Early-life predictors of lung function in the Raine Study

The natural history of lung function is characterized by various stages of development. The first phase includes lung function increasing to a peak around young adulthood followed by a plateau phase, and finally a physiological decline with age. Early-life lung function predicts later lung function and events that happened during the lifespan might influence the lung function trajectories of an individual, resulting in poorer lung health. The fetal and the first years of life are considered vulnerable periods in which the lungs undertake rapid and dramatic changes. Investigating early life risk factors and their impact on lung function trajectories from childhood to young adulthood is critically important as a first step in preventing long term lung impairments. Indeed, there is the need to further understand which risk factors are involved in the impairment of lung function trajectories. With this thesis, I aimed to characterize lung function trajectories and investigate early-life predictors related to low lung function trajectories identified. A total of 1512 participants with at least two spirometry measurements were investigated using data from the Raine Study. Lung function trajectories for FEV1, FVC and FEV1/FVC (z-scores) were identified using group-based trajectory modelling for data available at 6, 14- and 22-year follow-ups. Multivariable analysis for childhood, parental and environmental risk factors was assessed using multinomial logistic regression. We identified four lung function trajectories for FEV1, FVC and FEV1/FVC. Associations were found between low lung function trajectories of FVC and asthma (p=0.024), maternal smoking (p=0.015), and parental asthma (p=0.024). Childhood wheeze was associated with the very low trajectory of FEV1 (p=0.042) and females were more likely to belong to the low trajectory of FVC compared with males (p=0.026). Early-life exposures to PM2.5 and NO2 were not associated with lung function trajectories.This study provides evidence of a group of the population that followed a persistently low lung function trajectory, characterized of having asthma, wheeze, mothers smoke in pregnancy and during childhood, parental asthma and that may be partly established before six years of age.