There is evidence from epidemiologic studies in man to suggest that a minor respiratory illness or exposure to airborne pollutants during infancy is associated with the occurence of chronic lung disease in adulthood. However this association cannot provide causation. The purpose of this study is to use the developing lamb to test the hypothesis that apparently minor, self-limited lung injury during infancy will lead to a chronic state of increased airway responsiveness in the adult. The mechanisms of an altered responsiveness may be related to an immaturity of the alveolar epithelial barrier in the young animal and the immune function of the lung. The first phase of the study will be to measure the normal development of alveolar permeability and airway responsiveness in the growing lamb. Lambs will be studied approximately monthly starting from the first week of life and ending at adulthood (approximately 9 months of age). To measure airway responsiveness, the lambs are intubated using a flexible bronchoscope and studied in a specially constructed whole body plethysmograph which permits measurement of lung mechanics in the awake animal. Responsiveness to increasing concentrations of aerosol histamine, aerosol prostaglandin F2Alpha and citric acid will be measured. Alveolar permeability will be measured by injecting a radioisotope mixture into the trachea and measuring the amount of each radioisotope in arterial blood. Once the normal pattern with growth is established, alteration in airway responsiveness will be provoked by exposing one month old lambs to RSV virus, cigarette smoke, and Ascaris suum antigen. The mechanism of altered airway responsiveness will be assessed by examining the relationship to alveolar permeability and by examining the immunologic response of the lung. The latter will be studied by using the chronic lung lymph preparation. The duct from the lymph node draining the lung can be cannulated in the sheep and lung lymph collected over a period of several days. The effect of the various lung insults on the immunologic function of the lung can be examined by studying the specific cells and immunoglobulins appearing in the lung lymph.
| Wagner, M H; Evermann, J F; Gaskin, J et al. (1991) Subacute effects of respiratory syncytial virus infection on lung function in lambs. Pediatr Pulmonol 11:56-64 |
| Sauder, R A; McNicol, K J; Stecenko, A A (1986) Effect of age on lung mechanics and airway reactivity in lambs. J Appl Physiol 61:2074-80 |
| Stecenko, A; McNicol, K; Sauder, R (1986) Effect of passive smoking on the lung of young lambs. Pediatr Res 20:853-8 |
| Hutchison, A A; McNicol, K J; Loughlin, G M (1985) The effect of age on pulmonary epithelial permeability in unanesthetized lambs. Pediatr Pulmonol 1:52-7 |
