Inflammatory State of Macrophages and COPD Exacerbation

Acute flare up of respiratory symptoms, or exacerbation, is the major cause of morbidity and mortality in Chronic Obstructive Pulmonary Disease (COPD).  Infection due to microorganisms are thought to contribute to the development of COPD exacerbations. Immune cells that reside in the lung, including cells called alveolar macrophages (AM), play an important role in the defense against infections. In COPD, these AM are defective in their ability to clear pathogens or the cells that die in the lung in the aftermath of an infection. Interestingly, it remains unclear whether AM’s defective clearing abilities cause more frequent or severe exacerbations.

In a pilot study, we reproduced the previously-reported defect in pathogen clearance and its association with severity of airflow obstruction in COPD. But we found no difference in AM’s ability to clear pathogens or cell debris between patients with and without exacerbation. In this research, we propose to examine the hypothesis that a different defect in AM, an imbalance in pro- and anti-inflammatory processes, is associated with the susceptibility to exacerbation in COPD patients. We will use state of the art approaches to analyze AM status and functionality and how that relates to the level of exacerbation. Furthermore, we will assess the gene expression changes in defective AM from COPD patients and identify potential biomarkers that could be therapeutically targeted. Therefore, results of this study would delineate the pathogenesis of COPD exacerbation and guide efforts to develop a new class of therapeutics based on AM biology.