ikke fullstendig belyst. Diagnostikk av allergisk astma og AR inkluderer påvisning av allergen-spesifikt immunglobulin E (sIgE). Lite data er publisert om sammenhengen mellom nivåer av serum sIgE målt med Siemens IMMULITE® 2000 system (IMMULITE®) og hud prikk test (SPT) resultater hos barn. Det er ikke etablert kliniske grenseverdier for serum sIgE målt med IMMULITE® for å diagnostisere AR hos barn. Formålene med studien var å undersøke prevalensen av astma, AR og eksem blant barn i en subarktisk befolkning, å kartlegge FENO nivåer i relasjon til astma og AR samt og undersøke effekten av anstrengelse på FENO. Likeledes ønsket vi å etablere kliniske grensenivåer for serum sIgE for å diagnostisere AR hos barn samt å utforske relasjonen mellom serum sIgE, total IgE og FENO. Avhandlingen er basert på data fra fase I og fase II i studien `Astma og allergi blant skolebarn i Nordland`. Fase I var en tverrsnittstudie basert på et spørreskjema. Skolebarn (n=4150) i alderen 7-14 år fra 65 tilfeldige utvalgte skoler i Nordland fylke ble inkludert i denne undersøkelsen. Prevalensrater fra 2008 ble sammenlignet med data fra 1985 og 1995. Fase II var en klinisk undersøkelse av 801 skolebarn, rekruttert fra fase I. Foreldene besvarte et spørreskjema og et strukturert intervju. Videre ble det utført en klinisk undersøkelse, FENO målinger, spirometri, anstrengelsestest samt SPT og blodprøver. Resultater fra fase I viste at prevalensen av astma, AR og eksem det siste året var 2-3 doblet fra 1995 til 2008. Livstidsprevalensen av astma og AR økte mens prevalensen av eksem, etter en økning mellom 1985 og 1995, var uendret i siste periode. Resultater fra fase II viste at FENO nivåene var signifikant økt blant astmatiske barn sammenlignet med ikke-astmatiske barn, og signifikant høyere blant astmatiske og ikke-astmatiske barn med AR sammenlignet med barn uten AR. Barn med allergisk astma hadde de høyeste FENO verdiene. Ett minutt etter en submaksimal anstrengelsestest var FENO redusert hos både astmatiske og ikke astmatiske barn. FENO var ikke tilbake til utgangsnivået etter 30 min. Barn med AR viste større reduksjon i absolutt FENO verdi (parts per billion) enn barn uten AR, uavhengig av astma. Imidlertid var effekten av anstrengelse, målt som % endring i Ln (naturlig log) FENO størst hos barn uten AR. Analyser av `Receiver operating characteristic` (ROC) kurver viste at IMMULITE® har generelt god nøyaktighet. Serum sIgE predikerte AR til allergenene pollen, dyr og husstøvmidd. For disse allergenene var sIgE cut-off nivåer med den beste kombinasjon av sensitivitet og spesifisitet høyere enn deteksjonsgrensen for IMMULITE® (0.23-1.1 kU/L). Serum sIgE for Alternaria tenius, Cladosporium herbarium og kakerlakk kunne imidlertid ikke predikere AR. Blant barn med AR, fant vi en positiv korrelasjon mellom FENO og serum total IgE samt sIgE mot katt og hund, men ikke til de andre testede allergenene. Vi konkluderer med at prevalensen av astma, AR og eksem siste året økte betydelig mellom 1995 og 2008. Livstidsprevalensen for astma og AR økte fra 1985 til 2008 mens livstids-prevalensen for eksem nådde et platå. Videre har astmatiske og ikke-astmatiske barn med AR høyere FENO enn barn uten AR. FENO reduseres signifikant etter en standardisert anstrengelsestest og er ikke tilbake til utgangsverdi etter 30 min. Derfor kan FENO verdier bli underestimert hvis barn er fysisk aktiv før FENO målinger. Dette er mest uttalt blant barn med AR som har de høyeste utgangsverdiene og det største fallet i FENO verdier etter anstrengelse. Serum sIgE cut-off verdier for å diagnostisere AR er avhengig av den allergiske fenotypen. Blant sju av de ti testede allergenene var sIgE cut-off verdiene over IMMULITE® sin deteksjonsgrense. Dersom man bruker deteksjonsgrensen for sIgE som beslutningspunkt for å diagnostisere AR så vil dette bidra til å over-diagnostisere AR. Asthma and allergic rhinoconjunctivitis (AR) are the commonest chronic diseases in children in the Western world. During the past decades, the prevalences of these diseases have increased: those of asthma and AR vary greatly, and recent reports indicate a levelling off for asthma in some European countries. In clinical practice, the diagnosis of asthma and AR are supported by laboratory tests. Analyses of exhaled breath biomarkers have been assessed to uncover pathological mechanisms of airway inflammation. Fractional exhaled nitric oxide (FENO) is the only exhaled biomarker that has been standardized for clinical paediatric application. FENO is a marker of eosinophilic airway inflammation and is extensively studied, although the impact of exercise on its release is not fully elucidated. Furthermore, the diagnosis of allergic airway diseases involves confirming sensitization by detecting allergen-specific immunoglobulin E (sIgE). Little comparative data have been available for sIgE testing using the Siemens IMMULITE® 2000 system (IMMULITE®) and skin prick test (SPT) results in children. Paediatric cut-off values for serum sIgE using IMMULITE® to diagnose AR have not been determined. The aims of the study were to investigate the following: the prevalences and time trends of asthma, AR and eczema in a subarctic childhood population, the FENO levels in relation to asthma and AR, and the impact of exercise on FENO. Likewise, it was an aim to establish paediatric serum sIgE cut-off values for diagnosing AR and to explore the relationship between serum sIgE, total IgE and FENO. This thesis is based on data from Phase I and Phase II of the study `Asthma and allergy among schoolchildren in Nordland`. Phase I was a cross-sectional questionnaire-based survey and included 4150 schoolchildren aged 7-14 years from 65 randomly selected schools in Nordland County. Prevalence rates of asthma, AR and eczema in 2008 were compared with results from 1985 and 1995. Phase II was a clinical investigation of 801 schoolchildren recruited during Phase I. The parents completed a questionnaire and a structured interview. FENO measurements, spirometry, an exercise challenge test, SPT and blood sampling were performed. The Phase I survey revealed that the prevalence of current asthma, AR and eczema doubled and trebled between 1995 and 2008. The prevalence of asthma and AR ever increased between 1985 and 2008, while the prevalence of eczema ever, after an increase between 1985 and 1995, remained unchanged in the last period. In Phase II of the study, we found that the FENO level was significantly increased in asthmatics compared to non-asthmatics, and was significantly elevated in asthmatics and non-asthmatics with AR compared to individuals without AR. The highest FENO values were found in children with current allergic asthma. FENO decreased significantly in non-asthmatic and asthmatic children after a submaximal exercise test, and did not return to baseline value within 30 min. Children with AR demonstrated a significantly greater reduction in FENO value (parts per billion) than children without AR, irrespective of asthma. Although, the effect of heavy exercise (% change in natural log FENO) was more pronounced in subjects without AR. Receiver operating characteristic (ROC) analysis demonstrated that the overall accuracy of IMMULITE® was good. Serum sIgE predicted AR to the tested pollen, animal and house dust mite allergens. sIgE cut-off values with the best combined sensitivity and specificity were above the detection limit of IMMULITE® for these allergens (0.23-1.1 kU/L). The sIgEs for Alternaria tenius, Cladosporium herbarium and German cockroach were not significant predictors of AR. In children with AR, positive correlations were found between FENO and serum total IgE, sIgE to cat and dog but not to the other tested allergens. In conclusion, the prevalence of current asthma, AR and eczema in schoolchildren increased considerably between 1995 and 2008. The prevalence of asthma and AR ever increased between 1985 and 2008, while the prevalence of eczema ever reached a plateau. Non-asthmatic and asthmatic children with AR expressed higher FENO values than children without AR. FENO decreased in all children after a submaximal exercise challenge and did not return to baseline level within 30 min. Hence, if children are physically active before FENO measurements, FENO values could be underestimated. This is especially pronounced in children with AR who have the highest baseline FENO and the largest decline in FENO value. Cut-off values for diagnosing AR using serum sIgE were dependent on the allergic phenotype and were above the IMMULITE® detection limit for seven of ten inhalant allergens. Consequently, using the detection limit for serum sIgE as the decision point would result in over-diagnosing AR.

Texto completo. Acesso restrito. p. 60-72 Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-07-09T17:53:43Z No. of bitstreams: 1 444444444444444.pdf: 160267 bytes, checksum: ade2601295df2ca3de4d639cc82e69b0 (MD5) Made available in DSpace on 2013-07-09T17:53:43Z (GMT). No. of bitstreams: 1 444444444444444.pdf: 160267 bytes, checksum: ade2601295df2ca3de4d639cc82e69b0 (MD5) Previous issue date: 2013 Background Most childhood asthma in poor populations in Latin America is not associated with aeroallergen sensitization, an observation that could be explained by the attenuation of atopy by chronic helminth infections or effects of age. Objective To explore the effects of geohelminth infections and age on atopy, wheeze, and the association between atopy and wheeze. Methods A case-control study was done in 376 subjects (149 cases and 227 controls) aged 7–19 years living in rural communities in Ecuador. Wheeze cases, identified from a large cross-sectional survey, had recent wheeze and controls were a random sample of those without wheeze. Atopy was measured by the presence of allergen-specific IgE (asIgE) and skin prick test (SPT) responses to house dust mite and cockroach. Geohelminth infections were measured in stools and anti-Ascaris IgE in plasma. Results The fraction of recent wheeze attributable to anti-Ascaris IgE was 45.9%, while those for SPT and asIgE were 10.0% and 10.5% respectively. The association between atopy and wheeze was greater in adolescents than children. Although Anti-Ascaris IgE was strongly associated with wheeze (adj. OR 2.24 (95% CI 1.33–3.78, P = 0.003) and with asIgE (adj. OR 5.34, 95% CI 2.49–11.45, P < 0.001), the association with wheeze was independent of asIgE. There was some evidence that the association between atopy and wheeze was greater in uninfected subjects compared with those with active geohelminth infections. Conclusions and clinical relevance Atopy to house dust mite and cockroach explained few wheeze cases in our study population, while the presence of anti-Ascaris IgE was an important risk factor. Our data provided only limited evidence that active geohelminth infections attenuated the association between atopy and wheeze in endemic areas or that age modified this association. The role of allergic sensitization to Ascaris in the development of wheeze, independent of atopy, requires further investigation. Salvador

Background Most childhood asthma in poor populations in Latin America is not associated with aeroallergen sensitization, an observation that could be explained by the attenuation of atopy by chronic helminth infections or effects of age. Objective To explore the effects of geohelminth infections and age on atopy, wheeze, and the association between atopy and wheeze. Methods A case-control study was done in 376 subjects (149 cases and 227 controls) aged 7–19 years living in rural communities in Ecuador. Wheeze cases, identified from a large cross-sectional survey, had recent wheeze and controls were a random sample of those without wheeze. Atopy was measured by the presence of allergen-specific IgE (asIgE) and skin prick test (SPT) responses to house dust mite and cockroach. Geohelminth infections were measured in stools and anti-Ascaris IgE in plasma. Results The fraction of recent wheeze attributable to anti-Ascaris IgE was 45.9%, while those for SPT and asIgE were 10.0% and 10.5% respectively. The association between atopy and wheeze was greater in adolescents than children. Although Anti-Ascaris IgE was strongly associated with wheeze (adj. OR 2.24 (95% CI 1.33–3.78, P = 0.003) and with asIgE (adj. OR 5.34, 95% CI 2.49–11.45, P < 0.001), the association with wheeze was independent of asIgE. There was some evidence that the association between atopy and wheeze was greater in uninfected subjects compared with those with active geohelminth infections. Conclusions and clinical relevance Atopy to house dust mite and cockroach explained few wheeze cases in our study population, while the presence of anti-Ascaris IgE was an important risk factor. Our data provided only limited evidence that active geohelminth infections attenuated the association between atopy and wheeze in endemic areas or that age modified this association. The role of allergic sensitization to Ascaris in the development of wheeze, independent of atopy, requires further investigation.

Submitted by Maria Creuza Silva (mariakreuza@yahoo.com.br) on 2012-11-03T04:25:17Z No. of bitstreams: 1 The efect Per Intern 2012.pdf: 151918 bytes, checksum: 3cb35f6f28103a45dc6d2792a7313309 (MD5) Made available in DSpace on 2012-11-03T04:25:17Z (GMT). No. of bitstreams: 1 The efect Per Intern 2012.pdf: 151918 bytes, checksum: 3cb35f6f28103a45dc6d2792a7313309 (MD5) Previous issue date: 2012-02 Background: The current epidemic of asthma and atopy has been explained by alterations in immune responses related to reduction in childhood infections. However, the findings of epidemiologic studies investigating the association between infection with atopy and asthma have been inconsistent. Objective: We sought to investigate the effect of single or multiple infections (pathogen burden) on atopy and wheeze in urban children from Latin America. Methods: Specific IgE against aeroallergens (sIgE) and skin prick test (SPT) reactivity for the most common local allergens were measured in 1128 children aged 4 to 11 years. Data on wheezing and potential confounders were collected by questionnaire. Infections by 8 pathogens were assessed by using serology and stool examination. Associations of wheeze and atopic outcomes with single and multiple infections were analyzed by means of logistic regression. Results: Negative results for Toxoplasma gondii were associated with a higher prevalence of sIgE (>0.70 kU/L), whereas negative results for Ascaris lumbricoides, T gondii, erpes simplex virus, and EV were associated with a higher prevalence of SPT reactivity. Children with 3 or fewer infection markers had a higher prevalence of sIgE and SPT rectivity compared with those with 4 or more infection markers. However, isolated infections or pathogen burden were not associated with the prevalence of atopic or nonatopic wheeze. Conclusion: The findings provide support for the idea that the hygiene hypothesis is operating in an urban Latin American context, but its expression is thus far restricted to the atopic status of patients and not the perceived asthma symptoms. Canadá

Texto completo: acesso restrito. p. 359–367 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-08-25T14:49:23Z No. of bitstreams: 1 Neuza Maria Alcantara Neves.pdf: 151918 bytes, checksum: 3cb35f6f28103a45dc6d2792a7313309 (MD5) Approved for entry into archive by Patricia Barroso (pbarroso@ufba.br) on 2014-08-25T17:33:59Z (GMT) No. of bitstreams: 1 Neuza Maria Alcantara Neves.pdf: 151918 bytes, checksum: 3cb35f6f28103a45dc6d2792a7313309 (MD5) Made available in DSpace on 2014-08-25T17:33:59Z (GMT). No. of bitstreams: 1 Neuza Maria Alcantara Neves.pdf: 151918 bytes, checksum: 3cb35f6f28103a45dc6d2792a7313309 (MD5) Previous issue date: 2012 Background The current epidemic of asthma and atopy has been explained by alterations in immune responses related to reduction in childhood infections. However, the findings of epidemiologic studies investigating the association between infection with atopy and asthma have been inconsistent. Objective We sought to investigate the effect of single or multiple infections (pathogen burden) on atopy and wheeze in urban children from Latin America. Methods Specific IgE against aeroallergens (sIgE) and skin prick test (SPT) reactivity for the most common local allergens were measured in 1128 children aged 4 to 11 years. Data on wheezing and potential confounders were collected by questionnaire. Infections by 8 pathogens were assessed by using serology and stool examination. Associations of wheeze and atopic outcomes with single and multiple infections were analyzed by means of logistic regression. Results Negative results for Toxoplasma gondii were associated with a higher prevalence of sIgE (≥0.70 kU/L), whereas negative results for Ascaris lumbricoides, T gondii, herpes simplex virus, and EBV were associated with a higher prevalence of SPT reactivity. Children with 3 or fewer infection markers had a higher prevalence of sIgE and SPT reactivity compared with those with 4 or more infection markers. However, isolated infections or pathogen burden were not associated with the prevalence of atopic or nonatopic wheeze. Conclusion The findings provide support for the idea that the hygiene hypothesis is operating in an urban Latin American context, but its expression is thus far restricted to the atopic status of patients and not the perceived asthma symptoms.

Background An in vitro elicitation test employing human high-affinity IgE receptor-expressing rat mast cell lines appears to be a useful method for measuring mast cell activation using a patient's IgE and an allergen; however, such cell lines are sensitive to human complements in the serum. We have recently developed a new luciferase-reporting mast cell line (RS-ATL8) to detect IgE crosslinking-induced luciferase expression (EXiLE) with relatively low quantities of serum IgE. Methods A total of 30 patients suspected of having egg white (EW) allergy were subjected to an oral food challenge (OFC) test; then, the performances of EW-specific serum IgE (CAP-FEIA), EW-induced degranulation, and EXiLE responses in RS-ATL8 cells were compared using receiver-operating characteristic (ROC) curve analysis. The patients' sera were diluted to 1:100, which causes no cytotoxicity when sensitizing the RS-ATL8 cells for the degranulation and EXiLE tests. Results The area under the ROC curves was highest in the EXiLE test (0.977), followed by CAP-FEIA (0.926) and degranulation (0.810). At an optimal cutoff range (1.648-1.876) calculated from the ROC curve of the EXiLE test, sensitivity and specificity were 0.944 and 0.917, respectively. A 95% positive predictive value was given at a cutoff level of 2.054 (fold increase in luciferase expression) by logistic regression analysis. Conclusions: In contrast to in vivo tests, the EXiLE test appears to be a useful tool in diagnosing patients suspected of having IgE-dependent EW allergy without the risk of severe systemic reactions.

BACKGROUND: Epidemiological evidence indicates that atopic asthma correlates with high serum IgE levels though the contribution of allergen specific IgE to the pathogenesis and the severity of the disease is still unclear. METHODS: We developed a microarray immunoassay containing 103 allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals belonging to families whose members have a documented history of asthma and atopy. We employed k-means clustering, to investigate whether a particular IgE reactivity profile correlated with asthma and other atopic conditions such as rhinitis, conjunctivitis and eczema. RESULTS: Both case-control and parent-to-siblings analyses demonstrated that while the presence of specific IgE against individual allergens correlated poorly with pathological conditions, particular reactivity profiles were significantly associated with asthma (p

p. 1-157 Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-04-24T21:12:07Z No. of bitstreams: 1 22222222222tttt.pdf: 2420212 bytes, checksum: d208a267b6fe5b14ae33b31fc9319a4a (MD5) Approved for entry into archive by Maria Creuza Silva(mariakreuza@yahoo.com.br) on 2013-05-04T17:08:10Z (GMT) No. of bitstreams: 1 22222222222tttt.pdf: 2420212 bytes, checksum: d208a267b6fe5b14ae33b31fc9319a4a (MD5) Made available in DSpace on 2013-05-04T17:08:10Z (GMT). No. of bitstreams: 1 22222222222tttt.pdf: 2420212 bytes, checksum: d208a267b6fe5b14ae33b31fc9319a4a (MD5) Previous issue date: 2011 O objetivo deste estudo foi investigar a influência de fatores ambientais, antropométricos e de estilo de vida em asma e atopia em uma área rural do Equador. Foi conduzido um estudo transversal, a partir do qual foram identificadas crianças e adolescentes, com e sem chiado no peito no ultimo ano, para serem incluídas no estudo caso-controle. Inicialmente, um estudo exploratório foi realizado para identificar se diferentes fatores (sócioeconômicos, ambientais, famíliares, estilo de vida, infecção por helmintos) estariam associados com sibilo atópico e não-atópico na área rural. Os resultados mostraram que sibilo não-atópico foi o fenótipo mais comum nesta área, e foi observado um padrão diferente de fatores de risco para sibilância atópica e não-atópica, o que pode sugerir que diferentes mecanismos podem estar envolvidos. Vários estudos nas áreas rurais e urbanas pobres na América Latina têm reportado que a asma não é atribuída a atopia. Da mesma forma, uma dissociação entre a IgE específica e reatividade ao teste cutâneo tem sido observada. Assim, testamos a hipótese de que na nossa população, infecções por helmintos, poderiam estar modificando estas associações. Os resultados mostram uma relação complexa entre helmintos, asma e atopia. Notou-se que a associação entre os marcadores de atopia foi mais débil nos indivíduos com presença de sensibilização para Ascaris, e a associação entre o teste cutâneo e sibilo, foi atenuada em indivíduos com infecção ativa com Ascaris e / ou Trichuris. Adicionalmente a IgE anti-Ascaris, mas não infecção ativa, incrementou o risco de sibilo, independentemente de IgE específica a alérgenos. Finalmente, uma nova hipótese sugere que a adoção de novos estilos de vida estaria conduzindo a um aumento da asma e atopia. Assim, estudou-se excesso de peso, por ser considerado um marcador de recentes mudanças nos padrões de vida e que, por sua vez, estaria associado com asma e atopia. A presença de teste cutâneo e IgE específica a alérgenos foi de 1,85 e 2,20 vezes maior em crianças com excesso de peso do que em crianças eutróficas/déficit, respectivamente. No entanto, o efeito em sibilo foi decorrente de um mecanismo não-atópico. Embora esses resultados precisem ser confirmados por estudos longitudinais, certamente contribuirão para uma melhor compreensão dos mecanismos da asma não-atopica nas aéreas rurais, que tem sido muito pouco compreendidos. Salvador

p. 1-157 Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-04-24T21:12:07Z No. of bitstreams: 1 22222222222tttt.pdf: 2420212 bytes, checksum: d208a267b6fe5b14ae33b31fc9319a4a (MD5) Approved for entry into archive by Maria Creuza Silva(mariakreuza@yahoo.com.br) on 2013-05-04T17:08:10Z (GMT) No. of bitstreams: 1 22222222222tttt.pdf: 2420212 bytes, checksum: d208a267b6fe5b14ae33b31fc9319a4a (MD5) Made available in DSpace on 2013-05-04T17:08:10Z (GMT). No. of bitstreams: 1 22222222222tttt.pdf: 2420212 bytes, checksum: d208a267b6fe5b14ae33b31fc9319a4a (MD5) Previous issue date: 2011 O objetivo deste estudo foi investigar a influência de fatores ambientais, antropométricos e de estilo de vida em asma e atopia em uma área rural do Equador. Foi conduzido um estudo transversal, a partir do qual foram identificadas crianças e adolescentes, com e sem chiado no peito no ultimo ano, para serem incluídas no estudo caso-controle. Inicialmente, um estudo exploratório foi realizado para identificar se diferentes fatores (sócioeconômicos, ambientais, famíliares, estilo de vida, infecção por helmintos) estariam associados com sibilo atópico e não-atópico na área rural. Os resultados mostraram que sibilo não-atópico foi o fenótipo mais comum nesta área, e foi observado um padrão diferente de fatores de risco para sibilância atópica e não-atópica, o que pode sugerir que diferentes mecanismos podem estar envolvidos. Vários estudos nas áreas rurais e urbanas pobres na América Latina têm reportado que a asma não é atribuída a atopia. Da mesma forma, uma dissociação entre a IgE específica e reatividade ao teste cutâneo tem sido observada. Assim, testamos a hipótese de que na nossa população, infecções por helmintos, poderiam estar modificando estas associações. Os resultados mostram uma relação complexa entre helmintos, asma e atopia. Notou-se que a associação entre os marcadores de atopia foi mais débil nos indivíduos com presença de sensibilização para Ascaris, e a associação entre o teste cutâneo e sibilo, foi atenuada em indivíduos com infecção ativa com Ascaris e / ou Trichuris. Adicionalmente a IgE anti-Ascaris, mas não infecção ativa, incrementou o risco de sibilo, independentemente de IgE específica a alérgenos. Finalmente, uma nova hipótese sugere que a adoção de novos estilos de vida estaria conduzindo a um aumento da asma e atopia. Assim, estudou-se excesso de peso, por ser considerado um marcador de recentes mudanças nos padrões de vida e que, por sua vez, estaria associado com asma e atopia. A presença de teste cutâneo e IgE específica a alérgenos foi de 1,85 e 2,20 vezes maior em crianças com excesso de peso do que em crianças eutróficas/déficit, respectivamente. No entanto, o efeito em sibilo foi decorrente de um mecanismo não-atópico. Embora esses resultados precisem ser confirmados por estudos longitudinais, certamente contribuirão para uma melhor compreensão dos mecanismos da asma não-atopica nas aéreas rurais, que tem sido muito pouco compreendidos. Salvador

No Abstract##.