Morphogenesis of Pulmonary Emphysema

A resume of a continuing program of study of pulmonary emphysema is presented. An orderly sequence was observed in alveolar septa of emphysematous human lungs proceeding from simple inflammation to dissolution on one hand or interstitial alveolar fibrosis on the other. In addition, quantitative methods showed a decreased number of nonrespiratory (“terminal”) bronchioles and reduced mean cross sectional lumen area of those bronchioles that remained. Measurements, however, failed to demonstrate that either increased bulk of wall or epithelium accounted for the bronchiolar narrowing in emphysema. Rather, a close correlation was demonstrated between stenosis and diminished, circumferential alveolar attachments. It seemed likely that a single process could account for many, and possibly most, of the morphologic processes seen in emphysema. Essentially, that was inflammation of peripheral portions of the lungs with departitioning and interstitial alveolar fibrosis. Secondary collapse and obliteration of air passages, particularly nonrespiratory bronchioles, occurring in association with parenchymal inflammation and destruction, provided a logical basis for air trapping and abnormal mechanical tensions. Emphysema, then, was considered to be largely the result of an interplay between inflammatory and secondary mechanical factors. Dust was considered as a factor of possible secondary importance. In order to test the suggested hypothesis, parenchymal inflammation (nitric acid) and increased mechanical forces (intratracheal valve) were combined in dogs. The resulting lung defect fulfilled standard morphologic definition of the disease in man.