High-intensity non-invasive ventilation during exercise-training versus without in people with very severe COPD and chronic hypercapnic respiratory failure: a randomised controlled trial

BACKGROUND: People with very severe chronic obstructive pulmonary disease (COPD) using nocturnal non-invasive ventilation (NIV) for chronic hypercapnic respiratory failure (CHRF) experience reduced exercise capacity and severe dyspnoea during exercise training (ET). The use of NIV during ET can personalise training during pulmonary rehabilitation (PR) but whether high-intensity NIV (HI-NIV) during exercise is accepted and improves outcomes in these extremely physically limited patients is unknown. The aim of this trial was to determine if ET with HI-NIV during PR was more effective than without at improving exercise capacity and reducing dyspnoea during exercise. METHODS: Patients with COPD, CHRF and nocturnal-NIV were randomised to supervised cycle-ET as part of PR with HI-NIV or without (control). Primary outcome was change in cycle endurance time (ΔCET(time)), while secondary outcomes were dyspnoea at isotime during the cycle endurance test and during ET-sessions and for the HI-NIV group, post-trial preferred exercising method. RESULTS: Twenty-six participants (forced expiratory volume in 1 s 22±7%pred, PaCO(2)51±7 mm Hg) completed the trial (HI-NIV: n=13, ET: IPAP 26±3/EPAP 6±1 cm H(2)O; control n=13). At completion of a 3 week ET-programme, no significant between-group differences in ΔCET(time) were seen (HI-NIV-control: Δ105 s 95% CI (−92 to 302), p=0.608). Within-group ΔCET(time) was significant (HI-NIV: +246 s 95% CI (61 to 432); control: +141 s 95% CI (60 to 222); all p<0.05). The number of responders (Δ>minimal important difference (MID)(101 s): n=53.8%) was the same in both groups for absolute ΔCET(time) and 69.2% of control and 76.9% of the HI-NIV group had a %change>MID(33%). Compared with control, the HI-NIV group reported less isotime dyspnoea (Δ−2.0 pts. 95% CI (−3.2 to −0.8), p=0.005) and during ET (Δ−3.2 pts. 95% CI (−4.6 to −1.9), p<0.001). Most of the HI-NIV group (n=12/13) preferred exercising with NIV. CONCLUSION: In this small group of patients with very severe COPD requiring nocturnal NIV, participation in an ET-programme during PR significantly improved exercise capacity irrespective of HI-NIV use. Reported dyspnoea was in favour of HI-NIV. TRIAL REGISTRATION NUMBER: NCT03803358.