Effects of N-acetylcysteine on Cardiorespiratory Control in COPD Patients With Mild-to-moderate Airflow Obstruction

Phase 4

Completed

Brief Summary: The main purpose of this study is to determine whether pharmacological treatment with N-acetylcysteine improves central and peripheral cardiorespiratory control and physical capacity in COPD patients with mild-to-moderate airflow obstruction.

Detailed Description: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Cardiovascular complications constitute the main causes of poor physical capacity and healthcare resources utilization in COPD. There is emerging evidence that these impairments have a major impact on the health of patients with mild-to-moderate disease, the largest sub-population of COPD. This important problem, however, is currently neglected as no specific pharmacological treatment is offered to these patients. Recent studies indicate that vascular abnormalities are mediated, at least in part, by circulating inflammatory substances and direct damage of the arteries by oxygen radicals (oxidative stress). The current investigation will test the hypothesis that N-acetylcysteine (NAC), via its anti-inflammatory and antioxidant properties, improves systemic vascular function and physical capacity in COPD patients with mild-to-moderate airflow obstruction.

Recruitment & Eligibility

Inclusion Criteria

stable COPD with mild-to-moderate airflow obstruction as indicated by the low ratio between forced expiratory volume in one second and forced vital capacity (FEV1/FVC<0.7) together with post-bronchodilator FEV1≥60% predicted under optimized clinical treatment as judged by the accompanying physician

Exclusion Criteria

unable to perform all experimental procedures and/or provide informed consent;
hospital admission in the previous 6 weeks;
exercise training program in the previous 6 months;
any condition that could interfere with the ability to exercise;
diagnosed psychiatric or cognitive disorders;
type I insulin-dependent diabetes mellitus;
excessively over-weight (BMI>35kg/m²);
other diagnosed cardiorespiratory disorders (e.g., chronic heart failure, peripheral artery disease).

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Treatment with placebo pills
N-acetylcysteine	N-acetylcysteine	Pharmacological treatment with N-acetylcysteine (NAC) pills

Primary Outcome Measures

Name	Time	Method
Plasma Redox Status - Circulating Glutathione	pre-exercise value (day 4)	Fluorescent detection of plasma glutathione from samples collected during day 4 of each experimental arm (placebo vs. N-acetylcysteine)
Exercise Capacity - Time to Exhaustion	end-exercise value (Day 4)	Cycling time to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine)

Secondary Outcome Measures

Name	Time	Method
Change in Skeletal Muscle Deoxygenation - Dynamics (Mean Response Time)	Day 4	Mean response time (MRT) evaluated during cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine)
Change in Pulmonary Oxygen Uptake - Dynamics (Mean Response Time)	Day 4	Mean response time (MRT) evaluated during cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine)
Change in Central Cardiovascular Function - Cardiac Output	end-exercise value (Day 4)	During cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine)
Change in Skeletal Muscle Vascular Function - Capillary Blood Flow Dynamics (Mean Response Time)	Day 4	Mean response time (MRT) evaluated during cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine)
Change in Pulmonary Ventilation - Minute Ventilation (VE)	end-exercise value (Day 4)	During cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine)