To ascertain whether chronic cigarette smoke exposure induces increase
d airway responsiveness, we performed methacholine response tests in S
prague-Dawley rats by calculating pulmonary resistance after nebulizat
ion of-saline followed by an increasing concentration of methacholine.
We also calculated the concentration of methacholine which doubled th
e baseline resistance (R200). Tests were performed at baseline and aft
er 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-expose
d group and 7 rats remaining in the control group. Airway morphology w
as assessed using a point counting technique. We found that (1) chroni
c exposure to cigarette smoke did not alter either the baseline resist
ance or the R200; (2) the saline baseline resistance decreased over ti
me in the control animals; and (3) at the 12-month time point, smokers
with increased baseline airway resistance had greater amounts of airw
ay smooth muscle compared with the smoke-exposed animals without incre
ased resistance. We conclude that in this animal model, long term expo
sure 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.