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 visco-elasticity; 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 COPD subjects, mean FEV₁ 53% predicted. Lung volumes (Vl), V'_exp, esophageal pressure (Pes), Ti and end tidal PCO₂ (PetCO₂) were measured during 6 tidal breaths followed by an inspiratory capacity (IC), breathing air and at 3 levels of HC. V'_exp and V' with sub-maximal forced vital capacities breathing air (V'_sFVC) were compared. Pulmonary resistance (Rl) was measured from the Pes-V' relationship. Results: 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 0.023 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.

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