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: Prebronchodilator FEV₁ z-scores determined at age 8, 16, and 24 years in the Swedish population-based birth cohort BAMSE (Swedish abbreviation for Child [Barn], Allergy, Milieu, Stockholm, Epidemiological study) (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 or very low states to normal or high or very high states, and growth failure as moving from normal or high or very high states to low or 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 (Prevention and Incidence of Asthma and Mite Allergy) 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 or very low states and 36 (2.4%) participants with normal or high or 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 IL-6 and CXCL10 (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.

Keywords: asthma; early life risk factors; inflammation; multiple-breath washout; respiratory health.

Figure 1.

Alluvial plot that illustrates transition of lung function states from childhood to early adulthood. Participants with two or more lung function measures recorded were included. The width of each line is proportional to the number of participants included. The numbers behind Figure 1 are available in Table E6.

Figure 2.

Prevalence of catch-up (left) and growth failure (right) at different age bins (8–16 yr, 16–24 yr, and 8–24 yr). A subgroup of participants contributed lung function data only at 8 and 24 years (but not 16 yr); therefore, the total proportion of subjects (gray) does not always match the sum of 8–16 (blue) and 16–24 (orange) year proportions. The numbers behind Figure 2 are available in Table E7.

Figure 3.

Individual FEV₁ z-scores in participants with lung function (A) catch-up and (B) growth failure. (C) Prevalence and (D) OR of catch-up and growth failure by the number of associated risk factors coexisting in the same participants. The risk factors included in the association with catch-up were maternal smoking during pregnancy, parental smoking during 0–1 years, and early bronchitis. The risk factors included in the association with growth failure were preterm birth, early bronchitis, respiratory syncytial virus/pneumonia during infancy, sensitization to food allergens during 4–8 years, and childhood asthma during 0–8 years. CI = confidence interval; OR = odds ratio; Ref = reference.