While signal transducer and activator of transcription protein 6 (STAT6) is important in interleukin-4 (IL-4)-induced commitment of CD4(+) T cells to the T helper cell, type 2 (Th2) phenotype and IgE isotype switching in B cells, its role in other IL-4-mediated events and their impact upon the allergic response is less evident. In the present study we demonstrate the critical role of STAT6 in the development of allergic airway eosinophilia and airway hyperresponsiveness (AHR) after allergen sensitization and challenge. STAT6-deficient (STAT6-/-) mice did not develop a Th2 cytokine response or an allergen-specific IgE response. Further, STAT6-/- mice had a reduced constitutive and allergen-induced expression of CD23 as well as lower mucus production in the airway epithelium. Critically, we show that IL-5 alone can reconstitute airway eosinophilia and AHR in sensitized and challenged STAT6-/- mice. This emphasizes the essential nature of the IL-4-dependent signaling of T cells to the Th2 phenotype and secretion of IL-5, resulting in the airway eosinophilia and AHR. These observations underscore the importance of targeting this pathway in new antiallergic asthma drug development.

We propose a likelihood-based model for correlated count data that display under- or overdispersion within units (e.g. subjects). The model is capable of handling correlation due to clustering and/or serial correlation, in the presence of unbalanced, missing or unequally spaced data. A family of distributions based on birth-event processes is used to model within-subject underdispersion. A computational approach is given to overcome a parameterization difficulty with this family, and this allows use of common Markov Chain Monte Carlo software (e.g. WinBUGS) for estimation. Application of the model to daily counts of asthma inhaler use by children shows substantial within-subject underdispersion, between-subject heterogeneity and correlation due to both clustering of measurements within subjects and serial correlation of longitudinal measurements. The model provides a major improvement over Poisson longitudinal models, and diagnostics show that the model fits well.

RATIONALE: Urban children with asthma are commonly skin test positive to indoor allergens. We evaluated the relationship between home exposures and skin test sensitivity of children with asthma or asthma-like symptoms attending two Dallas Independent School District elementary schools. METHODS: Students, ages 6-12, with asthma or asthma symptoms were skin tested to cockroach, dust mite, cat, dog, and rodent (rat, mouse) allergens. Students who were skin positive to at least one indoor allergen were invited to participate. We evaluated study participants' homes for environmental exposures thought to be related to indoor allergen levels. RESULTS: Seventy-eight students entered the study. The skin test sensitivity profiles were similar for children attending either school. Dust mite, either Dermatophagoides farinae or D. pteronyssinus, mouse and cockroach were the most prevalent skin test sensitivities (67.9%, 50% and 46.2% respectively). Fifty-three percent reported problems with cockroaches but only fourteen percent reported problems with mice during the previous year. Apartment living significantly increased the likelihood of cockroach sensitivity (odds ratio 3.824, 95%CI: 1.472 -9.933; p=.006), as well as leaks in the home in the previous 12 months (odds ratio 2.857, 95%CI: 1.119 -7.293; p=.037). While most children had wall-to-wall carpeting in their bedroom (88%), it was not significantly associated with dust mite skin sensitivity (p>.05), nor were reported problems with mice significantly associated with mouse skin test sensitivity (p>.05). CONCLUSIONS: Our study indicates that apartment living and leaks in the home increase the risk of cockroach sensitivity in school-age children with asthma or asthma-like symptoms attending Dallas schools. Funding: ExxonMobil

Peak concentrations of ambient fine particulate are associated with early increases in bronchodilator use and urinary leukotriene E4 levels among children with persistent asthma, despite the use of controller medications.

No abstract

No abstract

Improved understanding of the sources of air pollution that are most harmful could aid in developing more effective measures for protecting human health. The Denver Aerosol Sources and Health (DASH) study was designed to identify the sources of ambient fine particulate matter (PM2.5) that are most responsible for the adverse health effects of short-term exposure to PM 2.5. Daily 24-hour PM2.5 sampling began in July 2002 at a residential monitoring site in Denver, Colorado, using both Teflon and quartz filter samplers. Sampling is planned to continue through 2008. Chemical speciation is being carried out for mass, inorganic ionic compounds (sulfate, nitrate and ammonium), and carbonaceous components, including elemental carbon, organic carbon, temperature-resolved organic carbon fractions and a large array of organic compounds. In addition, water soluble metals were measured daily for 12 months in 2003. A receptor-based source apportionment approach utilizing positive matrix factorization (PMF) will be used to identify PM 2.5 source contributions for each 24-hour period. Based on a preliminary assessment using synthetic data, the proposed source apportionment should be able to identify many important sources on a daily basis, including secondary ammonium nitrate and ammonium sulfate, diesel vehicle exhaust, road dust, wood combustion and vegetative debris. Meat cooking, gasoline vehicle exhaust and natural gas combustion were more challenging for PMF to accurately identify due to high detection limits for certain organic molecular marker compounds. Measurements of these compounds are being improved and supplemented with additional organic molecular marker compounds. The health study will investigate associations between daily source contributions and an array of health endpoints, including daily mortality and hospitalizations and measures of asthma control in asthmatic children. Findings from the DASH study, in addition to being of interest to policymakers, by identifying harmful PM2.5 sources may provide insights into mechanisms of PM effect.

No abstract