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Early life exposures and lung function development

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posted on 2024-09-03, 05:59 authored by Björn LundbergBjörn Lundberg

BACKGROUND: Lung development is a dynamic process, vulnerable to adverse environmental exposures. Starting in utero, development continues postnatally, and although lung structure is mainly set at around two years of age, the maturation process continues into young adulthood. Preterm birth and air pollution are two adverse exposures of high relevance in infancy. Preterm birth affects approximately 10 % of all births globally and is a known risk factor for respiratory morbidity and lung function deficits later in life. Per definition, preterm birth hinders normal prenatal lung development as the respiratory system is exposed to the extra-uterine environment earlier than what is physiologically optimal. Air pollution exposure affects a majority of the world’s population and is considered as the greatest environmental threat to human health. Early life air pollution exposure has been associated with respiratory morbidity and lung function deficits throughout childhood and into adulthood. However, little is known regarding early life air pollution exposure and lung function in infancy. Further, there are lacking knowledge on longitudinal development of lung function deficits associated with preterm birth shown in childhood into later life, as well as physiologic lung function phenotyping in this group in childhood and beyond.

AIM: The overall aim of this thesis was to investigate associations between adverse events in infancy, preterm birth and air pollution exposure, and lung function from infancy into young adulthood.

METHODS: In study I, lung function was assessed at six months of age in 177 infants from two cohorts, using infant spirometry, and analysed in relation to time-weighted average air pollution levels at residential addresses from birth and onwards. In study II, feasibility, correlations and test characteristics between spirometry and impulse oscillometry (IOS) were investigated in a cohort of children born extremely preterm (n=88) and age‐matched term controls (n=84) at six years of age. In study III, lung function was assessed longitudinally from adolescence (16 years of age) to young adulthood (24 years of age) in a population-based cohort (n=110 moderate-to-late preterm subjects and n=1895 term subjects) using spirometry, and further in young adulthood using multiple breath nitrogen wash-out and fractional exhaled nitric oxide. All cohorts included participants recruited in Stockholm County, Sweden. In study I and III, data were analysed using regression models adjusted for smoking. Study III additionally used data-driven latent class analysis to phenotype individuals at 24 years of age.

RESULTS: In study I, there were significant inverse relations between early life air pollution exposure and forced expiratory volume at 0.5 s (FEV0.5) as well as forced vital capacity (FVC) in infants at six months of age. As an example, for particulate matter with an aerodynamic diameter < 10 μm (PM10.) exposure, the decline was 10.1 ml (95% confidence interval 1.3–18.8) and 10.3 ml (0.5–20.1) in FEV0.5 and FVC, respectively, for an interquartile increase of 5.3 μg/m3. In study II, success rate for spirometry (60 %) was lower than for IOS (93 %) but there was no difference between the extremely preterm and term groups (56 % and 64 % for spirometry, p=0.25; and 92 % and 94 % for IOS, p=0.61). Correlations between spirometry and IOS outcomes were weak to moderate (Spearman's r =-0.31 to -0.56) in the extremely preterm group. IOS within reference identified 69 % to 90 % of individuals with spirometry within reference and a negative predictive value of 90 % was found for the difference between resistance at 5 and 20 Hz versus FEV0.75/FVC in this group. In study III, males born moderate-to-late preterm had lower FEV1 at 24 years of age (-0.28 z-score, p=0.045), when compared to males born at term. In females, no difference was seen at 24 years, partly explained by a significant catch-up in FEV1 between 16 and 24 years (0.18, p=0.01, change in z-score over time in preterm females compared to term). Three latent lung function phenotypes described as “asthma-like”, “dysanapsis” and “preterm reference” were identified within the preterm group. Maternal overweight in early pregnancy was associated with “asthma-like” group membership (OR 3.59, p=0.02).

CONCLUSIONS: Early life air pollution exposure was associated with impaired infant lung function measures related to both airway caliber and lung volume. Our results suggest that comparatively low air pollution levels negatively affect lung function in infants. Young children born extremely preterm were found to have the same difficulties in performing spirometry as children born at term. IOS was found to be more feasible than spirometry and to potentially be used to exclude obstructive airway diseases as measured by spirometry in this group. Hence, IOS may be considered as an alternative to spirometry in follow‐up programs of children born extremely preterm, especially at younger ages. Males born moderate-to-late preterm had impaired spirometry indices associated with obstructive airway disease in young adulthood, whereas females had significant catch-up to this point in this regard. The demonstrated lung function deficits suggest that moderate-to-late preterm birth might predispose for later respiratory morbidity, but also that there might be a difference between the sexes in ability for lung function catch-up. Further, latent “asthma-like” and “dysanapsis” lung function phenotypes were identified in young adults born moderate-to-late preterm, where especially “asthma-like” phenotype might represent a treatable trait.

List of scientific papers

I. Lundberg B, Gruzieva O, Eneroth K, Melén E, Persson Å, Hallberg J, Pershagen G. Air pollution exposure impairs lung function in infants. Acta Paediatrica. 2022 Sep;111(9):1788-1794.
https://doi.org/10.1111/apa.16412

II. Lundberg B, Melén E, Thunqvist P, Norman M, Hallberg J. Agreement between spirometry and impulse oscillometry for lung function assessment in 6-year-old children born extremely preterm and at term. Pediatric Pulmonology. 2020 Oct;55(10):2745-2753.
https://doi.org/10.1002/ppul.24976

III. Lundberg B, Kebede Merid S, Um-Bergström P, Wang G, Bergström A, Ekström S, Kull I, Melén E, Hallberg J. Lung function in young adulthood in relation to moderate-to-late preterm birth. [Manuscript]

History

Defence date

2023-04-21

Department

  • Department of Clinical Science and Education, Södersjukhuset

Publisher/Institution

Karolinska Institutet

Main supervisor

Hallberg, Jenny

Co-supervisors

Melén, Erik; Norman, Mikael; Pershagen, Göran

Publication year

2023

Thesis type

  • Doctoral thesis

ISBN

978-91-8016-922-6

Number of supporting papers

3

Language

  • eng

Original publication date

2023-03-27

Author name in thesis

Lundberg, Björn

Original department name

Department of Clinical Science and Education, Södersjukhuset

Place of publication

Stockholm

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