Perturbation of metabolic pathways mediates the association of air pollutants with asthma and cardiovascular diseases

Gianfranco Lovison, Jelle Vlaanderen, Pekka Keski-Rahkonen, Sara Grioni, Claudia Galassi, Akram Ghantous, Claudia Agnoli, Soterios Kyrtopoulos, Agneta Kiss, Nivonirina Robinot, Vittorio Krogh, Giovanni Fiorito, Nahid Mostafavi, Alessio Naccarati, Ayoung Jeong, Medea Imboden, Agneta Kiss, Jelle Vlaanderen, Roel Vermeulen, Hans GmuenderAndrea Ranzi, Alessio Naccarati, Carlotta Sacerdote, Nicole Probst-Hensch, Zdenko Herceg, Augustin Scalbert, Roel Vermeulen, Paolo Vineis

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Background: Epidemiologic evidence indicates common risk factors, including air pollution exposure, for respiratoryand cardiovascular diseases, suggesting the involvement of common altered molecular pathways.Objectives: The goal was to find intermediate metabolites or metabolic pathways that could be associated withboth air pollutants and health outcomes (“meeting-in-the-middle”), thus shedding light on mechanisms andreinforcing causality.Methods: We applied a statistical approach named ‘meet-in-the-middle’ to untargeted metabolomics in two independent case-control studies nested in cohorts on adult-onset asthma (AOA) and cardio-cerebrovascular diseases(CCVD). We compared the results to identify both common and disease-specific altered metabolic pathways.Results: A novel finding was a strong association of AOA with ultrafine particles (UFP; odds ratio 1.80 [1.26,2.55] per increase by 5000 particles/cm3). Further, we have identified several metabolic pathways that potentiallymediate the effect of air pollution on health outcomes. Among those, perturbation of Linoleate metabolismpathway was associated with air pollution exposure, AOA and CCVD. Conclusions: Our results suggest common pathway perturbations may occur as a consequence of chronic exposureto air pollution leading to increased risk for both AOA and CCVD.
Original languageEnglish
Pages (from-to)334-345
Number of pages12
JournalENVIRONMENT INTERNATIONAL
Volume119
Publication statusPublished - 2018

All Science Journal Classification (ASJC) codes

  • General Environmental Science

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