title: Acute and chronic inflammatory responses induced by smoking in individuals susceptible and non-susceptible to development of COPD: from specific disease phenotyping towards novel therapy. Protocol of a cross-sectional study.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with pulmonary and extra-pulmonary manifestations. Although COPD is a complex disease, diagnosis and staging are still based on simple spirometry measurements. Different COPD phenotypes exist based on clinical, physiological, immunological and radiological observations. Cigarette smoking is the most important risk factor for COPD, but only 15-20% of smokers develop the disease, suggesting a genetic predisposition. Unfortunately, little is known about the pathogenesis of COPD, and even less on the very first steps that are associated with an aberrant response to smoke exposure. This study aims to investigate the underlying local and systemic inflammation of different clinical COPD phenotypes, and acute effects of cigarette smoke exposure in individuals susceptible and non-susceptible for the development of COPD. Furthermore, we will investigate mechanisms associated with corticosteroid insensitivity. Our study will provide valuable information regarding the pathogenetic mechanisms underlying the natural course of COPD.
  
  
  METHODS
  This cross-sectional study will include young and old individuals susceptible or non-susceptible to develop COPD. At a young age (18-40 years) 60 'party smokers' will be included who are called susceptible or non-susceptible based on COPD prevalence in smoking family members. In addition, 30 healthy smokers (age 40-75 years) and 110 COPD patients will be included. Measurements will include questionnaires, pulmonary function, low-dose CT scanning of the lung, body composition, 6 min walking distance and biomarkers in peripheral blood, sputum, urine, exhaled breath condensate, epithelial lining fluid, bronchial brushes and biopsies. Non-biased approaches such as proteomics will be performed in blood and epithelial lining fluid.
  
  
  BACKGROUND
  This multicentre study was approved by the medical ethical committees of UMC Groningen and Utrecht, the Netherlands. The study findings will be presented at conferences and will be reported in peer-reviewed journals.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT00807469 (study 1) and NCT00850863 (study 2).
authors: Department of Respiratory Medicine,  University Medical Center Utrecht, Utrecht , The Netherlands.
authors: Adèle T
authors: AT
authors: Lo Tam Loi
authors: Susan J M
authors: SJ
authors: Hoonhorst
authors: Lorenza
authors: L
authors: Franciosi
authors: Rainer
authors: R
authors: Bischoff
authors: Roland F
authors: RF
authors: Hoffmann
authors: Irene
authors: I
authors: Heijink
authors: Antoon J M
authors: AJ
authors: van Oosterhout
authors: H Marike
authors: HM
authors: Boezen
authors: Wim
authors: W
authors: Timens
authors: Dirkje S
authors: DS
authors: Postma
authors: Jan-Willem
authors: JW
authors: Lammers
authors: Leo
authors: L
authors: Koenderman
authors: Nick H T
authors: NH
authors: Ten Hacken
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