Study objectives: Cigarette smoking has been associated with impaired endothelium-dependent relaxation responses in the brachial and coronary arteries (endothelial dysfunction). The aim of the present study was to determine whether the airway circulation is also affected and whether pharmacologic treatment has an effect on endothelial function in patients with COPD.
Methods and patients: Airway blood flow (Q̇aw) responses to therapy with inhaled albuterol, which causes endothelium-dependent vasodilation, were measured with a noninvasive soluble-gas-uptake technique in age-matched healthy current smokers (n = 10), healthy ex-smokers (n = 10), ex-smokers with COPD (n = 10), and healthy lifetime nonsmokers. In the ex-smokers with COPD, the albuterol responsiveness measurement was repeated after 4 weeks of treatment with fluticasone/salmeterol and after a drug washout period of 4 or 8 weeks.
Results: The mean (± SE) baseline Q̇aw values ranged between 40.7 ± 3.9 and 50.9 ± 2.8 μL/min/mL anatomic dead space in the four groups (differences were not significant). The mean FEV1 was 53.4 ± 2.3% predicted in the ex-smokers with COPD. Albuterol inhalation increased mean Q̇aw significantly in lifetime nonsmokers (50.1 ± 8.3% predicted; p < 0.05) and healthy ex-smokers (37.2 ± 3.4% predicted; p < 0.05), but not in healthy current smokers (13.9 ± 3.2% predicted; difference was not significant) and ex-smokers with COPD (9.7 ± 4.5% predicted; difference was not significant). While fluticasone/salmeterol did not change Q̇aw significantly, it restored albuterol responsiveness (67.6 ± 11.1% predicted; p < 0.05) in the ex-smokers with COPD; this effect was no longer seen after the drug washout period.
Conclusions: Cigarette smoking is associated with a blunted vasodilator response to inhaled albuterol in the airway as an expression of endothelial dysfunction, with a partial recovery of albuterol responsiveness after smoking cessation in healthy ex-smokers but not in ex-smokers with COPD. In the latter group, combined glucocorticoid/long-acting β2-adrenergic agonist treatment restores albuterol responsiveness. The role of endothelial dysfunction in the physiopathology of COPD remains to be examined.