ENVIRONMENTAL-EFFECTS ON PULMONARY MECHANICS AND THE RESPONSE TO INHALED METHACHOLINE

To investigate the role of environmental exposure from birth on airway and lung parenchymal responsiveness to inhaled methacholine (Mch), th ree litters of puppies (n = 14) were studied when 8-10 weeks of age. T wo litters, one mongrel (n = 7) and one foxhound-beagle cross (n = 3), were born and raised in a clean animal house environment (clean mongr els and clean cross, respectively). Another litter of mongrels was bor n (n = 4) and raised in an external environment (external mongrels), e xposed to normal rural environmental contaminants. Animals were studie d open-chested with alveolar capsules used to partition mechanics into airway and parenchymal components. Lung mechanics were measured after abrupt flow interruptions. The animals born and raised in the externa l environment were significantly more responsive to inhaled Mch than t hose born and raised in the clean environment. This finding was true f or both airway and parenchymal responsiveness. The group mean effectiv e dose of Mch that produced a doubling of airway resistance (ED(200)Ra w) for the external mongrel group was 4.40 mg/ml compared with 19.44 m g/ml for the clean mongrel group and 16.34 mg/ml for the clean cross g roup (P < 0.02). The group mean effective dose of Mch that produced a doubling of pressure difference in airways after the initial rapid ris e in airway pressure (ED(200)Pdif) for the external mongrel group was 0.79 mg/ml compared with 3.90 mg/ml for the clean mongrel group and 10 .78 mg/ml for the clean cross group (P < 0.01). Generalized linear mod eling analysis showed that both ''environment'' and ''breed'' were sig nificant factors in determining ED(200)Pdif, but only ''environment'' significantly influenced ED(200)Raw. In summary, the present study has demonstrated that the environment in which an animal is born and rais ed can influence lung mechanics and responsiveness to methacholine. Th is finding is particularly true for the lung parenchyma. (C) 1998 Wile y-Liss, Inc.