Dyspnea and Exercise Limitation in Mild COPD: The Value of CPET

Abstract

The majority of smokers with chronic obstructive pulmonary disease (COPD) have mild airflow limitation as determined by simple spirometry. Although small airway dysfunction is the hallmark of COPD, many studies attest to complex heterogeneous physiological impairments beyond increased airway resistance. These impairments are related to inflammation of lung parenchyma and its microvasculature, which is obscured by simple spirometry. Recent studies using advanced radiological imaging have highlighted significant structural abnormalities in smokers with relatively preserved spirometry. These important studies have generated considerable interest and have reinforced the pressing need to better understand the physiological consequences of various morphological abnormalities, and their impact on the clinical outcomes and natural history of COPD. The overarching objective of this review is to provide a concise overview of the importance and utility of cardiopulmonary exercise testing (CPET) in clinical and research settings. CPET uniquely allows evaluation of integrated abnormalities of the respiratory, cardio-circulatory, metabolic, peripheral muscle and neurosensory systems during increases in physiologic stress. This brief review examines the results of recent studies in mild COPD that have uncovered consistent derangements in pulmonary gas exchange and development of "restrictive" dynamic mechanics that together contribute to exercise intolerance. We examine the evidence that compensatory increases in inspiratory neural drive from respiratory control centers are required during exercise in mild COPD to maintain ventilation commensurate with increasing metabolic demand. The ultimate clinical consequences of this high inspiratory neural drive are earlier onset of critical respiratory mechanical constraints and increased perceived respiratory discomfort at relatively low exercise intensities.

Keywords: cardiopulmonary exercise testing; chronic obstructive pulmonary disease; dyspnea; gas exchange; neural drive; respiratory mechanics.

Figure 1

Ventilatory drive and respiratory mechanical response to exercise in patients with mild chronic obstructive pulmonary disease (COPD) compared to healthy controls. (A) The ratio of diaphragmatic electromyography (EMGdi) to maximal EMGdi (EMGdi,max) relative to work rate, (B) dyspnea intensity (measured by modified 10-point Borg scale) relative to the ratio of EMGdi/EMGdi,max (C) ventilation (V_E) relative to the ratio of EMGdi/EMGdi,max (D) the ratio of transdiaphragmatic pressure (Pdi) relative to maximal Pdi (Pdi,max) relative to work rate (E) neuromechanical dissociation (represented as the ratio of EMGdi/EMGdi,max to Pdi/Pdi,max) relative to work rate (F) total work of breathing relative to work rate. Data are presented as Mean ± SEM. Triangles represent the tidal volume/minute ventilation inflection point. Reproduced with permission of the © ERS 2020: Guenette et al. (7).

Figure 2

Exertional dyspnea intensity (Borg scale; A), ventilation (B), ventilatory equivalent for carbon-dioxide (V_E/VCO2; C), partial pressure of end-tidal CO2 (P_ETCO₂; D), and oxygen saturation by pulse oximetry (SpO₂; E); all for a given oxygen uptake during symptom-limited incremental cycle exercise in chronic obstructive pulmonary disease patients with normal single-breath diffusing capacity of the lung for carbon monoxide (DLCO; open symbols) and those with low DLCO (closed symbols) in the first tertile of forced expiratory volume in 1 s (FEV1). Tertile 1 (FEV1 > 73.5%predicted, square symbols). Data are means ± SE. *P < 0.05, normal vs. low DLCO.^†P < 0.05, difference in dyspnea/oxygen uptake slope between normal and low DLCO. Elbehairy et al. (12).

Figure 3

(A–I) Proposed panel displays during interpretation of an incremental cardiopulmonary exercise test. Data showing selected perceptual, ventilatory control, dynamic respiratory mechanics, and breathing pattern response to incremental cycle exercise in patients with mild chronic obstructive pulmonary disease (COPD) and age-matched healthy controls. Data are presented as Mean ± SEM. V_E/VCO₂: ventilatory equivalent for carbon dioxide; IRV: inspiratory reserve volume; F_b: breathing frequency; P_ETCO₂: partial pressure of end-tidal carbon dioxide; SpO₂: arterial oxygen saturation measured by pulse oximetry; TLC: total lung capacity. *p < 0.05 mild COPD versus healthy controls at rest, at standardized work rates or at peak exercise. Adapted with permission of the American Thoracic Society. Copyright © 2020 American Thoracic Society. All rights reserved. Cite: Author(s)/Year/Title/Journal title/Volume/Pages. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society. Readers are encouraged to read the entire article for the correct context at https://www.atsjournals.org/doi/full/10.1164/rccm.201211-1970OC The authors, editors, and The American Thoracic Society are not responsible for errors or omissions in adaptations.