Phenotyping Cardiopulmonary Exercise Limitations in Chronic Obstructive Pulmonary Disease

Abstract

Background: 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. 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.

Methods: Patients 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 (V_Epeak)/maximal ventilatory capacity (MVC) ≥ 85% or MVC-V_Epeak ≤ 11 L/min, and peak heart rate (HR_peak) < 90%pred], cardiovascular (V_Epeak/MVC < 85% or MVC-V_Epeak > 11 L/min, and HR_peak ≥ 90%pred), or combined (V_Epeak/MVC ≥ 85% or MVC-V_Epeak ≤ 11 L/min, and HR_peak ≥ 90%pred).

Results: FEV₁ 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 V_Epeak (60.8 ± 11.5 L/min vs. 45.3 ± 15.5 L/min, p = 0.002), cardiopulmonary fitness (VO_2peak: 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.

Conclusion: Distinct 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.

Keywords: COPD; cardiopulmonary exercise testing; clinical exercise physiology; exercise limitations; exercise prescription.

Figure 1

Study participant flow.

Figure 2

The distribution of airflow limitation severity in patients with chronic obstructive pulmonary disease (COPD) who have a ventilatory, combined, or cardiovascular exercise limitation phenotype. Phenotype quadrants are differentiated by a dash horizontal and vertical line representing the classification criteria for a ventilatory limitation (V_Epeak/MVC ≥ 85%) and cardiovascular limitation (HR_peak ≥ 90%pred), respectively. GOLD severity is represented by the symbols to show the range of airflow limitation severity within each phenotype. GOLD I (mild airflow limitation) is represented by triangles. GOLD II (moderate airflow limitation) is represented by squares. GOLD III–IV (severe to very severe airflow limitation) is represented by circles.

Figure 3

Phenotype responses in (A) absolute ventilation, (B) relative ventilation (expressed as percentage of estimated MVC), (C) tidal volume, and (D) breathing frequency during an incremental CPET. Between phenotype comparisons: ^*p = 0.05, ventilatory vs. cardiovascular. ^†p = 0.05, ventilatory vs. combined. ^‡p = 0.05, combined vs. cardiovascular.

Figure 4

Phenotype responses in (A) absolute heart rate, (B) relative heart rate (expressed as a percentage of estimated maximal heart rate), and (C) O₂pulse during an incremental CPET. Between phenotype comparisons: ^*p = 0.05, ventilatory vs. cardiovascular.

Figure 5

Phenotype responses in (A) relative end-expiratory lung volume (EELV) and end-inspiratory lung volume (EILV), (B) inspiratory capacity, (C) inspiratory reserve volume, and (D) the relationship between dyspnea and inspiratory reserve volume during an incremental CPET. Between phenotype comparisons: ^*p = 0.05, ventilatory vs. cardiovascular. ^†p = 0.05, ventilatory vs. combined. ^‡p = 0.05, combined vs. cardiovascular.