Bronchial reactivity to inhaled methacholine in cigarette-smoking baboons

We expected that cigarette smoking would increase airway reactivity to inhaled methacholine. To remove the self-selection bias inherent among humans, we randomly assigned young male baboons (Papio cynocephalus) to cigarette-smoking or sham-smoking groups. The animals were taught to puff on lit cigarettes (smokers) or on a similar resistance (shams). After 6 pack-yr of smoking (40 cigarettes/day for 3 yr), we studied airway reactivity. The animals were anesthetized and intubated for measurement of lung volumes, compliance, and expiratory flow with air and with 80% helium-20% oxygen using both partial expiratory flow-volume and maximal expiratory flow-volume maneuvers. Baseline lung function was similar in smokers and shams. Following methacholine, residual volume increased significantly (P less than 0.05) in shams but not in smokers. Smokers showed significantly (P less than 0.04) greater postchallenge flow rates than did shams, and the dose of methacholine required to produce a 20% decrement in flow was significantly (P less than 0.05) greater in smokers. Chronic cigarette smoking in a nonhuman primate model decreases airway reactivity to inhaled methacholine even when base-line lung function is normal.