Childhood Pollution Exposure May Trigger COPD Polygenic Risk

A polygenic risk score for chronic obstructive pulmonary disease (COPD) was associated with reduced lung function growth from infancy to age 6, but only among children exposed to high levels of air pollution, according to data presented at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain, held September 5 to 9.¹

Applying adult-derived COPD polygenic risk scores (PRS) in childhood may help elucidate early-life risk factors influencing lung function growth, according to the study investigators.¹ Researchers led by Carla da Silva Sena, MD, of University Children's Hospital Basel UKBB and Bern University Hospital, analyzed longitudinal lung function data from 484 children enrolled in the Basel-Bern Infant Lung Development (BILD) cohort, an ongoing Swiss birth cohort study following children born between 1999 and 2020.²

“COPD develops through a combination of genetic factors and environmental exposures across the lifespan, leading to an accelerated decline in lung function,” said da Silva Sena, who presented the findings.² “Studying these trajectories from the earliest stages of life is key to understanding how COPD develops.”

What were lung function trajectories and polygenic risk in the BILD cohort?

Investigators assessed lung function using the infant tidal breathing test (tPTEF/tE) in the first month of life and spirometry (FEV1, FVC) at age 6, converting results to comparable z-scores.¹,² A COPD PRS derived from adult genome-wide association studies was calculated from blood samples, and outdoor exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) was estimated from birth to age 6. Associations between PRS and lung function trajectories were modeled using linear mixed-effects models with a PRS-by-time interaction term, stratified by the highest versus lower tertiles of PM2.5 and NO2 exposure.¹

In stratified analysis, a 1-SD increase in COPD PRS was associated with a decrease in tPTEF/tE-FEV1 z-score over time among children in the highest PM2.5 tertile (β = -0.47; 95% CI, -0.80 to -0.14; n = 140) and the highest NO2 tertile (β = -0.61; 95% CI, -0.99 to -0.24; n = 148).¹ No significant association was observed among children in the lower exposure tertiles (β = -0.15; 95% CI, -0.37 to 0.07; n = 344).¹

How does air pollution act as an effect modifier?

A similar pattern was observed for tPTEF/tE-FVC z-score, but only in the highest NO2 tertile (β = -0.66; 95% CI, -1.11 to -0.22; n = 108).¹ The high-exposure PM2.5 tertile averaged 15.3 μg/m³, and the high-exposure NO2 tertile averaged 28.3 μg/m³, according to the study investigators.² The pattern suggests a gene-environment interaction, in which genetic susceptibility to reduced lung growth becomes apparent only under sufficient pollution exposure.

Investigators noted 2 limitations: infant and school-age lung function were assessed using different tests, requiring statistical harmonization for longitudinal comparison, and the PRS was developed using populations of European ancestry, so findings may not directly apply to children from other backgrounds.² The prospective cohort design allowed researchers to link genetic risk, air pollution exposure, and lung function measured before children displayed respiratory symptoms.

“This shows how genes and environment in the early years can combine to set children on a path to lung disease much later in life,” said Barbara Hoffmann, MD, chair of the ERS Advocacy Council at the University of Dusseldorf, who was not involved in the research.² “It may help explain why COPD can also occur in non-smokers.”

Hoffmann said the findings align with a 2022 Lancet Commission report describing COPD as shaped by risk pathways across the lifespan rather than by adult smoking alone.² Researchers plan to follow the BILD cohort into adolescence and adulthood to determine whether the early lung function differences persist or widen over time.²

References

1. da Silva Sena CR, Gorlanova O, Gwerder M, et al. Early-life lung function trajectories are associated with COPD polygenic risk score only in the presence of high air pollution exposure from infancy to school age. Abstract 6810. Presented at: European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.

2. European Respiratory Society. Origins of COPD may lie in how some children's lungs develop, but only when they are exposed to polluted air. Published September 6, 2026. Accessed September 6, 2026. https://www.ersnet.org/news-and-features/news/origins-of-copd-may-lie-in-how-some-childrens-lungs-develop-but-only-when-they-are-exposed-to-polluted-air/