Increased airway responsiveness and decreased alveolar attachment points following in utero smoke exposure in the guinea pig

Maternal smoking during pregnancy has been shown to result in abnormalities in lung function in newborn infants, including reduced expiratory flow and increased airway responsiveness to inhaled agonists. The mechanisms by whi ch this occurs remain unclear. Using a guinea pig model of in utero smoke e xposure, we measured airway responsiveness and lung morphology in a group o f neonatal guinea pigs 21 d after delivery. Pregnant guinea pigs were expos ed to cigarette smoke from Day 28 to term (Day 68 of gestation). After deli very newborn animals did not receive any smoke exposure. Airway wall thickn ess, smooth muscle area, and the number of points where the alveoli attache d to the airway adventitia were measured. Airway responsiveness was increas ed (p < 0.05) and the mean distance between alveolar attachment points was increased (mean 0.052 +/- SE 0.001 mm versus 0.046 +/- 0.001, p = 0.001) in animals exposed to cigarette smoke in utero compared with nonexposed anima ls. Although not statistically significant, both the inner and outer airway wall and the smooth muscle area were greater in exposed animals compared w ith nonexposed animals. The increased mean distance between alveolar attach ments in the smoke-exposed group was the result of a reduction in the numbe r of attachments and an increase in the outer airway wall perimeter. These findings suggest that the increased airway responsiveness observed in postn atal animals, subsequent to in utero cigarette smoke exposure, may be the r esult of decreased alveolar attachment points to the airways and changes in airway dimensions.