Effects of Nitrogen Dioxide on Airway Inflammation in Allergic Asthmatic Subjects

Colin Solomon; J Balmes; M Kleinman

Final report for the California Air Resources Board and the California Environmental Protection Agency. Nitrogen dioxide (NO2) can enhance both early and late airway narrowing after inhaled antigen in allergic asthmatic subjects. We hypothesized that NO2 may also increase airway inflammation during the late response. Nitrogen dioxide has been shown to cause airway inflammation in healthy subjects without asthma. We also hypothesized that individuals with asthma may have increased non-allergic airway inflammation after exposure to NO2. To test these hypotheses, we designed two experiments with the following specific aims: Experiment 1) To determine the effect of a single exposure to NO2 on allergen-induced airway inflammation. Experiment Two: To determine the effect of NO2 exposure on non-allergic airway inflammation. Experiment One: 15 house dust mite (HDM)-sensitive asthmatic subjects were exposed for 3 hours to filtered air or 0.4 ppm NO2 followed immediately by inhalation of HDM allergen. Lung function was measured before and after each exposure and after allergen challenge, hourly for 6 hours. Sputum (airway lining fluid) was obtained at 6 hours and 26 hours after allergen challenge and assessed for inflammatory cells and biochemical markers of inflammation. There was no significant effect of NO2 exposure on early or late airway narrowing after HDM allergen for the group as a whole. However, three subjects did have substantially greater early airway narrowing with HDM allergen inhalation after NO2. A significant decrease in a type of inflammatory cell (eosinophils) was observed in sputum obtained 6 hours after NO2, but there was no significant NO2-related difference for any other measure of inflammation. These results suggest that in most asthmatic individuals a 3-hour exposure to a high ambient concentration of NO2 does not increase the late airway inflammatory response to inhaled allergen. There may, however, be a subset of allergic asthmatic individuals in whom NO2 exposure does increase early airway narrowing. Future research should be directed towards understanding the determinants of why some asthmatic individuals are more susceptible to NO2. Experiment Two: 10 asthmatic subjects were exposed for 3 hours to filtered air or 0.4 ppm NO2 followed by sputum sampling. Lung function was measured before and after each exposure. Sputum was obtained at 6 hours and 26 hours after exposure and assessed for inflammatory cells and biochemical markers of inflammation. There was no significant effect of NO2 exposure on lung function or any measures of inflammation in sputum. These results suggest that in mild asthmatic individuals a 3-hour exposure to a high ambient level of NO2 does not cause either airway narrowing or non-allergic airway inflammation.

Effects of Nitrogen Dioxide on Airway Inflammation in Allergic Asthmatic Subjects

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