Particulate Matter: Well-documented Cause of Chronic Disease, Premature Death
In response to: Particulate Matter: Widespread and Deadly
Environmental regulation has emerged as a key difference between the two major political parties and has become a prominent stroke in the different portraits painted by political candidates of this country's future. Physicians should have a central role in this debate because the medical and toxicological research has become overwhelming in establishing that environmental protection is public health protection.
Air pollution in particular plays a much larger role in longevity and multiple chronic diseases than was recognized even ten years ago. As advocates for our patients and for the health of the public at large, physicians should be become familiar with the research and be willing to step forward in defense of public policy that steers our nation toward pollution mitigation.
Of the multiple components of typical urban air pollution, particulate matter is considered the most toxic of the high-volume pollutants and has been the most heavily researched. The signature physiologic and pathologic consequence of particulate air pollution is essentially the same as cigarette smoke: a low-grade arterial inflammation, arteriolar narrowing, and vascular prothrombotic changes. (1,2, 3, 4, 5, 6) As with cigarette smoke, the effect can be almost immediate (7) and chronic exposure to even low concentrations of pollution are associated with signiﬁcant arteriolar narrowing (8). Even in young healthy adults, air pollution increases biomarkers of inﬂammation and thrombosis (5).
These vascular changes cause average blood pressure to increase -- as soon as minutes after exposure (9) -- and therefore all organs are affected, especially those with the highest metabolic rate or the most tenuous blood supply, i.e. the heart, lungs, brain, and the placenta. Rates of heart attack and stroke increase with air pollution and are the primary cause for increased community mortality rates (10,11,12,13, 14, 15). Those rates increase within hours after exposure and stay elevated for as long as 30 days after the exposure has ended.
Particulate pollution exacerbates virtually all pulmonary diseases and likely plays a causative role in reactive airways disease. It is associated with increased rates of hospitalization and death from respiratory diseases from neonates to the elderly (20, 21, 22, 23). Particulate pollution permanently inhibits lung growth in children, preventing them from achieving their full adult lung capacity (24, 25). Brief exposure to either ozone or particulate matter reduces lung function even in young healthy adults and the reduction can last for a week after the pollution exposure is over (26, 27).
Particulate pollution causes morphologic changes in the placenta, inhibiting blood transfer to the fetus (28). Pregnant women exposed to more air pollution have multiple adverse pregnancy outcomes including higher blood pressure, higher rates of pre- eclampsia, intrauterine growth retardation, premature births, low birth weight syndrome and neonates with smaller head circumference (29, 30, 31, 32, 33). Air pollution is associated with higher rates of birth defects, including neural tube and cardiac birth defects (34).
The systemic inﬂammation caused by particulate pollution also affects the brain. Air pollution components reach the brain not only through the vascular system, but translocate via the nasal mucosa, along axons of the olfactory and trigeminal nerves into the central nervous system (CNS), allowing deep penetration into the parenchyma and brain stem (35, 36). Furthermore, many of the compounds adsorbed to particulate matter, like heavy metals, are neurotoxic. Through this mechanism, particulate pollution causes CNS oxidative stress, neuroinﬂammation, neuronal damage, cortical stress measured by EEG, enhancement of Alzheimer type-abnormal ﬁlamentous proteins, BBB changes, and cerebrovascular damage. Many of these changes can be found in children and young adults. Greater air pollution exposure is associated with lower intelligence, poorer motor function, attention deﬁcits and behavioral problems in children, decreased cognition in adults, higher rates of strokes, multiple sclerosis, autism, Parkinson's and other neurodegenerative diseases (37, 38, 39, 40, 41, 42, 43, 44).
By triggering the inflammatory cascade, particulate pollution causes systemic oxidative stress, cytotoxicity, and can penetrate cellular structures, including the cell nucleus, causing chemically mediated epigenetic changes to chromosomal function. This genotoxicity may represent air pollution's greatest impact on public health. Pregnant women exposed to more air pollution give birth to babies with signiﬁcantly more chromosomal aberrations and epigenetic changes which can be passed on to multiple subsequent generations (45, 46, 47, 48, 49, 50, 51).
When exposure even to brief episodes of pollution occurs at critical stages in the development of the human embryo, it can result in increased likelihood of multiple chronic diseases, including those of the heart, lungs, immune system and brain and even obesity, diabetes and cancer (52, 53, 54, 55, 56). Exposure to intermittent air pollution is associated with sperm DNA damage (57) and consequent increase in the rates of male infertility, miscarriages and other adverse reproductive outcomes. Children living near petrochemical industries are exposed to high PAH levels which appear to be particularly capable of provoking DNA damage. Industrial pollution is even more genotoxic than trafﬁc pollution. Air pollution also shortens the telomeres on chromosomes, thereby accelerating the aging process (58).
In May 2010, the American Heart Association published guidelines based on hundreds of epidemiologic studies offering a quantitative assessment of particulate pollution's mortality impact (16). For every 1 ug/m3 increase in PM2.5 (particulate matter less than 2.5 microns in size), community mortality rates from all causes increase about 1%. Research since then suggests that the number should be closer to 1.4% (17). That means that the air pollution in a typical urban setting, where most Americans live, increases the mortality rate between 10 and 14%. Concomitantly, average life expectancy has improved by about five months from just 20 years worth of reduced particulate pollution, thanks to implementation of the Clean Air Act (18).
Mortality plotted against particulate pollution concentrations shows no safe threshold, even at levels well below EPA national ambient air quality standards (NAAQS). Furthermore this curve is not linear (19). The steepest part of the curve is at low doses, i.e. small reductions in air pollution have even greater public health beneﬁt when the concentrations are already low.
Medical research does not support the concept of a safe level of particulate air pollution any more than it does a safe level of cigarette smoke and for much the same reason. It is indeed regrettable that science-based public health protection has become politicized. The antipathy towards strengthening environmental regulations seems to be merely a capitulation to the profit demands of industry and cannot be justified by anyone who self-identifies as a medical scientist. Physicians should advocate for public health and environmental policy that reflects the science. Our patients, our families, our children, and our pregnant mothers deserve to breathe air as clean as realistically possible.
1. Kunzil N, Jerrett M, Garcia-Esteban, R, et al. Ambient Air Pollution and the Progression of Atherosclerosis in Adults. PloS ONE, 2010; 2010; 5 (2): e9096 DOI: 10.1371/journal.pone.0009096
2. Jacobs L, Emmerechts J, Mathieu C, Hoylaerts MF, Fierens F, Hoet PH, Nemery B, Nawrot TS. Air pollution related prothrombotic changes in persons with diabetes. Environ Health Perspect. 2010 Feb;118(2):191-6.
3. American College of Cardiology (2008, August 14). Air Pollution Damages More Than Lungs: Heart And Blood Vessels Suffer Too.
4. Ruckerl, R. et al. (2007) Air pollution and inflammation (interleukin-6, C- reactive protein, ?brinogen) in myocardial infarction survivors. Environ. Health Perspect. 115, 1072–1080.
5. Rich D, Kipen H, Huang W, Wang G, Wang Y, Zhu P, et al. Association Between Changes in Air Pollution Levels During the Beijing Olympics and Biomarkers of In?ammation and Thrombosis in Healthy Young Adults JAMA. 2012;307(19):2068-2078. doi:10.1001/jama.2012.3488
6. Kampfrath T, Maiseyeu A, Ying Z, Shah Z, Deiuliis JA, et al. Chronic Fine Particulate Matter Exposure Induces Systemic Vascular Dysfunction via NADPH Oxidase and TLR4 Pathways. Circulation Research, 2011; 108 (6): 716 DOI: 10.1161/CIRCRESAHA.110.237560
7. Brook RD, Shin HH, Bard RL, Burnett RT, Vette A, Croghan C, et al. 2011. Exploration of the Rapid Effects of Personal Fine Particulate Matter Exposure on Arterial Hemodynamics and Vascular Function during the Same Day. Environ Health Perspect 119:688-694. doi:10.1289/ehp.1002107
8. Adar SD, Klein R, Klein BE, Szpiro AA, Cotch MF, Wong TY, O'Neill MS, Shrager S, Barr RG, Siscovick DS, Daviglus ML, Sampson PD, Kaufman JD. Air Pollution and the Microvasculature: A Cross-Sectional Assessment of In Vivo Retinal Images in the Population-Based Multi-Ethnic Study of Atherosclerosis (MESA). PLoS Med. 2010 Nov 30;7(11):e1000372
9. Urch B, Silverman F, Corey P, Brook J, Lukic K, Rajagopalan S, Brook R. Acute Blood Pressure Responses in Healthy Adults During Controlled Air Pollution Exposures. Environ Health Perspect. 2005 August; 113(8): 1052–1055.
10. Pope CA III, Muhlestein JB, May HT et al. Ischemic Heart Disease Events Triggered by Short-term Exposure to Fine Particulate Air Pollution. Circulation 2006, 114:2443-2448.
11. Dockery DW, Stone PH. Cardiovascular Risks from Fine Particulate Air Pollution. NEJM 2007; 356:511-513
12. Miller KA, Siscovick DS, Sheppard L et al. Long-term Exposure to Air Pollution and Incidence of Cardiovascular Events in Women. NEJM 2007; 356:447-458.
13. Musta?" H, Jabre P, Caussin C, Murad M, et al. Main Air Pollutants and Myocardial Infarction: A Systematic Review and Meta-analysis. JAMA 2012. vol 307, no. 7 pg 713-721.
14. Wellenius G, Burger M, Coull B, Schwartz J, et al. Ambient Air Pollution and the Risk of Acute Ischemic Stroke. Arch Intern Med. 2012;172(3):229-234. doi: 10.1001/archinternmed.2011.732
15. Peters A, von Klot S, Heier M, et al. Exposure to Traffic and the Onset of Myocardial Infarction. NEJM Vol. 351:1721-1730.
16. Brook R, Rajagopalan S, Pope CA, Brook J, Bhatnagar A, et al. AHA Scientific Statement: Particulate Matter Air Pollution and Cardiovascular Disease; An Update to the Scientific Statement From the American Heart Association. Circulation. 2010;121:2331-2378.
17. 11. Lepeule J, Laden F, Dockery D, Schwartz J. Chronic Exposure to Fine Particles and Mortality: An Extended Follow-Up of the Harvard Six Cities Study from 1974 to 2009. Environ Health Perspect. 2012 Mar 28. [Epub ahead of print]
18. Pope, CA III, Ezzate, M., Dockery, D. Fine-Particulate Air Pollution and Life Expectancy in the United States. NEJM. Vol. 360:376-386 Jan. 22, 2009 Num. 4.
19. Calle E, Thun M, Pope, CA, Burnett R, Krewski D, Jerrett M, Shi Y. Cardiovascular Mortality and Exposure to Airbourne Fine Particulate Matter and Cigarette Smoke. Circulation. 2009;120:941-948.
20. Andersen Z, Hvidberg M, Jensen S, et al. Chronic Obstructive Pulmonary Disease and Long-Term Exposure to Traf?c-Related Air Pollution: A Cohort Study. Am. J. Respir. Crit. Care Med. 2010, doi:10.1164/rccm.201006-0937OC. Published ahead of print on September 24, 2010
21. Wichmann et al. Increased asthma and respiratory symptoms in children exposed to petrochemical pollution. Journal of Allergy and Clinical Immunology, 2009; 123 (3): 632 DOI: 10.1016/j.jaci.2008.09.052
22. Faustini A, Stafoggia M, Berti G, Bisanti L, Chiusolo M, Cernigliaro A, Mallone S, Primerano R, Scarnato C, Simonato L, Vigotti MA, Forastiere F; The relationship between ambient particulate matter and respiratory mortality: a multi-city study in Italy. Eur Respir J. 2011 Jan 13. [Epub ahead of print]
23. Forbes LJ, Kapetanakis V, Rudnicka AR, Cook DG, Bush T, Stedman JR, Whincup PH, Strachan DP, Anderson HR. Chronic exposure to outdoor air pollution and lung function in adults. Thorax. 2009 Aug;64(8):657-63. Epub 2009 Apr 8.
24. Gauderman WJ, Gilliland GF, Vora H, et al. Association between Air Pollution and Lung Function Growth in Southern California Children: results from a second cohort. Am J Respir Crit Care Med 2002;166:76-84.
25. Gauderman WJ, Gilliland GF, Vora H, et al. The effect of air pollution on lung development from 10 to 18 years of age. NEJM 2004;351:1057-67.
26. Steinvil A, Fireman E, Kordova-Biezuner L, Cohen M, Shapira I, Berliner S, Rogowski O. Environmental air pollution has decremental effects on pulmonary function test parameters up to one week after exposure. Am J Med Sci. 2009 Oct; 338(4):273-9.
27. Thaller, E., Petronella, S., Hochman, D. et al. Moderate increases in Ambient PM 2.5 and Ozone Are Associated With Lung Function Decreases in Beach Lifeguards. Journal of Occupational and Environmental Medicine. 50(2):202-211, Feb. 2008.
28. Veras MM, Damaceno-Rodregues N, Caldini E, Ribeiro A, et al. Particulate Urban Air Pollution Affects the Functional Morphology of Mouse Placenta. Biology of Reproduction Sept. 1, 2008 vol. 79 no. 3 578-584.
29. van den Hooven EH, de Kluizenaar Y, Pierik FH, Hofman A, van Ratingen SW, Zandveld PY, Mackenbach JP, Steegers EA, Miedema HM, Jaddoe VW. Air Pollution, Blood Pressure, and the Risk of Hypertensive Complications During Pregnancy: The Generation R Study. Hypertension. 2011 Jan 10. [Epub ahead of print]
30. Rahman, Anisur. Arsenic Exposure and Risk of Spontaneous Abortion, Stillbirth, and Infant Mortality. Epidemiology. November 2010 - Volume 21 - Issue 6 - pp 797-804 doi: 10.1097/EDE.0b013e3181f56a0d
31. Hansen C, Barnett A, Prichard G. The Effect of Ambient Air Pollution during Early Pregancy on Fetal Ultrasound Measurements during Mid-Pregnancy. Environ Health Persp Vol. 116, Number 3, March 2008
32. Wu J, Ren C, Del?no RJ, Chung J, Wilhelm M, Ritz B 2009. Association between Local Traf?c-Generated Air Pollution and Preeclampsia and Preterm Delivery in the South Coast Air Basin of California. Environ Health Perspect 117:1773-1779. doi:10.1289/ehp.0800334
33. Darrow LA, Klein M, Strickland MJ, Mulholland JA, Tolbert PE 2011. Ambient Air Pollution and Birth Weight in Full-Term Infants in Atlanta, 1994–2004. Environ Health Perspect 119:731-737. doi:10.1289/ehp.1002785
34. Vrijheid M, Martinez D, Manzanares S, Dadvand P, Schembari A, Rankin J, Nieuwenhuijsen M. Ambient Air Pollution and Risk of Congenital Anomalies: A Systematic Review and Meta-Analysis. Environ Health Perspect. 2010 Dec 3. [Epub ahead of print]
35. Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, and Cox C. Translocation of Inhaled Ultra?ne Particles to the Brain. Inhalation Toxicology 2004, Vol. 16, No. 6-7, Pages 437-445
36. Peters, A. et al. (2006) Translocation and potential neurological effects of fine and ultrafine particles a critical update. Part. Fibre Toxicol. 3, 13
37. Calderon-Garciduenas, L. et al. (2002) Air pollution and brain damage. Toxicol. Pathol. 30, 373–389
38. Calderon-Garciduenas, L. et al. (2003) DNA damage in nasal and brain tissues of canines exposed to air pollutants is associated with evidence of chronic brain inflammation and neurodegeneration. Toxicol. Pathol. 31, 524–538
39. Mateen F, Brook R. Air Pollution as an Emerging Global Risk Factor for Stroke JAMA j2011;305(12):1240-1241.doi:10.1001/jama.2011.352
40. Power MC, Weisskopf MG, Alexeeff SE, Coull BA, Spiro A III, Schwartz J 2011. Traffic-Related Air Pollution and Cognitive Function in a Cohort of Older Men. Environ Health Perspect 119:682-687. doi:10.1289/ehp.1002767
41. Suglia SF, et al. Association of Black Carbon with Cognition among Children in a Prospective Birth Cohort Study Am J Epidemiology 2008 167:280-286.
42. Perera, FP, L Zhigang, R Whyatt, L Hoepner, S Wang, D Camann and V Rauh. 2009. 2009. Prenatal airborne polycyclic aromatic hydrocarbon exposure and child IQ at age 5 years. Pediatrics doi: 10.1542/peds.2008-3506.
43. Weuve J, Puett R, Schwartz J, Yanosky J, Laden F, Grodstein F. Exposure to Particulate Air Pollution and Cognitive Decline in Older Women Arch Intern Med. 2012;172(3):219-227. doi:10.1001/archinternmed.2011.683
44. Perera FP, Tang D, Wang S, Vishnevetsky J, Zhang B, Diaz D, Camann D, Rauh V. Prenatal Polycyclic Aromatic Hydrocarbon (PAH) Exposure and Child Behavior at age 6-7. Environ Health Perspect. 2012 Mar 22. [Epub ahead of print]
45. Perera F, Tang W, Herbstman J. Relation of DNA Methylation of 5-CpG Island of ACSL3 to Transplacental Exposure to Airborne PAH and Childhood Asthma. PloS ONE. Feb. 16, 2009.
46. Bocskay K, Tang D, Orjuela M, et al. Chromosomal Aberrations in Cord Blood Are Associated with Prenatal Exposure to Carcinogenic Polycyclic Aromatic Hydrocarbons. Cancer Epidem Biomarkers and Prev. Vol. 14, 506-511, Feb 2005
47. Baccarelli A. Breathe deeply into your genes: genetic variants and air pollution effects. Am J Respir Crit Care Med. 2009 Mar 15;179(6):431-2.
48. Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Rapid DNA methylation changes after exposure to traf?c particles. Am J Respir Crit Care Med. 2009 Apr 1;179(7):523-4.
49. Jedrychowski WA, Perera FP, Maugeri U, Mroz E, Klimaszewska-Rembiasz M, Flak E, Edwards S, Spengler JD. Effect of prenatal exposure to fine particulate matter on ventilatory lung function of preschool children of non-smoking mothers. Paediatr Perinat Epidemiol. 2010 Sep;24(5):492-501.
50. Pedersen M, Wichmann J, Autrup H, Dang DA, Decordier I, Hvidberg M, Bossi R, Jakobsen J, Loft S, Knudsen LE. Increased micronuclei and bulky DNA adducts in cord blood after maternal exposures to traf?c-related air pollution. Environ Res. 2009 Nov;109(8):1012-20. Epub 2009 Sep 23.
51. Møller P, Folkmann JK, Danielsen PH, Jantzen K, Loft S. Oxidative Stress Generated Damage to DNA by Gastrointestinal Exposure to Insoluble Particles. Curr Mol Med. 2012 Jan 27. [Epub ahead of print]
52. Herr CE, Dostal M, Ghosh R, Ashwood P, Lipsett M, Pinkerton KE, Sram R, Hertz-Picciotto I. Air pollution exposure during critical time periods in gestation and alterations in cord blood lymphocyte distribution: a cohort of livebirths. Environ Health. 2010 Aug 2;9(1):46.
53. Rundle A, Hoepner L, Hassoun A, et al. Association of Childhood Obesity With Maternal Exposure to Ambient Air Polycyclic Aromatic Hydrocarbons During Pregnancy. Am. J. Epidemiol. online April 13, 2012 doi:10.1093/aje/kwr45
54. Topinka J, Rossner P Jr, Milcova A, Schmuczerova J, Svecova V, Sram RJ. DNA Adducts and Oxidative DNA Damage Induced by Organic Extracts From PM2.5 in an Acellular Assay. Toxicol Lett. 2011 Feb 14. [Epub ahead of print]
55. Gualtieri M, Ovrevik J, Mollerup S, Asare N, Longhin E, Dahlman HJ, Camatini M, Holme JA. Airborne urban particles (Milan winter-PM2.5) cause mitotic arrest and cell death: Effects on DNA, mitochondria, AhR binding and spindle organization. Mutat Res. 2011 May 30. [Epub ahead of print]
56. Janssen BG, Munters E, Pieters N, Smeets K, Cox B, Cuypers A, et al. 2012. Placental Mitochondrial DNA Content and Particulate Air Pollution During in Utero Life. Environ Health Perspect :-. http://dx.doi.org/10.1289/ehp.1104458
57. Rubes J, Selevan S, Evenson D, Zudova D, Vozdova M, Zudova Z, Robbins W, Perreault S. Episodic air pollution is associated with increased DNA fragmentation in human sperm without other changes in semen quality. Human Reproduction Vol.20, No.10 pp. 2776–2783, 2005 doi:10.1093/humrep/dei122. Advance Access publication June 24, 2005.
58. Hoxha M, Dioni L, Bonzini M, et al. Association between leukocyte telomere shortening and exposure to traffic pollution: a cross-sectional study on traffic officers and indoor of?ce workers. Environ Health. 2009; 8: 41. Published online 2009 September 21. doi: 10.1186/1476-069X-8-41
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