Relationship between improved airflow limitation and changes in airway caliber induced by inhaled anticholinergics in chronic obstructive pulmonary disease

Abstract

Rationale: Although airflow limitation improved by inhaled anticholinergic drugs varies among individuals with chronic obstructive pulmonary disease (COPD), the relationship between actual bronchodilation and improved pulmonary function and where in the lung such bronchodilation occurs remains unknown.

To determine the relationship between improved pulmonary function and changes in airway caliber at various sites among airways in response to inhaled anticholinergics in patients with COPD, using 3-dimensional computed tomography (CT).

Methods: We performed CT at deep inspiration and detailed pulmonary function tests before and 1 week after daily inhalations of tiotropium bromide in 15 patients with clinically stable COPD. We analyzed the airway luminal area at the 3rd (segmental) to the 6th generations of 8 bronchi in the right lung.

Measurements and main results: Bronchodilation was demonstrated as an overall average of a 39% increase in the inner luminal area, and the mean forced expiratory volume in 1 sec (FEV₁) increased from 1.23 ± 0.11 to 1.47 ± 0.13 (SE). The magnitude of bronchodilation closely correlated with improved pulmonary function, particularly with that of FEV₁ (r = 0.843, p < 0.001). Such correlations were significant at the 4th to the 6th, but not at the 3rd generation of bronchi, and the slope of regression lines became steeper from the 3rd to the 6th generation.

Conclusions: Inhaled anticholinergics induce overall bronchodilation in proportion to improvements in FEV1 in patients with COPD, and bronchodilation at distal, rather than proximal airways is the determinant of functional improvement.