Can Circulating Biomarkers Identify Different FEV ₁ Trajectories of COPD Patients?

Abstract

Background and Objectives: Different life-time lung function trajectories can lead to chronic obstructive pulmonary disease (COPD) in adulthood. Identifying the trajectory that COPD patients have followed, or may be primed to follow, can provide an opportunity for differential interventions. We conducted the first study to investigate whether circulating biomarkers could identify different lung function trajectories that lead to or follow COPD.

Methods: Based on FEV₁ trajectories from age 7 to 53 years in the TAHS cohort, we classified those who had COPD at 53 years into two groups: “accelerated decline” (n=60) or “early low, normal decline” (n=94). In the ECLIPSE cohort, those who had COPD at age 63 years were divided into “accelerated decline” (n=817) or “normal decline” (n=492) based on FEV₁ change from age 63 to 66 years. Levels of selected pro- and anti-inflammatory biomarkers were compared between the two COPD groups in both cohorts, and ROC curve analysis was used to investigate predictive values.

Results: TAHS COPD patients in the “accelerated decline” lung function trajectory had significantly lower levels of CC16 and higher levels of CRP than those in the “early low, normal decline” trajectory. Furthermore, CC16 (AUC=68.7 [95%CI: 56.1-81.0]), CRP (AUC=62.5 [53.3-72.0]) and their combination (AUC=71.9 [60.2-83.1]) were able to discriminate between these groups. ECLIPSE COPD patients in the “accelerated decline” group had significantly lower CC16 but not CRP levels, when compared to those in the “normal decline” group. Neither CC16 nor CRP were able to discriminate well between the two COPD groups in ECLIPSE.

Interpretation: Both CC16 and CRP identified lung function trajectories that lead to COPD in middle age, but only CC16 was associated with subsequent accelerated lung function decline in older COPD patients.

Funding Statement: TAHS was supported by the National Health and Medical Research Council (NHMRC) of Australia under NHMRC project grant scheme (299901, 1021275) and NHMRC European collaborative grant scheme (1101313) as part of ALEC (Ageing Lungs in European Cohorts funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 633212); The University of Melbourne; Clifford Craig Medical Research Trust of Tasmania; the Victorian, Queensland & Tasmanian Asthma Foundations; The Royal Hobart Hospital; Helen MacPherson Smith Trust; and GlaxoSmithKline. SCD, AL, JP, CL and EHW are supported by the NHMRC of Australia.

Declaration of Interests: Authors have no conflicts of interest.

Ethics Approval Statement: Follow-up of TAHS was approved by Ethic Committees of all participating institutions, and all participants provided informed consent.