Remodeling of Airway Walls in Fatal Asthmatics Decreases Lymphatic Distribution; Beyond Thickening of Airway Smooth Muscle Layers

Abstract

We previously reported the phenotypic distribution patterns of airway smooth muscles in fatal asthmatics; Type I asthmatics with smooth muscle bundle thickening only in large airways and Type II in whole airways. We hypothesized that increased smooth muscle bundles in the airway walls would disrupt airway lymphatics to impair airway clearance in these fatal asthmatics. The autopsy lungs of seven fatal asthmatics (three Type I, four Type II asthmatics) and five controls were examined by immunohistochemistry to reveal the lymphatics distributed in the airway walls. The total area of lymphatics around each cross-sectioned airway was measured and its airway radius was calculated using an image analyzer system. Finally, the distribution areas of lymphatics in the same level of airways of bronchial trees were compared among Type I, Type II asthmatics and controls. The total area of airway lymphatics in each lung was found to be positively correlated with the airway radius (R). The distribution areas of lymphatics in larger airways (1.5 < R < 2.0 mm) of both types of asthmatics were significantly decreased than controls, and Type I asthmatics contained much less lymphatics than Type II asthmatics in these airways. The lymphatics around smaller airways (0.5 < R < 1.0 mm) were also reduced in both phenotypes of asthmatics without statistic difference between them. The airway lymphatics of these fatal asthmatics were observed to be interrupted by thickened muscle bundle layers, and by fibrotic tissues developed around these airways as well. These results indicate that distribution of lymphatics were decreased in the airway walls of fatal asthmatics which contained muscle bundles and fibro-connective tissues both of which were augmented in these airway walls to disrupt lymphatics, impair airway clearance and accelerate mucosal edema which would cause refractory status of these patients.