Biomarkers of Pre-COPD Lung Function Trajectories in Middle Age: A Prospective Study From 1st to 6th Decade

Identifying impaired lifetime lung function trajectories and their underlying biological pathways is key to characterising the preclinical phase of COPD (Pre-COPD) and its progression. However, this is challenging in practice as repeated spirometry measurements from childhood are rarely available. We investigated potential blood biomarkers associated with pre-COPD trajectories.

The Tasmanian Longitudinal Health Study has unique lung function data from 7 to 53 years, from which lifetime FEV₁/FVC trajectories were modelled (n = 2442). Serum levels of CC16, sRAGE, CRP, ECP, SPD, fibrinogen and a range of cytokines were quantified at 53 years of age. These were related to respective FEV₁/FVC trajectories. Classification And Regression Tree (CART) analysis was used to investigate biomarker combinations in relation to the distribution of pre-COPD FEV₁/FVC trajectories.

Among six FEV₁/FVC trajectories, three trajectories at increased risk of COPD (pre-COPD trajectories) were 'Early Low-Rapid Decline', 'Early Normal-Rapid Decline' and 'Early Low-Normal Decline'. CC16, sRAGE, SPD, IL-17A, IL-5 and IL-10 differed significantly between these three pre-COPD and the normal trajectory. Notably, within the pre-COPD trajectories, these biomarkers also differentiated two rapid decline trajectories from the relatively stable one. CART analysis identified different combinations of biomarkers that distinguish different pre-COPD trajectories.

This is the first study to show that established COPD biomarkers are already active during the pre-COPD phase and could distinguish pre-COPD lung function trajectories. Biomarkers, particularly together with clinical history, may have the potential to identify those at risk and optimise management of both Pre-COPD and COPD.