Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter January 4, 2021

Ambient air pollution and multiple sclerosis: a systematic review

  • Mohammad Amin Farahmandfard , Ahmad Naghibzadeh-Tahami and Narges Khanjani EMAIL logo



Some studies have shown that environmental risk factors, including air pollution, might be related to the incidence or recurrence of multiple sclerosis (MS). This systematic review was conducted to investigate the relation between air pollution and MS.


A systematic search was conducted in PubMed, Scopus, Science Direct, Embase, and Web of Science; until January 2020 with no restrictions. The search strategy was conducted with air pollution key words such as CO, PM2.5, PM10, SO2, and NO2, for exposure and the key word “Multiple sclerosis” as the outcome.


Eventually, after applying the inclusion and exclusion criteria, 17 articles were included. The methodologies and outcomes reported were heterogeneous and different metrics had been used in the results; therefore conducting a meta-analysis was not possible. Eight studies had analyzed the relation between particulate matter (PM) and the prevalence or relapse of MS and had observed a significant relation. NO2 and NOx were associated with recurrence or prevalence of MS in three studies. But, in three cohort studies, no association was observed between air pollution and recurrence or occurrence of MS.


The results of this systematic review show that outdoor air pollution, especially PM and nitrogen oxides might be related to the prevalence or relapse of MS.

Corresponding author: Prof Narges Khanjani, Department of Epidemiology and Biostatistics, School of Public Health, Kerman University of Medical Sciences, 76169-13555 Kerman, Iran; Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran; and Environmental Health Engineering Research Center, Kerman University of Medical Sciences, Kerman, Iran, Phone: 034 3132 5102, Fax: 034 3132 5102, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors have no conflicts of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.


1. Moghaddam, VK, Sarmadi, M, Tatari, M, Najafi, F, Esmaeili, A, Hadei, M. Epidemiology of multiple sclerosis in Torbat-e Heydarieh (Northeast of Iran) during 1982–2016. Mult Scler Relat Disord 2018;24:184–9. in Google Scholar

2. Benamer, HT, Ahmed, ES, Al-Din, AS, Grosset, DG. Frequency and clinical patterns of multiple sclerosis in Arab countries: a systematic review. J Neurol Sci 2009;278:1–4. in Google Scholar

3. Cristiano, E, Patrucco, L, Rojas, J. A systematic review of the epidemiology of multiple sclerosis in South America. Eur J Neurol 2008;15:1273–8. in Google Scholar

4. Browne, P, Chandraratna, D, Angood, C, Tremlett, H, Baker, C, Taylor, BV, et al.. Atlas of multiple sclerosis 2013: a growing global problem with widespread inequity. Neurology 2014;83:1022–4. in Google Scholar

5. Evans, C, Beland, S-G, Kulaga, S, Wolfson, C, Kingwell, E, Marriott, J, et al.. Incidence and prevalence of multiple sclerosis in the Americas: a systematic review. Neuroepidemiology 2013;40:195–210. in Google Scholar

6. Kira, J-I. Multiple sclerosis in the Japanese population. Lancet Neurol 2003;2:117–27. in Google Scholar

7. Wasay, M, Khatri, I, Khealani, B, Sheerani, M. MS in Asian countries. Int MS J 2006;13:58.10.1177/1352458506072339Search in Google Scholar

8. Elhami, S-R, Mohammad, K, Sahraian, MA, Eftekhar, H. A 20-year incidence trend (1989–2008) and point prevalence (March 20, 2009) of multiple sclerosis in Tehran, Iran: a population-based study. Neuroepidemiology 2011;36:141–7. in Google Scholar

9. Heydarpour, P, Amini, H, Khoshkish, S, Seidkhani, H, Sahraian, MA, Yunesian, M. Potential impact of air pollution on multiple sclerosis in Tehran, Iran. Neuroepidemiology 2014;43:233–8. in Google Scholar

10. Sahraian, MA, Khorramnia, S, Ebrahim, MM, Moinfar, Z, Lotfi, J, Pakdaman, H. Multiple sclerosis in Iran: a demographic study of 8,000 patients and changes over time. Eur Neurol 2010;64:331–6. in Google Scholar

11. Lozano, R, Naghavi, M, Foreman, K, Lim, S, Shibuya, K, Aboyans, V, et al.. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2095–128. in Google Scholar

12. Murray, CJ, Vos, T, Lozano, R, Naghavi, M, Flaxman, AD, Michaud, C, et al.. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2197–223. in Google Scholar

13. Pakpoor, J, Ramagopalan, S. Multiple sclerosis and the Iranian revolution: reply to the comment by Magzhi et al. Neuroepidemiology 2012;40:70. in Google Scholar PubMed

14. Sawcer, S, Hellenthal, G, Pirinen, M, Spencer, CC, Patsopoulos, NA, Moutsianas, L, et al.. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011;476:214. in Google Scholar PubMed PubMed Central

15. Franklin, GM, Nelson, L. Environmental risk factors in multiple sclerosis: causes, triggers, and patient autonomy. Neurology 2003;61:1032–4. in Google Scholar PubMed

16. Koch, MW, Metz, LM, Kovalchuk, O. Epigenetic changes in patients with multiple sclerosis. Nat Rev Neurol 2013;9:35–43. in Google Scholar PubMed

17. Dadbakhsh, M, Khanjani, N, Bahrampour, A. Death from cardiovascular diseases and air pollution in Shiraz, Iran (March 2006–March 2012). J Epidemiol Prev Med 2016;2:114.10.19104/jepm.2016.114Search in Google Scholar

18. Dastoorpoor, M, Goudarzi, G, Khanjani, N, Idani, E, Aghababaeian, H, Bahrampour, A. Lag time structure of cardiovascular deaths attributed to ambient air pollutants in Ahvaz, Iran, 2008–2015. Int J Occup Med Environ Health 2018;31:459–73. in Google Scholar PubMed

19. Dastoorpoor, M, Idani, E, Goudarzi, G, Khanjani, N. Acute effects of air pollution on spontaneous abortion, premature delivery, and stillbirth in Ahvaz, Iran: a time-series study. Environ Sci Pollut Control Ser 2018;25:5447–58. in Google Scholar PubMed

20. Dastoorpoor, M, Khanjani, N, Bahrampour, A, Goudarzi, G, Aghababaeian, H, Idani, E. Short-term effects of air pollution on respiratory mortality in Ahvaz, Iran. Med J Islam Repub Iran 2018;32:30. in Google Scholar PubMed PubMed Central

21. Dastoorpoor, M, Masoumi, K, Vahedian, M, Aghababaeian, H, Sekhavatpour, Z, Khanjani, N, et al.. Associations of short-term exposure to air pollution with respiratory hospital admissions in Ahvaz, Iran. Process Saf Environ Protect 2019;123:150–60. in Google Scholar

22. Dastoorpoor, M, Sekhavatpour, Z, Masoumi, K, Mohammadi, MJ, Aghababaeian, H, Khanjani, N, et al.. Air pollution and hospital admissions for cardiovascular diseases in Ahvaz, Iran. Sci Total Environ 2019;652:1318–30. in Google Scholar PubMed

23. Dehghan, A, Khanjani, N, Bahrampour, A, Goudarzi, G, Yunesian, M. The relation between air pollution and respiratory deaths in Tehran, Iran-using generalized additive models. BMC Pulm Med 2018;18:49. in Google Scholar PubMed PubMed Central

24. Dehghan, A, Khanjani, N, Bahrampour, A, Goudarzi, G, Yunesian, M. Short-term effects of ambient (outdoor) air pollution on cardiovascular death in Tehran, Iran–a time series study. Toxin Rev 2019;39:1–13. in Google Scholar

25. Hashemi, S, Khanjani, N. Air pollution and cardiovascular hospital admissions in Kerman. Iran J Heart Cardiol 2016;2:1–6. in Google Scholar

26. Khanjani, N, Kalankesh, LR, Mansouri, F. Air pollution and respiratory deaths in Kerman, Iran (from 2006 till 2010). Iran J Epidemiol 2012;8:58–65.Search in Google Scholar

27. Raji, H, Riahi, A, Borsi, SH, Masoumi, K, Khanjani, N, AhmadiAngali, K, et al.. Acute effects of air pollution on hospital admissions for asthma, COPD, and bronchiectasis in Ahvaz, Iran. Int J Chronic Obstr Pulm Dis 2020;15:501. in Google Scholar PubMed PubMed Central

28. Rezaei, S, Khanjani, N, Senjedkooh, SM, Fard, ZD. The effect of air pollution on respiratory disease visits to the emergency department in Kerman, Iran. J Health Dev 2015;4:306–14.Search in Google Scholar

29. Vahedian, M, Khanjani, N, Mirzaee, M, Koolivand, A. Associations of short-term exposure to air pollution with respiratory hospital admissions in Arak, Iran. J Environ Health Sci Eng 2017;15:17. in Google Scholar PubMed PubMed Central

30. Vahedian, M, Khanjani, N, Mirzaee, M, Koolivand, A. Ambient air pollution and daily hospital admissions for cardiovascular diseases in Arak, Iran. ARYA Atheroscler 2017;13:117.Search in Google Scholar

31. Organization WH. Burden of disease from ambient air pollution for 2012. Geneva, Switzerland: World Health Organization; 2014.Search in Google Scholar

32. Genc, S, Zadeoglulari, Z, Fuss, SH, Genc, K. The adverse effects of air pollution on the nervous system. J Toxicol 2012;2012:782462. in Google Scholar PubMed PubMed Central

33. Calderón-Garcidueñas, L, Azzarelli, B, Acuna, H, Garcia, R, Gambling, TM, Osnaya, N, et al.. Air pollution and brain damage. Toxicol Pathol 2002;30:373–89. in Google Scholar PubMed

34. Guo, L, Zhu, N, Guo, Z, Li, G-K, Chen, C, Sang, N, et al.. Particulate matter (PM10) exposure induces endothelial dysfunction and inflammation in rat brain. J Hazard Mater 2012;213:28–37. in Google Scholar PubMed

35. Ashtari, F, Esmaeil, N, Mansourian, M, Poursafa, P, Mirmosayyeb, O, Barzegar, M, et al.. An eight-year study of people with multiple sclerosis in Isfahan, Iran: association between environmental air pollutants and severity of disease. J Neuroimmunol 2018;319:106–11. in Google Scholar PubMed

36. Bergamaschi, R, Cortese, A, Pichiecchio, A, Berzolari, FG, Borrelli, P, Mallucci, G, et al.. Air pollution is associated to the multiple sclerosis inflammatory activity as measured by brain MRI. Mult Scler J 2018;24:1578–84. in Google Scholar

37. Chen, H, Kwong, JC, Copes, R, Tu, K, Villeneuve, PJ, van Donkelaar, A, et al.. Living near major roads and the incidence of dementia, Parkinson’s disease, and multiple sclerosis: a population-based cohort study. Lancet 2017;389:718–26. in Google Scholar

38. Gregory, ACII, Shendell, DG, Okosun, IS, Gieseker, KE. Multiple sclerosis disease distribution and potential impact of environmental air pollutants in Georgia. Sci Total Environ 2008;396:42–51. in Google Scholar PubMed

39. Jeanjean, M, Bind, M-A, Roux, J, Ongagna, J-C, De Sèze, J, Bard, D, et al.. Ozone, NO2 and PM10 are associated with the occurrence of multiple sclerosis relapses. Evidence from seasonal multi-pollutant analyses. Environ Res 2018;163:43–52. in Google Scholar PubMed PubMed Central

40. Lavery, AM, Waldman, AT, Casper, TC, Roalstad, S, Candee, M, Rose, J, et al.. Examining the contributions of environmental quality to pediatric multiple sclerosis. Mult Scler Relat Disord 2017;18:164–9. in Google Scholar PubMed PubMed Central

41. Lavery, AM, Waubant, E, Casper, TC, Roalstad, S, Candee, M, Rose, J, et al.. Urban air quality and associations with pediatric multiple sclerosis. Ann Clin Transl Neurol 2018;5:1146–53. in Google Scholar PubMed PubMed Central

42. Mehrpour, M, Shams-Hosseini, NS, Rezaali, S, Sahraiian, MA, Taki, S. Effect of air pollutant markers on multiple sclerosis relapses. Iran J Public Health 2013;42:1167.Search in Google Scholar

43. Oikonen, M, Laaksonen, M, Laippala, P, Oksaranta, O, Lilius, E-M, Lindgren, S, et al.. Ambient air quality and occurrence of multiple sclerosis relapse. Neuroepidemiology 2003;22:95–9. in Google Scholar PubMed

44. Palacios, N, Munger, K, Fitzgerald, K, Hart, J, Chitnis, T, Ascherio, A, et al.. Exposure to particulate matter air pollution and risk of multiple sclerosis in two large cohorts of US nurses. Environ Int 2017;109:64–72. in Google Scholar PubMed

45. Roux, J, Bard, D, Le Pabic, E, Segala, C, Reis, J, Ongagna, J-C, et al.. Air pollution by particulate matter PM10 may trigger multiple sclerosis relapses. Environ Res 2017;156:404–10. in Google Scholar PubMed

46. Tateo, F, Grassivaro, F, Ermani, M, Puthenparampil, M. PM2.5 levels strongly associate with multiple sclerosis prevalence in the Province of Padua, Veneto Region, North-East Italy. Mult Scler J 2019;25:1719–27. in Google Scholar PubMed

47. Vojinović, S, Savić, D, Lukić, S, Savić, L, Vojinović, J. Disease relapses in multiple sclerosis can be influenced by air pollution and climate seasonal conditions. Vojnosanit Pregl 2015;72:44–9. in Google Scholar PubMed

48. Bai, L, Burnett, RT, Kwong, JC, Hystad, P, van Donkelaar, A, Brook, JR, et al.. Long-term exposure to air pollution and the incidence of multiple sclerosis: a population-based cohort study. Environ Res 2018;166:437–43. in Google Scholar PubMed

49. Angelici, L, Piola, M, Cavalleri, T, Randi, G, Cortini, F, Bergamaschi, R, et al.. Effects of particulate matter exposure on multiple sclerosis hospital admission in Lombardy region, Italy. Environ Res 2016;145:68–73. in Google Scholar PubMed PubMed Central

50. Carmona, R, Linares, C, Recio, A, Ortiz, C, Díaz, J. Emergency multiple sclerosis hospital admissions attributable to chemical and acoustic pollution: Madrid (Spain), 2001–2009. Sci Total Environ 2018;612:111–8. in Google Scholar PubMed

51. Hogancamp, WE, Rodriguez, M, Weinshenker, BG, The epidemiology of multiple sclerosis. Mayo Clinic Croc. 1997;72:871–8. in Google Scholar PubMed

52. Becker, S, Soukup, JM. Exposure to urban air particulates alters the macrophage-mediated inflammatory response to respiratory viral infection. J Toxicol Environ Health Part A 1999;57:445–57. in Google Scholar PubMed

53. Holian, A, Hamilton, RFJr, Morandi, MT, Brown, SD, Li, L. Urban particle-induced apoptosis and phenotype shifts in human alveolar macrophages. Environ Health Perspect 1998;106:127–32. in Google Scholar PubMed PubMed Central

54. Mousavi, SE, Heydarpour, P, Reis, J, Amiri, M, Sahraian, MA. Multiple sclerosis and air pollution exposure: mechanisms toward brain autoimmunity. Med Hypotheses 2017;100:23–30. in Google Scholar PubMed

55. Heusinkveld, HJ, Wahle, T, Campbell, A, Westerink, RH, Tran, L, Johnston, H, et al.. Neurodegenerative and neurological disorders by small inhaled particles. Neurotoxicology 2016;56:94–106. in Google Scholar PubMed

56. Bascom, RBP, Costa, DL, Devlin, R, Dockery, DW, Frampton, MW, Lambert, W, et al.. Health effects of outdoor air pollution. Part 2. Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society. Am J Respir Crit Care Med 1996;153:477–98. in Google Scholar PubMed

57. Oikonen, MK, Erälinna, J-P. Beta-interferon protects multiple sclerosis patients against enhanced susceptibility to infections caused by poor air quality. Neuroepidemiology 2008;30:13–9. in Google Scholar

58. Donaldson, K, Tran, L, Jimenez, LA, Duffin, R, Newby, DE, Mills, N, et al.. Combustion-derived nanoparticles: a review of their toxicology following inhalation exposure. Part Fibre Toxicol 2005;2:10. in Google Scholar

59. Gerlofs-Nijland, ME, van Berlo, D, Cassee, FR, Schins, RP, Wang, K, Campbell, A. Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain. Part Fibre Toxicol 2010;7:12. in Google Scholar

60. Guimond, C, Lee, JD, Ramagopalan, SV, Dyment, DA, Hanwell, H, Giovannoni, G, et al.. Multiple sclerosis in the Iranian immigrant population of BC, Canada: prevalence and risk factors. Mult Scler J 2014;20:1182–8. in Google Scholar

61. Shafa, MA, Ebrahimi, HA, Kha, N. A study of the seasonal incidence of multiple sclerosis attacks in Kerman, Iran. J Kerman Univ Med Sci 2014;21:376–83.Search in Google Scholar

62. Jin, Y-P, de Pedro-Cuesta, J, Söderström, M, Stawiarz, L, Link, H. Seasonal patterns in optic neuritis and multiple sclerosis: a meta-analysis. J Neurol Sci 2000;181:56–64. in Google Scholar

63. Watad, A, Azrielant, S, Soriano, A, Bracco, D, Much, AA, Amital, H. Association between seasonal factors and multiple sclerosis. Eur J Epidemiol 2016;31:1081–9. in Google Scholar

64. Koch-Henriksen, N, Sørensen, PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol 2010;9:520–32. in Google Scholar

65. Agarwal, K, Mughal, M, Upadhyay, P, Berry, J, Mawer, E, Puliyel, J. The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi, India. Arch Dis Child 2002;87:111–3. in Google Scholar PubMed PubMed Central

66. Hosseinpanah, F, Pour, SH, Heibatollahi, M, Moghbel, N, Asefzade, S, Azizi, F. The effects of air pollution on vitamin D status in healthy women: a cross sectional study. BMC Publ Health 2010;10:519. in Google Scholar PubMed PubMed Central

67. Kelishadi, R, Sharifi-Ghazvini, F, Poursafa, P, Mehrabian, F, Farajian, S, Yousefy, H, et al.. Determinants of hypovitaminosis D in pregnant women and their newborns in a sunny region. Int J Endocrinol 2013;2013:460970. in Google Scholar PubMed PubMed Central

Received: 2020-06-23
Accepted: 2020-12-09
Published Online: 2021-01-04
Published in Print: 2021-12-20

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 5.3.2024 from
Scroll to top button