• cigarette smoke retention [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  

• (hs)CRP [ Time Frame: 3 times within 2 hours for each arm ] [ Designated as safety issue: Yes ]
  
• fibrinogen [ Time Frame: 3 times within 2 hours for each arm ] [ Designated as safety issue: Yes ]
  
• respiratory function [ Time Frame: at baseline and repeatedly around medication inhalation for 1.5 hours ] [ Designated as safety issue: No ]
  
• smoking pattern: smoke inhalation and smoke exhalation time and volume [ Time Frame: during smoking cigarettes: twice for each arm. ] [ Designated as safety issue: No ]
  

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.