Biomarkers of early chronic obstructive pulmonary disease (COPD) in smokers and former smokers. Protocol of a longitudinal study.

BACKGROUND Chronic obstructive pulmonary disease (COPD) is an irreversible disease, diagnosed predominantly in smokers. COPD is currently the third leading cause of death worldwide. Far more than 15 % of smokers get COPD: in fact, most develop some amount of pulmonary impairment. Smoking-related COPD is associated with both acute exacerbations and is closely correlated to comorbidities, such as cardiovascular disease and lung cancer. The objective of our study (KOL-Örestad) is to identify biomarkers in smokers and ex-smokers, with early signs of COPD, and compare these biomarkers with those of non-smokers and healthy smokers/ex-smokers. The participants in the study are recruited from Örestadskliniken, a primary health care clinic in Malmö, Sweden. METHODS Two hundred smokers and ex-smokers diagnosed with COPD with airflow restriction according to GOLD stages 1-4 will be included and compared with 50 healthy never-smokers, and 50 healthy smokers/ex-smokers without airflow restriction (total n = 300). The age distribution is 35-80 years. The participants undergo a health examination including medical history, smoking history, lung function measurements, and respond to a "Quality of Life" questionnaire. Blood samples are drawn every 6 months during a period of 5 years. Additional blood sample collection is performed if participants are experiencing an exacerbation. The blood fractions will be analyzed by standard clinical chemistry assays and by proteomics utilizing mass spectrometry platforms. Optimal sample integrity is ensured by rapid handling with robotic biobank processing followed by storage at -80 °C. The study has been approved by the Regional Ethical Review Board in Lund ( http://epn.se/en ), (Approval number: DNR 2013/480), and registered at the NIH clinical trial registry ( http://clinicaltrials.gov ). RESULTS AND DISCUSSION Currently, 220 subjects are enrolled in the study. CONCLUSIONS AND FUTURE DIRECTIONS The study design will enable discovery of new biomarkers by using novel mass spectrometric techniques that define early changes of COPD. Such panels of novel biomarkers may be able to distinguish COPD from closely related diseases, co-morbidities, and contribute to an increased understanding of these diseases. Graphical abstract KOL-Örestad Study.