title: Early detection of COPD patients in GOLD 0 population: an observational non-interventional cohort study - MARKO study.
abstract: Main risk factor for the development of chronic obstructive pulmonary disease (COPD) is smoking, although only less than 1/3 of smokers develop clinically manifest COPD. COPD's progressive nature with high disability and mortality makes it plausible to detect it as early as possible thus allowing for an early intervention. The only tool for an early diagnosis that could be used on the global scale is spirometry, even though symptoms and deprivation of health related quality of life (HRQoL) precede relevant spirometric changes. Existing HRQoL questionnaires are too complicated or not developed for an early detection of COPD. The aim of our study was to develop a new simple HRQoL tool that will allow (alone or in combination with other markers) early detection of patients with COPD.
  
  
  
  A multicenter prospective cohort study recruiting 500 subjects at risk for COPD (smokers/ex-smokers ≥20 pack-years, 40-65 years, both sexes, with no prior diagnosis of COPD) will be carried out in two phases: (1) cross-sectional - development and validation of a new questionnaire; and (2) prospective - follow-up of a cohort of patients at risk for COPD. Subjects were recruited by 25 GPs and assessed for COPD by dedicated pulmonologists in 7 hospital centers using a predefined protocol: HRQoL, history, physical, blood sampling, exhaled breath temperature (EBT), lung function, 6-min walk test (6MWT). Patients without COPD and those in GOLD stage 1 at initial assessment will be reassessed for disease progression by the same pulmonologist after 2 and 5 years.
  
  
  
  This is one of the first cohort studies attempting to establish the incidence of COPD in the pre-symptomatic stage before significant end organ damage. We intend to assess the validity, predictability and discriminative power ('healthy' smokers vs. pre-symptomatic phase in newly developed COPD) of newly developed HRQoL tool alone or in combination with other markers; EBT, lung function, 6MWT, genomics, transcriptomics, proteomics). We expect that the results of this study can improve our understanding of the development of COPD, identify some new underlying pathophysiological pathways, and offer to sensitive smokers/ex-smokers new preventive and early intervention measures thus improving the management of COPD.
  
  
  
  Clinicaltrial.gov NCT01550679 retrospectively registered February 28, 2012.
authors.affiliation: Department of Pulmonology and Immunology, General Hospital Dubrovnik, Dr. Roka Mišetića 2, Dubrovnik, Croatia.|University of Dubrovnik, Branitelja Dubrovnika 29, Dubrovnik, Croatia.
authors.forename: Žarko
authors.initials: Ž
authors.lastname: Vrbica
authors.affiliation: Department of Pulmonology, University Hospital Center Osijek, Josipa Huttlera 4, Osijek, Croatia.|Faculty of Medicine, J.J. Strossmayer University of Osijek, Ulica cara Hadrijana 10E, Osijek, Croatia.
authors.forename: Marina
authors.initials: M
authors.lastname: Labor
authors.affiliation: Department of Pulmonology, University Hospital Center Split, Spinčićeva 1, Split, Croatia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Gudelj
authors.affiliation: Department of Pulmonology, University Hospital Center Osijek, Josipa Huttlera 4, Osijek, Croatia.|Faculty of Medicine, J.J. Strossmayer University of Osijek, Ulica cara Hadrijana 10E, Osijek, Croatia.
authors.forename: Slavica
authors.initials: S
authors.lastname: Labor
authors.affiliation: Department of Internal Medicine, University Hospital Center Osijek, Josipa Huttlera 4, Osijek, Croatia.
authors.forename: Iva
authors.initials: I
authors.lastname: Jurić
authors.affiliation: Faculty of Medicine, J.J. Strossmayer University of Osijek, Ulica cara Hadrijana 10E, Osijek, Croatia. plavec@bolnica-srebrnjak.hr.|Research Department, Children's Hospital Srebrnjak, Srebrnjak 100, Zagreb, Croatia. plavec@bolnica-srebrnjak.hr.
authors.forename: Davor
authors.identifier: 0000-0003-2020-8119
authors.initials: D
authors.lastname: Plavec
mesh_terms: D000328:Adult; D000368:Aged; D017523:Croatia / Q000453:epidemiology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004198:Disease Susceptibility; D042241:Early Diagnosis; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000453:epidemiology; D011788:Quality of Life; D012107:Research Design; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013147:Spirometry; D011795:Surveys and Questionnaires; D000070857:Walk Test
keywords: Biological markers; Chronic obstructive pulmonary disease (COPD); Cigarette smoking; Disease susceptibility; Early diagnosis