title: A method to study the effect of bronchodilators on smoke retention in COPD patients: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is a common disease, associated with cardiovascular disease. Many patients use (long-acting) bronchodilators, whilst they continue smoking alongside. We hypothesised an interaction between bronchodilators and smoking that enhances smoke exposure, and hence cardiovascular disease. In this paper, we report our study protocol that explores the fundamental interaction, i.e. smoke retention.
  
  
  METHODS
  The design consists of a double-blinded, placebo-controlled, randomised crossover trial, in which 40 COPD patients smoke cigarettes during both undilated and maximal bronchodilated conditions. Our primary outcome is the retention of cigarette smoke, expressed as tar and nicotine weight. The inhaled tar weights are calculated from the correlated extracted nicotine weights in cigarette filters, whereas the exhaled weights are collected on Cambridge filters. We established the inhaled weight calculations by a pilot study, that included paired measurements from several smoking regimes. Our study protocol is approved by the local accredited medical review ethics committee.
  
  
  CONCLUSIONS
  Our study is currently in progress. The pilot study revealed valid equations for inhaled tar and nicotine, with an R2 of 0.82 and 0.74 (p < 0.01), respectively. We developed a method to study pulmonary smoke retentions in COPD patients under the influence of bronchodilation which may affect smoking-related disease. This trial will provide fundamental knowledge about the (cardiovascular) safety of bronchodilators in patients with COPD who persist in their habit of cigarette smoking.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00981851.
authors.affiliation: Department of Primary and Community Care, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. w.vandijk@aios.umcn.nl
authors.forename: W D
authors.initials: WD
authors.lastname: van Dijk
authors.forename: P T J
authors.initials: PT
authors.lastname: Scheepers
authors.forename: R
authors.initials: R
authors.lastname: Cremers
authors.forename: J W M
authors.initials: JW
authors.lastname: Lenders
authors.forename: W
authors.initials: W
authors.lastname: Klerx
authors.forename: C
authors.initials: C
authors.lastname: van Weel
authors.forename: T R J
authors.initials: TR
authors.lastname: Schermer
authors.forename: Y
authors.initials: Y
authors.lastname: Heijdra
mesh_terms: D000280:Administration, Inhalation; D001944:Breath Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000209:etiology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D009426:Netherlands; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D012107:Research Design; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D011795:Surveys and Questionnaires
chemical_list: D001993:Bronchodilator Agents