Rationale Infants exposed to environmental tobacco smoke (ETS) have more severe respiratory syncytial virus (RSV) bronchiolitis. RSV bronchiolitis is associated with elevated cysteinyl leukotrienes and ETS exposure is associated with a Th2 phenotype, which may ultimately result in a greater production of cysteinyl leukotrienes. Cysteinyl leukotrienes can produce bronchoconstriction, edema, and mucus secretion, hallmarks of bronchiolitis. We hypothesized that infants hospitalized with RSV bronchiolitis who were exposed to ETS would have higher cysteinyl leukotrienes in their urine. Methods Urine was collected from infants ≤24 months of age admitted with RSV bronchiolitis. Patients were excluded if they had asthma, chronic lung or heart disease, or immunodeficiency. The urine was analyzed with an enzyme immunoassay for leukotriene E4 (LTE4), liquid chromatography with tandem mass spectophotometry for cotinine, a metabolite of nicotine, and colorometric technique for creatinine. Results None of the caretakers reported that the infant was exposed to smoke in the home. However, 6 of 23 infants had a urinary cotinine/creatinine ratio of >30ng/mg indicating exposure to ETS. LTE4 was 134% higher in infants exposed to ETS (P=0.005, single factor ANOVA). Among the infants exposed to ETS, cotinine/creatinine ratio correlated with LTE4 (r2=0.82, P=0.01). Conclusions ETS exposure may worsen RSV bronchiolitis by enhancing production of cysteinyl leukotrienes.

Twenty-four infant rhesus monkeys (30 days old) were exposed to 11 episodes of filtered air (FA), house dust mite allergen aerosol (HDMA), ozone (O3), or HDMA + O3 (5 days each followed by 9 days of FA). Ozone was delivered for 8 h/day at 0.5 ppm. Twelve of the monkeys were sensitized to house dust mite allergen (Dermatophagoides farinae) at ages 14 and 28 days by subcutaneous inoculation (SQ) of HDMA in alum and intraperitoneal injection of heat-killed Bordetella pertussis cells. Sensitized monkeys were exposed to HDMA aerosol for 2 h/day on days 3-5 of either FA (n = 6) or O3 (n = 6) exposure. Nonsensitized monkeys were exposed to either FA (n = 6) or O3 (n = 6). During the exposure regimen, parameters of allergy (i.e., serum IgE, histamine, and eosinophilia), airways resistance, reactivity, and structural remodeling were evaluated. Eleven repeated 5-day cycles of inhaling 0.5 ppm ozone over a 6-month period had only mild effects on the airways of nonsensitized infant rhesus monkeys. Similarly, the repeated inhalation of HDMA by HDMA-sensitized infant monkeys resulted in only mild airway effects, with the exception of a marked increase in proximal airway and terminal bronchiole content of eosinophils. In contrast, the combined cyclic inhalation of ozone and HDMA by HDMA sensitized infants monkeys resulted in a marked increase in serum IgE, serum histamine, and airways eosinophilia. Furthermore, combined cyclic inhalation of ozone and HDMA resulted in even greater alterations in airway structure and content that were associated with a significant elevation in baseline airways resistance and reactivity. These results suggest that ozone can amplify the allergic and structural remodeling effects of HDMA sensitization and inhalation.