James MD; Phillips DB; Vincent SG; Abdallah SJ; Donovan AA; de-Torres JP;
Neder JA; Smith BM; Jensen D; O’Donnell DE;

Journal of Physiology. 600(18):4227-4245, 2022 Sep.VI 1

In patients with chronic obstructive pulmonary disease (COPD), exertional
dyspnoea generally arises when there is imbalance between ventilatory
demand and capacity, but the neurophysiological mechanisms are unclear. We
therefore determined if disparity between elevated inspiratory neural
drive (IND) and tidal volume (VT ) responses (neuromechanical
dissociation) impacted dyspnoea intensity and quality during exercise,
across the COPD severity spectrum. In this two-centre, cross-sectional
observational study, 89 participants with COPD divided into tertiles of
FEV1 %predicted (Tertile 1 = FEV1 = 87 +/- 9%, Tertile 2 = 60 +/- 9%,
Tertile 3 = 32 +/- 8%) and 18 non-smoking controls, completed a
symptom-limited cardiopulmonary exercise test (CPET) with measurement of
IND by diaphragm electromyography (EMGdi (%max)). The association between
increasing dyspnoea intensity and EMGdi (%max) during CPET was strong (r =
0.730, P < 0.001) and not different between the four groups who showed
marked heterogeneity in pulmonary gas exchange and mechanical
abnormalities. Significant inspiratory constraints (tidal
volume/inspiratory capacity (VT /IC) >= 70%) and onset of neuromechanical
dissociation (EMGdi (%max):VT /IC > 0.75) occurred at progressively lower
minute ventilation ( V E ${\dot{V}}_{{\rm{E}}}$ ) from Control to Tertile
3. Lower resting IC meant earlier onset of neuromechanical dissociation,
heightened dyspnoea intensity and greater propensity (93% in Tertile 3) to
select qualitative descriptors of ‘unsatisfied inspiration’. We concluded
that, regardless of marked variation in mechanical and pulmonary gas
exchange abnormalities in our study sample, exertional dyspnoea intensity
was linked to the magnitude of EMGdi (%max). Moreover, onset of critical
inspiratory constraints and attendant neuromechanical dissociation
amplified dyspnoea intensity at higher exercise intensities. Simple
measurements of IC and breathing pattern during CPET provide useful
insights into mechanisms of dyspnoea and exercise intolerance in
individuals with COPD.

KEY POINTS: Dyspnoea during exercise is a common
and troublesome symptom reported by patients with chronic obstructive
pulmonary disease (COPD) and is linked to an elevated inspiratory neural
drive (IND). The precise mechanisms of elevated IND and dyspnoea across
the continuum of airflow obstruction severity in COPD remains unclear. The
present study sought to determine the mechanisms of elevated IND (by
diaphragm EMG, EMGdi (%max)) and dyspnoea during cardiopulmonary exercise
testing (CPET) across the continuum of COPD severity. There was a strong
association between increasing dyspnoea intensity and EMGdi (%max) during
CPET across the COPD continuum despite significant heterogeneity in
underlying pulmonary gas exchange and respiratory mechanical impairments.
Critical inspiratory constraints occurred at progressively lower
ventilation during exercise with worsening severity of COPD. This was
associated with the progressively lower resting inspiratory capacity with
worsening disease severity. Earlier critical inspiratory constraint was
associated with earlier neuromechanical dissociation and greater
likelihood of reporting the sensation of ‘unsatisfied inspiration’.