Ambient Air Pollution and Increases in Blood Pressure
2015; Lippincott Williams & Wilkins; Volume: 66; Issue: 3 Linguagem: Inglês
10.1161/hypertensionaha.115.05563
ISSN1524-4563
AutoresWayne E. Cascio, M. Ian Gilmour, David B. Peden,
Tópico(s)COVID-19 impact on air quality
ResumoHomeHypertensionVol. 66, No. 3Ambient Air Pollution and Increases in Blood Pressure Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBAmbient Air Pollution and Increases in Blood PressureRole for Biological Constituents of Particulate Matter Wayne E. Cascio, M. Ian Gilmour and David B. Peden Wayne E. CascioWayne E. Cascio From the Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC (W.E.C., M.I.G.); and Center for Environmental Medicine, Asthma, and Lung Biology, and Department of Pediatrics, University of North Carolina at Chapel Hill (D.B.P.). , M. Ian GilmourM. Ian Gilmour From the Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC (W.E.C., M.I.G.); and Center for Environmental Medicine, Asthma, and Lung Biology, and Department of Pediatrics, University of North Carolina at Chapel Hill (D.B.P.). and David B. PedenDavid B. Peden From the Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC (W.E.C., M.I.G.); and Center for Environmental Medicine, Asthma, and Lung Biology, and Department of Pediatrics, University of North Carolina at Chapel Hill (D.B.P.). Originally published29 Jun 2015https://doi.org/10.1161/HYPERTENSIONAHA.115.05563Hypertension. 2015;66:469–471Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2015: Previous Version 1 See related article, pp 509–516Particulate matter (PM) is a complex mixture of extremely small particles and liquid droplets made up of several components including elemental carbon, organic chemicals, metals, acids (such as nitrates and sulfates), and soil and dust particles. Epidemiological studies consistently show that exposure to PM in urban areas across the globe is associated with increases in short- and long-term cardiovascular mortality and morbidity, most notably for myocardial infarction, heart failure, and ischemic stroke.1 The range in strength of these associations is likely related to variation in PM sources and composition across space and time and attests to the need to understand the contribution of specific sources to ultimately inform regulatory, public health, and clinical strategies to reduce risk.A systematic review and meta-analysis published in 2014 reported a positive association between short-term exposure to PM2.5 and blood pressure (BP).2 The article discussed potential mechanisms including PM-induced activation of pulmonary nociceptive receptors, pulmonary inflammatory responses, and release of endothelin-1 and suggested that activation of pulmonary receptors and vagal afferents could lead to shifts in autonomic balance and vasoconstriction. Other effects including oxidative stress and decreased NO availability, as well as systemic inflammation and endothelial dysfunction, have also been widely reported in association with PM components such as transition metals and organic carbon species. In this issue of Hypertension, Zhong et al3 provide evidence that the level of microbial components (specifically endotoxin and β-1,3-d-glucan) in inhaled ambient PM were directly correlated with increased BP which might elevate the risk of cardiovascular disease and stroke and contribute to the burden of disease in the US attendant to ambient air PM exposure. It is also worth noting that these ubiquitous biological molecules are key initiators of the innate immune system, although the relationship between immune cell activation and regulation of BP is not well understood.Are These Findings Believable?Although much has been learned about the chemical and biological components of PM, identification of specific constituents responsible for biological and physiological responses with resultant clinical cardiovascular events remains elusive. The Health Effects Institute's National Particle Component Toxicology Initiative was the most comprehensive study of PM components and health effects4 and included coordinated epidemiological and animal toxicological approaches in several regions of the United States. The studies found that secondary sulfate and traffic-related sources were associated with adverse health outcomes but were unable to narrow effects down to specific components of PM. In fact, despite this enormous effort the results highlighted a continued need to establish more robust measures of exposure at the level of the individual and population to more accurately define the relationship between specific sources, PM components, and subsequent health effects.Zhong et al overcame the limitations of source apportionment and component exposure assessment inherent to epidemiological studies using a human challenge experimental method,5 also known as a controlled human exposure study. In a small group of volunteers from an urban Toronto, Canada location, they directly measured differential physiological and biochemical responses after inhalation of fine or coarse concentrated ambient PM, filtered clean air or medical air for 130 minutes using a single-blind, randomized crossover exposure design. These acute exposures were on a mass basis, comparable with the total PM dose inhaled within a 24-hour period in large urban centers in North America. PM samples collected contemporaneously with the exposures were evaluated for endotoxin and β-1,3-d-glucan and the specific levels were correlated with changes in BP and urinary vascular endothelial growth factor. The crossover design increased the power to detect small changes in BP in association with PM or its components. In brief, they (1) reported that short-term exposure to ambient particle-associated endotoxin and β-1,3-d-glucan, but not total PM, was positively associated with increases in systolic and diastolic BP measured immediately and 1 day (diastolic only) after exposure; (2) endotoxin exposure was associated with increased urine vascular endothelial growth factor level 30 minutes after exposure; and (3) BP increased more in those individuals with negative or small increases in postexposure urine vascular endothelial growth factor.Can Toll-Like Receptor 4 Activation Affect BP?Activation of the Toll-like receptor 4 (TLR4) and upregulation of renin-angiotensin system–induced6 hypertension increase oxidative stress via TLR4 signaling.7 In addition, lipopolysaccharide is known to induce preeclampsia (characterized by inflammation and hypertension) in rodent models,8 and in humans, specific TLR4 polymorphisms are associated with increased risk for preeclampsia.9 Thus, in models of spontaneous hypertension and preeclampsia, there is support for the hypothesis that TLR4 activation causes hypertension. Consequently, direct activation of TLR4 by inhaled endotoxin, and perhaps by inhaled β-1,3-d-glucan, might explain the observed BP response. Increases in BP associated with endotoxin were attenuated in those with higher urinary vascular endothelial growth factor suggesting an adaptive response. The absence of such an interaction between vascular endothelial growth factor and the changes in BP associated with β-1,3-d-glucan might indicate a different mechanism underlying the change in BP.What Are the Limitations of the Study?The conclusions are based on the responses of only a small number of individuals exposed to PM collected from a single airshed (Toronto) composed of a mixture of fresh and aged local sources, and long-range transport of PM. The current research cannot address whether the relationships will hold true in other environs, such as other urban or rural areas, nor can they explain increases in BP associated with controlled exposures to diluted diesel exhaust, a pollutant presumably devoid of endotoxin or β-1,3-d-glucan.10 Also, it is important to remember that we are rarely exposed to a single pollutant, but instead are confronted with a complex mixture of gas phase and particulate materials in different size fractions. After exposure the resultant biochemical or physiological response will likely be the sum total of all of these effects, some of which may increase BP, whereas others may decrease BP. The experimental method did not allow for investigation of the interaction of other common pollutants nor nonchemical or clinical factors that could affect the dose–response relationship. Finally, the study design is most relevant to short-term exposures to PM and cannot inform whether chronically elevated background levels of endotoxin or β-1,3-d-glucan contained in PM could explain some of the long-term adverse cardiovascular effects of air particle pollution.Are These Findings Important?Elevated BP is an important risk factor for heart disease and stroke. Exposure to outdoor air PM pollution is estimated to account for >3 million deaths worldwide11 and is ranked in the top 10 among risk factors contributing to deaths in the United States.12 Endotoxin and β-1,3-d-glucan are ubiquitous in our environment and if the findings are confirmed, the observation will have significant impact on our understanding of at least 1 factor accounting for increases in BP. Overall, the study by Zhong et al provides new knowledge showing (1) indirect evidence that endotoxin and β-1,3-d-glucan might be involved in the control of BP presumably through TLR4 signaling; (2) that characterization of the sources and chemical components of PM is important for explaining biological and physiological effects of ambient air PM; and confirming (3) the safety and utility of human challenge studies to address critically important mechanisms and better determine the factors that might be attributable to specific sources. Along with continued study of PM sources, this knowledge could help focus risk assessment, risk management, and regulatory policy as well as public health and clinical mitigations strategies.What Are the Next Steps?Although these findings are new and potentially important for defining the effect of biological constituents of ambient air PM on BP, many key unanswered questions remain. To what extent might responses to biological components of ambient PM, or for that matter other constituents of PM be associated with increases in BP? Could exposure to PM be modified by subclinical conditions such as altered autonomic tone or endothelial dysfunction, or by clinical conditions such hypertension, diabetes mellitus, atherosclerosis, ischemic heart disease, and heart failure. By extension what is the relevance of PM exposure to short-term clinical effects in vulnerable populations? Further research is needed to better define the various sources and their components that drive the health effects of air PM pollution, their interaction with other pollutants, and with other environmental and social stressors. Because endotoxin and β-1,3-d-glucan are so ubiquitous, if these findings are confirmed, the observations will not only have relevance to our understanding of the drivers of the health effects of air pollutants, thereby facilitating improved risk-management, but will also provide new insights into the interaction between the innate immune system, vasomotor regulation, and BP. Confirmation and extension of these findings perhaps may also offer new therapeutic strategies for resistant hypertension.Sources of FundingThis work was supported by the US Environmental Protection Agency (grant no. CR-83578501) to D.B. Peden.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.This article has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does the mention of trade names of commercial products constitute endorsement or recommendation for use.Correspondence to Wayne E. Cascio, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, MD#58A, Research Triangle Park, NC 27711. E-mail [email protected]References1. Newby DE, Mannucci PM, Tell GS, et al; ESC Working Group on Thrombosis, European Association for Cardiovascular Prevention and Rehabilitation; ESC Heart Failure Association. Expert position paper on air pollution and cardiovascular disease.Eur Heart J. 2015; 36:83–93b. doi: 10.1093/eurheartj/ehu458.CrossrefMedlineGoogle Scholar2. 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Saleh T and Khader A (2022) Urban Particulate Matter Hazard Mapping and Monitoring Site Selection in Nablus, Palestine, Atmosphere, 10.3390/atmos13071134, 13:7, (1134) Huang M, Chen J, Yang Y, Yuan H, Huang Z and Lu Y (2021) Effects of Ambient Air Pollution on Blood Pressure Among Children and Adolescents: A Systematic Review and Meta‐Analysis, Journal of the American Heart Association, 10:10, Online publication date: 18-May-2021. Wang Q, Gracely E and Liu L (2020) Evidence linking air pollution and blood pressure mediated by body weight in China, Air Quality, Atmosphere & Health, 10.1007/s11869-020-00821-x, 13:5, (585-592), Online publication date: 1-May-2020. Yang H, Teng C, Hu J, Zhu X, Wang Y, Wu J, Xiao Q, Yang W, Shen H and Liu F (2019) Short-term effects of ambient particulate matter on blood pressure among children and adolescents:A cross-sectional study in a city of Yangtze River delta, China, Chemosphere, 10.1016/j.chemosphere.2019.124510, 237, (124510), Online publication date: 1-Dec-2019. Lin J, Wang H, Yan F, Tang K, Zhu H, Weng Z and Wang K (2017) Effects of occupational exposure to noise and dust on blood pressure in Chinese industrial workers, Clinical and Experimental Hypertension, 10.1080/10641963.2017.1368534, 40:3, (257-261), Online publication date: 3-Apr-2018. Gaddi A (2018) Air Pollution and Cardiovascular Diseases (Risk Factors and the Myocardial Cell Defence) Clinical Handbook of Air Pollution-Related Diseases, 10.1007/978-3-319-62731-1_16, (303-313), . Vencloviene J, Braziene A, Dedele A, Lopatiene K and Dobozinskas P (2017) Associations of short-term exposure to ambient air pollutants with emergency ambulance calls for the exacerbation of essential arterial hypertension, International Journal of Environmental Health Research, 10.1080/09603123.2017.1405246, 27:6, (509-524), Online publication date: 2-Nov-2017. Heusinkveld H, Wahle T, Campbell A, Westerink R, Tran L, Johnston H, Stone V, Cassee F and Schins R (2016) Neurodegenerative and neurological disorders by small inhaled particles, NeuroToxicology, 10.1016/j.neuro.2016.07.007, 56, (94-106), Online publication date: 1-Sep-2016. September 2015Vol 66, Issue 3 Advertisement Article InformationMetrics © 2015 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.115.05563PMID: 26123685 Originally publishedJune 29, 2015 PDF download Advertisement SubjectsHypertension
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