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

Abstract

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 ~52% and ~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.

Keywords: COPD; COSYCONET cohort; chronic obstructive pulmonary disease; clinical respiratory medicine; cytokine; hyperinflation; inflammation; respiratory function tests.

FIGURE 1

Disease progression at month 18 in COSYCONET. One thousand and twenty six patients completing 18‐months follow‐up were examined for changes in selected markers. Combinations were given in an upset plot with baseline FEV₁% predicted and KCO % predicted as catplots. ΔSGRQ ≥ + 6: increase of at least 6 points of SGRQ; ΔRV/TLC ≥ + 0.02: increase of RV/TLC by at least 0.02; ΔFEV₁ ≥ + 150 mL: decrease of FEV₁ by at least 150 mL; ΔKCO% ≥ + 7.5%: decrease of KCO % predicted by at least 7.5%; 18‐mo EXA‐grade = 2: hospitalization for acute exacerbation in the last 12 months FEV₁, forced expiratory volume in the first second; KCO, CO transfer coefficient; RV/TLC, residual volume/total lung capacity; SGRQ, St. George's Respiratory Questionnaire.