title: Combined respiratory effects of cold air with SO(2) or NO(2) in repeated 10-minute exposures of hyperventilating guinea pigs.
abstract: Previous studies in asthmatic subjects and guinea pigs have demonstrated attenuation of bronchoconstriction in repeated exposures to clean cold dry air. In the present animal study, we have simulated short-lasting human exposures to subfreezing urban air containing sulfur dioxide (SO(2)) and nitrogen dioxide (NO(2)). The anesthetized, paralyzed, and mechanically ventilated guinea pigs had 4 consecutive 10-min exposures either to clean cold dry air or to cold air with graded concentrations of SO(2) (0-5 ppm) or NO(2) (0-4 ppm). Peak expiratory flow (PEF) and tidal volume (V(T)) were continuously measured both during and after highly controlled exposures. Bronchoalveolar lavage fluid (BALF) and histological samples were obtained after finishing the consecutive exposures. Cold air + SO(2) at 1 and 2.5 ppm (n = 12) produced immediate concentration-dependent increases in the lung function responses compared to the preceding single exposure to clean cold dry air in the same animals (DeltaPEF = -32.7 +/- 6.1% and -35.6 +/- 6.5% vs. -27.0 +/- 3.1%; DeltaV(T) = -22.4 +/- 4.4% and -28.3 +/- 4.7% vs. -18.1 +/- 2.9%). In a multivariate analysis, these responses were significantly larger than the attenuated lung function responses to the corresponding second and third clean cold dry air exposures (p <. 05). The fourth exposure to cold air + SO(2) at 5 ppm produced a smaller response (DeltaPEF = -25.3 +/- 4.8% and DeltaV(T) = -17.8 +/- 3.7%) than cold air with the lower SO(2) concentrations. Cold air + NO(2) 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 the consecutive exposures to clean cold dry air. The largest decreases in lung functions (DeltaPEF = -33.8 +/- 6.7% and DeltaV(T) = -26.2 +/- 6.8%) were recorded during the fourth exposure, which was to cold air + NO(2) at 4 ppm. In the cold air + SO(2) group, there was a significantly lower proportion of macrophages in the differential count of BALF white cells compared to the clean cold dry air group. In addition, there was eosinophilic infiltration within and below the tracheal epithelium in all guinea pigs exposed to either clean cold dry air, cold air + SO(2), or cold air + NO(2). In conclusion, the addition of moderate concentrations of SO(2) or NO(2) to clean cold dry air counteracted the attenuation of bronchoconstriction induced by repeated cold dry air exposures in guinea pigs. Cold air + SO(2) also decreased the proportion of macrophages in BALF white cells.
authors.affiliation: National Public Health Institute, Department of Environmental Medicine, PO Box 95, FIN-70701 Kuopio, Finland.
authors.forename: A I
authors.initials: AI
authors.lastname: Hälinen
authors.forename: R O
authors.initials: RO
authors.lastname: Salonen
authors.forename: A S
authors.initials: AS
authors.lastname: Pennanen
authors.forename: V M
authors.initials: VM
authors.lastname: Kosma
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects; D002452:Cell Count; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D004802:Eosinophilia; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D006985:Hyperventilation / Q000473:pathology / Q000503:physiopathology*; D019570:Inhalation Exposure; D008264:Macrophages / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D009585:Nitrogen Dioxide / Q000009:adverse effects*; D011433:Propranolol / Q000494:pharmacology; D012123:Pulmonary Ventilation / Q000187:drug effects; D012121:Respiration, Artificial / Q000379:methods; D013458:Sulfur Dioxide / Q000009:adverse effects*; D013990:Tidal Volume / Q000187:drug effects; D014132:Trachea / Q000473:pathology
chemical_list: D000393:Air Pollutants; D013458:Sulfur Dioxide; D011433:Propranolol; D009585:Nitrogen Dioxide