Claire Duguet
Research Mentor(s): John Osterholzer
Mentor Department: Internal Medicine, Pulmonary Division
Authors:
Session: Session 5 (2:00pm – 2:50pm)
Presentation Type: Poster 86
Abstract
A subset of soldiers, exposed to potential airborne toxins during deployment to Southwest Asia and Afghanistan, were diagnosed with deployment-related constrictive bronchiolitis (DCRB), a small airway lung disease characterized by thickening of bronchioles due to collagen deposition. Currently, definitive diagnosis of DRCB requires an invasive lung biopsy, and no proven treatment is available. Club cells are critical for repairing the small airway epithelium after injury, but sustained depletion may overwhelm their regenerative capacity and lead to scarring. Our research group has previously shown that sustained club cell injury in mice leads to histopathological features consistent with DRCB. The aim of this project was to evaluate whether azithromycin, known to be effective in other small airway diseases, can prevent the development of peribronchiolar fibrosis in this animal model. In this study, doxycycline was given to inducible transgenic CC-DTA (club cell diphtheria toxin A) mice for 10 consecutive days to elicit murine constrictive bronchiolitis. Littermate mice were used as control groups. Azithromycin or vehicle (water) was given daily by oral gavage for 20 days, beginning one day before doxycycline administration. Lungs were harvested at day 20 to evaluate small airway fibrosis. Picrosirius red (PSR)-stained lung sections were analyzed for width and collagen content of small airway walls using image J software. Data were normalized to the perimeter of the basement membrane. Comparative morphometric analysis demonstrated that azithromycin prevented club cell injury-induced thickening of small airway walls. Quantification of fluorescence intensity also revealed that collagen content of small airways decreased in mice treated with azithromycin. We plan to explore mechanisms underlying these findings, particularly whether azithromycin protects against club cells apoptosis and/or modulates host immune function. Our results form a rationale to examine the potential therapeutic effect of azithromycin using this model and may lead to future studies in clinical settings.
