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• W4221119835 abstract "Vol. 130, No. 3 Response to LetterOpen AccessResponse to “Comment on ‘Invited Perspective: The NO2 and Mortality Dilemma Solved? Almost There!’”is accompanied byInvited Perspective: The NO2 and Mortality Dilemma Solved? Almost There!is a reply to letterComment on “Invited Perspective: The NO2 and Mortality Dilemma Solved? Almost There!” Francesco Forastiere and Annette Peters Francesco Forastiere Address correspondence to Francesco Forastiere, Via Pasquale Baffi 14, 00149 Rome, Italy. Email: E-mail Address: [email protected] Institute for Biomedical Research and Innovation – National Research Council, Palermo, Italy Environmental Research Group, Imperial College, London, UK Search for more papers by this author and Annette Peters Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany Institute of Epidemiology, Ludwig-Maximilians Universität, Munich, Germany Search for more papers by this author Published:16 March 2022CID: 038002https://doi.org/10.1289/EHP11156AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit We thank Dr. Paolo Crosignani for his comments on our perspective1 and the opportunity to clarify our arguments. First, we stated that “It is important to note that all the studies together span at least three decades and took place in multiple cities and continents; consequently, combustion-related air pollution mixtures were quite different between study populations. Therefore, even if other important copollutants of NO2 [nitrogen dioxide] were not assessed in these settings, it is unlikely that the observed associations of NO2 and mortality are solely attributable to one of those copollutants.” This reasoning follows the recommendation to apply a triangulation from different approaches for evidence synthesis.2 Here we explain how we reached our conclusion.The systematic review conducted by Huangfu and Atkinson3 for the update of the World Health Organization (WHO) Air Quality Guidelines4 was based on 10 studies from Europe (high prevalence of diesel vehicles) and 11 studies from North America (low prevalence of diesel vehicles). They reported identical effect estimates for the two continents, namely 1.03 [95% confidence interval (CI): 1.02, 1.03] and 1.03 (95% CI: 1.01, 1.04) per 10 μg/m3NO2, respectively. In addition, the latest report5 from the large Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) project in Europe showed that adjusting for fine particulate matter (PM2.5), black carbon, and ozone did not alter the effect estimate of NO2 on mortality: single pollutant 1.044 (95% CI: 1.019, 1.069); with PM2.5, 1.042 (95% CI: 1.020, 1.065); with black carbon, 1.041 (95% CIL 1.009, 1.073); and with ozone, 1.040 (95% CI: 1.012, 1.069). This evidence suggests that NO2 is not merely an indicator of other pollutants from diesel exhaust.Second, the evidence from mechanistic studies is indeed limited, but a number of recent studies link short-term and long-term ambient NO2 concentrations to changes in pathophysiological function both in patients with cardiovascular disease6,7 and in healthy adults.8 These studies support the observed mortality associations. Given the overwhelming evidence from epidemiological studies on NO2, the precautionary principle may call for action rather than another decade of research on the “dilemma.”Third, the combined evidence and the new WHO guidelines4 clearly recommend a concerted approach toward the reduction of all criteria pollutants, including NO2. We certainly do not propose regulating only NO2 and nothing else.9 With new evidence accumulating rapidly, we believe the WHO guidelines have immense potential to improve public health globally by regulating NO2 and other pollutants jointly.References1. Forastiere F, Peters A. 2021. Invited perspective: the NO2 and mortality dilemma solved? Almost there!Environ Health Perspect 129(12):121304, PMID: 34962423, 10.1289/EHP10286. Link, Google Scholar2. Steenland K, Schubauer-Berigan MK, Vermeulen R, Lunn RM, Straif K, Zahm S, et al.2020. Risk of bias assessments and evidence syntheses for observational epidemiologic studies of environmental and occupational exposures: strengths and limitations. Environ Health Perspect 128(9):95002, PMID: 32924579, 10.1289/EHP6980. Link, Google Scholar3. Huangfu P, Atkinson R. 2020. Long-term exposure to NO2 and O3 and all-cause and respiratory mortality: a systematic review and meta-analysis. Environ Int 144:105998, PMID: 33032072, 10.1016/j.envint.2020.105998. Crossref, Medline, Google Scholar4. WHO (World Health Organization).2021. WHO Global Air Quality Guidelines. Particulate Matter (PM2.5 and PM10), Ozone, Nitrogen Dioxide, Sulfur Dioxide and Carbon Monoxide. Geneva, Switzerland: World Health Organization. Google Scholar5. Stafoggia M, Oftedal B, Chen J, Rodopoulou S, Renzi M, Atkinson RW, et al.2022. Long-term exposure to low ambient air pollution concentrations and mortality among 28 million people: results from seven large European cohorts within the ELAPSE project. Lancet Planet Health 6(1):e9–e18, PMID: 34998464, 10.1016/S2542-5196(21)00277-1. Crossref, Medline, Google Scholar6. Ciampi Q, Russo A, D’Alise C, Ballirano A, Villari B, Mangia C, et al.2021. Nitrogen dioxide component of air pollution increases pulmonary congestion assessed by lung ultrasound in patients with chronic coronary syndromes. Environ Sci Pollut Res Int, PMID: 34888735, 10.1007/s11356-021-17941-1. Crossref, Medline, Google Scholar7. Fecht D, Chadeau-Hyam M, Owen R, Gregson J, Halliday BP, Lota AS, et al.2022. Exposure to elevated nitrogen dioxide concentrations and cardiac remodeling in patients with dilated cardiomyopathy. J Card Fail S1071–S9164(21):00492–00499, PMID: 35027315, 10.1016/j.cardfail.2021.11.023. Crossref, Medline, Google Scholar8. Kim KN, Ha B, Seog W, Hwang IU. 2022. Long-term exposure to air pollution and the blood lipid levels of healthy young men. Environ Int 161:107119, PMID: 35123376, 10.1016/j.envint.2022.107119. Crossref, Medline, Google Scholar9. Peters A, Künzli N, Forastiere F, Hoffmann B. 2019. Promoting clean air: combating fake news and denial. Lancet Respir Med 7(8):650–652, PMID: 31221566, 10.1016/S2213-2600(19)30182-1. Crossref, Medline, Google ScholarThe authors declare they have no conflicts of interest.FiguresReferencesRelatedDetailsRelated articlesInvited Perspective: The NO2 and Mortality Dilemma Solved? Almost There!Dec 28, 2021, 12:00:00 AMEnvironmental Health PerspectivesComment on “Invited Perspective: The NO2 and Mortality Dilemma Solved? Almost There!”Mar 16, 2022, 12:00:00 AMEnvironmental Health Perspectives Vol. 130, No. 3 March 2022Metrics Downloaded 488 times About Article Metrics Publication History Manuscript received23 February 2022Manuscript accepted24 February 2022Originally published16 March 2022 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days." @default.
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