Inspiratory Plus Expiratory Neuromuscular Electrical Stimulation Versus Diaphragm Pacing for Rehabilitation in Severe COPD Patients: A Randomized Controlled Trial

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease, which might be improved by neuromuscular electrical stimulation. To date, no trials of intervention of inspiratory plus expiratory neuromuscular electrical stimulation have been conducted. This study aimed to evaluate the effect and safety of in patients with severe COPD. Methods: In this prospective, multicenter controlled trial, 120 stable patients with severe COPD who received standard medical treatment were assigned 1:1 to receive either inspiratory plus expiratory neuromuscular electrical stimulation (study intervention) or stimulation of the phrenic nerve, called diaphragm pacing (control intervention). Intention-to-treat analysis was carried out. The primary outcome was to analyze the changes in functional exercise capacity, estimated as six-minute walk distance (6MWD), following four weeks of electrical stimulation intervention.Results: The change in 6MWD was greater in the study intervention (65.53 ± 39.45m) than in the control intervention (26.66 ± 32.65m). The mean between-group difference at four weeks was 29.07 m ([95% CI, 16.098 to 42.035];  < 0.001). There was no significant between-group difference in secondary (modified Medical Research Council, forced expiratory volume in 1 second (FEV1), FEV1% predicted, and FEV1 ratio forced vital capacity (FEV1/FVC)) outcomes after four weeks of electrical stimulation. For GOLD 4 subjects, FEV1 and FEV1/FVC had improved in the study intervention ( < 0.05). No electrical stimulation-related serious adverse events were observed in either group.Conclusion: Functional exercise capacity were significantly improved in the study intervention in stable patients with severe COPD after four weeks of treatment. Trial registration: ChiCTR, ChiCTR2000032681. Registered 6 May 2020- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=53086.