During pulmonary rehabilitation, a subset of subjects with COPD requires adjunct therapy to achieve high-intensity training. Both noninvasive ventilation (NIV) and inspiratory muscle training (IMT) are available to assist these subjects. We aimed to prime the respiratory muscles before NIV with IMT, anticipating additive effects for maximal exercise tolerance (T-lim) and dyspnea/leg fatigue relief throughout the exercise as primary outcomes. Changes in the respiratory pattern were secondary outcomes. COPD subjects performed a total of four identical constant work rate tests on a cycle ergometer at 75% of maximum work rate, under control ventilation (SHAM, 4 cmH2O) or proportional assisted ventilation (PAV, individually adjusted), before and after 10 sessions of high-intensity IMT (three times/week) during 30 days. Two-way RM ANOVA with appropriate corrections were performed. Final analysis in nine subjects showed improved T-lim (delta 111 s) and lower minute-ventilation (delta 4 L/min) at exhaustion, when comparing the IMT effects within the PAV modality (p = 0.001 and p = 0.036, respectively) and improved T-lim for PAV versus SHAM (PAV main-effect p = 0.001; IMT main-effect p = 0.006; PAV versus IMT interaction p = 0.034). In addition, IMT+PAV association, compared to PAV alone, resulted in lower respiratory frequency (IMT main-effect p = 0.009; time main-effect p < 0.0001; IMT versus time interaction p = 0.242) and lower inspiratory time related to duty cycle (IMT main-effect p = 0.018; time main-effect p = 0.0001; IMT versus time interaction p = 0.004) throughout exercise. The addition of IMT prior to a PAV-supported aerobic bout potentiates exercise tolerance and dyspnea relief and induces favourable changes in ventilatory pattern in severe COPD during high-intensity training (Brazilian Registry of Clinical Trials number RBR-6n3dzz).

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