Interaction in Chronic Obstructive Pulmonary Disease Experiment

Study Overview
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Brief Summary
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The final purpose of this study is to determine whether bronchodilation and cigarette smoking in Chronic Obstructive Pulmonary Disease (COPD) patients interact, resulting in an increase of cardiovascular disease. The aim of this part of the study is to demonstrate the basic mechanism: Does increased respiratory function after administration of a bronchodilator in patients with COPD lead to elevated pulmonary retention of the harmful compounds in inhaled cigarette smoke and to short-term biological effects associated with cardiovascular disease?

Detailed Description
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COPD currently is one of the most frequent diseases. In more than 80% of COPD patients, the disease is caused by smoking. About half of the COPD patients are active smokers, although smoking is also the most important prognostic factor. Also, smoking is an important cause as well as an important prognostic factor in cardiovascular disease. The corner stone of medical treatment in COPD is bronchodilation; more than half of the patients use a long-acting bronchodilator. An increase of the pathogenic effect of smoking by an increased lung function after bronchodilation is likely though, since more pathogenic particles would penetrate the lung. We hypothesize that bronchodilators increase cardiovascular disease in COPD patients who smoke. In order to demonstrate the basic mechanism of our hypothesis, COPD patients receive a bronchodilator at one time and a placebo at another time, preceded and followed by cigarette smoking during one hour as by a strict time schedule. Smoke retention, lung function and blood biomarkers are repeatedly measured.

Official Title
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A Hazardous Combination of Cigarette Smoking and Bronchodilation in Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease, Cardiovascular Disease, Smoking, Bronchodilation

Intervention / Treatment
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* Drug: Tiotropium (Spiriva) + Salbutamol (Ventolin)
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD Gold stage II-III (FEV1/FVC<0,70 and FEV1 30-80% of predicted value). Current cigarette smoking (at the time of performing the study). Willing to provide written informed consent. Refrain from smoking and bronchodilators > 8 hours (depends on treatment) before the test. Registered in one of the recruitment institutes. Exclusion Criteria: COPD gold stage I or IV. Asthmatic component: History of asthma, present asthma by complaints, eosinophilia or reversibility ≥ 10% of predicted. Unable to communicate. Physically unable to perform any of the tests. Non-COPD respiratory disorders. Previous lung-volume reduction surgery and/or lung transplantation. Evidence of alcohol, drug or solvent abuse. Known α-1 antitrypsin deficiency.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: beta 2 agonist + anticholinergic aerosol<br> | Drug: Tiotropium (Spiriva) + Salbutamol (Ventolin)<br>* 1 time inhalation of 5 mcg of Tiotropium bromide by Respimat and 400 mcg of Salbutamol by Volume Spacer. cigarette smoking<br>* Other names: Ventolin Aerosol;|
| Placebo Comparator: placebo inhalation<br> | Drug: placebo<br>* 1 time inhalation of placebo with the amount of puffs similar to the active comparator. cigarette smoking<br>* Other names: Ventolin placebo and Spiriva placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cigarette smoke retention |  | retention measurement is during smoking. smoking is 1 cigarette before and 1 cigarette 45 minutes after medication inhalation for each arm. 1 week between arms | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (hs)CRP |  | 3 times within 2 hours for each arm | 
| fibrinogen |  | 3 times within 2 hours for each arm | 
| respiratory function |  | at baseline and repeatedly around medication inhalation for 1.5 hours | 
| smoking pattern: smoke inhalation and smoke exhalation time and volume |  | during smoking cigarettes: twice for each arm. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intervention study, interaction, COPD