Both individual air pollutants and joint air pollution exposure were positively associated with incident pulmonary hypertension, with circulating metabolic alterations (particularly lipoprotein-related measures, fatty acids, and amino acids) potentially mediating a portion of these associations.
Key Findings
Results
Higher joint air pollution exposure (Air Pollution Score) was associated with increased risk of incident pulmonary hypertension.
Hazard ratio per 1-SD increment in APS was 1.12 (95% CI, 1.08–1.17)
The APS combined PM2.5, PM10, NO2, and NOx into a single weighted score
During a median follow-up of 13.58 years, 2328 participants developed PH out of 444,346 participants without PH at baseline
Participants with air pollution exposure estimates and nuclear magnetic resonance metabolomics data were included
Results
Each individual air pollutant (PM2.5, PM10, NO2, and NOx) was positively associated with incident pulmonary hypertension.
Hazard ratios ranged from 1.06 to 1.93 per 10-μg/m³ increment across the four pollutants
All four pollutants were assessed as individual exposures in addition to the joint APS
Cox proportional hazards models were used to evaluate these associations
105 metabolites were identified for the APS-related metabolic signature
52 to 123 metabolites were identified for pollutant-specific metabolic signatures
Metabolomics data were derived from nuclear magnetic resonance (NMR) spectroscopy
The main metabolite classes involved were lipoprotein-related measures, fatty acids, and amino acids
Results
Pollution-related metabolic signatures were independently associated with incident pulmonary hypertension.
HRs per 1-SD increment in metabolic signatures ranged from 1.12 to 1.24 across APS and pollutant-specific signatures
Associations were evaluated using Cox proportional hazards models
Both the overall APS metabolic signature and individual pollutant-specific signatures showed significant positive associations with PH
Results
Circulating metabolic alterations partially mediated the association between air pollution exposure and incident pulmonary hypertension.
The overall metabolic signature mediated 11.74% (95% CI, 7.91%–18.95%) of the APS–PH association
Pollutant-specific metabolic signatures mediated 11.38% to 26.00% of the corresponding pollutant–PH associations
Mediation analyses were used to evaluate the potential mediating contributions of metabolic signatures
The mediation findings suggest metabolic pathways are one mechanism, though not the sole mechanism, linking pollution to PH
Methods
This was a large prospective cohort study with a long follow-up period examining the pollution–pulmonary hypertension relationship.
444,346 participants without PH at baseline were included
Median follow-up was 13.58 years
2328 participants developed incident PH during follow-up
Air pollution exposure estimates were linked with NMR metabolomics data for all participants
What This Means
This research suggests that breathing polluted air over many years is linked to a higher risk of developing pulmonary hypertension (PH), a serious condition involving high blood pressure in the lungs. Using data from over 444,000 people followed for nearly 14 years, the study found that four common air pollutants—fine particles (PM2.5), coarser particles (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx)—were each individually associated with greater PH risk, and that combined exposure made the risk even clearer. For every standard deviation increase in the combined air pollution score, the risk of developing PH increased by about 12%.
The study also examined whether changes in blood chemistry (metabolomics) might help explain why air pollution raises PH risk. Using a sophisticated statistical technique, researchers identified groups of blood metabolites—particularly those related to lipoproteins (cholesterol-carrying particles), fatty acids, and amino acids—that changed in response to air pollution exposure. These metabolic changes were themselves associated with higher PH risk and were found to mediate roughly 12% to 26% of the link between pollution and PH, depending on the specific pollutant.
This research suggests that long-term exposure to common urban air pollutants may contribute to pulmonary hypertension partly by altering how the body processes fats and proteins in the blood. Because the metabolic changes only explained part of the pollution–PH link, other biological pathways are also likely involved. The findings highlight the potential public health importance of reducing air pollution exposure and point toward metabolic disruption as one possible pathway connecting air quality to cardiovascular lung disease.
Kuang L, Huang E, Zhang B, Chen H, Lai S, Huang H, et al.. (2026). Long-term ambient air pollution exposure, metabolomic signatures, and incident pulmonary hypertension: A large prospective cohort study.. Ecotoxicology and environmental safety. https://doi.org/10.1016/j.ecoenv.2026.120778