Some middle age biomarkers can identify impaired lifetime lung function trajectories: a prospective study from 1st to 6th decade

<bold>Background:</bold> Identifying impaired lifetime lung function trajectories is key to identifying preclinical phase of COPD (Pre-COPD) or prognosis of COPD. We investigated potential blood biomarkers to detect impaired trajectories. <bold>Methods:</bold> The Tasmanian Longitudinal Health Study has unique lung function data from 7 to 53 years, from which lifetime FEV1/FVC trajectories were modelled using Group-Based Trajectory Modelling (n=2442). Serum levels of CC16, sRAGE, CRP, ECP, SPD, fibrinogen and a range of cytokines were quantified at 53 years. These were related to respective FEV1/FVC trajectories. Classification And Regression Tree (CART) analysis was used to investigate the predictive ability of biomarkers. A risk score chart was developed. <bold>Results:</bold> Among six FEV1/FVC trajectories, three trajectories at increased risk of COPD (obstructive 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 obstructive and the normal trajectory. Notably, within the obstructive trajectories, these biomarkers also differentiated two rapidly progressive decline trajectories from the relatively stable one. CART analysis identified different combinations of these biomarkers that predict different obstructive trajectories. CART findings were translated into a risk score chart that can be used to differentiate obstructive from non-obstructive, and relatively stable from rapidly progressive trajectories. <bold>Conclusions:</bold> This is the first study to show that some biomarkers in middle age can detect impaired lifetime obstructive lung function trajectories. Our risk score chart based on biomarkers has the potential to identify those at risk and optimise management of both Pre-COPD and COPD