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Background: There is growing public awareness regarding the risk associated with poor indoor air quality in the home and workplace. Because Americans spend approximately 22 hours every day indoors, susceptible individuals are at much greater risk of adverse health effects from chronic low levels of exposure to indoor air pollutants over time. Along with particulate matter, gases such as ozone, nitrogen dioxide, carbon monoxide, and sulfur dioxide; microbial and chemical volatile organic compounds; passive smoke; and outdoor ambient air are the most common types of air pollutants encountered indoors. Objective: To provide the allergists with necessary information that will assist them in making useful recommendations to patients seeking advice regarding indoor environmental triggers beyond traditional perennial allergens. Methods: Review of the literature pertaining to indoor exposure and health effects of gaseous and particular matter. Results: Indoor pollutants act as respiratory irritants, toxicants, and adjuvants or carriers of allergens. Conclusion: The allergist should be prepared to evaluate patient exposure to allergic and nonallergic triggers and understand how outdoor air pollution is affecting indoor environments. This requires being familiar with methodologies for monitoring and interpreting indoor air quality and interpreting results in the context of the patients exposure history and advising patients about rational environmental control interventions. [Copyright &y& Elsevier]

Background: Increased exposure to microbial products early in life may protect from development of atopic disorders in childhood. Few studies have examined the relationship of endotoxin exposure and pet ownership on atopy and wheezing during infancy. Objective: Evaluate relationships among high endotoxin exposure, pet ownership, atopy, and wheezing in high-risk infants. Methods: Infants (n = 532; mean age, 12.5 ± 0.8 months) with at least 1 parent with confirmed atopy were recruited. A complete medical history and skin prick testing to foods and aeroallergens were performed at age 1 year. House dust samples were analyzed for endotoxin. Results: Prevalences of wheezing were not independently associated with dog or cat ownership or endotoxin levels. Percutaneous reactivity to at least 1 allergen was observed in 28.6% of infants. Univariate analyses showed significant associations of any wheezing, recurrent wheezing, and recurrent wheezing with an event with daycare attendance, number of siblings, respiratory infections, maternal smoking, and history of parental asthma. Logistic regression adjusting for the latter variables showed that recurrent wheezing (odds ratio, 0.4; 95% CI, 0.1-0.9) as well as 2 other wheeze outcomes were significantly reduced in homes with high endotoxin exposure in the presence of 2 or more dogs. Conclusion: Pet ownership or endotoxin did not independently modify aeroallergen sensitization or wheezing during infancy. However, high endotoxin exposure in the presence of multiple dogs was associated with reduced wheezing in infants. Clinical implications: A home environment with many dogs and high levels of endotoxin may be conducive to reduced wheezing in infancy. [Copyright &y& Elsevier]

Background Allergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity. Objective We sought to determine the mechanism by which fungi affect asthma development and severity. Methods We integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity. Results We report that fungal exposure enhances allergen-driven T H 2 responses, promoting severe allergic asthma. This effect is independent of fungal sensitization and can be reconstituted with β-glucan and abrogated by neutralization of IL-17A. Furthermore, this severe asthma is resistant to steroids and characterized by mixed T H 2 and T H 17 responses, including IL-13 + IL-17 + CD4 + double-producing effector T cells. Steroid resistance is dependent on fungus-induced T H 17 responses because steroid sensitivity was restored in IL-17rc −/− mice. Similarly, in children with asthma, fungal exposure was associated with increased serum IL-17A levels and asthma severity. Conclusion Our data demonstrate that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens. Furthermore, our results provide a strong rationale for combination treatment strategies targeting IL-17A for this subgroup of fungus-exposed patients with difficult-to-treat asthma. [ABSTRACT FROM AUTHOR]

Background: It is well accepted that mold exposure is a major contributor to the development of asthma, and beta-glucans are often used as a surrogate for mold exposure in the environment. Beta-glucans are an important component of mold spores and are recognized by the immune system by their receptor, Dectin-1. Cladosporium cladosporioides spores have a high beta-glucan content, but the beta-glucans are not available on the surface of live spores. Objective: We sought to determine whether altering the exposure of beta-glucans in C cladosporioides through heat killing could alter the immune response through binding to Dectin-1. Methods: In a murine model of mold-induced asthma, mice were repeatedly exposed to either live or heat-killed C cladosporioides and the phenotype was determined by the measurement of airway hyperresponsiveness, airway inflammation, and cytokine production. Pro-inflammatory cytokines from dendritic cells were measured by using quantitative PCR and ELISA. Results: Live C cladosporioides induced robust airway hyperresponsiveness, eosinophilia, and a predominately TH2 response, while heat-killed C cladosporioides induced a strong TH17 response and neutrophilic inflammation, but very mild airway hyperresponsiveness. Heat killing of C cladosporioides spores effectively exposed beta-glucans on the surface of the spores and increased binding to Dectin-1. In the absence of Dectin-1, heat-killed spores induced a predominantly TH2 response analogous to live spores. Furthermore, the production of TH17-skewing IL-6, IL-23, and TNF-α by dendritic cells in response to heat-killed C cladosporioides was dependent on Dectin-1. Conclusions: The host immune response to C cladosporioides is dependent on the surface availability of beta-glucans rather than the total beta-glucan content. [Copyright &y& Elsevier]

Background: The specific cause or causes of asthma development must be identified to prevent this disease. Objective: Our hypothesis was that specific mold exposures are associated with childhood asthma development. Methods: Infants were identified from birth certificates. Dust samples were collected from 289 homes when the infants were 8 months of age. Samples were analyzed for concentrations of 36 molds that comprise the Environmental Relative Moldiness Index (ERMI) and endotoxin, house dust mite, cat, dog, and cockroach allergens. Children were evaluated at age 7 years for asthma based on reported symptoms and objective measures of lung function. Host, environmental exposure, and home characteristics evaluated included a history of parental asthma, race, sex, upper and lower respiratory tract symptoms, season of birth, family income, cigarette smoke exposure, air conditioning, use of a dehumidifier, presence of carpeting, age of home, and visible mold at age 1 year and child''s positive skin prick test response to aeroallergens and molds at age 7 years. Results: Asthma was diagnosed in 24% of the children at age 7 years. A statistically significant increase in asthma risk at age 7 years was associated with high ERMI values in the child''s home in infancy (adjusted relative risk for a 10-unit increase in ERMI value, 1.8; 95% CI, 1.5-2.2). The summation of levels of 3 mold species, Aspergillus ochraceus, Aspergillus unguis, and Penicillium variabile, was significantly associated with asthma (adjusted relative risk, 2.2; 95% CI, 1.8-2.7). Conclusion: In this birth cohort study exposure during infancy to 3 mold species common to water-damaged buildings was associated with childhood asthma at age 7 years. [Copyright &y& Elsevier]

Background: Although evidence suggests that ambient exposures to endotoxin and other immunostimulants during early life influence allergic risk, efforts to understand this host-environment relationship have been hampered by a paucity of relevant assays. Objectives: These investigations determined whether parameters of house dust extract (HDE) bioactivity were predictive of allergen skin prick test (SPT) reactivity for infants at high risk of allergy participating in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). Methods: We conducted a nested case-control study, selecting 99 CCAAPS children who had positive SPT results to at least 1 aeroallergen at age 3 years and 101 subjects with negative SPT results. HDEs were prepared from dust samples collected from the subjects’ homes at age 1 year. Murine splenocytes and bone marrow–derived dendritic cells were incubated with HDEs, and supernatant cytokine concentrations were determined by means of ELISA. Alternatively, bone marrow–derived dendritic cells were preincubated with HDEs, and then LPS-induced IL-6 responses were assessed. HDE endotoxin levels were determined by using the limulus amebocyte lysate assay. Results: HDEs derived from the homes of children with positive (cases) and negative (control subjects) SPT results had similar bioactivities. However, when cases were considered in isolation, HDEs with higher levels of bioactivity were significantly associated with children who had lower numbers of positive SPT results. Analogous statistical analyses did not identify any association between HDE endotoxin levels and the aeroallergen sensitization profiles of children included in this study. Conclusion: HDE immunostimulatory activities predicted the aeroallergen sensitization status of CCAAPS subjects better than HDE endotoxin levels. These results provide the first published evidence that HDE bioassays have clinical relevance in predicting atopic risk. [ABSTRACT FROM AUTHOR]

Background: Infant predictors of early childhood allergic rhinitis (AR) are poorly understood. Objective: We sought to identify environmental exposures and host factors during infancy that predict AR at age 3 years. Methods: High-risk children from greater Cincinnati were followed annually from ages 1 to 3 years. AR was defined as sneezing, runny, or blocked nose in the prior 12 months and a positive skin prick test (SPT) response to 1 or more aeroallergens. Environmental and standardized medical questionnaires determined exposures and clinical outcomes. Primary activity area dust samples were analyzed for house dust endotoxin (HDE) and (1-3)-β-D-glucan. Fine particulate matter sampled at 27 monitoring stations was used to estimate personal elemental carbon attributable to traffic exposure by using a land-use regression model. Results: Of 361 children in this analysis, 116 had AR, and 245 were nonatopic and nonsymptomatic. Prolonged breast-feeding in African American children (adjusted odds ratio [aOR], 0.8; 95% CI, 0.6-0.9) and multiple children in the home during infancy was protective against AR (aOR, 0.4; 95% CI, 0.2-0.8). Food SPT response positivity and tree SPT response positivity in infancy increased the risk of AR at age 3 years (aOR of 4.4 [95% CI, 2.1-9.2] and aOR of 6.8 [95% CI, 2.5-18.7], respectively). HDE exposure was associated with AR; the effect was dependent on exposure level. Elemental carbon attributable to traffic and environmental tobacco smoke exposure showed no effect on AR. Conclusion: Prolonged breast-feeding in African American subjects and multiple children in the home during infancy reduced the risk of AR at age 3 years. SPT response positivity to food and tree allergens enhanced risk. The HDE effect on AR was related to exposure. [Copyright &y& Elsevier]