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Background: Infection with rhinovirus (RV) is a major risk factor for disease exacerbations in patients with allergic asthma. This study analysed a broad set of cytokines in the noses of children and adults with asthma during RV infection in order to identify immunophenotypes that may link to virus-induced episodes., Methods: Nasal wash specimens were analysed in children (n = 279 [healthy, n = 125; stable asthma, n = 64; wheeze, n = 90], ages 2-12) who presented to a hospital emergency department, and in adults (n = 44 [healthy, n = 13; asthma, n = 31], ages 18-38) who were experimentally infected with RV, including a subset who received anti-IgE. Cytokines were measured by multiplex bead assay and data analysed by univariate and multivariate methods to test relationships to viral load, allergic status, airway inflammation, and clinical outcomes., Results: Analysis of a core set of 7 cytokines (IL-6, CXCL8/IL-8, IL-15, EGF, G-CSF, CXCL10/IP-10 and CCL22/MDC) revealed higher levels in children with acute wheeze versus those with stable asthma or controls. Multivariate analysis identified two clusters that were enriched for acutely wheezing children; one displaying high viral load ("RV-high") with robust secretion of CXCL10, and the other displaying high IgE with elevated EGF, CXCL8 and both eosinophil- and neutrophil-derived mediators. Broader assessment of 39 cytokines confirmed that children with acute wheeze were not deficient in type 1 anti-viral responses. Analysis of 18 nasal cytokines in adults with asthma who received RV challenge identified two clusters; one that was "RV-high" and linked to robust induction of anti-viral cytokines and anti-IgE; and the other associated with more severe symptoms and a higher inflammatory state featuring eosinophil and neutrophil factors., Conclusions: The results confirm the presence of different immunophenotypes linked to parameters of airway disease in both children and adults with asthma who are infected with RV. Such discrepancies may reflect the ability to regulate anti-viral responses., (© 2022 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Early-life exposures to geohelminths may protect against development of wheeze/asthma and atopy., Objective: To study the effect of maternal geohelminths and infections in children during the first 5 years on atopy, wheeze/asthma and airways reactivity/inflammation at 8 years., Methods: Birth cohort of 2404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO) and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy., Results: 1933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and 45.5% of children to 5 years. Frequencies of outcomes at 8 years were as follows: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%) and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced SPT prevalence (OR 0.72). Childhood Trichuris trichiura infections during the first 5 years were associated with reduced wheeze (OR 0.57) but greater parasite burdens with Ascaris lumbricoides at 5 years were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite-specific effects on wheeze/asthma and airways reactivity and inflammation were observed in non-atopic children., Conclusions: Our data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086)., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Rhinovirus frequently causes asthma exacerbations among children and young adults who are allergic. The interaction between allergen and rhinovirus-induced symptoms and inflammation over time is unclear., Objective: Our aim was to compare the response to an experimental inoculation with rhinovirus-16 in allergic asthmatics with the response in healthy controls and to evaluate the effects of administrating omalizumab before and during the infection., Methods: Two clinical trials were run in parallel. In one of these trials, the response to an experimental inoculation with rhinovirus-16 among asthmatics with high levels of total IgE was compared to the response in healthy controls. The other trial compared the effects of administering omalizumab versus placebo to asthmatics in a randomized, double-blind placebo-controlled investigation. The primary outcome for both trials compared lower respiratory tract symptoms (LRTSs) between study groups over the first 4 days of infection., Results: Frequent comparisons of symptoms, lung function, and blood eosinophil counts revealed differences that were more pronounced among allergic asthmatics than among controls by days 2 and 3 after virus inoculation. Additionally, an augmentation of upper respiratory tract symptom scores and LRTS scores occurred among the atopic asthmatics versus the controls during the resolution of symptoms (P < .01 for upper respiratory symptom tract scores and P < .001 for LRTS scores). The beneficial effects of administering omalizumab on reducing LRTSs and improving lung function were strongest over the first 4 days., Conclusions: LRTSs and blood eosinophil counts were augmented and lung function was reduced among allergic asthmatics early after rhinovirus inoculation but increased late in the infection during symptom resolution. The effect of administering omalizumab on the response to rhinovirus was most pronounced during the early/innate phase of the infection., (Copyright © 2020. Published by Elsevier Inc.)

Background: Allergic asthmatic subjects are uniquely susceptible to acute wheezing episodes provoked by rhinovirus. However, the underlying immune mechanisms and interaction between rhinovirus and allergy remain enigmatic, and current paradigms are controversial., Objective: We sought to perform a comprehensive analysis of type 1 and type 2 innate and adaptive responses in allergic asthmatic subjects infected with rhinovirus., Methods: Circulating virus-specific T H 1 cells and allergen-specific T H 2 cells were precisely monitored before and after rhinovirus challenge in allergic asthmatic subjects (total IgE, 133-4692 IU/mL; n = 28) and healthy nonallergic controls (n = 12) using peptide/MHCII tetramers. T cells were sampled for up to 11 weeks to capture steady-state and postinfection phases. T-cell responses were analyzed in parallel with 18 cytokines in the nose, upper and lower airway symptoms, and lung function. The influence of in vivo IgE blockade was also examined., Results: In uninfected asthmatic subjects, higher numbers of circulating virus-specific PD-1 + T H 1 cells, but not allergen-specific T H 2 cells, were linked to worse lung function. Rhinovirus infection induced an amplified antiviral T H 1 response in asthmatic subjects versus controls, with synchronized allergen-specific T H 2 expansion, and production of type 1 and 2 cytokines in the nose. In contrast, T H 2 responses were absent in infected asthmatic subjects who had normal lung function, and in those receiving anti-IgE. Across all subjects, early induction of a minimal set of nasal cytokines that discriminated high responders (G-CSF, IFN-γ, TNF-α) correlated with both egress of circulating virus-specific T H 1 cells and worse symptoms., Conclusions: Rhinovirus induces robust T H 1 responses in allergic asthmatic subjects that may promote disease, even after the infection resolves., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Fetal oxidative balance (achieved when protective prenatal factors counteract sources of oxidative stress) might be critical for preventing asthma and allergic disease., Objective: We examined prenatal intakes of hypothesized protective nutrients (including antioxidants) in conjunction with potential sources of oxidative stress in models of adolescent asthma and allergic disease., Methods: We used data from 996 mother-child pairs in Project Viva. Exposures of interest were maternal prepregnancy body mass index and prenatal nutrients (energy-adjusted intakes of vitamins D, C, and E; β-carotene; folate; choline; and n-3 and n-6 polyunsaturated fatty acids [PUFAs]), air pollutant exposures (residence-specific third-trimester black carbon or particulate matter with a diameter of less than 2.5 μm [PM 2.5 ]), acetaminophen, and smoking. Outcomes were offspring's current asthma, allergic rhinitis, and allergen sensitization at a median age of 12.9 years. We performed logistic regression. Continuous exposures were log-transformed and modeled as z scores., Results: We observed protective associations for vitamin D (odds ratio [OR], 0.69 [95% CI, 0.53-0.89] for allergic rhinitis), the sum of the n-3 PUFAs eicosapentaenoic acid and docosahexaenoic acid (OR, 0.81 [95% CI, 0.66-0.99] for current asthma), and the n-3 PUFA α-linolenic acid (OR, 0.78 [95% CI, 0.64-0.95] for allergen sensitization and OR, 0.80 [95% CI 0.65-0.99] for current asthma). Black carbon and PM 2.5 were associated with an approximately 30% increased risk for allergen sensitization. No multiplicative interactions were observed for protective nutrient intakes with sources of oxidative stress., Conclusions: We identified potential protective prenatal nutrients (vitamin D and n-3 PUFAs), as well as adverse prenatal pro-oxidant exposures that might alter the risk of asthma and allergic disease into adolescence., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Asthma is a common cause of emergency care attendance in low- and middle-income countries (LMICs). While few prospective studies of predictors for emergency care attendance have been undertaken in high-income countries, none have been performed in a LMIC.We followed a cohort of 5-15-year-old children treated for asthma attacks in emergency rooms of public health facilities in Esmeraldas City, Ecuador. We collected blood and nasal wash samples, and performed spirometry and exhaled nitric oxide fraction measurements. We explored potential predictors for recurrence of severe asthma attacks requiring emergency care over 6 months' follow-up.We recruited 283 children of whom 264 (93%) were followed-up for ≥6 months or until their next asthma attack. Almost half (46%) had a subsequent severe asthma attack requiring emergency care. Predictors of recurrence in adjusted analyses were (adjusted OR, 95% CI) younger age (0.87, 0.79-0.96 per year), previous asthma diagnosis (2.2, 1.2-3.9), number of parenteral corticosteroid courses in previous year (1.3, 1.1-1.5), food triggers (2.0, 1.1-3.6) and eczema diagnosis (4.2, 1.02-17.6). A parsimonious Cox regression model included the first three predictors plus urban residence as a protective factor (adjusted hazard ratio 0.69, 95% CI 0.50-0.95). Laboratory and lung function tests did not predict recurrence.Factors independently associated with recurrent emergency attendance for asthma attacks were identified in a low-resource LMIC setting. This study suggests that a simple risk-assessment tool could potentially be created for emergency rooms in similar settings to identify higher-risk children on whom limited resources might be better focused., Competing Interests: Conflict of interest: C. Ardura-Garcia has nothing to disclose. Conflict of interest: E. Arias has nothing to disclose. Conflict of interest: P. Hurtado has nothing to disclose. Conflict of interest: L.J. Bonnett has nothing to disclose. Conflict of interest: C. Sandoval has nothing to disclose. Conflict of interest: A. Maldonado has nothing to disclose. Conflict of interest: L.J. Workman has nothing to disclose. Conflict of interest: T.A.E. Platts-Mills has nothing to disclose. Conflict of interest: P.J. Cooper reports grants from PATH Vaccines and National Institutes of Health Research, outside the submitted work. Conflict of interest: J.D. Blakey reports personal fees and non-financial support from Astra Zeneca, Boehringer Ingelheim and Napp, personal fees from Teva and non-financial support from Novartis, outside the submitted work., (Copyright ©ERS 2019.)

Thomas Platts-Mills and Matthew Perzanowski provide their expert Perspective on a translational study from Custovic and colleagues that identifies pairings of IgE that show value in estimating risk of concurrent asthma., Competing Interests: The authors have declared that no competing interests exist.

It has been 50 years since the dust mite was first appreciated to be a major source of allergen in house dust, and by extension a key trigger of allergic respiratory disease. Since that time a number of protein allergens have been identified and characterized, mainly from mite feces, and standardized mite extracts and IgE assays have been developed. Insights into the lifecycle of dust mites and aspects of mite allergen biology have shed light on the mechanisms that lead to respiratory disease and to the development of interventions that can minimize dust mite allergen exposure. It is now clear that dust mite allergy is a key contributor to asthma in many parts of the world, and that long-term avoidance can be effective for preventing sensitization and minimizing the development and severity of respiratory disease. Here, we discuss the evidence linking dust mites with respiratory disease, outline studies that support the efficacy of home environmental interventions, and highlight practical methods that have been shown to be effective as part of a multifaceted approach to dust mite avoidance., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Although sensitization to indoor allergens is strongly associated with asthma, there are questions as to how this relates to asthma symptoms., Objective: We sought to study the relevance of IgE antibodies to cat and dog allergens in an area in which (1) the climate discourages cockroach, fungal, and mite growth and (2) dander allergens are known to be present in schools and houses without animals., Methods: IgE to 8 allergens was tested in 963 sera from a population-based study on 19-year-olds, and associations with asthma symptoms, diagnosis, and treatment were examined. In positive sera IgE to specific cat and dog allergens was also assayed., Results: IgE specific for animal dander had the highest prevalence and strongest relationship to asthma diagnosis. Furthermore, asthma severity, as judged by the frequency of symptoms and use of treatment, was directly associated with the titer of IgE antibodies to animal dander. Among the 103 subjects who had current asthma at age 19 years, 50 had asthma before age 12 years. Among those 50, the odds ratios for asthma related to any IgE antibodies to animal dander or high-titer IgE antibodies (≥17.5 IU/mL) were 9.2 (95% CI, 4.9-17) and 13 (95% CI, 6.9-25), respectively. In multivariable analysis IgE antibodies to Fel d 1 and Can f 5 were each associated with current asthma., Conclusion: High-titer IgE antibodies to cat and dog allergens were strongly associated with the diagnosis, severity, and persistence of asthma; however, a large proportion of patients with current asthma did not live in a house with a cat or dog., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The fall peak in childhood asthma exacerbations is thought to be related to an increase in viral infections and allergen exposure when children return to school. Whether the seasonality of asthma attacks among children from different geographic regions follows similar trends is unclear., Objective: To compare seasonal trends in asthma exacerbations among school-age children who lived in different geographic locations, with different climates, within the United States., Methods: Hospital billing data bases were examined to determine the monthly number of school-age children who were hospitalized or treated in the emergency department (ED) for asthma exacerbations. Data from four cities within three states were compared. Climate data were obtained from archives of the National Climate Data Center, U.S. Department of Commerce., Results: An annual peak in asthma exacerbations was observed during the fall months (September through November) among children who lived in Charlottesville, Virginia, as well as throughout the state of Virginia. An increase in exacerbations, which peaked in November, was observed for exacerbations among children who lived in Tucson, Arizona, and Yuma, Arizona. In contrast, exacerbations among children from New Orleans, Louisiana, increased in September but remained elevated throughout the school year. Although there was annual variation in the frequency of exacerbations over time, the seasonal patterns observed remained similar within the locations from year to year. A nadir in the frequency of attacks was observed during the summer months in all the locations., Conclusion: Seasonal peaks for asthma exacerbations varied among the children who lived in geographic locations with different climates, and were not restricted to the beginning of the school year., Competing Interests: The authors have no conflicts of interest to declare pertaining to this article

Background: Childhood asthma is a global problem affecting the respiratory health of children. Physical activity (PA) plays a role in the relationship between asthma and respiratory health. We hypothesized that a low level of PA would be associated with asthma in children and adolescents. The objectives of our study were to (1) summarize the evidence available on associations between PA and asthma prevalence in children and adolescents and (2) assess the role of PA in new-onset or incident asthma among children and adolescents., Methods: We searched Medline, the Cochrane Library, and Embase and extracted data from original articles that met the inclusion criteria. Summary odds ratios (ORs) and confidence intervals (CIs) were used to express the results of the meta-analysis (forest plot). We explored heterogeneity using funnel plots and the Graphic Appraisal Tool for Epidemiology (GATE)., Results: We retrieved 1,571 titles and selected 11 articles describing three cohort and eight cross-sectional studies for inclusion. A meta-analysis of the cohort studies revealed a risk of new-onset asthma in children with low PA (OR [95 % CI] 1.32 [0.95; 1.84] [random effects] and 1.35 [1.13; 1.62] [fixed effects]). Three cross-sectional studies identified significant positive associations between childhood asthma or asthma symptoms and low PA., Conclusions: Children and adolescents with low PA levels had an increased risk of new-onset asthma, and some had a higher risk of current asthma/or wheezing; however, there was some heterogeneity among the studies. This review reveals a critical need for future longitudinal assessments of low PA, its mechanisms, and its implications for incident asthma in children. The systematic review was prospectively registered at PROSPERO (registration number: CRD42014013761; available at: http://www.crd.york.ac.uk/PROSPERO [accessed: 24 March 2016]).

Background: Despite the high asthma rates described in Latin America, asthma risk factors in poor urban settings are not well established. We investigated risk factors for acute asthma among Ecuadorian children., Methods: A matched case-control study was carried out in a public hospital serving a coastal city. Children with acute asthma were age- and sex-matched to non-asthmatics. A questionnaire was administered, and blood, as well as stool, and nasopharyngeal swabs were collected., Results: Sixty cases and 119 controls aged 5-15 were evaluated. High proportions of cases were atopic with population-attributable fractions for atopy of 68.5% for sIgE and 57.2% for SPT. Acute asthma risk increased with greater titers of mite IgE (3.51-50 kU/l vs. <0.70kU/l - OR 4.56, 95% CI 1.48-14.06, p = 0.008; >50kU/l vs. <0.70kU/l - OR 41.98, 95% CI: 8.97-196.39, p < 0.001). Asthma risk was significantly independently associated with bronchiolitis (adj. OR: 38.9, 95% CI 3.26-465), parental educational level (adj. OR 1.26, 95% CI: 1.08-1.46), and presence of sIgE (adj. OR: 36.7, 95% CI: 4.00-337), while a reduced risk was associated with current contact with pets (adj. OR: 0.07, 95% CI: 0.01-0.56). Rhinovirus infection was more frequent in cases (cases 35.6% vs. controls 7.8%, p = 0.002). None of the cases were on maintenance therapy with inhaled corticosteroids and most relied on emergency department for control., Conclusions: A high proportion of children presenting to a public hospital with acute asthma were allergic to mite, particularly at high IgE titer. Poor asthma control resulted in overuse of emergency care., (© 2015 The Authors. Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd.)

The prevalence of allergy to furry animals has been increasing, and allergy to cats, dogs, or both is considered a major risk factor for the development of asthma and rhinitis. An important step forward in the diagnosis of allergy to furry animals has been made with the introduction of molecular-based allergy diagnostics. A workshop on furry animals was convened to provide an up-to-date assessment of our understanding of (1) the exposure and immune response to the major mammalian allergens, (2) the relationship of these responses (particularly those to specific proteins or components) to symptoms, and (3) the relevance of these specific antibody responses to current or future investigation of patients presenting with allergic diseases. In this review research results discussed at the workshop are presented, including the effect of concomitant exposures from other allergens or microorganisms, the significance of the community prevalence of furry animals, molecular-based allergy diagnostics, and a detailed discussion of cat and dog components., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The relevance of allergic sensitization, as judged by titers of serum IgE antibodies, to the risk of an asthma exacerbation caused by rhinovirus is unclear., Objective: We sought to examine the prevalence of rhinovirus infections in relation to the atopic status of children treated for wheezing in Costa Rica, a country with an increased asthma burden., Methods: The children enrolled (n= 287) were 7 through 12 years old. They included 96 with acute wheezing, 65 with stable asthma, and 126 nonasthmatic control subjects. PCR methods, including gene sequencing to identify rhinovirus strains, were used to identify viral pathogens in nasal washes. Results were examined in relation to wheezing, IgE, allergen-specific IgE antibody, and fraction of exhaled nitric oxide levels., Results: Sixty-four percent of wheezing children compared with 13% of children with stable asthma and 13% of nonasthmatic control subjects had positive test results for rhinovirus (P< .001 for both comparisons). Among wheezing subjects, 75% of the rhinoviruses detected were group C strains. High titers of IgE antibodies to dust mite allergen (especially Dermatophagoides species) were common and correlated significantly with total IgE and fraction of exhaled nitric oxide levels. The greatest risk for wheezing was observed among children with titers of IgE antibodies to dust mite of 17.5 IU/mL or greater who tested positive for rhinovirus (odds ratio for wheezing, 31.5; 95% CI, 8.3-108; P< .001)., Conclusions: High titers of IgE antibody to dust mite allergen were common and significantly increased the risk for acute wheezing provoked by rhinovirus among asthmatic children., (Published by Mosby, Inc.)

Rationale: IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract., Objectives: To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens., Methods: Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131)., Measurements and Main Results: Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001)., Conclusions: These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled.

Purpose of Review: The objective is to discuss recent progress in our understanding of the role of the indoor environment in asthma, focusing on the special role of cat allergens., Recent Findings: Sensitization to Fel d 1 is the dominant event in inhalant responses to cat; however, there are also IgE responses to the lipocalin (Fel d 4), to cat albumin (Fel d 2), and to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) on cat IgA (Fel d 5w) and other molecules. The dose response and routes of sensitization for these allergens are now thought to be diverse. It is important to remember that exposure outside a house with a cat is sufficient to cause sensitization. Furthermore, the only solid evidence about a role in asthma relates to Fel d 1. Recently, it has been shown that tolerance associated with early exposure to cats can persist to age 18 and that IgE to alpha-gal (on cat IgA) is not related to asthma. In addition, a recent study of anti-IgE reinforces the evidence that IgE antibodies to indoor allergens make a major contribution to asthma severity., Summary: Exposure to Fel d 1 in a home with a cat is far higher than the levels necessary to induce an allergic (IgE antibody) response. In keeping with that, children may develop tolerance, which can be long-lived. In addition, there is increasing evidence that IgE antibodies to an inhalant allergen, such as Fel d 1, dust mite, or cockroach, are causally related to lung inflammation and asthma.

Background: Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease., Methods/design: A cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3) during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also., Discussion: The study will provide information on the potential effects of early exposures to geohelminths (during pregnancy and the first 2 years of life) on the development of vaccine immunity and allergy. The data will inform an ongoing debate of potential effects of geohelminths on child health and will contribute to policy decisions on new interventions designed to improve vaccine immunogenicity and protect against the development of allergic diseases., Trial Registration: Current Controlled Trials ISRCTN41239086.

Background: Whereas some evidence suggests that antigen sensitization may begin prenatally, the influence of maternal allergen exposure during pregnancy has not been fully elucidated., Objectives: We examined the relationship between prenatal maternal aeroallergen exposure and cord blood total IgE and the potential mediating/indirect effect of maternal immune response., Methods: This study was performed in 301 mother-infant pairs enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project, a study examining the effects of prenatal and early life social and physical environmental exposures on urban asthma risk. Dust samples collected prenatally from mothers' bedrooms were analyzed for cockroach and dust mite allergens. Cord blood was analyzed for total IgE, and maternal serum collected during pregnancy for total and specific IgE. We assessed the relationship between prenatal exposure and cord blood total IgE and the potential mediation effect adjusting for maternal age, race, education, smoking status, and dust collection season; and child's sex and season of birth., Results: In multivariate models, elevated prenatal dust mite levels (>0.2 microg/g) increased cord blood IgE concentrations by 29% (P = .08), and continuous dust mite concentration was associated with a significant nonlinear increase in cord blood IgE (P = .02). Elevated prenatal exposure to cockroach allergen (>2 U/g) was not associated with cord blood IgE, but showed a significant indirect relationship through maternal total IgE (beta = 0.23; 95% CI, 0.08-0.41)., Conclusion: These results demonstrate that maternal prenatal exposure to household allergens may affect cord blood IgE, albeit the underlying mechanism may be allergen-specific.

Decreasing exposure to indoor allergens has been studied extensively and is a well accepted part of the treatment for allergic disease. The 2007 revision of the evidence-based guidelines recommends allergen avoidance as part of the management of asthma. In contrast, a recent meta-analysis concluded that dust mite avoidance is "of no use" in the treatment of asthma. There are obvious sources of bias that could have influenced the evaluation of published trials either by the guideline panel or by the group conducting the meta-analysis. An important issue is whether meta-analysis is a valid method of evaluating studies such as those on dust mite avoidance that are highly variable. Reading the published series of 4 meta-analyses on this subject from the Cochrane Library suggests that decisions about which trials to include can have a major effect on the outcome. The process of meta-analysis may also have other potential conflicts. The recent meta-analysis on dust mite avoidance appears to be seriously flawed because of the decisions about inclusion and exclusion as well as the way in which studies were evaluated. The conclusion is that the criticisms of the recommendations in the 2007 guidelines were not well founded.

The American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma and Immunology Executive Committees formed the Omalizumab Joint Task Force with the purpose of reviewing the Genentech Xolair (omalizumab) clinical trials and postmarketing surveillance data on anaphylaxis and anaphylactoid reactions. Using the definition of anaphylaxis proposed at a 2005 multidisciplinary symposia, the Omalizumab Joint Task Force concluded that 35 patients had 41 episodes of anaphylaxis associated with Xolair (omalizumab) administration between June 1, 2003, and December 31, 2005. With 39,510 patients receiving Xolair (omalizumab) during the same period of time, this would correspond to an anaphylaxis-reporting rate of 0.09% of patients. Of those 36 events for which the time of reaction was known, 22 (61%) reactions occurred in the first 2 hours after one of the first 3 doses. Five (14%) of the events after the fourth or later doses occurred within 30 minutes. Considering the timing of these 36 events, an observation period of 2 hours for the first 3 injections and 30 minutes for subsequent injections would have captured 75% of the anaphylactic reactions. The OJTF report provides recommendations for physicians who prescribe Xolair (omalizumab) on (1) the suggested wait periods after administration and (2) patient education regarding anaphylaxis.

Background: There has been no longitudinal study of the relation between concurrent exposure to dust mite allergen and endotoxin in early life and asthma and atopy at school age., Objectives: To examine the relation between exposure to dust mite allergen and endotoxin at age 2 to 3 months and asthma, wheeze, and atopy in high-risk children., Methods: Birth cohort study of 440 children with parental history of atopy in the Boston metropolitan area., Results: In multivariate analyses, early exposure to high levels of dust mite allergen (> or =10 microg/g) was associated with increased risks of asthma at age 7 years (odds ratio [OR], 3.0; 95% CI, 1.1-7.9) and late-onset wheeze (OR, 5.0; 95% CI, 1.5-16.4). Exposure to endotoxin levels above the lowest quartile at age 2 to 3 months was associated with reduced odds of atopy at school age (OR, 0.5; 95% CI, 0.2-0.9). In contrast with its inverse association with atopy, endotoxin exposure in early life was associated with an increased risk of any wheeze between ages 1 and 7 years that did not change significantly with time (hazard ratio for each quartile increment in endotoxin levels, 1.23; 95% CI, 1.07-1.43)., Conclusion: Among children at risk of atopy, early exposure to high levels of dust mite allergen is associated with increased risks of asthma and late-onset wheeze. In these children, endotoxin exposure is associated with a reduced risk of atopy but an increased risk of wheeze., Clinical Implications: Early endotoxin exposure may be a protective factor against atopy but a risk factor for wheeze in high-risk children.

Background: It is unknown whether focal changes of airflow obstruction within the lungs of patients with asthma vary or are fixed in location with time or repeated bronchoconstriction. With hyperpolarized helium-3 magnetic resonance (H(3)HeMR) imaging, the airspaces are depicted and focal areas of airflow obstruction are shown as "ventilation defects.", Objective: To investigate the regional changes of airflow obstruction with time and repeated bronchoconstriction., Methods: H(3)HeMR and spirometry were performed before (pre) and immediately after (post) methacholine challenge in 10 young patients with asthma on 2 days that were 7-476 days (mean, 185.3 +/- 37.2 days) apart. Pair-wise image comparisons were performed to determine the change in location of ventilation defects within the lung and their change in size., Results: When comparing premethacholine versus premethacholine and postmethacholine versus post-methacholine images of the 2 days, 41% +/- 10% and 69% +/- 5% (P = .017) of defects, respectively, were in the same location, and of those, 69% +/- 12% and 43% +/- 5% (P = .022), respectively, did not change size. Comparing premethacholine versus postmethacholine images, 58% +/- 9% of defects were in the same location on day 1 and 73% +/- 7% (P = .088) on day 2. On both days, the percent increase in defect number from premethacholine to postmethacholine was much greater than the percent decrease in spirometric values (P < .001)., Conclusion: Many of the ventilation defects persisted or recurred in the same location with time or repeated bronchoconstriction, suggesting that the regional changes of airflow obstruction are relatively fixed within the lung., Clinical Implications: The findings give new insight into the regional airflow variability within the lungs of patients with asthma.

Background: The prevalence of asthma is strikingly different in some Westernized countries: approximately 20% in New Zealand and approximately 8% in northern Sweden., Objective: We investigated differences in total IgE and in the prevalence of wheezing related to the observation that high exposure to dust mite allergens induces high titers of IgE antibodies., Methods: Two age-matched, population-based cohorts-1155 children in New Zealand (224 sera) and 3431 children (797 sera) in the Norrbotten area of Sweden-were studied. Sera were assayed for total IgE and specific IgE antibodies to relevant allergens., Results: The mean total IgE among wheezing children was higher in New Zealand than Sweden (218 IU/mL vs 65.2 IU/mL; P < .001). In addition, the prevalence of high titer specific IgE antibody (> or =50 IU/mL) was greater among the wheezing children in New Zealand compared with Sweden (35.7% vs 13.0%; P < .001). Specific IgE antibody to mite in New Zealand was significantly related to high total IgE (> or =200 IU/mL; r = 0.47; P < .001), whereas the IgE antibody response to cat allergens did not make a significant contribution to high total IgE in either country., Conclusion: The quantity of IgE antibody produced to dust mite provides a possible explanation for the higher total IgE levels found in children in New Zealand and may help to explain the differences in prevalence and severity of asthma between these 2 countries., Clinical Implications: Specific IgE antibody responses to dust mite and cat allergens may contribute differently to total serum IgE and to the prevalence of allergic disease.

Background: Increased cord blood IgE levels, in conjunction with a family history of atopy, are associated with the development of allergic diseases in children. However, little is known about predictors of cord blood IgE levels., Objective: Our objective was to identify predictors of cord blood IgE levels among infants at increased risk of atopy., Methods: Cord blood IgE levels were measured in 874 infants who were screened for participation in a birth cohort. Questionnaires were administered after birth of the infant, and maternal and cord blood was obtained for measurement of IgE levels. Logistic and tobit regression models were used to study the association between perinatal factors and cord blood IgE levels., Results: In multivariable models infant male sex, increased maternal total IgE level, maternal allergen sensitization, Hispanic ethnicity, and residence in low-income areas were associated with detectable or increased cord blood IgE levels, whereas increasing maternal age was associated with undetectable or lower cord blood IgE levels. Although maternal smoking during pregnancy was positively associated with cord blood IgE levels in univariable models, the effect did not persist after adjusting for potential confounders., Conclusion: Maternal allergen sensitization, markers of socioeconomic disadvantage and race/ethnicity, maternal age, and infant sex might influence fetal production of IgE. We found no association of maternal parity, mode of delivery, gestational age, or season of birth with cord blood IgE levels., Clinical Implications: The identification of these definable familial and environmental factors that predict cord blood IgE levels might help in the early detection of infants at risk for atopic disorders.

None of the explanations proposed for the increase in paediatric asthma have been adequate. It is becoming apparent that the cause of the increase in asthma must be multi-factorial. Increasing attention has been focused on the role of lifestyle in the development of asthma. Lifestyle changes that have occurred in children are those in diet and decreased physical activity, with obesity being the product of these changes. The increase in asthma, obesity and a sedentary lifestyle have occurred together. However, a temporal relationship between asthma, obesity and decreased physical activity has not been determined in the paediatric literature. Limited data suggest that decreased physical activity could be playing a role in the aetiology of asthma independent of obesity. Furthermore, there has been substantial research on the benefits of exercise programmes for paediatric patients with asthma. Longitudinal trials monitoring physical activity, obesity and the development of asthma are needed.

Despite the strong and consistent association between immediate hypersensitivity, allergy, asthma and exposure, there is still controversy about the role inhaled allergen plays and about the timing of events related to sensitization. However, IgE antibodies are essential for the asthmatic response and the symptoms are much more closely associated with IgE antibodies to perennial than to seasonal allergens. Although there have been many changes in our environment, none of these alone explains the consistency or the scale of the rise in asthma over the 40 years between 1960 and 2000.

Background: At least 101 serotypes of rhinoviruses have been identified. Rhinoviruses have often been associated with trivial upper respiratory infections but more recent evidence suggests that they play a significant role in the pathogenesis of asthma exacerbations., Methods: The impact of rhinoviruses as a cause of respiratory morbidity in infancy and the role of rhinoviruses in causing asthma exacerbations in the children and adult population is discussed. Past and current experimental and epidemiologic evidence was assessed to suggest a causal role rather than just an association. Mechanism of susceptibility to virus infection in asthmatics were discussed, as were data indicating important interactions between allergic sensitization and rhinovirus infections in risk of asthma exacerbations., Results: Asthmatic individuals have increased severity and duration of lower airway symptoms and greater declines in lung function upon infection with rhinovirus, suggesting greater susceptibility to rhinovirus infection because of impaired antiviral immunity. Early virus-induced apoptosis, which aborts virus replication, was impaired in asthmatics. Treating allergic airway inflammation may reduce the frequency and severity of symptoms triggered by rhinoviruses., Conclusions: The evidence in children and young adults suggests that atopy and allergic inflammation in the airways may be critical determinants of an adverse response to rhinovirus. Increased awareness of the spectrum of age groups that are affected by rhinoviruses is needed to encourage the development of new treatments and strategies that may be helpful in reducing the frequency and severity of symptoms triggered by rhinoviruses.

There is little doubt that the cause of the increased prevalence and severity of asthma is multifactorial. Although the factors of allergen exposure and hygiene are almost certainly necessary for its development, there is a growing body of literature that implicates lifestyle change, specifically decreased physical activity, as a contributor to the increase in asthma prevalence and severity. Several literature reviews of exercise conditioning in patients with asthma have been published. These reviews and recent controlled trials emphasize that although many of the studies of exercise conditioning in asthmatic patients involved different methods and outcome measures, the overwhelming majority of studies demonstrated the capacity for asthmatic subjects to exercise safely and significantly improve their cardiovascular fitness and quality of life. There are several proposed pathophysiologic mechanisms responsible for the effects of decreased activity on the lung function of patients with asthma. A prescription for exercise has been endorsed for all asthmatic subjects by the American College of Sports Medicine and the American Thoracic Society. The allergy community has placed emphasis on medical therapy and allergen avoidance; in addition, exercise [correction] has not been formally incorporated into the National Asthma Education and Prevention Program guidelines. It is our belief that an exercise prescription should be part of the treatment for all cases of asthma. The real question is whether prolonged physical activity and, in particular, outdoor play of children plays a role in prophylaxis against persistent wheezing. If so, the decrease in physical activity might have played a major role in recent increases in asthma prevalence and severity.

Exposure to allergens is a trigger for symptoms in sensitized individuals with asthma. This is especially true for allergens primarily found indoors but can be true for outdoor allergens with sufficiently high exposure. The role of allergens in attacks can be subtle in that they provide the underlying inflammation necessary for other nonspecific agents to have an effect.

In a cohort of 849 infants with an asthmatic sibling, the authors examined the relations of exposure to allergens (dust mite, cockroach, cat, and dog), nitrogen dioxide, and mold with symptoms of wheeze and persistent cough in the first year of life (1998-2000). Among infants whose mothers had physician-diagnosed asthma, neither dust mite allergen nor dog allergen was associated with either symptom. Exposure to cockroach allergen (Bla g 1 at >or=2 U/g) modestly increased the risk for wheeze (odds ratio (OR) = 1.87, 95% confidence interval (CI): 0.94, 3.71), and exposure to cat allergen modestly decreased the risk (OR = 0.60, 95% CI: 0.35, 1.03). Among infants of mothers with no asthma history, exposure to gas stoves (OR = 1.50, 95% CI: 1.05, 2.15) and wood-burning stoves (OR = 2.09, 95% CI: 1.12, 3.91) increased the risk of persistent cough. Similarly, measured nitrogen dioxide concentration was associated with persistent cough (OR = 1.21, 95% CI: 1.05, 1.40). Persistent mold affected both infants of mothers with asthma (for wheeze, OR = 2.27, 95% CI: 1.27, 4.07; for cough, OR = 1.83, 95% CI: 1.04, 3.22) and infants of mothers without asthma (for cough, OR = 1.55, 95% CI: 1.04, 2.31). Reported exposure was confirmed by an association of measured fungi with wheeze (OR = 1.23, 95% CI: 1.01, 1.49). This appears to have been the first study to measure all of these home exposures (indoor allergens, nitrogen dioxide, fungi) and to prospectively measure the frequency of infant wheeze and persistent cough.

Background: Imaging of gas distribution in the lungs of patients with asthma has been restricted because of the lack of a suitable gaseous contrast agent. Hyperpolarized helium-3 (HHe3) provides a new technique for magnetic resonance imaging of lung diseases., Objective: We sought to investigate the use of HHe3 gas to image the lungs of patients with moderate or severe asthma and to assess changes in gas distribution after methacholine and exercise challenge., Methods: Magnetic resonance imaging was performed in asthmatic patients immediately after inhalation of HHe3 gas. In addition, images were obtained before and after methacholine challenge and a standard exercise test., Results: Areas of the lung with no signal or sharply reduced HHe3 signal (ventilation defects) are common in patients with asthma, and the number of defects was inversely related to the percent predicted FEV(1) (r = 0.71, P <.002). After methacholine challenge (n = 3), the number of defects increased. Similarly, imaging of the lungs after exercise (n = 6) showed increased ventilation defects in parallel with decreases in FEV(1). The increase in defects after challenge in these 9 asthmatic patients was significant both for the number (P <.02) and extent (P <.02) of the defects. The variability and speed of changes in ventilation and the complete lack of signal in many areas is in keeping with a model in which the defects result from airway closure., Conclusion: HHe3 magnetic resonance provides a new technique for imaging the distribution of inhaled air in the lungs. The technique is suitable for following responses to treatment of asthma and changes after methacholine or exercise challenge.

Background: Although most children and young adults with asthma are atopic, exacerbations of asthma are frequently associated with viral respiratory tract infections, especially those caused by rhinovirus (HRV)., Objective: Young atopic adults with mild asthma were evaluated before and during an experimental HRV infection to test the hypothesis that airway inflammation before virus inoculation may be a risk factor for an adverse response to HRV., Methods: Experimental HRV infections were evaluated in 16 allergic volunteers with mild asthma and 9 nonatopic control patients (age, 18 to 30 years). Before virus inoculation, each participant was screened with tests for lung function, prick skin tests for sensitization to common aeroallergens, measurements of total serum IgE, and serum neutralizing antibody to rhinovirus-16 (the serotype used for inoculation). The response to infection was monitored for 21 days by using symptom diary cards, tests for lung function, and markers of airway inflammation in nasal washes, blood, and expired air., Results: During the infection, asthmatic patients had cumulative upper and lower respiratory tract symptom scores that were significantly greater over the course of 21 days than scores from the control patients. At baseline, the asthmatic patients also had increased sensitivity to methacholine and significantly lower values for FEV(1) (percent predicted) than the control patients (geometric mean and intraquartile values: 87% [79% to 91%] for the asthmatic patients and 101% [90% to 104%] for the control patients, P <.03). Among the patients with mild asthma, 6 had levels of total serum IgE that were substantially elevated (range, 371 to 820 IU/mL) compared with 10 who had lower levels (range, 29 to 124 IU/mL). Those with high levels of IgE had significantly greater lower respiratory tract symptom scores during the initial 4 days of the infection than the low IgE group. They also had higher total blood eosinophil counts at baseline, increased eosinophil cationic protein in their nasal washes (>200 ng/mL), and augmented levels of expired nitric oxide at baseline and during peak cold symptoms. In contrast, levels of soluble intracellular adhesion molecule-1 in nasal wash supernatants from the asthmatic patients with high IgE were diminished, both at baseline and during the infection., Conclusions: The reduced lung function and increased markers of inflammation observed before virus inoculation in the asthmatic patients who had high levels of total serum IgE may be risk factors for an adverse response to infections with HRV.

Background: The inappropriate closure of the vocal cords is characteristic of vocal cord dysfunction (VCD). These patients present with wheezing and frequently receive a misdiagnosis of asthma., Objective: To demonstrate the ability of computed tomography (CT) scored for the presence and extent of sinus disease and markers of inflammation to distinguish patients with VCD from patients with asthma., Methods: Comparisons of 13 patients with VCD were made to 77 patients presenting to the emergency room with acute asthma, 31 non-acute asthmatic patients, and 65 nonasthmatic controls. Evaluation consisted of exhaled nitric oxide gas (eNO), circulating eosinophils, and total serum immunoglobulin (Ig)E, as well as the sinus CT scan., Results: Extensive sinus CT changes were present in 23 of 74 acute asthmatic patients, 5 of 29 non-acute asthmatic patients, and 2 of 59 nonasthmatic controls. In addition, absolute eosinophil counts, eNO, and total IgE were significantly elevated among the asthmatic patients. Sinus symptoms reported by questionnaire did not predict sinus CT findings. Among the patients with VCD, none had extensive sinus disease. They also had normal eNO, low IgE, and normal eosinophil count. Five of the patients presenting to the emergency room who were identified as acute asthmatic were identified with VCD by laryngoscopy and were all characterized by the absence of significant inflammation on their sinus CT scan, low IgE, and normal eosinophil count., Conclusions: Among patients presenting with intermittent or reversible airway obstruction, patients with VCD can be distinguished from asthma by minimum or absence of inflammation in their sinuses as shown by CT scan. Clinical symptom scores are not predictive of presence or extent of sinus disease in most cases.

An inverse relationship has been proposed between exposure to high quantities of cat allergen at home and both asthma and cat allergy. First- and second-grade children from Luleå, Kiruna, and Piteå, Sweden participated in an asthma questionnaire study (n = 3,431) and incidence was evaluated over the next 3 years. Skin testing was performed on the children in Luleå and Kiruna (n = 2,149). The strongest risk factor for incident cases of asthma was Type 1 allergy (relative risk [RR], 4.9 [2.9-8.4]), followed by a family history of asthma (RR, 2.83 [1.8-4.5]). Living with a cat was inversely related both to having a positive skin test to cat (RR, 0.62 [0.47-0.83]) and incidence of physician-diagnosed asthma (RR, 0.49 [0.28-0.83]). This effect on incident asthma was most pronounced among the children with a family history of asthma (RR, 0.25 [0.08-0.80]). The evidence also suggests that many of the children exposed to cats at home can develop an immune response that does not include immunoglobulin E. Weaker protective trends were seen with dog ownership. The traditional thinking that not owning cats can provide protection against developing allergy and asthma among those with a family history of allergy needs to be re-evaluated. In a community where cat sensitization was strongly associated with asthma, owning a cat was protective against both prevalent and incident asthma.

Objective: The purpose of this study was to evaluate differences in the relationship between asthma and immune responses to allergens in children living in rural and urban areas of Kenya., Study Design: Children (mean age, 11 years) from Kabati (n = 136), a rural village, and Thika (n = 129), a small town, were studied by skin testing and serum immunoglobulin E (IgE) and immunoglobulin G (IgG) antibody measurement. Asthma was evaluated by symptoms, as well as spirometry before and after vigorous exercise to test for exercised-induced bronchospasm (EIB). School children from a study performed in Atlanta, Georgia, were used for comparison of anthropometric and immunologic results., Results: Compared with the urban area of Kenya, children living in the rural area had a lower percentage of body fat, smaller and fewer skin test responses to allergens, a higher prevalence of IgE antibodies to Ascaris (67% vs 26%) and 10-fold higher total IgE. In the urban area of Kenya, there was a strong correlation between EIB and atopy determined both by IgE antibodies (P =.02) and skin tests (P =.002). By contrast, in the rural area, none of the 13 children with EIB were skin-test positive (vs 13/109 of children without EIB)., Conclusions: Among the rural children, there was no association between immune responses to allergens and airway-related symptoms or reactivity. The association between asthma and atopy seen in the town of Thika may represent an important step in the increase in asthma seen both in urban Africa and in the West.

Home exposures to aeroallergens are an important environmental factor in allergic sensitization and in the development and exacerbation of asthma. We assessed variations in home concentrations of dust mite, cockroach, cat, and dog allergens in dust collected in the main living areas of asthmatics' homes by family income, mother's education, dwelling type, population density, household population density, and ethnicity in Connecticut and south-central Massachusetts. Dust samples were collected at the time of home interview in 999 homes as part of an ongoing longitudinal birth cohort study of 1,002 infants and their asthmatic siblings. The analysis employed lower and upper cut points for group 1 dust mite (> or = 2.0 microg/g and > or = 10 microg/g), cockroach (> or = 1.0 U/g and > or = 4.0 U/g), cat (> or = 1.0 microg/g and > or = 8.0 ug/g), and dog (> or = 2.0 microg/g and > or = 10.0 microg/g) allergens. Subject residences were geocoded to assess population density from the U.S. Census, and multiple logistic regression was used to control for confounding. The portion of homes at the lower cut point for dust mite, cockroach, cat, and dog allergens were 46.9%, 24.9%, 42.2%, and 35.6%, respectively; the upper cut point for each of the allergens was reached in 22.4%, 13.4%, 21.0%, and 22.9% of the homes, respectively. In all, 86.0% of the homes had at least one allergen at the lower cut point, and 58.0% had at least one allergen at the upper cut point. Forty-nine percent of the homes had two or more allergens at the lower cut point, and 19.7% had two or more allergens at the upper cut point. Higher education of the mother, higher household income, living in a single-family home in a less densely populated area with fewer people per room, and being a white household were associated with elevated dust mite, cat, and dog allergens and low cockroach allergen. In contrast, low income, living in a multifamily home in a high population density area with a higher occupancy rate per room, and being a Hispanic or black household were associated with elevated cockroach allergens and low concentrations of dust mite, cat, and dog allergens. Although the presence of an individual allergen is more likely associated with one or more socioeconomic or ethnic factors, most homes typically have multiple allergen burdens in excess of concentrations thought to be associated with sensitization and exacerbation of asthma. Mite and cockroach allergens have distinct and opposite associations with socioeconomic factors and population density.

Longitudinal evidence that indoor allergen exposure causes morbidity in sensitized individuals with asthma is scarce. We evaluated the association of allergen sensitization and home exposure to short- and long-term morbidity in 140 women with asthma and to asthma prevalence in 458 women from metropolitan Boston. Cockroach (Blattella germanica), dust mite (Dermatophagoides farinae), and cat (Felis domesticus) allergens in home dust samples, and specific immunoglobulin E antibodies were measured at outset, and doctor-diagnosed asthma and markers of asthma morbidity were ascertained by questionnaire during a 4-year follow-up. Cat- and cockroach-sensitive (immunoglobulin E immunocap [Cap] class > or = 1) women with asthma reported greater morbidity in the past year at the start, and during follow-up, if high levels of the relevant allergen were found. Women with asthma sensitized to cat allergen and with concentrations at 8 microg/g or greater were more likely to have used steroid (adjusted odds ratio [95% confidence interval] 2.7 [1.2-6.2]) and wheezed without a cold (odds ratio 6.8 [3.3- 14.0]) during follow-up. Those sensitized and exposed to cockroach (Bla g 1 or 2 > or = 2 U/g) were at least three times more likely to have used steroid and to have attended a hospital emergency room; the size of the effect upon steroid use was maintained, but the precision was reduced and the 95% confidence interval included one (p = 0.07), with adjustment for race and poverty. We conclude that cockroach and cat allergens may contribute to asthma morbidity in sensitized women.

Despite the strong and consistent association between immediate hypersensitivity and asthma, there is still controversy about the role inhaled allergens play and about the timing of events related to sensitization. Recent studies have provided further evidence on the nature of the immune response to allergens, the timing of this response, and, in particular, whether any response to allergens occurs in utero. Some of the studies also provide a better explanation for why there is not a simple dose response relationship between allergens and asthma. The new studies also raise major issues about the nature of the immune response in nonallergic individuals. Taken together, the findings do not support a simple view about the balance between TH1 and TH2 responses, but strongly support the relevance of IgE to the risk of asthma.