Air pollution as a contributing factor of relapses and cases of multiple sclerosis

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C. Zhukovsky1, M.-A. Bind2, I. Boström3, A.-M. Landtblom4


1Department of Neurosciences, Uppsala University, 3 Husargatan, Uppsala, SE-752 36, Sweden
2Department of Statistics, Harvard University, MA 02138, Massachusetts Hall, Cambridge, USA
3Departments of Neurology and Clinical and Experimental Medicine, Linköping University, SE-581 83,
Linköping, Sweden
4Uppsala University Hospital, SE-751 85, Uppsala, Sweden


The role of air pollution exposure in multiple sclerosis (MS) incidence and relapse worldwide has not yielded a consensus; some studies have reported positive associations, which have failed to reject the null hypothesis. Potential reasons for these contradictory results can in part be explained by differences in study designs and their associated limitations. Of note, rat and canine studies in 2010 and 2013, respectively, have shown that expression of HO-1 enzyme and inflammatory factors increased due to PM10 and diesel engine exhaust (DEE) exposure. Of the eight non-null epidemiological studies scrutinized, the majority included a retrospective study design with air pollution monitoring data, which may be an advantage due to large number of study participants and a disadvantage with possible air pollution measurement error for personal exposure. The studies included analyses of PM10, PM2.5, SO2, NO2, NOx and/or O3 with PM10 as the common denominator between all of them. Studies from 2003, 2014–2019 from Finland, France, Iran, Italy, and Serbia
all provide evidence of an association between PM10 and incidence or relapse of MS. Though one 2018 study likewise described associations between exposures to NO2, O3, and PM10 and MS relapses using a case-crossover design, the multi-pollutant model only associated O3. Of the epidemiological studies that fail to reject the null hypothesis, there was no evidence of an association between PM10 exposure and MS relapse or incidence. Though air pollution has not been conclusively proven to be a cause of MS, evidence from multiple studies have associated incidence and relapse with exposure to pollutants, particularly PM10.

air pollution, multiple sclerosis, relapse, particle matter, exposure, pollutants.
Zhukovsky C., Bind M.-A., Boström I., Landtblom A.-M. Air pollution as a contributing factor of relapses and cases of multiple sclerosis. Health Risk Analysis, 2020, no. 3, pp. 169–175. DOI: 10.21668/health.risk/2020.3.20.eng
  1. Hemmer B., Kerschensteiner M., Korn T. Role of the innate and adaptive immune responses in the course of multiple sclerosis. Lancet Neurol, 2015. vol. 14, no. 4, pp. 406–419. DOI: 10.1016/S1474-4422(14)70305-9
  2. Moutsianas L., Jostins L., Beecham A.H., Dilthey A.T., Xifara D.K., Ban M., Shah T.S., Patsopoulos N.A. [et al.]. Class II HLA interactions modulate genetic risk for multiple sclerosis. Nat Genet, 2015. vol. 47, no. 10, pp. 1107–1113. DOI: 10.1038/ng.3395
  3. Sawcer S., Hellenthal G., Pirinen M., Spencer C.C.A., Patsopoulos N.A., Moutsianas L., Dilthey A., Su Zh. [et al.]. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature, 2011. vol. 476, no. 7359, pp. 214–219. DOI: 10.1038/nature10251
  4. Lossius A., Riise T., Pugliatti M., Bjørnevik K., Casetta I., Drulovic J., Granieri E., Kampman M.T. [et al.]. Season of infectious mononucleosis and risk of multiple sclerosis at different latitudes; the EnvIMS Study. Mult. Scler., 2014. vol. 20, no. 6, pp. 669–674. DOI: 10.1177/1352458513505693
  5. Bjørnevik K., Riise T., Bostrom I., Casetta I., Cortese M., Granieri E., Holmøy T., Kampman M.T. [et al.]. Negative interaction between smoking and EBV in the risk of multiple sclerosis: The EnvIMS study. Mult. Scler., 2017. vol. 23, no. 7, pp. 1018–1024. DOI: 10.1177/1352458516671028
  6. Bjørnevik K., Riise T., Casetta I., Drulovic J., Granieri E., Holmøy T., Kampman M.T., Landtblom A.-M. [et al.]. Sun exposure and multiple sclerosis risk in Norway and Italy: The EnvIMS study. Mult. Scler., 2014. vol. 20, no. 8, pp. 1042–1049. DOI: 10.1177/1352458513513968
  7. Magalhaes S., Pugliatti M., Riise T., Myhr K.-M., Ciampi A., Bjornevik K., Wolfson C. Shedding light on the link between early life sun exposure and risk of multiple sclerosis: results from the EnvIMS Study. Int. J. Epidemiol, 2019. vol. 48, no. 4, pp. 1073–1082. DOI: 10.1093/ije/dyy269
  8. Cortese M., Riise T., Bjørnevik K., Holmøy T., Kampman M.T., Magalhaes S., Pugliatti M., Wolfson C., Myhr K.-M. Timing of use of cod liver oil, a vitamin D source, and multiple sclerosis risk: The EnvIMS study. Mult. Scler., 2015, vol. 21, no. 14, pp. 1856–1864. DOI: 10.1177/1352458515578770
  9. Wesnes K., Riise T., Casetta I., Drulovic J., Granieri E., Holmøy T., Kampman M.T., Landtblom A.-M. [et al.]. Body size and the risk of multiple sclerosis in Norway and Italy: the EnvIMS study. Mult. Scler., 2015. vol. 21, no. 4, pp. 388–395. DOI: 10.1177/1352458514546785
  10. Landtblom A.M., Kristoffersson A., Boström I. Organic solvent exposure as a risk factor for multiple sclerosis: An updated review. Rev Neurol (Paris), 2019, vol. 175, no. 10, pp. 625–630. DOI: 10.1016/j.neurol.2019.07.014
  11. Hedström A.K., Hössjer O., Katsoulis M., Kockum I., Olsson T., Alfredsson L. Organic solvents and MS susceptibility: Interaction with MS risk HLA genes. Neurology, 2018. vol. 91, no. 5, pp. e455–e462. DOI: 10.1212/WNL.0000000000005906
  12. Olsson T., Barcellos L.F., Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol, 2017, vol. 13, no. 1, pp. 25–36. DOI: 10.1038/nrneurol.2016.187
  13. Avakian M.D., Dellinger B., Fiedler H., Gullet B., Koshland C., Marklund S., Oberdörster G., Safe S. [et al.]. The origin, fate, and health effects of combustion by-products: a research framework. Environ Health Perspect, 2002. vol. 110, no. 11, pp. 1155–1162. DOI: 10.1289/ehp.021101155
  14. Donaldson K., Tran L., Albert Jimenez L., Duffin R., Newby D.E., Mills N., MacNee W., Stone V. Combustionderived nanoparticles: a review of their toxicology following inhalation exposure. Part. Fibre. Toxicol., 2005. vol. 21, no. 2, pp. 10. DOI: 10.1186/1743-8977-2-10
  15. Calderon-Garciduenas L., Maronpot R.R., Torres-Jardon R., Henríquez-Roldán C., Schoonhoven R., Acuña-Ayala H., Villarreal-Calderón A., Nakamura J. [et al.]. 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., 2003. vol. 31, no. 5, pp. 524–538. DOI: 10.1080/01926230390226645
  16. van Berlo D., Albrecht C., Knaapen A.M., Cassee F.R., Gerlofs-Nijland M.E., Kooter I.M., Palomero-Gallagher N., Bidmon H.-J. [et al.]. Comparative evaluation of the effects of short-term inhalation exposure to diesel engine exhaust on rat lung and brain. Arch. Toxicol., 2010. vol. 84, no. 7, pp. 553–562. DOI: 10.1007/s00204-010-0551-7
  17. Farina F., Sancini G., Battaglia C., Tinaglia V., Mantecca P., Camatini M., Palestini P. Milano summer particulate matter (PM10) triggers lung inflammation and extra pulmonary adverse events in mice. PLoS One, 2013, vol. 8, no. 2, pp. e56636. DOI: 10.1371/journal.pone.0056636
  18. Mehindate K., Sahlas D.J., Frankel D., Mawal Y., Liberman A., Corcos J., Dion S., Schipper H.M. Proinflammatory cytokines promote glial heme oxygenase-1 expression and mitochondrial iron deposition: Implications for multiple sclerosis. Journal of Neurochemistry, 2001, vol. 77, no. 5, pp. 1386–1395. DOI: 10.1046/j.1471-4159.2001.00354.x
  19. Rose J.W., Hill K.E., Watt H.E., Carlson N.G. Inflammatory cell expression of cyclooxygenase-2 in the multiple sclerosis lesion. J. Neuroimmunol., 2004, vol. 149, no. 1–2, pp. 40–49. DOI: 10.1016/j.jneuroim.2003.12.021
  20. Heydarpour P., Amini H., Khoshkish S., Seidkhani H., Sahraian M.A., Yunesian M. Potential impact of air pollution on multiple sclerosis in Tehran, Iran. Neuroepidemiology, 2014, vol. 43, no. 3–4, pp. 233–238. DOI: 10.1159/000368553
  21. Jeanjean M., Bind M.-A., Roux J., Ongagna J.-C., de Sèze J., Bard D., Ozone L.E. NO2 and PM10 are associated with the occurrence of multiple sclerosis relapses. Evidence from seasonal multi-pollutant analyses. Environ. Res., 2018, vol. 163, pp. 43–52. DOI: 10.1016/j.envres.2018.01.040
  22. Angelici L., Piola M., Cavalleri T., Randi G., Cortini F., Bergamaschi R., Baccarelli A.A., Bertazzi P.A., Pesatori A.C., Bollati V. Effects of particulate matter exposure on multiple sclerosis hospital admission in Lombardy region, Italy. Environ. Res., 2016, vol. 145, pp. 68–73. DOI: 10.1016/j.envres.2015.11.017
  23. Oikonen M., Laaksonen M., Laippala P., Oksaranta O., Lilius E.-M., Lindgren S., Rantio-Lehtimäki A., Anttinen A., Koski K., Erälinna J.-P. Ambient air quality and occurrence of multiple sclerosis relapse. Neuroepidemiology, 2003, vol. 22, no. 1, pp. 95–99. DOI: 10.1159/000067108
  24. Roux J., Bard D., Le Pabic E., Segala C., Reis J., Ongagna J.-C., de Sèze J., Leray E. Air pollution by particulate matter PM10 may trigger multiple sclerosis relapses. Environ. Res., 2017, vol. 156, pp. 404–410. DOI: 10.1016/j.envres.2017.03.049
  25. Vojinovic 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, vol. 72, no. 1, pp. 44–49. DOI: 10.2298/vsp140121030v
  26. Bergamaschi R., Cortese A., Pichiecchio A., Gigli Berzolari F., Borrelli P., Mallucci G., Bollati V., Romani A. [et al.]. Air pollution is associated to the multiple sclerosis inflammatory activity as measured by brain MRI. Mult Scler, 2018, vol. 24, no. 12, pp. 1578–1584. DOI: 10.1177/1352458517726866
  27. Tateo F., Grassivaro F., Ermani M., Puthenparampil M., Gallo P. PM2.5 levels strongly associate with multiple sclerosis prevalence in the Province of Padua, Veneto Region, North-East Italy. Mult. Scler., 2019, vol. 25, no. 13, pp. 1719–1727. DOI: 10.1177/1352458518803273
  28. Esmaeil Mousavi S., Heydarpour P., Reis J., Amiri M., Sahraian M.A. Multiple sclerosis and air pollution exposure: Mechanisms toward brain autoimmunity. Med. Hypotheses., 2017, vol. 100, pp. 23–30. DOI: 10.1016/j.mehy.2017.01.003
  29. Palacios N., Munger K.L., Fitzgerald K.C., Hart J.E., Chitnis T., Ascherio A., Laden F. Exposure to particulate matter air pollution and risk of multiple sclerosis in two large cohorts of US nurses. Environ. Int., 2017, vol. 109, pp. 64–72. DOI: 10.1016/j.envint.2017.07.013
  30. Bai L., Burnett R.T., Kwong J.C., Hystad P., van Donkelaar A., Brook J.R., Tu K., Copes R. [et al.]. Long-term exposure to air pollution and the incidence of multiple sclerosis: A population-based cohort study. Environ. Res., 2018, vol. 166, pp. 437–443. DOI: 10.1016/j.envres.2018.06.003
  31. Tremlett H., van der Mei I.A.F., Pittas F., Blizzard L., Paley G., Mesaros D., Woodbaker R., Nunez M. [et al.]. Monthly ambient sunlight, infections and relapse rates in multiple sclerosis. Neuroepidemiology, 2008, vol. 31, no. 4, pp. 271–279. DOI: 10.1159/000166602
  32. Pashley N.E., Bind M.-A.C. Causal Inference for Multiple Non-Randomized Treatments using Fractional Factorial Designs. Cornell University Statistics, 2019. Available at: (03.06.2020).

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