Role of bronchodilation and pattern of breathing in increasing tidal expiratory flow with progressive induced hypercapnia in chronic obstructive pulmonary disease

Abstract

Hypercapnia (HC) in vitro relaxes airway smooth muscle; in vivo, it increases respiratory effort, tidal expiratory flows (V̇exp), 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 V̇exp 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), V̇exp, esophageal pressure (Pes), Ti, and end-tidal Pco2 ([Formula: see text]) were measured during six tidal breaths followed by an inspiratory capacity (IC), breathing air, and at three levels of HC. V̇exp and V̇ with submaximal forced vital capacities breathing air (V̇sFVC) were compared. Pulmonary resistance ( Rl) was measured from the Pes-V̇ relationship. V̇exp and Pes at end-expiratory lung volume (EELV) + 0.3 tidal volume [V̇(0.3Vt) and Pes(0.3Vt), respectively], Ti, and Rl correlated with [Formula: see text] ( P < 0.001 for all) and were independent of tiotropium. [Formula: see text], Ti, and Pes(0.3Vt) predicted the increasing V̇(0.3Vt)/V̇sFVC(0.3Vt) [multiple regression analysis (MRA): P = 0.001, 0.004, and 0.025, respectively]. At [Formula: see text] ≥ 50 Torr, V̇(0.3Vt)/V̇sFVC(0.3Vt) exceeded unity in 30 of 36 measurements and was predicted by [Formula: see text] and Pes(0.3Vt) (MRA: P = 0.02 and 0.025, respectively). Rl decreased at [Formula: see text] 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 V̇exp 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.