Small airways ventilation heterogeneity and hyperinflation in COPD: Response to tiotropium bromide

Sylvia Verbanck, Daniël Schuermans, Walter Vincken

Respiratory Division, University Hospital Brussels, Belgium

Abstract: In chronic obstructive pulmonary disease (COPD) patients tiotropium bromide has been shown to improve forced expiratory volume in one second (FEV₁) and inspiratory capacity (IC). We investigated whether the mechanism leading to these improvements is related to small airways ventilation heterogeneity, assessed by multiple breath washout tests. Forty stable tiotropium-free COPD patients (FEV₁: 27%–78% predicted) were studied before and 90 min after administration of tiotropium bromide on visit0, and following 3 and 6 weeks of tiotropium bromide treatment (visit_3wks, visit_6wks). After study completion, COPD patients were classified into two subgroups according to degree of hyperinflation at visit₀ (Hyp–, Hyp+). The Hyp+ group showed significant increases in trough (ie, pre-dose) FEV₁ and IC after 3 and 6 weeks of tiotropium bromide, and the 90 min tiotropium bromide responses of FEV₁ and IC were significant at visit₀ (p ≤ 0.001 for both) but not during subsequent visits. The Hyp- group showed significant FEV₁ increases 90 min after tiotropium bromide on all three visits (all p < 0.005) but no sustained increase in trough values. In both COPD subgroups, the grossly abnormal ventilation heterogeneity barely showed any significant improvements with tiotropium bromide in the conductive airways (without changes in trough value) and no changes at all in the acinar airways. We conclude that the sustained improvements in trough IC and FEV₁ with tiotropium bromide predominantly observed in COPD patients with considerable hyperinflation, are unrelated to small airways ventilation heterogeneity.

Keywords: COPD, hyperinflation, small airways, ventilation heterogeneity