Trajectories of airflow limitation from childhood to early adulthood: an analysis of six population-based birth cohorts

BACKGROUND: Lung function during childhood is an important predictor of subsequent health and disease. Understanding patterns of lung function and development of airflow limitation through childhood is necessary to inform lung function trajectories in relation to health and chronic airway disease. We aimed to derive trajectories of airflow limitation from childhood (age 5-8 years) into early adulthood (age 20-26 years) using repeated spirometry data from birth cohorts.

METHODS: In this study, we drew forced expiratory volume in 1 s (FEV 1) and forced vital capacity (FVC) data from six population-based birth cohorts: the UK-based Avon Longitudinal Study of Parents and Children (ALSPAC), Isle of Wight cohort (IOW), Manchester Asthma and Allergy Study (MAAS), and Aberdeen Study of Eczema and Asthma (SEATON) as well as the Swedish Child (Barn), Allergy, Milieu, Stockholm, Epidemiological survey (BAMSE) and the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. For the discovery analysis, we pooled data from ALSPAC, IOW, MAAS, and BAMSE with spirometry data recorded at middle childhood (age 8-10 years), adolescence (age 15-18 years), and early adulthood (age 20-26 years). For the replication analysis, we pooled middle childhood and adolescence spirometry data from PIAMA and SEATON. We used latent class trajectory modelling to derive trajectory classes based on joint modelling of FEV 1 and FEV 1/FVC ratio regression residuals ascertained from all age groups. The final model was selected using the lowest Bayesian information criterion. Participants were assigned to the trajectory with the highest posterior probability. Weighted random-effect multinomial logistic regression models were used to investigate factors associated with joining each trajectory, the results of which are reported as relative risk ratios (RRRs) with 95% CIs.

FINDINGS: The discovery population included 8114 participants: 4710 from ALSPAC, 808 from IOW, 586 from MAAS, and 2010 from BAMSE and was modelled into one of four lung function trajectories that showed normal airflow (6555 [80·8%] of 8114 people), persistent airflow obstruction (1280 [15·8%]), worsening airflow obstruction (161 [2·0%]), and improved airflow obstruction (118 [1·5%]). Both improvement in and worsening airflow obstruction by early adulthood were seen from all initial severity levels. Whereas improvement in airflow obstruction was more prominent between middle childhood and adolescence (57·8%) than between adolescence and early adulthood (13·4%), worsening airflow obstruction was more prominent between adolescence and early adulthood (61·5%) than between middle childhood and adolescence (32·6%). Among current wheezers, higher BMI was associated with a lower relative risk of joining the trajectory with improvement in airflow obstruction (RRR 0·69 [95% CI 0·49-0·95]), whereas among non-wheezers, higher BMI increased the relative risk of being in the improved airflow obstruction trajectory (1·38 [1·04-1·85]). A higher BMI at first lung function assessment was associated with a higher relative risk of joining the trajectory for improvement in airflow obstruction trajectory in participants with low birthweight and no current asthma diagnosis (RRR 2·44 [1·17-5·12]); by contrast, higher BMI is associated with a lower relative risk of joining the trajectory with improvement in airflow obstruction among those with low birthweight and current asthma diagnosis (0·37 [0·18-0·76]). Results in replication cohorts (n=1337) were consistent with those in the discovery cohort.

INTERPRETATION: Worsening and improvement in airflow limitation from school age to adulthood might occur at all ages and all airflow obstruction severity levels. Interventions to optimise healthy weight, including tackling overweight and obesity (particularly among children with wheezing) as well as treating underweight among non-wheezers, could help to improve lung health across the lifespan.

FUNDING: UK Medical Research Council and CADSET European Respiratory Society Clinical Research Collaboration.