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In people with COPD, pulmonary gas-exchange efficiency may be impaired because of abnormal alveolar ventilation (V˙A), capillary perfusion (Q˙c), or both. Both have been reported in early and mild stages of the disease. Such derangements often accompany significant clinical consequences such as activity-related dyspnea and exercise intolerance. Although much attention has been paid to pharmacologic treatment of mechanical abnormalities in COPD (eg, bronchodilators to deflate the lungs), increasing neurochemical afferent activity, secondary to gas-exchange inefficiency, has remained elusive as a therapeutic target. Hence, in this invited review, we first summarize how dyspnea, leading to poor exercise tolerance in COPD, may be explained by an increased venous admixture resulting from low V˙A/Q˙c, or wasted ventilation related to high V˙A/Q˙c, or both. We review the conflicting evidence supporting current treatments for gas-exchange inefficiency and exercise tolerance that act primarily on V˙A (bronchodilators, antiinflammatory medications) or Q˙c (oral and inhaled vasodilators, almitrine, and supplemental oxygen). Finally, to address the current knowledge and health care gaps, we propose two independent clinical research foci that may lead to a better understanding of the role of pulmonary gas-exchange inefficiency and activity-related dyspnea in COPD: (1) enhanced and deeper phenotyping of patients with COPD with V˙A/Q˙c abnormalities and (2) evaluation of existing and novel pharmacologic treatments to improve gas-exchange inefficiency, exertional dyspnea, and exercise tolerance across the spectrum of COPD severity. [ABSTRACT FROM AUTHOR]

Study objectives: Several validated instruments are used to measure outcomes, such as exercise performance, dyspnea, and health-related quality of life after pulmonary rehabilitation (PR) in patients with COPD. However, no study has simultaneously compared the responsiveness of the most frequently used outcome measurements after PR. We designed this study to investigate the capacity of several of the most frequently used outcome measurements to detect changes after PR in a population of patients with severe COPD who qualified for lung volume reduction surgery. Design, patients, and interventions: We evaluated 37 patients with severe COPD (FEV[sub 1] < 40%) before and after 6 to 8 weeks of outpatient PR. The following frequently used tools were evaluated: the 6-min walk distance (6MWD); functional dyspnea with the Medical Research Council (MRC) scale; baseline and transitional dyspnea index (BDI/TDI); resting and 6MWD visual analog scale (VAS); quality of life with a generic tool (the Short Form-36 [SF-36]); and two disease-specific tools, the Chronic Respiratory Disease Questionnaire (CRQ) and the St. George's Respiratory Questionnaire (SGRQ). Results: After PR, mean ± SD 6MWD increased in 33 of 37 patients (89%), from 285 ± 97 to 343 ± 92 m (p = 0.009). Improvements were seen also in the MRC scale in 23 of 37 patients (62%; from 2.27 ± 0.8 to 1.86 ± 0.6; p = 0.01); in CRQ dyspnea in 25 of 37 patients (67%; from 3.25 ± 0.9 to 3.90 ± 1.4; p = 0.02); in CRQ mastery in 22 of 37 patients (60%; from 4.37 ± 1.4 to 5.14 ± 1.3; p = 0.01); and in BDUTDI functional in 24 of 37 patients (64%; from 1.4 ± 0.8 to 0.7 ± 1.1; p = 0.002). There were smaller improvements in the SGRQ in 18 of 37 patients (48%) and in the SF-36 in 19 of 37 patients (51%), but they were not statistically significant. There were good correlations between the dyspnea components of all the tools. The 6MWD change did not... [ABSTRACT FROM AUTHOR]