Title: An investigation into the use of selective serotonin reuptake inhibitors for improving low lung function and pulmonary exacerbations
Description: Chronic obstructive pulmonary disease (COPD) is characterized by periodic episodes of worsening symptom (e.g., shortness of breath, irregular breathing, and worse coughing with increased phlegm production), also called pulmonary exacerbations. Inflammation is an important cause of reduced lung function as inflammation contributes to airflow obstruction in the small airways and lung parenchyma. Even in individuals with mild COPD, inflammation reduces lung function, accelerates decline in lung function overtime, and increases the risk for respiratory exacerbations. Agents that reduce systemic inflammation are hypothesized to decrease the inflammation in the lungs, resulting in improvements in lung function and a decrease in exacerbation frequency. We hypothesize that antidepressants have a beneficial effect on lung function. In addition to having anti-inflammatory properties, antidepressants act upon serotonin, which is integral in central breathing control. The combination of the anti-inflammatory and serotonergic effects may provide users of selective serotonin reuptake inhibitors with a lung function benefit while avoiding the side effects of steroids.

This dissertation assesses whether selective serotonin reuptake inhibitors increase concurrent lung function and reduce the risk for respiratory exacerbations. It consists of three parts: a systematic literature review and two analytic papers using large prospective databases. The systematic review of the literature identified limitations concerning the effect of selective serotonin reuptake inhibitors on lung function. Overall, the analytic papers found no support for a beneficial association between selective serotonin reuptake inhibitors and spirometry, dyspnea or pulmonary exacerbations; indeed the association was in the opposite direction as hypothesized. In addition, there was no support for meaningful mediation by inflammatory markers. Further research is needed to determine if selective serotonin reuptake inhibitors have a harmful effect on lung function and pulmonary exacerbations.