Diffusion capacity and static hyperinflation as markers of disease progression predict 3-year mortality in COPD: Results from COSYCONET

Background and Objective: Chronic obstructive pulmonary disease (COPD) exhibits diverse patterns of disease progression, due to underlying disease activity. We hypothesized that changes in static hyperinflation or KCO % predicted would reveal subgroups with disease progression unidentified by preestablished markers (FEV1, SGRQ, exacerbation history) and associated with unique baseline biomarker profiles. We explored 18-month measures of disease progression associated with 18-54-month mortality, including changes in hyperinflation parameters and transfer factor, in a large German COPD cohort. Methods: Analysing data of 1364 patients from the German observational COSYCONET-cohort, disease progression and improvement patterns were assessed for their impact on mortality via Cox hazard regression models. Association of biomarkers and COPD Assessment test items with phenotypes of disease progression or improvement were evaluated using logistic regression and random forest models. Results: Increased risk of 18-54-month mortality was linked to decrease in KCO % predicted (7.5% increments) and FEV1 (20 mL increments), increase in RV/TLC (2% increments) and SGRQ (>= 6 points), and an exacerbation grade of 2 at 18 months. Decrease in KCO % predicted >= 7.5% and an increase of RV/TLC >= 2% were the most frequent measures of 18-month disease progression occurring in similar to 52% and similar to 46% of patients, respectively. IL-6 and CRP thresholds exhibited significant associations with medium- and long-term disease measures. Conclusion: In a multicentric cohort of COPD, new markers of current disease activity predicted mid-term mortality and could not be anticipated by baseline biomarkers.