Trajectories of restrictive pattern of lung function FEV1/FVC to physiological peak and their relationship with early life risk-factors and cardiac markers

Objectives: lung function in early adulthood is an important determinant of all-cause mortality and COPD. We aimed to model data from multiple cohorts from pre-school age to physiological peak in early adulthood to derive FEV1/FVC trajectories. We then investigated the association of the derived trajectories with early-life risk factors and markers of cardiovascular risk in adulthood.Method: using latent profile modelling, we studied three population-based birth cohorts (ALSPAC, MAAS, IOW) with repeat spirometry data from childhood into early adulthood to identify trajectories of FEV1/FVC. We performed echocardiogram and measured seated systolic blood pressure in ~3200 participants in ALSPAC at age 24 years. We used multinomial logistic regression models to investigate early-life predictors of the derived trajectories. We then ascertained the extent of the association between the derived FEV1/FVC trajectories and blood pressure and echocardiographic markers of increased cardiovascular risk and stroke in later adulthood.Results: we identified four distinct FEV1/FVC ratio trajectories with strikingly similar latent profiles in three independent birth cohorts: Above average (49.5%); Average (38.3%); Below average (10.6%); and Persistently low (1.7%). Male gender and history of allergic symptoms (wheeze, cough, asthma and sensitization) were significant associates of diminished lung function trajectories in all cohorts. We found strong evidence of the increase in cardiovascular risk markers ascertained by echocardiography (including left ventricular mass indexed to height and carotid intima-media thickness) with decreasing FEV1/FVC trajectory (with p-values for the mean effects per trajectory ranging from 0.005 to 11.17×10−7). The average seated systolic blood pressure (mm Hg) increased significantly per decreasing FEV1/FVC trajectory (p = 2.8×10−9)Conclusions: childhood lung function trajectories may serve as important predictors in the development of not only future lung disease, but also the cardiovascular disease and multimorbidity in adulthood. Our findings highlight the importance of measuring lung function throughout childhood and early adulthood