Effects of Long Acting Bronchodilators on CARDiac Autonomic Control in Chronic Obstructive Pulmonary Disease (COPD)
Effects of Long Acting Bronchodilators on CARDiac Autonomic Control in Chronic Obstructive Pulmonary Disease (COPD)
The aim of this interventional, randomized, double-blind, monocentric, cross-over study is to
 quantify the possible deleterious effect on the cardiac autonomic nervous system control of
 two long-acting anticholinergic bronchodilatators (tiotropium and glycopyrronium) and one
 beta-2 agonist long-acting bronchodilatator (indacaterol ) in patients with mild COPD.
This is a cross-over study with randomization in terms of 4 treatments: two long-acting
 muscarinic antagonists (tiotropium and glycopyrronium), one long-acting beta-adrenoceptor
 agonist(indacaterol) and placebo.

 Each subject will pass 4 experimental random sessions, separated by at least 48 hours given
 the pharmacokinetic properties of the drugs tested. During each of the 4 sessions, blood
 pressure will be measured. Drugs inhaled by the patient will be prepared and administered by
 the nurse according to the randomization schedule. Patients and investigators will be blinded
 regarding the administered drug/placebo (anonymized inhaler). After 15 minutes (at rest, at
 neutral temperature), patients will have continuous measurement of blood pressure and heart
 rate (by a sphygmomanometer) (1) in supine position and (2) after a passive tilt test on a
 tilt test table.

 A flow-volume loop (BDV) will be performed after the tilt table test (measurement of Forced
 expiratory volume in 1 second (FEV1) and FVC).
Inclusion Criteria:

 -  patients with FEV1 / FVC <70%

 Exclusion Criteria:

 -  beta blocker

 -  supraventricular rhythm disorder

 -  previous history of respiratory disease other than COPD

 -  diabetes

 -  autonomic dysfunction

 -  dysautonomia

 -  renal failure

 -  long-term oxygen therapy

 -  history of psychiatric illness