Phenotyping Cardiopulmonary Exercise Limitations in Chronic Obstructive Pulmonary Disease.

Jinelle Gelinas,Gregory Dumanoir,Bernie Melzer,Megan Harper,John Sasso,Gloria Agar,Stephen Wright,J Douglass Rolf,Michael Roman,Jordan Guenette,Neil Eves

doi:10.3389/fphys.2022.816586

Abstract

BackgroundExercise limitation in chronic obstructive pulmonary disease (COPD) is commonly attributed to abnormal ventilatory mechanics and/or skeletal muscle function, while cardiovascular contributions remain relatively understudied. To date, the integrative exercise responses associated with different cardiopulmonary exercise limitation phenotypes in COPD have not been explored but may provide novel therapeutic utility. This study determined the ventilatory, cardiovascular, and metabolic responses to incremental exercise in patients with COPD with different exercise limitation phenotypes.MethodsPatients with COPD (n = 95, FEV1:23–113%pred) performed a pulmonary function test and incremental cardiopulmonary exercise test. Exercise limitation phenotypes were classified as: ventilatory [peak ventilation (VEpeak)/maximal ventilatory capacity (MVC) ≥ 85% or MVC-VEpeak ≤ 11 L/min, and peak heart rate (HRpeak) < 90%pred], cardiovascular (VEpeak/MVC < 85% or MVC-VEpeak > 11 L/min, and HRpeak ≥ 90%pred), or combined (VEpeak/MVC ≥ 85% or MVC-VEpeak ≤ 11 L/min, and HRpeak ≥ 90%pred).ResultsFEV1 varied within phenotype: ventilatory (23–75%pred), combined (28–90%pred), and cardiovascular (68–113%pred). The cardiovascular phenotype had less static hyperinflation, a lower end-expiratory lung volume and larger tidal volume at peak exercise compared to both other phenotypes (p < 0.01 for all). The cardiovascular phenotype reached a higher VEpeak (60.8 ± 11.5 L/min vs. 45.3 ± 15.5 L/min, p = 0.002), cardiopulmonary fitness (VO2peak: 20.6 ± 4.0 ml/kg/min vs. 15.2 ± 3.3 ml/kg/min, p < 0.001), and maximum workload (103 ± 34 W vs. 72 ± 27 W, p < 0.01) vs. the ventilatory phenotype, but was similar to the combined phenotype.ConclusionDistinct exercise limitation phenotypes were identified in COPD that were not solely dependent upon airflow limitation severity. Approximately 50% of patients reached maximal heart rate, indicating that peak cardiac output and convective O2 delivery contributed to exercise limitation. Categorizing patients with COPD phenotypically may aid in optimizing exercise prescription for rehabilitative purposes.

Highlights

Chronic obstructive pulmonary disease (COPD) is a complex heterogenous condition with diverse clinical presentations and prognoses that cannot be entirely explained by differences in airflow limitation and dyspnea (Agusti et al, 2010; Casanova et al, 2011)
MRC dyspnea score, measured with the medical research council breathlessness scale; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; VC, vital capacity; TLC, total lung capacity; RV, residual volume; FRC, functional residual capacity; DLCO, diffusion capacity of the lungs for carbon monoxide; DLCO/VA, diffusion capacity of the lungs for carbon monoxide corrected for alveolar ventilation
FEV1/FVC and FEV1 were significantly different between phenotypes with a wide range within each: ventilatory (FEV1:23– 75%pred), combined (28–90%pred), and cardiovascular (68–113%pred; Figure 2)

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a complex heterogenous condition with diverse clinical presentations and prognoses that cannot be entirely explained by differences in airflow limitation and dyspnea (Agusti et al, 2010; Casanova et al, 2011). The greater mechanical work associated with breathing at higher lung volumes and at a greater frequency increases inspiratory neural drive, while the ability to efficiently increase minute ventilation (VE) is reduced (O’Donnell et al, 2006, 2012; Ofir et al, 2008; Laveneziana et al, 2011; Guenette et al, 2014). Exercise limitation in chronic obstructive pulmonary disease (COPD) is commonly attributed to abnormal ventilatory mechanics and/or skeletal muscle function, while cardiovascular contributions remain relatively understudied. The integrative exercise responses associated with different cardiopulmonary exercise limitation phenotypes in COPD have not been explored but may provide novel therapeutic utility. This study determined the ventilatory, cardiovascular, and metabolic responses to incremental exercise in patients with COPD with different exercise limitation phenotypes

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