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

Background and Objective 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. Methods The Tasmanian Longitudinal Health Study has unique lung function data from 7 to 53 years, from which lifetime FEV 1 /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 FEV 1 /FVC trajectories. Classification And Regression Tree (CART) analysis was used to investigate biomarker combinations in relation to the distribution of pre‐COPD FEV 1 /FVC trajectories. Results Among six FEV 1 /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. Conclusion 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.