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

Hypercapnia (HC) in vitro relaxes airway smooth muscle; in vivo, it increases respiratory effort, tidal expiratory flows (Vexp), 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. Vexp and V with submaximal forced vital capacities breathing air (VsFVC) were compared. Pulmonary resistance (Rl) was measured from the Pes-V relationship.Vexp 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)/VsFVC(0.3Vt) [multiple regression analysis (MRA): P = 0.001, 0.004, and 0.025, respectively]. At PETCO2 > 50 Torr, V (0.3Vt)/VsFVC(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.