Lung function trajectories from pre-school age to adulthood and their associations with early life factors: a retrospective analysis of three population-based birth cohort studies

Background: Maximal lung function in early adulthood is an important determinant of mortality and COPD. We investigated whether distinct trajectories of lung function are present during childhood and whether these extend to adulthood and infancy. Methods: To ascertain trajectories of FEV₁, we studied two population-based birth cohorts (MAAS and ALSPAC) with repeat spirometry from childhood into early adulthood (1046 participants from 5–16 years and 1390 participants from 8–24 years). We used a third cohort (PIAF) with repeat lung function measures in infancy (V'_maxFRC) and childhood (FEV₁; 196 participants from 1 month to 18 years of age) to investigate whether these childhood trajectories extend from early life. We identified trajectories using latent profile modelling. We created an allele score to investigate genetic associations of trajectories, and constructed a multivariable model to identify their early-life predictors. Findings: We identified four childhood FEV₁ trajectories: persistently high, normal, below average, and persistently low. The persistently low trajectory (129 [5%] of 2436 participants) was associated with persistent wheezing and asthma throughout follow-up. In genetic analysis, compared with the normal trajectory, the pooled relative risk ratio per allele was 0·96 (95% CI 0·92–1·01; p=0·13) for persistently high, 1·01 (0·99–1·02; p=0·49) for below average, and 1·05 (0·98–1·13; p=0·13) for persistently low. Most children in the low V'_maxFRC trajectory in infancy did not progress to the low FEV₁ trajectory in childhood. Early-life factors associated with the persistently low trajectory included recurrent wheeze with severe wheezing exacerbations, early allergic sensitisation, and tobacco smoke exposure. Interpretation: Reduction of childhood smoke exposure and minimisation of the risk of early-life sensitisation and wheezing exacerbations might reduce the risk of diminished lung function in early adulthood. Funding: None.