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Environ Int. 2018 Oct;119:334-345. doi: 10.1016/j.envint.2018.06.025. Epub 2018 Jul 7.

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

Author information

1
Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
2
Italian Institute for Genomic Medicine (IIGM), Turin, Italy; Department of Medical Sciences - University of Turin, Italy.
3
International Agency for Research on Cancer, Lyon, France.
4
Genedata AG, Basel, Switzerland.
5
Utrecht University, Institute for Risk Assessment Sciences, Environmental Epidemiology Division, Utrecht, Netherlands.
6
National Hellenic Research Foundation, Athens, Greece.
7
University of Palermo, Palermo, Italy.
8
Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.
9
Environmental Health Reference Center, Regional Agency for Prevention, Environment and Energy of Emilia-Romagna, Modena, Italy.
10
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
11
Piedmont Reference Center for Epidemiology and Cancer Prevention (CPO Piemonte), Via Santena 7, 10126 Turin, Italy.
12
Italian Institute for Genomic Medicine (IIGM), Turin, Italy.
13
Italian Institute for Genomic Medicine (IIGM), Turin, Italy; MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, UK. Electronic address: p.vineis@imperial.ac.uk.
14
Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address: nicole.probst@unibas.ch.

Abstract

BACKGROUND:

Epidemiologic evidence indicates common risk factors, including air pollution exposure, for respiratory and 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 with both air pollutants and health outcomes ("meeting-in-the-middle"), thus shedding light on mechanisms and reinforcing 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 potentially mediate the effect of air pollution on health outcomes. Among those, perturbation of Linoleate metabolism pathway was associated with air pollution exposure, AOA and CCVD.

CONCLUSIONS:

Our results suggest common pathway perturbations may occur as a consequence of chronic exposure to air pollution leading to increased risk for both AOA and CCVD.

KEYWORDS:

Adult-onset asthma; Air pollution; Cardio-cerebrovascular diseases; Metabolic pathways; Untargeted metabolomics

PMID:
29990954
DOI:
10.1016/j.envint.2018.06.025
[Indexed for MEDLINE]
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