Plasticity of Individual Lung Function States from Childhood to Adulthood

Abstract

RATIONALE: Recent evidence highlights the importance of optimal lung development during childhood for health throughout life. OBJECTIVES: To explore the plasticity of individual lung function states during childhood. METHODS: Pre-bronchodilator FEV1 z-scores determined at age 8, 16 and 24 years in the Swedish population-based birth cohort BAMSE (N=3,069) were used. An unbiased, data-driven dependent mixture model was applied to explore lung function states and individual state chains. Lung function catch-up was defined as participants moving from low/very low states to normal/high/very high states, and growth failure as moving from normal/high/very high states to low/very low states. At 24 years, we compared respiratory symptoms, small airway function (multiple-breath washout), and circulating inflammatory protein levels, by using proteomics, across states. Models were replicated in the independent Dutch population-based PIAMA cohort. MEASUREMENTS AND MAIN RESULTS: Five lung function states were identified in BAMSE. Lung function catch-up and growth failure were observed in 74 (14.5%) BAMSE participants with low/very low states and 36 (2.4%) participants with normal/high/very high states, respectively. The occurrence of catch-up and growth failure was replicated in PIAMA. Early-life risk factors were cumulatively associated with the very low state, as well as with catch-up (inverse association) and growth failure. The very low state as well as growth failure were associated with respiratory symptoms, airflow limitation, and small airway dysfunction at adulthood. Proteomics identified Interleukin-6 and C-X-C motif chemokine 10 as potential biomarkers of impaired lung function development. CONCLUSIONS: Individual lung function states during childhood are plastic, including catch-up and growth failure.