title: Growth differentiation factor-15 is a predictor of important disease outcomes in patients with COPD.
abstract: Increased levels of growth differentiation factor-15 (GDF15) are associated with cachexia, cardiovascular disease and all-cause mortality. The role of GDF15 in chronic obstructive pulmonary disease (COPD) is unknown.The study included 413 patients with COPD from the Bergen COPD Cohort Study. All patients had a forced expiratory volume in 1 s (FEV1) <80% predicted, a FEV1to forced vital capacity (FVC) ratio <0.7 and a history of smoking. Spirometry, fat free mass index, blood gases and plasma GDF15 were measured at baseline. Patients were followed for 3 years regarding exacerbations and changes in lung function, and 9 years for mortality. Yearly exacerbation rate, survival and yearly change in FEV1/FVC were evaluated with regression models.Median plasma GDF15 was 0.86 ng·mL-1(interquartile range 0.64-1.12 ng·mL-1). The distribution was not normal and GDF15 was analysed as a categorical variable. High levels of GDF15 were associated with a higher exacerbation rate (incidence rate ratio 1.39, 95% CI 1.1-1.74, p=0.006, adjusted values). Furthermore, high levels of GDF15 were associated with higher mortality (hazard ratio 2.07, 95% CI 1.4-3.1, p<0.001) and an increased decline in both FEV1(4.29%versus3.25%) and FVC (2.63%versus1.44%) in comparison to low levels (p<0.01 for both).In patients with COPD, high levels of GDF15 were independently associated with a higher yearly rate of exacerbations, higher mortality and increased decline in both FEV1and FVC.
authors.affiliation: Dept of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway Gunnar.Husebo@uib.no.|Dept of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Gunnar R
authors.identifier: 0000-0001-6880-8215
authors.initials: GR
authors.lastname: Husebø
authors.affiliation: Dept of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Grønseth
authors.affiliation: AVEO Oncology, Cambridge, MA, USA.
authors.forename: Lorena
authors.initials: L
authors.lastname: Lerner
authors.affiliation: AVEO Oncology, Cambridge, MA, USA.
authors.forename: Jeno
authors.initials: J
authors.lastname: Gyuris
authors.affiliation: Dept of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Jon A
authors.initials: JA
authors.lastname: Hardie
authors.affiliation: Dept of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Per S
authors.initials: PS
authors.lastname: Bakke
authors.affiliation: Dept of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway.|Dept of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Tomas M
authors.initials: TM
authors.lastname: Eagan
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology*; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking; D013147:Spirometry; D014797:Vital Capacity
chemical_list: D055436:Growth Differentiation Factor 15