effect of an inhaled glucocorticoid-long-acting beta adrenergic agonist on endothelial function in copd

Conditions: COPD

Summary: in the present study, the investigators wish to address the effect of a glucocorticoid/long-acting beta-agonist preparation on endothelial function in copd patients who do not currently smoke (ex-smokers) by measuring endothelium-dependent (albuterol response) and endothelium-independent (ntg response) vasodilation in the bronchial artery, reflecting endothelium-dependent and endothelium-independent vasodilation (drug-induced increase in qaw, δqaw). with this approach the investigators will test the hypothesis that in stable ics-naïve copd patients, endothelium-dependent vasodilation is restored with a glucocorticoid/long-acting beta-agonist preparation, presumably resulting from the glucocorticoid component.

to test the premise and to characterize the time dependence of the responses, the investigators propose the following two aims: 1. to determine the effect of a medium dose glucocorticoid/long-acting beta-agonist preparation (250 μg fluticasone plus 50 μg salmeterol) administered for 3 weeks on inhaled albuterol and sub-lingual ntg induced vasodilation in the bronchial artery, as assessed by δqaw in stable glucocorticoid-naïve copd patients, and to re-assess the responses after a 3 week glucocorticoid/long-acting beta-agonist washout period. 2. to determine inhaled albuterol and sub-lingual ntg-induced vasodilation (δqaw) before, and 30 min and 120 min after a single medium dose of an ics (220 μg fluticasone) in stable glucocorticoid- naïve copd patients. for both aims, the protocol design will be placebo-controlled and double-blind. for the second aim, only fluticasone pretreatment will be possible because the salmeterol component of the fluticasone/salmeterol combination preparation could influence albuterol responsiveness irrespective of any glucocorticoid effect. the timing of the endothelial function measurements in the long-term glucocorticoid/long-acting beta-agonist protocol and single dose ics protocol is based on the past experience with ics on airway vascular function. single dose effects were seen within 15-30 min and waned by 90 min (25,26), while long-term treatment effects were no longer seen 3 weeks after ics withdrawal (16).

Eligibility criteria:
inclusion criteria: * smoking history of at least 10 pack-years and to have quit smoking at least 1 year before the study. -diagnosis of copd * post-bronchodilator fev1 of less than 75% of predicted and fev1/fvc ratio less than 0.7 (gold stage ≥2). * at entry into the study, the subjects will have to be clinically stable; they will be allowed to use short-acting and long-acting β2 - adrenergic agonists and cholinergic antagonists as their usual airway medication. exclusion criteria: * women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women. * use of cardiovascular medications that cannot be held on the study days * use of oral airway medications or anti-inflammatory agents * subjects with known beta-adrenergic agonist or ntg intolerance * acute respiratory infection within four weeks prior to the study * a body mass index \> 30

Keywords: airway blood flow, copd, endothelial dysfunction inhaled corticosteroids