Prenatal and Early, but Not Late, Postnatal Exposure of Mice to Sidestream Tobacco Smoke Increases Airway Hyperresponsiveness Later in Life

BACKGROUND: Cigarette smoke exposure in utero and during early postnatal development increases the incidence of asthma and airway hyperresponsiveness (AHR) later in life, suggesting that a possible critical period of developmental sensitivity exists in the prenatal and early postnatal periods. OBJECTIVE: We investigated mechanisms of susceptibility during critical developmental periods to sidestream smoke (SS) exposure and evaluated the possible effects of SS on neural responses. METHODS: We exposed three different age groups of mice to either SS or filtered air (FA) for 10 consecutive days beginning on gestation day (GD) 7 by maternal exposure or beginning on postnatal day (PND) 2 or PND21 by direct inhalation. Lung function, airway substance P (SP) innervation, and nerve growth factor (NGF) levels in bronchoalveolar lavage fluid were measured after a single SS exposure on PND59. RESULTS: Methacholine (MCh) dose response for lung resistance (R-L) was significantly elevated, and dynamic pulmonary compliance (C-dyn) was significantly decreased, in the GD7 and PND2 SS exposure groups compared with the FA groups after SS exposure on PND59. At the same time points, the percent area of SP nerve fibers in tracheal smooth muscle and the levels of NGF were significantly elevated. MCh dose-response curves for R-L and C-dyn, SP nerve fiber density, and the level of NGF were not significantly changed in the PND21 exposure group after SS exposure on PND59. CONCLUSIONS: These results suggest that a critical period of susceptibility to SS exposure exists in the prenatal and early postnatal period of development in mice that results in increased SP innervation, increased NGF levels in the airway, and enhanced MCh AHR later in life.