Neural respiratory drive and breathlessness during incremental cycle and treadmill exercise in chronic obstructive pulmonary disease

Abstract

BackgroundBreathlessness is an important cause of exercise limitation and reduced quality of life for patients with chronic obstructive pulmonary disease (COPD). One of the challenges of breathlessness management in COPD is the lack of physiological markers that reliably correlate with patients' symptoms. The aim of this study was to test the hypothesis that neural respiratory drive (NRD), measured with diaphragm electromyogram (EMGdi) activity, is closely related to breathlessness in COPD. We also investigated whether neuroventilatory uncoupling, which is the dissociation of ventilation from NRD as a consequence of abnormal pulmonary mechanics, contributes to breathlessness intensity over an awareness of levels of NRD alone. MethodsEMGdi and ventilation were measured continuously during exhaustive incremental cycle and treadmill exercise in 12 patients with COPD (mean FEV1 38·7% predicted [SD 14·5]). EMGdi was expressed as a percentage of maximum (EMGdi%max), and relative to tidal volume expressed as a percentage of predicted vital capacity (EMGdi%max/VT%VCpred) to measure neuroventilatory uncoupling. Breathlessness (modified Borg scale) was recorded at baseline, at the end of each minute of exercise, and at completion of exercise. Linear regression analysis was used to determine the associations between breathlessness, EMGdi%max, neuroventilatory uncoupling, and ventilation. FindingsEMGdi%max was closely related to breathlessness in both cycle (r=0·98, p=0·0001) and treadmill exercise (r=0·94, p=0·005), this association being at least as strong as that between neuroventilatory uncoupling and breathlessness (cycle r=0·94, p=0·005; treadmill r=0·91, p=0·01). The association between breathlessness and ventilation was poor when expansion of tidal volume became restricted, whereas the association between EMGdi%max and breathlessness remained close. InterpretationEMGdi%max is closely related to the intensity of exertional breathlessness in COPD. These data suggest that breathlessness in COPD can be largely explained by an awareness of levels of NRD, rather than the association between NRD and achieved ventilation. EMGdi%max could provide a useful physiological biomarker for breathlessness, with advantages over mechanical and ventilatory indices in COPD and the many other diseases in which neuroventilatory uncoupling occurs. FundingUK Medical Research Council, British Council.