Immediate and delayed effects of nitrogen dioxide exposure at an ambient level on bronchial responsiveness to histamine in subjects with asthma.

The time-kinetics of NO2 induced effects on bronchial responsiveness are poorly known as most observations have been made shortly after exposure. The aim of this study was to measure nonspecific bronchial responsiveness, lung function and inflammatory markers at different times after NO2 exposure in asthmatics. Nineteen subjects with mild asthma were exposed to either purified air or 488 micrograms.m-3 (0.26 ppm) NO2 for 30 min during intermittent exercise. Airway responsiveness to histamine, specific airway resistance (sRaw) and thoracic gas volume (TGV) were measured 30 min, 5 h, 27 h and 7 days after exposure. Peripheral blood inflammatory mediators and the expression of an adhesion molecule, (Mac1) on granulocytes, were analysed 30 min and 27 h after exposure. Bronchial responsiveness to histamine was significantly increased 5 h after NO2 exposure when compared to air (median provocative dose of histamine required to cause 100% increase of sRaw ((PDsRaw,100%) 110 micrograms after NO2 exposure vs 203 micrograms on air). There was a tendency for an increase after 30 min, which was nonsignificant (median PDsRaw,100% 100 vs 153 micrograms). NO2 exposure did not affect sRaw, but TGV was significantly reduced after exposure. We found an increased expression of Mac-1 on granulocytes 30 min after NO2 exposure when compared to pre-exposure values. No effect was seen on tryptase, eosinophil cationic protein (ECP), or myeloperoxidase (MPO). These results suggest that exposure to an ambient level of NO2 causes a delayed effect on bronchial responsiveness in asthmatics. The increased expression of an adhesion molecule in peripheral blood may indicate a NO2-induced priming of human granulocytes.