Document Type

Thesis

Date of Award

3-2025

School/College

College of Science, Engineering, and Technology (COSET)

Degree Name

MS in Biology

Committee Chairperson

Dr. Alamelu Sundaresan

Committee Member 1

Dr. Lavannya Pandit

Committee Member 2

Dr. Shishir Shishodia

Committee Member 3

Dr. Ayodotun Sodipe

Keywords

Chronic Obstructive Pulmonary Disease, PMN-exosomes, Neutrophil Elastase, Chronic Bronchitis, Pulmonary Emphysema

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease that leads to chronic inflammation and, in turn, a high level of comorbidity and healthcare expense. An increasing body of evidence involves neutrophils, as well as their exosomes, in lung damage exacerbation via the protease-mediated degradation of the extracellular matrix (ECM). We hypothesize that the PMN-exosomes would be significantly increased in the active smoker COPD patient and that they would enhance disease progression by augmenting the proteolytic cascade and tissue damage. This multi-center clinical study included a total of 46 veterans separated into four cohorts: active smoking COPD patients, COPD individuals who did not smoke, healthy controls who experienced smoking, and healthy individuals who did not smoke. The concentrations of exosomal proteases, including the neutrophil elastase (NE), and cytokine profiles were evaluated. Pulmonary function tests were performed to measure how well the lungs are working based on how much air can be exhaled and how quickly. Sputum, blood, and quality-of-life measures were determined. Preliminary findings reveal heightened NE-associated exosomal activity in COPD patients, with significant differences observed between current and former smokers. Specifically, higher levels of NE expression and proteolytic activity were detected in PMN-exosomes from COPD patients compared to controls, and the highest exosome-associated NE activity was observed in patients who were current smokers. Indeed, very strong correlations were also found between exosome-mediated proteolytic functions and other clinical markers like lung function decline and symptom severity. In this study underscores the potential of PMN-exosomes for identifying biomarkers of COPD progression and for identifying therapeutic targets. Furthermore, understanding more fully the sometimes-opposing frames of inflammation and proteolysis in COPD will hopefully have meaningful implications for the development of personalized medicine. While these findings indicate that exosomal NE may represent a desirable biomarker, we believe that additional analyses should be done to evaluate levels across numerous populations of different disease severity, as well as their clinical value. The broader purpose of this study is, through its findings, to create knowledge that might lead the way toward developing strategies tailored to the diagnosis and management of the disease among actors in the care domain, particularly those veterans who are burdened with the greatest prevalence and healthcare use with COPD. Further studies should elucidate the role of PMN-exosomes during acute exacerbation and their modulation by pharmacological and behavioral interventions.

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