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 FEV 1 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.

Evolution of Lung Function within Individuals: Clinical Insights and Data-driven Methods

“…In this issue of the Journal , Wang and colleagues (pp. 406–415 ) report the analysis of lung function development from childhood to early adulthood in two unselected birth cohorts, which used a data-driven Markovian dependent mixture model to identify five lung function states (very low, low, normal, high, and very high) at three cross-sectional points through childhood ( 14 ). The model used in this study, like many others, is a simplification of reality, but a more complicated model must be balanced against interpretability.…”

“…We believe that we should triangulate available evidence now and then put this into the context of the modeling results in the forthcoming large multicohort analyses. In the study by Wang and colleagues, subjects in the very low lung function state were more likely to be male, be born prematurely, be exposed to higher air pollution, and have respiratory infections in early life ( 14 ). Previous studies have reported that similar in utero and early-life factors influence lung function trajectories through childhood, including nutritional deficits during pregnancy, preterm birth, poor intrauterine growth and low birth weight, early-life respiratory infections, early allergic sensitization, persistent wheezing, and exposure to tobacco smoke in utero .…”

Ambient air pollution exposure linked to long COVID among young adults: a nested survey in a population-based cohort in Sweden

“…We used data from the BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiology [in Swedish]) population-based prospective cohort, 32 which recruited 4089 children born in 1994–1996 who have been subsequently followed with repeated questionnaires and clinical examinations. The 24-year follow-up 33 was conducted during 2016–2019, with a total of 2270 participants attending both questionnaire survey and clinical examinations.…”

Obese asthma phenotypes display distinct plasma biomarker profiles

“…Changes in cytokine levels as well as altered immune responses have been suggested as potential mechanisms relating obesity to asthma 1,4 . Adipocytes and adipose tissue macrophages produce pro‐inflammatory cytokines such as IL‐6 which has been found in increased levels in asthmatics and has been related to low lung function 5,6 . Type 2 innate lymphoid cells have important functions in adipose tissue regulation of energy expenditure and metabolic homeostasis but are also related to asthma and asthma severity 4 .…”

“… 1 , 4 Adipocytes and adipose tissue macrophages produce pro‐inflammatory cytokines such as IL‐6 which has been found in increased levels in asthmatics and has been related to low lung function. 5 , 6 Type 2 innate lymphoid cells have important functions in adipose tissue regulation of energy expenditure and metabolic homeostasis but are also related to asthma and asthma severity. 4 Results from animal models suggest that systemic inflammation induced by obesity stimulate migration of innate lymphoid cells to the lungs where these cells could exhibit tissue dependant actions related to asthma.…”