Modification of Chronic Inflammation by Inhaled Carbon Monoxide in Patients With Stable Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether carbon monoxide is effective in the treatment of stable COPD.

Detailed Description
-----------------
COPD is characterised by a chronic pulmonary inflammation and a shifted oxidant/antioxidant balance. The main cause of this inflammation is smoking. After smoking cessation, this inflammation and shifted oxidant/antioxidant balance continues. This causes an increased deterioration of lung function compared to healthy persons of matching age. The ongoing inflammation appears to be relatively insensitive to corticosteroid therapy. Until now, there is no therapy for this inflammation. Both in vitro and in vivo studies show that carbon monoxide has, besides an antioxidant capacity, anti-inflammatory properties. The aim of this trial is to study whether the inflammation can be reduced by inhalation of carbon monoxide.

Official Title
-----------------
Modification of Chronic Inflammation by Inhaled Carbon Monoxide in Patients With Stable COPD

Conditions
-----------------
Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
-----------------
* Drug: carbon monoxide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women, age > 40 years. Women must be post-menopausal (i.e. at least one year must have passed after the last menstruation), surgically sterile or using acceptable contraceptives, as judged by the investigator. A diagnosis of COPD according to the criteria of the American Thoracic Society (ATS); a disease state characterised by the presence of chronic airway obstruction due to chronic bronchitis (cough/sputum on most days a week for 3 months a year for at least two successive years); or emphysema. FEV1 > 0.7 litres FEV1/FVC ratio < 70% (equation retrieval system [ERS] equations) A smoking history of > 10 pack years Completely stopped smoking > 1 year ago No upper or lower respiratory tract infection in the last 4 weeks In a stable phase of COPD, as judged by the investigator Signed and dated informed consent obtained before any study related procedures (including withdrawal of concomitant medication) are conducted Exclusion Criteria: Treatment with immune-modulating agents for any other disease History of asthma; former diagnosis of asthma Arterial oxygen tension (PaO2) < 8.0 kPa Any significant other pulmonary disease or disorder (e.g. alpha1-antitrypsin deficiency, bronchiectasies), as judged by the investigator Patients with other significant disease or disorder (like cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic [including diagnosed diabetes], malignant, psychiatric, major physical impairment), which, in the opinion of the investigator may either put the patient at risk because of participation in the study; or may influence the results of the study, or the patient's ability to participate in the study. Patients unable to blow reproducable lung function measurements Patients using medicine with anti-oxidant character like n-acetyl-cysteine.

Ages Eligible for Study
-----------------
Minimum Age: 40 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carbon monoxide|nan|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of neutrophils in induced sputum |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| methacholine provocation threshold |  |  | 
| exhaled CO/NO |  |  | 
| FEV1, FVC, RAW, sgaw |  |  | 
| inflammatory parameters in sputum and blood |  |  | 
| 8-isoprostane in exhaled breath |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
carbon monoxide, COPD, inflammation, sputum induction, stable COPD