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?

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.

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.