The effects of pulmonary rehabilitation on inflammatory biomarkers in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis

Chronic obstructive pulmonary disease (COPD) is associated with elevated levels of proinflammatory biomarkers which may contribute to pathophysiological changes in both the respiratory and extrapulmonary systems. Pulmonary rehabilitation (PR) is an effective intervention for symptom management in people with COPD. The impact of PR on systemic inflammation is currently unknown. Using the search terms “chronic obstructive pulmonary disease,” “pulmonary rehabilitation” and “inflammatory biomarkers,” 5 databases were searched from inception. Studies were eligible if they included: (1) participants with COPD undergoing PR with an exercise component of at least 4 weeks in length and (2) a systemic inflammation measurement pre- and post-PR. Our primary outcomes of interest were interleukin-6 (IL-6), fibrinogen and c-reactive protein (CRP) concentrations. A meta-analysis was performed using weighted mean difference and 95% confidence intervals. A total of 1339 participants were enrolled across all 18 eligible studies. A meta-analysis of the 5 randomized controlled trials (RCTs) found that CRP (MD −1.19, 95% CI −1.78 to −0.60, I2 = 86%) showed a greater response to PR than usual care. No difference between groups was noted for IL-6 (MD −3.38, 95% CI −13.03 to 6.28, I2 = 98%). Fibrinogen was not reported among included RCTs. A PR program with at least 4 weeks of exercise appears to reduce CRP levels but not IL-6 or fibrinogen in people with COPD. These results are based on small sample sizes and low-quality evidence and the impact of PR on systemic inflammation is uncertain.