Clinical trial NCT00981851: Interaction in Chronic Obstructive Pulmonary Disease Experiment
Official title: A Hazardous Combination of Cigarette Smoking and Bronchodilation in Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Cardiovascular Disease
Smoking
Bronchodilation
Keywords: intervention study
interaction
COPD
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2009-09-22
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: cigarette smoke retention
timeFrame: 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 outcomes:
measure: (hs)CRP
timeFrame: 3 times within 2 hours for each arm
measure: fibrinogen
timeFrame: 3 times within 2 hours for each arm
measure: respiratory function
timeFrame: at baseline and repeatedly around medication inhalation for 1.5 hours
measure: smoking pattern: smoke inhalation and smoke exhalation time and volume
timeFrame: during smoking cigarettes: twice for each arm.
Other outcomes:
Locations:
city: Groesbeek
country: Netherlands
facility: University Center for Chronic Diseases Dekkerswald
city: Nijmegen
country: Netherlands
facility: Primary care, general practitioners
Study officials:
affiliation: Radboud University Nijmegen Medical Center
name: Tjard RJ Schermer, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Dijk WD, Heijdra Y, Lenders JW, Klerx W, Akkermans R, van der Pouw A, van Weel C, Scheepers PT, Schermer TR. Cigarette smoke retention and bronchodilation in patients with COPD. A controlled randomized trial. Respir Med. 2013 Jan;107(1):112-9. doi: 10.1016/j.rmed.2012.09.019. Epub 2012 Oct 12.
citation: van Dijk WD, Scheepers PT, Cremers R, Lenders JW, Klerx W, van Weel C, Schermer TR, Heijdra Y. A method to study the effect of bronchodilators on smoke retention in COPD patients: study protocol for a randomized controlled trial. Trials. 2011 Feb 10;12:37. doi: 10.1186/1745-6215-12-37.