Morphometric Assessment of the Airwall Structure in Severe Asthmatics and Control Subjects

Grant Winners

Deans

Abstract

Asthma is a chronic, recurring inflammatory lung disease characterized by reversible bronchial obstruction-constriction and an increased responsiveness of the tracheobronchial tree to a variety of stimuli. This results in hyperemia, edema, submucosal gland and smooth muscle hyperplasia and eventually connective tissue deposition and airway remodeling. We hypothesize that all of these morphological components of the asthmatic response results in one common endpoint: increased thickness of the airway wall, with encroachment on the airway lumen. This outcome may result in a much more drastic narrowing of the susceptible airways when a subject is exposed to a minimal asthmatic stimulus, eliciting a disproportionally large effect on the chronically impaired asthmatic airways as compared to controls. In the present proposal, we intend to investigate the quantitative relationships between the airway wall thickness, its morphologic components and lumen size. We will measure connective tissue compartments, including smooth muscle, cartilage, vasculature, edema and submucosal glands in subjects that died in status asthmaticus and compare these with control subjects. This comparison is possible because the length of the internal airway perimeter remains remarkably constant even during the severe bronchial constriction due to the folding of mucosa. The major question asked here is which constituents of the airway wall are most responsible for the narrowing of airways in a severe asthma attack. To resolve this question, we propose to measure the airway wall structures in histological sections of human bronchial tissue with an image analysis program, Image-Pro® Plus. Our preliminary data from the morphometric analysis of small airways suggest that the submucosal glands in bronchi of asthmatic subjects are larger as compared to controls. This may not only contribute to the potentially more copious mucus secretion, but also to the increase of the airway wall volume, consequently contributing to the narrowing of the airway lumen.