Plasticity of Individual Lung Function States from Childhood to Adulthood
American Journal of Respiratory and Critical Care Medicine, 2022
Wang G., Hallberg J., Faner R., Koefoed H., Kebede Merid S., Klevebro S., Björkander S., Gruzieva O., Pershagen G., van Hage M., Guerra S., Bottai M., Georgelis A., Gehring U., Bergström A., Vonk J., Kull I., Koppelman G., Agusti A., Melén E.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Respiratory Diseases | Patient Stratification | Plasma |  Olink Target 96 |
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.