Khadijah Siddiqui
Pronouns: she/her/hers
Research Mentor(s): John Osterholzer
Co-Presenter:
Research Mentor School/College/Department: Internal Medicine, Pulmonary Division / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 6 – 4:40pm – 5:30 pm
Room: League Ballroom
Authors: Khadijah Siddiqui, Seagal Teitz-Tennenbaum, John Osterholzer
Presenter: 10
Abstract
Following deployment to Southwest Asia and Afghanistan, increased incidence of respiratory symptoms including cough, shortness of breath, and exercise intolerance has been identified in military personnel. In a subset of veterans, despite normal findings on pulmonary function tests and imaging, lung biopsies revealed scarring (fibrosis) of the walls of small airways (bronchioles), a condition coined deployment-related constrictive bronchiolitis (DRCB). DRCB is suspected to originate from exposure to inhalational toxins such as military base burn pit smoke known to contain sulfur dioxide (SO2), sulfur plant fires, sandstorms, and combat smoke. Prolonged exposure to airborne toxins is thought to injure club cells, critical progenitor cells that repair injury in small airways through cell division and differentiation, and lead to DRCB. The aim of this study was to develop methods to quantify focal fibrosis localized to the walls of small airways in the lung as means to evaluate and monitor disease progression in animal models of DRCB. CC-DTA are inducible transgenic mice that in response to doxycycline administration develop specific club cell death. CC-DTA (and control mice) were given doxycycline through their chow from day 0 to 9 to generate sustained club cell injury. Lungs were harvested at day 10, 20, and 30 and evaluated for Collagen alpha-1(I) chain (Col1a1) gene expression using qRT-PCR and for collagen content using hydroxyproline assay. C57BL/6J mice were exposed to 50 ± 5 ppm SO2 for one hour a day for five consecutive days (day 0-4). Unexposed mice served as controls. Lungs were harvested on day 5, 10, and 20. Collagen content in the walls of small airways was determined by morphometric analysis of Masson’s trichrome-stained sections and by measuring fluorescence intensity of picrosirius red-stained sections, and normalized to the length of the bronchiole basement membrane. The number and density of collagen fibers were calculated using CurveAlign software. The width and length of collagen fibers were determined using CT-Fire software. Lung Col1a1 transcript levels were increased in CC-DTA versus control mice at day 10 and 20 (p < 0.01). Lung hydroxyproline content was increased in CC-DTA versus control mice at day 20 and 30 (p < 0.01). In SO2 exposed mice, the area of collagen deposition surrounding the basement membrane of small airways was increased at day 10 and 20 versus day 0 and 5 (by up to 25%, p < 0.05). Moreover, the fluorescence intensity of picrosirius red within walls of small airways was substantially higher at day 20 versus day 0, 5, and 10 (by up to 2.7-fold, p < 0.001). The width, length, and number, but not density, of collagen fibers was increased at day 20 accounting for the observed increase in collagen content and small airway wall thickness. As no proven therapies are currently available for combating DRCB, these methods to quantify peribronchiolar fibrosis may prove useful in future studies designed to test new therapeutic strategies. Presentation link
Biomedical Sciences, Interdisciplinary, Natural/Life Sciences
