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), three litters of puppies (n = 14) were studied when 8-10 weeks of age. Two litters, one mongrel (n = 7) and one foxhound-beagle cross (n = 3), were born and raised in a clean animal house environment (clean mongrels and clean cross, respectively). Another litter of mongrels was born (n = 4) and raised in an external environment (external mongrels), exposed to normal rural environmental contaminants. Animals were studied 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 external environment were significantly more responsive to inhaled Mch than those born and raised in the clean environment. This finding was true for both airway and parenchymal responsiveness. The group mean effective dose of Mch that produced a doubling of airway resistance (ED200Raw) for the external mongrel group was 4.40 mg/ml compared with 19.44 mg/ml for the clean mongrel group and 16.34 mg/ml for the clean cross group (P < 0.02). The group mean effective dose of Mch that produced a doubling of pressure difference in airways after the initial rapid rise in airway pressure (ED200Pdif) 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 modeling analysis showed that both "environment" and "breed" were significant factors in determining ED200Pdif, but only "environment" significantly influenced ED200Raw. In summary, the present study has demonstrated that the environment in which an animal is born and raised can influence lung mechanics and responsiveness to methacholine. This finding is particularly true for the lung parenchyma.