Resting lung volume phenotypes in COPD: implications for exertional dyspnoea and exercise tolerance

Abstract

Background: Lung volumes and dyspnoea vary markedly at a given forced expiratory volume in 1 s in COPD. We aim to investigate whether hyperinflation (high total lung capacity (TLC)) adds value to simpler inspiratory capacity (IC) in predicting mechanical-ventilatory impairment and exertional dyspnoea in these patients.

Methods: 345 patients with mild to very severe COPD (190 men) underwent incremental cycling with measurements of dyspnoea (0-10 Borg) and operating lung volumes. Resting volumes by body plethysmography were compared with the 2021 z-score-based Global Lung Initiative standards. A novel artificial intelligence (AI)-based algorithm quantified the burden of mechanical-ventilatory constraints and dyspnoea as ventilation increased.

Results: Four lung volume phenotypes were identified: 168 patients with preserved IC and TLC, 51 with preserved IC and high TLC (hyperinflation), 52 with low IC but no hyperinflation, and 74 with low IC and hyperinflation. Patients with low IC and/or hyperinflation showed worse air trapping and lower transfer factor (p<0.05). Hyperinflated patients at a given IC presented with worse sensory and functional outcomes; similarly, patients showing low IC at a given TLC were more symptomatic and impaired (p<0.05). The highest and lowest odds ratios (95% confidence interval) for "very severe" mechanical-ventilatory constraints and dyspnoea according to the AI algorithm were found in hyperinflated patients with low IC (5.2 (4.7-7.5)) and non-hyperinflated patients with preserved IC (0.99 (0.71-1.16)), respectively.

Conclusion: By combining IC and TLC expressed as z-scores, clinicians can identify physiological phenotypes relevant to dynamic lung mechanical abnormalities on exertion, activity-related dyspnoea and exercise tolerance across the spectrum of COPD severity.

FIGURE 1

a) Lung volume distribution in the pre-specified phenotypes according to preserved (↔) or low (↓) inspiratory capacity (IC) and preserved or increased (↑) total lung capacity (TLC), i.e., hyperinflation. b) Forced expiratory volume in 1 s (FEV₁) scatters for each phenotype; FEV₁ impairment according to current recommendations based on z-scores [16]. See supplementary E-Figure 2 for IC, TLC and IC/TLC ratio at iso-FEV₁. FRC: functional residual capacity; VC: vital capacity; ERV: expiratory reserved volume; RV: residual volume. ^#: p<0.05 hyperinflated versus non-hyperinflated within the same IC category; ^¶: p<0.05 preserved IC versus low IC within the same TLC category; ⁺: p<0.05 preserved IC and non-hyperinflated versus reduced IC and hyperinflated; ^§: p<0.05 preserved IC and hyperinflated versus reduced IC and non-hyperinflated.

FIGURE 2

Metrics of a) ventilatory efficiency, b) ventilatory demand relative to capacity, c) inspiratory reserve and d–f) breathing pattern in the pre-specified phenotypes according to preserved or reduced inspiratory capacity (IC) and preserved or increased total lung capacity, i.e., hyperinflation (a). Arrows indicate the work rate associated with dyspnoea upward inflection, as shown in figure 4a. Horizontal lines in panels b and c indicate commonly used cut-offs to indicate abnormality at peak exercise. V′_E: ventilation; V′_CO2: carbon dioxide output; VR_dyn: dynamic ventilatory reserve (1 − V′_E related to estimated maximal voluntary ventilation); IR_dyn1: dynamic inspiratory reserve # 1 (1- tidal volume(VT)/exercise inspiratory capacity ratio tidal volume (V_T)/exercise inspiratory capacity ratio); f_B: breathing frequency.

FIGURE 3

a, b) Absolute and c, d) relative operating lung volumes as a function of exercise intensity in patients with preserved (left panels) or reduced (right panels) inspiratory capacity (IC) who showed or did not show a high total lung capacity (TLC), i.e., hyperinflation. EILV: end-inspiratory lung volume; V_T: tidal volume; EELV: end-expiratory lung volume.

FIGURE 4

Borg dyspnoea as a function of a) exercise intensity, b) ventilatory demand, c) ventilatory demand relative to capacity and d) inspiratory reserve in the pre-specified phenotypes according to preserved or reduced inspiratory capacity (IC) and preserved or increased total lung capacity, i.e., hyperinflation. Arrows indicate the work rate and ventilation associated with dyspnoea upward inflection: simultaneous mechanical events to those in figure 2 c–f. VR_dyn: dynamic ventilatory reserve (1 − V′_E related to estimated maximal voluntary ventilation); IR_dyn1: dynamic inspiratory reserve # 1 (1 − tidal volume (V_T)/exercise inspiratory capacity ratio).

FIGURE 5

a-d) Odds ratios with respective 95% confidence intervals (CI) for “very severe” submaximal dyspnoea (>95th centile) and mechanical constraints (<5th centile) versus ventilation during incremental CPET as established by an AI-based algorithm. Patients are separated by lung volume phenotypes according to preserved (↔) or low (↓) inspiratory capacity (IC) and preserved or increased (↑) total lung capacity (TLC), i.e., hyperinflation. IR_dyn1: dynamic inspiratory reserve # 1 (1 − tidal volume/exercise inspiratory capacity ratio); IR_dyn2: dynamic inspiratory reserve # 2 (1 − end-inspiratory volume/TLC).