Increased Chronic Obstructive Pulmonary Disease Exacerbations of Likely Viral Etiology Follow Elevated Ambient Nitrogen Oxides

Rationale: Epidemiologic research strongly supports an association between air pollution and chronic obstructive pulmonary disease exacerbations. Numerous mechanisms may underlie any association because pollutants are toxic to pulmonary cells and may increase susceptibility to respiratory infections. The relationship between ambient pollution and exacerbation etiology has not been studied. Objectives: To evaluate the characteristics of pollution-associated exacerbations and whether the association is specific to exacerbations of infective or noninfective etiology. Methods: We analyzed the effect of preceding ambient particulate matter less than or equal to 10 mm in aerodynamic diameter, oxides of nitrogen (NOx), and ozone on characterized chronic obstructive pulmonary disease exacerbations in a regression model adjusted for temperature, seasonality, and long-termtrend. Wespecifically examined associations with exacerbations of suspected viral and/or bacterial, or noninfective etiology. For the associations identified we further examined the characteristics of pollution-associated exacerbations. Measurements and Main Results: A total of 4,173 exacerbations occurred over the 20-year study period. Higher ambient NOx was consistently associated with increased viral-type exacerbations at 2-4 days lag (P = 0.010). Recovery for viral-type exacerbations after higher ambient NOx was significantly prolonged. These findings were consistent in the subset of 2,841 exacerbations treated with oral corticosteroids or antibiotics, with recovery 1.29 (95% confidence interval, 1.17-1.42; P < 0.001) times longer with viral-type exacerbations of onset 3 days after above-versus below-median ambient NOx. A likely bimodal association of particulate matter less than or equal to 10 mu m in aerodynamic diameter with infective exacerbations was also evident and supported by a daily time-series analysis. Conclusions: Higher levels of ambient NOx are associated with prolonged exacerbations of likely viral etiology, supporting toxicologic effects of air pollution that increase susceptibility to, and severity of, infection.