Systematic review and meta-analysis of cohort studies of long term outdoor nitrogen dioxide exposure and mortality.

<h4>Objective</h4>To determine whether long term exposure to outdoor nitrogen dioxide (NO2) is associated with all-cause or cause-specific mortality.<h4>Methods</h4>MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a libraria...

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Main Authors: David M Stieb, Rania Berjawi, Monica Emode, Carine Zheng, Dina Salama, Robyn Hocking, Ninon Lyrette, Carlyn Matz, Eric Lavigne, Hwashin H Shin
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0246451
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author David M Stieb
Rania Berjawi
Monica Emode
Carine Zheng
Dina Salama
Robyn Hocking
Ninon Lyrette
Carlyn Matz
Eric Lavigne
Hwashin H Shin
author_facet David M Stieb
Rania Berjawi
Monica Emode
Carine Zheng
Dina Salama
Robyn Hocking
Ninon Lyrette
Carlyn Matz
Eric Lavigne
Hwashin H Shin
author_sort David M Stieb
collection DOAJ
description <h4>Objective</h4>To determine whether long term exposure to outdoor nitrogen dioxide (NO2) is associated with all-cause or cause-specific mortality.<h4>Methods</h4>MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a librarian. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Conflicts were resolved through consensus and/or involvement of a third reviewer. Pooling of results across studies was conducted using random effects models, heterogeneity among included studies was assessed using Cochran's Q and I2 measures, and sources of heterogeneity were evaluated using meta-regression. Sensitivity of pooled estimates to individual studies was examined and publication bias was evaluated using Funnel plots, Begg's and Egger's tests, and trim and fill.<h4>Results</h4>Seventy-nine studies based on 47 cohorts, plus one set of pooled analyses of multiple European cohorts, met inclusion criteria. There was a consistently high degree of heterogeneity. After excluding studies with probably high or high risk of bias in the confounding domain (n = 12), pooled hazard ratios (HR) indicated that long term exposure to NO2 was significantly associated with mortality from all/ natural causes (pooled HR 1.047, 95% confidence interval (CI), 1.023-1.072 per 10 ppb), cardiovascular disease (pooled HR 1.058, 95%CI 1.026-1.091), lung cancer (pooled HR 1.083, 95%CI 1.041-1.126), respiratory disease (pooled HR 1.062, 95%CI1.035-1.089), and ischemic heart disease (pooled HR 1.111, 95%CI 1.079-1.144). Pooled estimates based on multi-pollutant models were consistently smaller than those from single pollutant models and mostly non-significant.<h4>Conclusions</h4>For all causes of death other than cerebrovascular disease, the overall quality of the evidence is moderate, and the strength of evidence is limited, while for cerebrovascular disease, overall quality is low and strength of evidence is inadequate. Important uncertainties remain, including potential confounding by co-pollutants or other concomitant exposures, and limited supporting mechanistic evidence. (PROSPERO registration number CRD42018084497).
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spelling doaj.art-f2183536924b431c92d13d1b9583afc52022-12-21T19:20:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01162e024645110.1371/journal.pone.0246451Systematic review and meta-analysis of cohort studies of long term outdoor nitrogen dioxide exposure and mortality.David M StiebRania BerjawiMonica EmodeCarine ZhengDina SalamaRobyn HockingNinon LyretteCarlyn MatzEric LavigneHwashin H Shin<h4>Objective</h4>To determine whether long term exposure to outdoor nitrogen dioxide (NO2) is associated with all-cause or cause-specific mortality.<h4>Methods</h4>MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a librarian. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Conflicts were resolved through consensus and/or involvement of a third reviewer. Pooling of results across studies was conducted using random effects models, heterogeneity among included studies was assessed using Cochran's Q and I2 measures, and sources of heterogeneity were evaluated using meta-regression. Sensitivity of pooled estimates to individual studies was examined and publication bias was evaluated using Funnel plots, Begg's and Egger's tests, and trim and fill.<h4>Results</h4>Seventy-nine studies based on 47 cohorts, plus one set of pooled analyses of multiple European cohorts, met inclusion criteria. There was a consistently high degree of heterogeneity. After excluding studies with probably high or high risk of bias in the confounding domain (n = 12), pooled hazard ratios (HR) indicated that long term exposure to NO2 was significantly associated with mortality from all/ natural causes (pooled HR 1.047, 95% confidence interval (CI), 1.023-1.072 per 10 ppb), cardiovascular disease (pooled HR 1.058, 95%CI 1.026-1.091), lung cancer (pooled HR 1.083, 95%CI 1.041-1.126), respiratory disease (pooled HR 1.062, 95%CI1.035-1.089), and ischemic heart disease (pooled HR 1.111, 95%CI 1.079-1.144). Pooled estimates based on multi-pollutant models were consistently smaller than those from single pollutant models and mostly non-significant.<h4>Conclusions</h4>For all causes of death other than cerebrovascular disease, the overall quality of the evidence is moderate, and the strength of evidence is limited, while for cerebrovascular disease, overall quality is low and strength of evidence is inadequate. Important uncertainties remain, including potential confounding by co-pollutants or other concomitant exposures, and limited supporting mechanistic evidence. (PROSPERO registration number CRD42018084497).https://doi.org/10.1371/journal.pone.0246451
spellingShingle David M Stieb
Rania Berjawi
Monica Emode
Carine Zheng
Dina Salama
Robyn Hocking
Ninon Lyrette
Carlyn Matz
Eric Lavigne
Hwashin H Shin
Systematic review and meta-analysis of cohort studies of long term outdoor nitrogen dioxide exposure and mortality.
PLoS ONE
title Systematic review and meta-analysis of cohort studies of long term outdoor nitrogen dioxide exposure and mortality.
title_full Systematic review and meta-analysis of cohort studies of long term outdoor nitrogen dioxide exposure and mortality.
title_fullStr Systematic review and meta-analysis of cohort studies of long term outdoor nitrogen dioxide exposure and mortality.
title_full_unstemmed Systematic review and meta-analysis of cohort studies of long term outdoor nitrogen dioxide exposure and mortality.
title_short Systematic review and meta-analysis of cohort studies of long term outdoor nitrogen dioxide exposure and mortality.
title_sort systematic review and meta analysis of cohort studies of long term outdoor nitrogen dioxide exposure and mortality
url https://doi.org/10.1371/journal.pone.0246451
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