Rationale: The influence of particulate air pollution on respiratory health starts in utero. Fetal lung growth and structural development occurs in stages; thus, effects on postnatal respiratory disorders may differ based on timing of exposure. Objectives: We implemented an innovative method to identify sensitive windows for effects of prenatal exposure to particulate matter with a diameter less than or equal to 2.5 μm (PM2.5) on children's asthma development in an urban pregnancy cohort. Methods: Analyses included 736 full-term (≥37 wk) children. Each mother’s daily PM2.5 exposure was estimated over gestation using a validated satellite-based spatiotemporal resolved model. Using distributed lag models, we examined associations between weekly averaged PM2.5 levels over pregnancy and physician-diagnosed asthma in children by age 6 years. Effect modification by sex was also examined. Measurements and Main Results: Most mothers were ethnic minorities (54% Hispanic, 30% black), had 12 or fewer years of education (66%), and did not smoke in pregnancy (80%). In the sample as a whole, distributed lag models adjusting for child age, sex, and maternal factors (education, race and ethnicity, smoking, stress, atopy, prepregnancy obesity) showed that increased PM2.5 exposure levels at 16–25 weeks gestation were significantly associated with early childhood asthma development. An interaction between PM2.5 and sex was significant (P = 0.01) with sex-stratified analyses showing that the association exists only for boys. Conclusions: Higher prenatal PM2.5 exposure at midgestation was associated with asthma development by age 6 years in boys. Methods to better characterize vulnerable windows may provide insight into underlying mechanisms.

Biological hypersensitivity to environmental stimuli is a fundamental feature of atopy predisposing to a number of clinically expressed disorders including allergic rhinitis, atopic dermatitis or eczema, and allergic asthma. There is provocative evidence that psychological stress constitutes an increased risk for atopy. This risk is thought to be mediated by the effects of stress on neuroimmunoregulation which in turn modulates the hypersensitivity response. The primary objective is to review recent evidence updating our understanding of the role for psychological stress in atopy. The Th1–Th2 paradigm has been central to interpreting quantitative differences in cytokine expression in response to environmental stimuli like stress. Here we argue that examination of other mechanisms (e.g. oxidative stress pathways, glucocorticoid resistance, nerve–mast cell interactions, intestinal dysbiosis) and a broader range of cytokines and neuropeptides produced by cells both within and outside the immune system may better delineate the true complexity of the underlying mechanisms linking stress to allergic sensitization and asthma. The role of genetics and gene by environment interactions – based on evolving knowledge of candidate genes that may be relevant to both the stress response in general and pathways linked specifically to atopy – is also discussed. Psychological stress may be conceptualized as a social pollutant that, when ‘breathed’ into the body, may disrupt biological systems related to inflammation through mechanisms potentially overlapping with those altered by physical pollutants and toxicants.

Objectives. We examined the association between exposure to violence and asthma among urban children. Methods. We obtained reports from caretakers (n = 851) of violence, negative life events, unwanted memories (rumination), caretaker-perceived stress, and caretaker behaviors (keeping children indoors, smoking, and medication adherence). Outcomes included caretaker-reported wheezing, sleep disruption, interference with play because of asthma, and effects on the caretaker (nights caretaker lost sleep because of child’s asthma). Results. Increased exposure to violence predicted higher number of symptom days (P = .0008) and more nights that caretakers lost sleep (P = .02) in a graded fashion after control for socioeconomic status, housing deterioration, and negative life events. Control for stress and behaviors partially attenuated this gradient, although these variables had little effect on the association between the highest level of exposure to morbidity, which suggests there are other mechanisms. Conclusions. Mechanisms linking violence and asthma morbidity need to be further explored.

The role of stress in the pathogenesis of childhood wheeze remains controversial. Caretaker stress might influence wheeze through stress-induced behavioral changes in caregivers (e.g., smoking, breast-feeding) or biologic processes impacting infant development (e.g., immune response, susceptibility to lower respiratory infections). The influence of caregiver stress on wheeze in infancy was studied in a genetically predisposed prospective birth-cohort (n = 496). Caregiver-perceived stress and wheeze in the children were ascertained bimonthly from the first 2 to 3 mo of life. Greater levels of caregiver-perceived stress at 2 to 3 mo was associated with increased risk of subsequent repeated wheeze among the children during the first 14 mo of life (RR, 1.6; 95% CI, 1.3 to 1.9). Caregiver-perceived stress remained significant (RR, 1.4; 95% CI, 1.1 to 1.9) when controlling for factors potentially associated with both stress and wheeze (parental asthma, socioeconomic status, birth weight, and race/ethnicity) as well as mediators through which stress might influence wheeze (maternal smoking, breast-feeding, indoor allergen exposures, and lower respiratory infections). Furthermore, caregiver stress prospectively predicted wheeze in the infants, whereas wheeze in the children did not predict subsequent caregiver stress. The effect of caregiver stress on early childhood wheeze was independent of caregiver smoking and breast-feeding behaviors, as well as allergen exposure, birth weight, and lower respiratory infections. These findings suggest a more direct mechanism may be operating between stress and wheeze in early childhood. Stress may contribute significantly to the population burden of preventable childhood respiratory illness.