Air pollution may be another environmental risk factor for developing multiple sclerosis (MS), new research suggests.
A large cohort study of almost 550,000 individuals living in Italy showed that participants living in areas with high levels of pollutants had a significantly greater risk of developing MS than those who lived in areas with low levels of pollutants.
The findings further confirm a relationship between exposure to air pollutants and risk for MS that has been shown in previous research, Roberto Bergamaschi, MD, PhD, director of the Multiple Sclerosis Center, IRCCS Mondino Foundation, Pavia, Italy, told Medscape Medical News.
“Countermeasures that cut air pollution can be important for public health, not only to reduce deaths related to cardiac and pulmonary diseases but also the risk of chronic autoimmune diseases such as MS,” Bergamaschi said.
The findings were presented at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual/online meeting because of the COVID-19 pandemic.
Several environmental factors may trigger an abnormal immune response that manifests in MS. The most studied of these are low vitamin D level, cigarette smoking, and an unhealthy diet, Bergamaschi said.
However, “other environmental factors deserve to be studied ― pollution included,” he added.
Among the most toxic air pollutants are particulate matter (PM), which is a mixture of fine solid and liquid particles suspended in the earth’s atmosphere. PM may range from 2.5 microns (PM2.5) to 10 microns (PM10) in diameter.
The main sources of such pollutants are household and commercial heating (53%) and industrial activities (17%), followed by road vehicle and non–road vehicle use, agriculture, and electricity production.
The World Health Organization estimates that more than 3.2 million individuals worldwide die prematurely every year because of lung cancer, cardiovascular disease, and other diseases related to air pollutants, said Bergamaschi.
Epidemiologic research has uncovered a relationship between air pollution and MS. A large American study published in 2008 in Science of the Total Environment showed a significant association between MS prevalence and PM10 levels (P < .001).
Other studies have shown an increase in the number of clinical relapses of MS that were linked to air pollution.
The current investigators assessed the association between PM2.5 levels and MS prevalence in the northern province of Pavis, which has a population of 547,251 individuals in 188 municipalities.
Pavia is situated in a flat territory that encompasses the highly industrialized regions of Piedmont, Lombardy, Emilia-Romagna, and Veneto. It has a high level of anthropogenic emissions, or environmental pollutants originating from human activity, Bergamaschi reported.
The region also has “peculiar” geographical features that “favor the accumulation of pollutants,” such as the natural barrier of the Alps in the north and low wind speed, he said.
The researchers identified 927 individuals with MS (315 male and 612 female) in the province. The overall MS prevalence rate was 169.4 per 100,000 population (95% confidence interval [CI], 158.8 – 180.6), which is 10-fold higher than 50 years ago, Bergamaschi said. In addition, this MS prevalence is higher than that in the United States, which is about 150 per 100,000 population.
Using sophisticated Bayesian disease mapping, the investigators looked for clusters of MS. They also gathered emission data for PM2.5 from 2010 to 2017 from the European Monitoring and Evaluation Programme database. They then divided the region on the basis of average winter concentrations of PM2.5.
Three distinct lateral areas of air pollution were identified. The more northern region, which includes the large urban center of Milan, had the highest level of air pollution. Concentrations decreased the further south the investigators looked.
After adjusting for age, urbanization (population density), and deprivation index, results showed that living in areas with high levels of pollutants was associated with increased MS risk.
When controlling for PM2.5 pollution, participants in urban areas had an increased risk for MS compared with rural dwellers (relative risk [RR], 1.16; 95% CI, 1.04 – 1.30; P = .003)
Bergamaschi said it is unclear whether this risk is higher for certain types of MS. “To my knowledge, no study has analyzed possible relationships between MS phenotypes and air pollution,” he noted.
Vitamin D’s Role?
Several mechanisms might help explain the relationship between air pollution and MS risk, he added. These include oxidative stress, which results in cell damage, inflammation, and proinflammatory cytokine release.
Vitamin D also likely plays some role, Bergamaschi said. Upon penetrating the lower strata of the earth’s atmosphere, ultraviolet B radiation is absorbed and scattered by suspended pollutants.
Several studies have highlighted the correlation between living in a polluted area and vitamin D hypovitaminosis; “so air pollution can contribute to increasing the risk of MS by reducing vitamin D synthesis,” he said.
Recent research has also shown that air pollution is associated with a higher risk for other autoimmune disorders, including systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes mellitus.
However, pollution alone is only part of the picture. MS prevalence in highly populated and polluted countries such as China and India is low, with no more than 30 to 40 cases per 100,000 population, Bergamaschi noted.
“This discrepancy is explained by different genetic backgrounds. While Caucasians are particularly susceptible to MS, Asians are not,” he said.
Study limitations cited included a possible bias because the analysis did not include other possible contributing risk factors, particularly other pollutants, Bergamaschi said.
Commenting for Medscape Medical News, Lily Jung Henson, MD, chief of neurology at Piedmont Healthcare in Stockbridge, Georgia, said the findings provide “a fascinating glimpse” into possible causative factors for MS and warrant further investigation.
“This research also suggests other opportunities to look at, such as progression of the degree of air pollution and the incidence of MS over time,” said Henson, who was not involved with the study.
Bergamaschi and Jung Henson have reported no relevant financial relationships.
Congress of the European Academy of Neurology (EAN) 2020: Abstract 1957. Presented May 23, 2020.