Impact of pulmonary emphysema on exercise capacity and its physiological determinants in chronic obstructive pulmonary disease

Abstract

Exercise limitation is common in chronic obstructive pulmonary disease (COPD). We determined the impact of pulmonary emphysema on the physiological response to exercise independent of contemporary measures of COPD severity. Smokers 40-79 years old with COPD underwent computed tomography, pulmonary function tesing, and symptom-limited incremental exercise testing. COPD severity was quantified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) by spirometry (GOLD 1-4); and symptom burden and exacerbation risk (GOLD A-D). Emphysema severity was quantified as the percent lung volume <-950 Hounsfield units. Regression models adjusted for age, gender, body size, smoking status, airflow limitation, symptom burden and exacerbation risk. Among 67 COPD subjects (age 67 ± 8 years; 75% male; GOLD 1-4: 11%, 43%, 30%, 16%), median percent emphysema was 11%, and peak power output (PPO) was 61 ± 32 W. Higher percent emphysema independently predicted lower PPO (-24 W per 10% increment in emphysema; 95%CI -41 to -7 W). Throughout exercise, higher percent emphysema predicted 1) higher minute ventilation, ventilatory equivalent for CO₂, and heart rate; and 2) lower oxy-hemoglobin saturation, and end-tidal PCO₂. Independent of contemporary measures of COPD severity, the extent of pulmonary emphysema predicts lower exercise capacity, ventilatory inefficiency, impaired gas-exchange and increased heart rate response to exercise.

Figure 1

Percent emphysema was associated with peak exercise capacity independent of airflow limitation severity, and symptom burden/exacerbation frequency. Peak power output-percent emphysema relationship stratified by airflow limitation (panel A), and GOLD A–D (panel B). To account for potential confounders, peak power output was calculated using linear regression to adjust for age, gender, height, body mass index, depth of inspiration at CT, smoking status, and FEV₁ percent predicted (panel A) or GOLD group A–D (panel B). GOLD group A–D was defined by symptom burden and exacerbation frequency (See Methods for details). Abbreviations: FEV₁ = forced expired volume in one second; COPD = chronic obstructive pulmonary disease; CT = computed tomography; and GOLD = Global Initiative for Chronic Obstructive Lung Disease.

Figure 2

Cardiorespiratory responses to symptom-limited incremental cycle exercise testing by quartile of percent emphysema independent of airflow limitation. Each panel depicts the relationship between percent emphysema quartile (Q1: 3.1%; Q2: 8.4%; Q3: 14.5%; Q4: 27.5%) and a cardiorespiratory response (Y-axis) throughout exercise (X-axis). Curves were derived from mixed model regression adjusting for age, gender, height, body mass index, depth of inspiration at CT, smoking status, and airflow limitation severity (GOLD 1–4). P-intercept is the probability that percent emphysema predicts no difference in cardiorespiratory response at the intercept (i.e., rest). P-slope is the probability that percent emphysema predicts no difference in slope between exercise intensity and cardiorespiratory response. P-linear is the probability that the percent emphysema association with the cardiorespiratory response is linear. NA denotes the model did not require a slope or nonlinear term for optimum fit (See Methods for details). Abbreviations: V_T = tidal volume; ${\dot{\mathrm{V}}O}_2$ = rate of O₂ uptake; ${\dot{\mathrm{V}}}_{\mathrm{E}}$ = minute ventilation; ${\dot{\mathrm{V}}\text{CO}}_2$ = rate of CO₂ output; P_ETCO₂ = end-tidal partial pressure of CO₂; S_pO₂ = pulse-oximeter estimated arterial oxy-hemoglobin saturation; CT = computed tomography; and GOLD = Global Initiative for Chronic Obstructive Lung Disease; NA = not applicable.