The link between elevated inspiratory neural drive, inspiratory constraints, and dyspnea across the continuum of COPD severity

Abstract

<b>Background:</b> Exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD) is associated with high inspiratory neural drive (IND). The contribution of critical inspiratory constraints (CIC) to high IND across the COPD severity continuum is unknown. <b>Aims:</b> To compare dyspnea, IND and CIC during exercise in mild to advanced COPD. <b>Methods:</b> A two-centre, cross-sectional study in which 18 controls (C) and 90 COPD participants, grouped in tertiles of FEV₁%predicted (T1:87±9%; T2:60±9%; T3:32±8%), completed cycle exercise with measurement of IND by diaphragm electromyography (EMGdi (%max)) and CIC by tidal volume/inspiratory capacity (V_T/IC). <b>Results:</b> IND and dyspnea during exercise were progressively elevated from C to T3 in conjunction with worsening resting and dynamic mechanics.&nbsp;CIC (V_T/IC&gt;70%) occurred at progressively lower ventilation (<i>V̇</i>_E) from C to T3, which was associated with progressively lower resting IC (r=0.57, p&lt;0.01). Strong associations were identified between V_T/IC, IND and dyspnea during exercise at&nbsp;V̇_E=25 L/min (Fig A). The close relationship between IND and both dyspnea (Fig B) and V_T/IC (Fig C) were similar between groups, despite major differences in resting and dynamic mechanics. <b>Conclusions:</b> Exertional dyspnea in COPD was mechanistically linked to abnormally elevated IND, which, in turn, was strongly influenced by CIC in mild to advanced COPD.