Combined respiratory effects of cold air with SO2 or NO2 in repeated 10-minute exposures of hyperventilating guinea pigs

Previous studies in asthmatic subjects and guinea pigs have demonstrated at tenuation of bronchoconstriction in repeated exposures to clean cold dry ai r. In the present animal study, we have simulated short-lasting human expos ures to subfreezing urban air containing sulfur dioxide (SO2) and nitrogen dioxide (NO2). The anesthetized, paralyzed, and mechanically ventilated gui nea pigs had 4 consecutive 10-min exposures either to clean cold dry air or to cold air with graded concentrations of SO2 (0-5 ppm) or NO2 (0-4 ppm). Peak expiratory flow (PEF) and tidal volume (V-T) were continuously measure d both during and after highly controlled exposures. Bronchoalveolar lavage fluid (BALF) and histological samples were obtained after finishing the co nsecutive exposures. Cold air + SO2 at 1 and 2.5 ppm (n = 12) produced imme diate concentration-dependent increases in the lung function responses comp ared to the preceding single exposure to clean cold dry air in the same ani mals (Delta PEF = -32.7 +/- 6.1% and -35.6 +/- 6.5% vs. -27.0 +/- 3.1%; Del ta V-T = -22.4 +/- 4.4% and -28.3 +/- 4.7% vs. -18.1 +/- 2.9%). In a multiv ariate analysis, these responses were significantly larger than the attenua ted lung function responses to the corresponding second and third clean col d dry air exposures (p < .05). The fourth exposure to cold air + SO2 at 5 p pm produced a smaller response (DPEF = -25.3 +/- 4. 8% and Delta V-T = -17. 8 +/- 3.7%) than cold air with the lower SO2 concentrations. Cold air + NO2 at 1 and 2.5 ppm (n = 12) produced roughly similar lung function responses to the preceding single exposure to clean cold dry air in the same animals , and there was no significant attenuation of bronchoconstriction as with t he consecutive exposures to clean cold dry air. The largest decreases in lu ng functions (DPEF = -33.8 +/- 6.7% and Delta V-T = -26.2 +/- 6.8%) were re corded during the fourth exposure, which was to cold air + NO2 at 4 ppm. In the cold air + SO2 group, there was a significantly lower proportion of ma crophages in the differential count of BALF white cells compared to the cle an cold dry air group. In addition, there was eosinophilic infiltration wit hin and below the tracheal epithelium in all guinea pigs exposed to either clean cold dry air, cold air + SO2, or cold air + NO2. In conclusion, the a ddition of moderate concentrations of SO2 or NO2 to clean cold dry air coun teracted the attenuation of bronchoconstriction induced by repeated cold dr y air exposures in guinea pigs. Cold air + SO2 also decreased the proportio n of macrophages in BALF white cells.