Research Appraisals

European respiratory review : an official journal of the European Respiratory Society

Muscle sympathetic nerve activity in COPD: a systematic review and meta-analysis

BACKGROUND: Cardiovascular disease is a primary driver of mortality in COPD. Elevated sympathetic nerve activity is a key proposed mechanism, but the magnitude of this autonomic overactivity has not been quantified in a pooled analysis. OBJECTIVE: To determine if adults with COPD exhibit higher resting muscle sympathetic nerve activity (MSNA) than healthy controls, assess associated cardiorespiratory effects, and evaluate the short-term impact of COPD interventions on MSNA. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, eight databases were searched from inception to 15 May 2025 to inform this systematic review and meta-analysis (PROSPERO CRD420251044931). Eligible studies included adults with spirometry-defined COPD in whom MSNA was measured by microneurography at rest. Primary outcomes were MSNA burst frequency (bursts·min-1) and incidence (bursts per 100 heartbeats). Secondary outcomes included resting heart rate and blood pressure. RESULTS: A total of 11 studies (171 COPD participants, 105 controls) met inclusion criteria. Compared with controls, COPD was associated with markedly higher MSNA, burst frequency (+18.5, 95% CI 9.4-27.7 bursts·min-1) and burst incidence (+21.3, 95% CI 9.2-33.4 bursts per 100 heartbeats). Resting heart rate was also elevated (+10.7, 95% CI 6.1-15.3 beats·min-1), while blood pressure did not differ significantly. Three studies on noninvasive ventilation or inhaled β2-agonists found no significant pooled changes in MSNA. CONCLUSIONS: Resting MSNA is significantly elevated in patients with COPD despite normal blood pressure. This chronic sympathetic excitation likely contributes to COPD-related cardiovascular morbidity and exercise intolerance, highlighting the importance of developing therapies that reduce sympathetic nerve activity.