Varun Naravetla
Pronouns: He/Him
Research Mentor(s): John Osterholzer
Research Mentor School/College/Department: Internal Medicine, Pulmonary Division / Medicine
Program:
Authors: Teitz-Tennenbaum Seagal
Session: Session 6: 3:40 pm – 4:30 pm
Poster: 56
Abstract
Background: Surgical lung biopsies on soldiers returning from the Gulf War and post-9/11 conflicts and experiencing undiagnosed respiratory symptoms despite medical evaluation have often revealed histopathological evidence of deployment-related constrictive bronchiolitis (DRCB), defined as a 20% increase in small airway wall thickness. There are no proven therapies for this condition, thus this study aimed to evaluate the therapeutic potential of pirfenidone, a drug used to treat idiopathic pulmonary fibrosis, in combating this disorder. Methods: CC-DTA transgenic mice express diphtheria toxin-A exclusively in club cells upon doxycycline exposure leading to targeted club cell death and, after sustained injury, to the development of CB. Four groups of mice (two CC-DTA and two control) were given doxycycline for ten consecutive days. After doxycycline exposure, mice were treated with pirfenidone (400 mg/kg/dose) or vehicle by daily oral gavage for 9 days and lungs were harvested one day after end of treatment. Lung sections were stained with picrosirius red or Masson’s trichrome. Collagen deposition in the wall of small airways was quantified using measurement of picrosirius red fluorescence intensity and area of collagen deposition using Image J analysis. Results: Analysis of PSR -stained slides showed that CC-DTA mice given vehicle had higher fluorescence intensity and a greater area of collagen in small airway walls compared to control mice given vehicle. Importantly, CC-DTA mice given pirfenidone versus vehicle exhibited reduced collagen deposition is small airway walls by both parameters mentioned above. Analysis of trichrome-stained slides is underway and expected to confirm these results. Discussion: These results show that pirfenidone can ameliorate the development of peribronchiolar fibrosis in mice exposed to sustain, targeted club cell injury. Our findings may inform the design of future clinical trials testing the therapeutic efficacy of pirfenidone in combating DRCB.
