Alveolar-capillary reserve during exercise in patients with chronic obstructive pulmonary disease

Abstract

Background: Factors limiting exercise in patients with COPD are complex. With evidence for accelerated pulmonary vascular aging, destruction of alveolar-capillary bed, and hypoxic pulmonary vasoconstriction, the ability to functionally expand surface area during exercise may become a primary limitation.

Purpose: To quantify measures of alveolar-capillary recruitment during exercise and the relationship to exercise capacity in a cohort of COPD patients.

Methods: Thirty-two subjects gave consent (53% male, with mean ± standard deviation age 66±9 years, smoking 35±29 pack-years, and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of 0-4: 2.3±0.8), filled out the St George's Respiratory Questionnaire (SGRQ) to measure quality of life, had a complete blood count drawn, and underwent spirometry. The intrabreath (IB) technique for lung diffusing capacity for carbon monoxide (IBDLCO) and pulmonary blood flow (IBQc, at rest) was also performed. Subsequently, they completed a cycle ergometry test to exhaustion with measures of oxygen saturation and expired gases.

Results: Baseline average measures were 44±21 for SGRQ score and 58±11 for FEV₁/FVC. Peak oxygen consumption (VO₂) was 11.4±3.1 mL/kg/min (49% predicted). The mean resting IBDLCO was 9.7±5.4 mL/min/mmHg and IBQc was 4.7±0.9 L/min. At the first workload, heart rate (HR) increased to 92±11 bpm, VO₂ was 8.3±1.4 mL/kg/min, and IBDLCO and IBQc increased by 46% and 43%, respectively, compared to resting values (p,0.01). The IBDLCO/Qc ratio averaged 2.0±1.1 at rest and remained constant during exercise with marked variation across subjects (range: 0.8-4.8). Ventilatory efficiency plateaued at 37±5 during exercise, partial pressure of mix expired CO₂/partial pressure of end tidal CO₂ ratio ranged from 0.63 to 0.67, while a noninvasive index of pulmonary capacitance, O₂ pulse × PetCO₂ (GxCap) rose to 138%. The exercise IBDLCO/Qc ratio was related to O₂ pulse (VO₂/HR, r=0.58, p<0.01), and subjects with the highest exercise IBDLCO/Qc ratio or the greatest rise from rest had the highest peak VO₂ values (r=0.65 and 0.51, respectively, p<0.05). Of the noninvasive gas exchange measures of pulmonary vascular function, GxCap was most closely associated with DLCO, DLCO/Qc, and VO₂ peak.

Conclusion: COPD patients who can expand gas exchange surface area as assessed with DLCO during exercise relative to pulmonary blood flow have a more preserved exercise capacity.

Keywords: COPD; airflow limitation; cardiopulmonary exercise testing; diffusion capacity; dyspnea; exercise intolerance; lung gas transfer.

Figure 1

Change in intrabreath DLCO from rest to first stage of exercise in patients with COPD. Abbreviation: DLCO, diffusing capacity for carbon monoxide.

Figure 2

Change in intrabreath DLCO relative to Qc from rest to first exercise workload in patients with COPD. Abbreviations: DLCO, diffusing capacity for carbon monoxide; Qc, pulmonary blood flow measured with soluble gas method.

Figure 3

Relationship of GxCap to DLCO in COPD patients. Abbreviations: DLCO, diffusing capacity for carbon monoxide; GxCap, O₂ pulse × PetCO₂; PetCO₂, partial pressure of end tidal CO₂.

Figure 4

Relationship of VO₂ peak (A) and VCO₂ peak (B) with DLCO/Qc. Abbreviations: DLCO, diffusing capacity for carbon monoxide; Qc, pulmonary blood flow; VCO₂, carbon dioxide production; VO₂, oxygen consumption.

Figure 5

Relationship of VO₂ with the change in GxCap from rest to peak exercise. Abbreviations: GxCap, O₂ pulse × PetCO₂; PetCO₂, partial pressure of end tidal CO₂; VO₂, oxygen consumption.

Figure 6

Relationship of DLCO/Qc relative to IC. Note: Qc measured with soluble gas method. Abbreviations: DLCO, diffusing capacity for carbon monoxide; IC, inspiratory capacity; Qc, pulmonary blood flow.