Efficacy of respiratory support therapies during pulmonary rehabilitation exercise training in chronic obstructive pulmonary disease patients: a systematic review and network meta-analysis.

The short version

This systematic review and network meta-analysis explored which kinds of breathing support, given while people with chronic obstructive pulmonary disease (COPD) do supervised exercise training, help most. COPD is a long-term lung disease that limits airflow and makes exercise uncomfortable, so many patients struggle to exercise hard enough to benefit from pulmonary rehabilitation. The authors compared six approaches: conventional oxygen through a nasal tube or mask, high-flow nasal cannula (HFNC, which delivers warmed, humidified air at high flow), noninvasive positive pressure ventilation (NPPV, a mask that pushes air in to ease breathing effort), nighttime NPPV, heliox (a helium-oxygen mix), and plain air. The protocol was registered with PROSPERO. The team searched five databases through December 2023 and included 35 randomized trials with 1321 patients from 19 countries. All had stable, severe COPD (GOLD stage III or IV), with average ages from 59 to 76 and mostly men. Programs ran 6 to 12 weeks, with two to three sessions weekly of 30 to 45 minutes. A network meta-analysis lets treatments be ranked even when they were not directly compared. Outcomes included the 6-minute walk test (distance covered in 6 minutes), peak work rate, endurance time, breathlessness on the Borg scale, oxygen uptake, and quality of life. NPPV performed best. Compared with plain air, NPPV improved walk distance (SMD 0.36, where SMD is a standardized effect size), peak work rate (0.69) and peak oxygen uptake (0.75), and it was the only option to do so on those measures. Versus oxygen, NPPV also improved walk distance (0.44) and peak work rate (0.56). It also lowered blood lactate and improved tidal volume and minute ventilation. For endurance time, both NPPV (0.38) and oxygen (0.31) beat air, and HFNC ranked highest. Breathlessness dropped more with NPPV (-0.47), HFNC (-0.46) and oxygen (-0.36) than with air. No therapy changed quality of life significantly, heliox showed no benefit, and nighttime NPPV did not reach significance. The evidence quality ranged from critically low to moderate. The authors suggest that NPPV is the most promising option for stable severe COPD during pulmonary rehabilitation exercise, while noting that results apply only to GOLD stage III or IV disease. They state limitations including small, varied trials, few direct comparisons, high risk of bias in many studies, and unclear best device settings. They call for larger trials that also examine safety, feasibility, cost and personalization. The authors add that the analysis used change from baseline to limit differences between groups, and that the lack of direct comparisons between some therapies weakens confidence in the rankings.

Key findings

• This analysis combined 35 randomized trials with 1321 people who had stable, severe COPD and compared six kinds of breathing support given during supervised exercise training in pulmonary rehabilitation.
• NPPV (a mask-based ventilator that pushes air in to ease breathing effort) ranked best, improving 6-minute walk distance, peak work rate, peak oxygen uptake, tidal volume and minute ventilation and lowering blood lactate compared with plain air or oxygen.
• Oxygen and high-flow nasal cannula also reduced breathlessness compared with plain air, and oxygen and NPPV lengthened endurance time, but none of the therapies changed quality of life significantly and heliox showed no benefit.
• The authors rate the certainty of evidence as critically low to moderate, note that results apply only to severe (GOLD stage III or IV) COPD, and call for further trials on safety, practicality and cost.

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