Role of bronchodilation and pattern of breathing in increasing expiratory flow during progressive hypercapnia in chronic obstructive pulmonary disease.

Hypercapnia (HC) in vitro relaxes airway smooth muscle; in vivo, it increases respiratory effort, tidal expiratory flows (V-exp), and, by decreasing inspiratory duration (Ti), increases elastic recoil pressure (Pel) via lung viscoelasticity; however, its effect on airway resistance is uncertain. We examined the contributions of bronchodilation, Ti, and expiratory effort to increasing V-exp with progressive HC in 10 subjects with chronic obstructive pulmonary disease (COPD): mean forced expiratory volume in 1 s (FEV1) 53% predicted. Lung volumes (Vl), V-exp, esophageal pressure (Pes), Ti, and end-tidal PCO2 (PETCO2) were measured during six tidal breaths followed by an inspiratory capacity (IC), breathing air, and at three levels of HC. V-exp and V. with submaximal forced vital capacities breathing air (V-sFVC) were compared. Pulmonary resistance (Rl) was measured from the Pes-V. relationship. V. exp and Pes at end-expiratory lung volume (EELV) + 0.3 tidal volume [V-(0.3Vt) and Pes((0.3Vt)), respectively], Ti, and Rl correlated with PETCO2 (P < 0.001 for all) and were independent of tiotropium. PETCO2, Ti, and Pes((0.3Vt)) predicted the increasing V-(0.3Vt)/V-sFVC(0.3Vt) [multiple regression analysis (MRA): P = 0.001, 0.004, and 0.025, respectively]. At PETCO2 > 50 Torr, V-(0.3Vt)/V-sFVC(0.3Vt) exceeded unity in 30 of 36 measurements and was predicted by PETCO2 and Pes((0.3Vt)) (MRA: P = 0.02 and 0.025, respectively). Rl decreased at PETCO2 45 Torr (P < 0.05) and did not change with further HC. IC and Vl((0.3Vt)) did not change with HC. We conclude that in COPD HC increases V-exp due to bronchodilation, increased Pel secondary to decreasing Ti, and increased expiratory effort, all promoting lung emptying and a stable EELV. NEW & NOTEWORTHY The response of airways to intrapulmonary hypercapnia (HC) is uncertain. In chronic obstructive pulmonary disease (COPD), progressive HC increases tidal expiratory flows by inducing bronchodilation and via an increased rate of inspiration and lung viscoelasticity, a probable increase in lung elastic recoil pressure, both changes increasing expiratory flows, promoting lung emptying and a stable end- expiratory volume. Bronchodilation with HC occurred despite optimal standard bronchodilator therapy, suggesting that in COPD further bronchodilation is possible.