Effects of Sulfur Thermal Water Inhalation on Airway Oxidative Stress in COPD Patients

Study Overview
=================
Brief Summary
-----------------
The chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways characterized by fixed airflow obstruction, with important systemic co-morbidities. The obstruction is usually progressive and irreversible despite chronic therapy. Cigarette smoking is the major cause of this disease. COPD is an important cause of morbidity and mortality worldwide. Numerous studies have shown that oxidative stress plays a key role in the pathogenesis of COPD. In particular, the active metabolites of oxygen such as superoxide anion and the hydroxyl radical are unstable molecules that can trigger significant oxidative processes at the cellular level. These molecules can alter the extracellular matrix remodeling, cell respiration, cell proliferation, cellular repair and the immune response in the lung. All these events are key elements in the pathogenesis of COPD. Currently available treatments for COPD (i.e. long-acting bronchodilators and inhaled corticosteroids) have not demonstrated a significant in vivo antioxidant effect. The thermal inhalation treatments are a therapeutic strategy used since many years in an empirical way in patients with COPD. Indeed, the evidence of effectiveness of spa treatment in patients with COPD are very limited. The aim of this in vivo study is to evaluate the modulatory effects of sulfur thermal water inhalation on oxidant stress in the airways of stable COPD patients.

Official Title
-----------------
Placebo Controlled Study Evaluating the Modulatory Effects of Sulfur Thermal Water Inhalation on Superoxide Anion Levels in Exhaled Breath Condensate in COPD Patients

Conditions
-----------------
Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
-----------------
* Other: Sulfur Thermal water
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Forty stable moderate to severe COPD patients (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 and 3), according to international guidelines. FEV1/FVC ratio post-bronchodilator <70% 30% < FEV1 < 80% Exclusion Criteria: Atopy Asthma Concomitant lung diseases (e.g. lung cancer) Acute infections of the respiratory tree in the previous 3 months including COPD exacerbation.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thermal water inhalation<br>Patients will perform 12 days of sulfur thermal water inhalation | Other: Sulfur Thermal water<br> <br> |
| Placebo Comparator: Isotonic saline inhalation<br>Patients will perform 12 days of isotonic saline inhalation | Other: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Superoxide anion levels in exhaled breath condensate | Levels of superoxide anion levels will be measured at recruitment (day 0) and after 12 days of inhalation. Changes between day 12 and day 0 will be evaluated. | 12 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Superoxide anion levels in exhaled breath condensate | Levels of superoxide anion will be measured at recruitment (day 0), after 12 days of inhalation (day 12) and one month after the last day oh inhalation (day 42). Changes between day 42, day 12 and day 0 will be evaluated. | 42 day | 
| Inflammatory cell counts in induced sputum | Inflammatory cell counts in induced sputum will be measured at recruitment (day 0), after 12 days of inhalation (day 12) and one month after the last day of inhalation (day 42). Changes between day 42, day 12 and day 0 will be evaluated. | 42 days | 
| Clinical outcomes | Spirometry and the impact of COPD on patient quality of life (performed by the COPD Assessment Test (CAT)) will be measured at recruitment (day 0), after 12 days of inhalation (day 12) and one month after the last day of inhalation (day 42). Changes between day 42, day 12 and day 0 will be evaluated. | 42 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COPD, Thermal water, Oxidative stress, Inflammation