Relationship between improved airflow limitation and changes in airway calibre induced by inhaled anticholinergic agents in COPD

Abstract

Background: 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. A study was undertaken to determine the relationship between improved pulmonary function and changes in airway calibre at various sites in the airways in response to inhaled anticholinergic agents in patients with COPD using three-dimensional computed tomography (CT). Methods: CT scans were performed 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. The airway luminal area was examined at the third (segmental) to the sixth generations of eight bronchi in the right lung. Results: Bronchodilation was demonstrated by an overall average increase of 39% in the inner luminal area, and the mean (SE) forced expiratory volume in 1 s (FEV 1 ) increased from 1.23 (0.11) l to 1.47 (0.13) l. The magnitude of bronchodilation was closely correlated with improved pulmonary function, particularly with that of FEV 1 (r = 0.843, p,0.001). Such correlations were significant at the fourth to the sixth generation but not at the third generation of bronchi, and the slope of the regression lines became steeper from the third to the sixth generation. Conclusions: Inhaled anticholinergic agents induce overall bronchodilation which is in proportion to improvements in FEV 1 in patients with COPD. Bronchodilation at the distal rather than the proximal airways is the determinant of functional improvement.Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation that is not fully reversible. It is caused by a mixture of abnormal inflammatory responses in the small airways and parenchymal destruction of the lungs, the relative contributions of which vary among individuals.

Effect of Emphysema on CT Scan Measures of Airway Dimensions in Smokers

“…[10][11][12][13] Using data from the COPDGene Study, we observed that emphysema mitigates the increasing effect of WA% on FEV 1 % predicted in subsegmental compared with segmental airways. CT scan measures of emphysema and lung volume adjusted for sex, age, height, pack-years of smoking, CT scanner brand/make, and lobar volume, lobar emphysema was directly related to subsegmental WA% in all bronchial paths but RB4.…”

“…10,11 It has since become the standard in quantitative CT image analyses to study the most peripheral airways. [12][13][14] African American smokers aged 45 to 80 years. Subjects with active lung disease other than asthma, emphysema, and COPD were excluded.…”

Effects of Tiotropium and Salmeterol/Fluticasone Propionate on Airway Wall Thickness in Chronic Obstructive Pulmonary Disease

“…The important role of small airway lesions has been well recognized in the airflow limitations in COPD [43]. Recently, it was reported that bronchodilation at the distal rather than the proximal airways determines functional improvement in airflow limitation in response to Tio in COPD [44]. If we had measured more peripheral sites of the airway dimensions through the development of CT technology, we may have provided some intriguing insights into the bronchodilator effect of Tio plus SFC.…”

Association Between Airway Caliber Changes With Lung Inflation and Emphysema Assessed by Volumetric CT Scan in Subjects With COPD

“…5,6 Furthermore, CT scanning is a recognized technique to assess the presence, extent, and location (ie, lobar level) of emphysema. 7 CT scan can be used to classify subjects with COPD into emphysemapredominant (EP) or airway-predominant (AP) subtypes.…”