Long term cigarette smoke exposure does not increase airway responsiveness in rats.

To ascertain whether chronic cigarette smoke exposure induces increased airway responsiveness, we performed methacholine response tests in Sprague-Dawley rats by calculating pulmonary resistance after nebulization of saline followed by an increasing concentration of methacholine. We also calculated the concentration of methacholine which doubled the baseline resistance (R200). Tests were performed at baseline and after 2, 4, 8, and 12 months of exposure to the smoke of seven cigarettes per day, 5 days each week; control animals were exposed to room air. At the completion of the study, there were 13 rats in the smoke-exposed group and 7 rats remaining in the control group. Airway morphology was assessed using a point counting technique. We found that (1) chronic exposure to cigarette smoke did not alter either the baseline resistance or the R200; (2) the saline baseline resistance decreased over time in the control animals; and (3) at the 12-month time point, smokers with increased baseline airway resistance had greater amounts of airway smooth muscle compared with the smoke-exposed animals without increased resistance. We conclude that in this animal model, long term exposure to cigarette smoke did not alter the response to methacholine but did increase airway smooth muscle and baseline resistance in some but not all animals.