Articles
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

https://doi.org/10.1016/S2213-2600(18)30099-7Get rights and content

Summary

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.

Introduction

Low FEV1 in early adulthood (24 years of age)—ie, near its physiological plateau—is as important in the genesis of chronic obstructive pulmonary disease (COPD) as is a rapid decline of FEV1 in later years.1, 2, 3 Furthermore, low lung function in young adult life is associated with early mortality,4 and low FEV1 is a marker of premature death from all causes.5 A recent study6 has shown that low lung function in early adulthood (around the time of the physiological plateau) is associated with earlier onset of COPD, other chronic diseases, and death.6 This result has highlighted the need to use longitudinal studies and modern statistical approaches to improve understanding of causal pathways, understand the critical windows for lung function development, and identify targets for early intervention.4, 5, 7, 8, 9, 10, 11

Hypothesis-driven analyses in unselected longitudinal cohorts and children with asthma have shown that lung function in adult life is in part determined by childhood events. The observation that FEV1 was consistently lower among individuals with clinical phenotypes such as severe asthma8 and persistent wheezing9 has provided foundations for the concept that lung function tracks from school age to adulthood.9, 10 This is supported by the data-driven analysis of spirometry records from childhood (age 11 years) to the fourth decade of life in the Tucson cohort, which identified two distinct lung function trajectories (low and normal).11 Persistently low trajectory comprised nearly 10% of participants, and individuals in this class were predisposed to COPD later in life.

We hypothesised that a population comprises several distinct groups of individuals with similar lung function trajectories from pre-school age—ie, younger than 5 years—to adolescence, which extend to the physiological plateau in early adulthood, and that these trajectories are in part established at birth. However, factors that determine lung function growth might differ from those affecting the rate of decline after the plateau,12 and inference from models that combine a small number of measures in childhood (before peak lung function is reached in early adulthood) with those in later adulthood (during the decline phase) might not adequately disaggregate the effects of risk factors that differentially affect growth and decline. To address our hypotheses and ascertain trajectories during lung function growth and their risk factors, we combined data from three population-based birth cohorts in which lung function was assessed on multiple occasions from infancy, through early school age and adolescence, into early adulthood. We first set out to establish whether a method to categorise FEV1 trajectories using latent profile analysis could be applied across different cohorts and whether it yields consistent results across different populations. We then identified genetic and early-life factors associated with FEV1 trajectories at the population level. Finally, we investigated whether FEV1 trajectories track back to lung function patterns in infancy.

Research in context

Evidence before this study

We did an informal search of the literature, including studies known to the authors, prior to this study. Early life factors, such as weight at birth, are associated with low lung function and chronic obstructive pulmonary disease (COPD) in late adulthood. Lung function development reaches a plateau in early adult life, and low lung function in young adults is associated with early mortality from all causes. Failure to attain maximal lung function at its plateau is associated with COPD in later life, even when the physiological rate of decline of lung function is maintained. This result strengthens the evidence that early life influences might be crucial for normal lung function in childhood and COPD pathogenesis.

Added value of this study

Using data from population-based, birth cohort studies, we demonstrated four discrete trajectories of FEV1 development from early childhood to young adulthood. Persistently low FEV1 was associated with wheezing and asthma through childhood and tobacco smoke exposure and was predicted by severe recurrent wheezing and allergic sensitisation by age 3 years. We were able to determine from a third independent cohort that most infants with low infant lung function trajectory during the first year after birth transitioned to normal or above average FEV1 trajectories.

Implications of all the available evidence

A persistently low trajectory of FEV1 development can be identified during childhood and is associated with potentially modifiable influences in early childhood. This trajectory was replicated in a companion study that followed FEV1 growth from childhood to late adulthood. Although perinatal factors are associated with low lung function during childhood and with later COPD, most infants with low lung function trajectories during the first year appeared to recover to average or above average FEV1 growth in later childhood. Interventions to maximise lung growth in early childhood might modify the risk of COPD in older age.

Section snippets

Study design, setting, and participants

We studied three population-based birth cohorts: the Manchester Asthma and Allergy Study (MAAS; 1184 participants recruited in 1995–97)13 and the Avon Longitudinal Study of Parents and Children (ALSPAC; 14 451 participants recruited in 1991–92)14 from the UK STELAR consortium15 and the Australian Perth Infant Asthma Follow-up (PIAF) study (253 participants recruited in 1987–91).16 All participants were recruited prenatally and followed prospectively. All studies were approved by research ethics

Results

We included 1046 participants from MAAS, 1390 from ALSPAC, and 196 from PIAF who had spirometry on at least one occasion, and 253 children from PIAF who had infant lung function measurements on at least one occasion. In ALSPAC, we restricted our analyses to the first tranche of 1390 participants in whom age 24-year data had been released, and who successfully completed FEV1 measurement (see appendix for trial profile).

We selected the four-class model in MAAS and ALSPAC because this model

Discussion

In two population-based birth cohorts, using data-driven analyses, we identified four distinct lung function trajectories extending from early school age (5 years), through mid-school age (8–11 years), into adolescence (15–16 years) and early adulthood (24 years). Participants assigned to the persistently low trajectory, representing approximately one in 20 participants, had low lung function in the third decade of life, around the time of the physiological plateau. Individuals in this

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