#MSPrevention: air pollution

Barts-MS rose-tinted-odometer: ★★

As MS is highly likely to be a preventable disease we should be doing everything we can to reduce our exposure to modifiable risk factors. Smoking, passive smoking, solvent exposure and air pollution have all been linked to an increased incidence of MS. It has always been argued that air pollution may work by acting as a filter for ultraviolet light and hence increases one’s risk of getting MS by reducing UVB exposure, which is important for vitamin D synthesis in the skin. However, I am not sure this is the case as common to all these exposures, including air pollution, is inflammation in the lungs. 

The current hypothesis is that inflammation in the lungs changes or alters proteins via a process called post-translational modification, which converts normal proteins in highly immunogenic autoantigens that trigger autoimmune disease. There is good support for the latter hypothesis in rheumatoid arthritis, but to the best of my knowledge outside of animal models, the evidence in MS remains speculative. Saying this who wouldn’t want to breathe clean air if one of the benefits is a lower risk of MS? 

The study below from Padua Province in Italy shows quite a strong correlation (r-0.89) between exposure to particulate matter in the air greater than 2.5  micrometres (PM2.5) and the prevalence of MS. Some epidemiologists say that when you start seeing R-values close to 0.9 it is hard to ignore them and suggest the relationship could be causal. I am not sure about this, but it is clear that we need to more interventional studies, to reduce air pollution, and track what happens to MS incidence. 

Air pollution over London.

In relation to the issue of air quality, there was a landmark ruling from an inquest yesterday that linked the tragic death of a nine-year-old girl, Ella Adoo-Kissi-Debrah, who died following an asthma attack 9 years ago to air pollution. Legal pundits have stressed the importance of this case, which will now create the legal precedent for the UK to modify its clean air act. The importance of the latter cannot be ignored as it may lead to a drop in the incidence of many diseases linked to air pollution including MS. 

The question we also need to ask ourselves is there anything we can do to address the problem of air pollution in low- and middle-income countries that are all seeing a rise in MS incidence? Let’s hope as we transition from a carbon-energy economy to other cleaner forms of energy we will see this problem improve across the world.

Arianna et al. Association of Multiple Sclerosis with PM 2.5 levels. Further evidence from the highly polluted area of Padua Province, Italy.  Mult Scler Relat Disord. 2020 Dec 6;48:102677. doi: 10.1016/j.msard.2020.102677. Online ahead of print.

Background: Fifty years of epidemiological survey and intra-regional differences in prevalence suggest that environmental factors may be associated with increased multiple sclerosis (MS) risk in Northern Italy. Based on the findings of a previous study carried out in the highly polluted Padan Plain, we further explored the relationship between PM2.5 levels and MS prevalence by comparing bordering areas characterized by quite different environmental conditions, namely the Municipality of Padua and the special protected zone (SPZ) of the Euganean Hills Regional Park, located 15 km from the City.

Methods: Three territories were identified; 1) the SPZ, extending over an area of 15.096 hectares and having a total population of 23,980 inhabitants, 2) the urban area of Padua, with a total population of 210,440 inhabitants and repeatedly recognized by the European Environmental Agency as one of the most polluted cities of Europe, 3) the Intermediate Zone (IZ), i.e., the area in between the previous two, including part of the urban territories of eight villages adjacent to the SPZ. Demographic and socio-economical data were obtained from official government sources (www.istat.it and http://www.regione.veneto.it). All Italian MS patients residing in these three areas on December 31, 2018, were registered. PM2.5 concentrations (annual average 1998-2018, μg/m3) were measured by satellite. The correlation between PM2.5 concentrations and MS prevalence was analysed.

Results: MS prevalence was significantly higher in Padua City (265/100.000) compared to both the SPZ of the Euganean Hills Park (160/100,000; p < 0.0001) and the IZ (194.4/100,000). Prevalence strongly associated with the annual average concentration of PM2.5 (r = 0.89 p < 0.00001).

Conclusion: In the Province of Padua, one of the most polluted areas of Europe, MS prevalence is strongly associated with PM2.5 exposure. Our findings suggest that air pollutants may be one of the possible environmental risk factors for MS in the Veneto Region of Italy.

Crowdfunding: Have you supported Prof G’s ‘Bed-to-5km Challenge’ yet? Please do, all the money collected is going towards supporting MS research. 

CoI: multiple

Twitter: @gavinGiovannoni                                              Medium: @gavin_24211

Air pollution and MS

We know that smoking, passive smoking and solvent exposure increase your risk of getting MS. The hypothesis, supported by animal work, suggests these risk factors alter antigens or proteins in the lung that then trigger autoimmunity. In other words, the altered proteins are interpreted as being foreign by the immune system. 

Particulate air pollution is another respiratory toxin that has been studied in Iran and is associated with an increased prevalence of MS. I suspect that particulate matter air pollution also increases your risk of getting MS based on similar mechanisms to smoking and solvent exposure. 

Another aspect of particulate matter air pollution exposure is that it drives comorbidities and is therefore likely to make MS progress more quickly. The second paper (below) in this week’s BMJ is quite shocking in that it shows you how high the health burden is for particulate air pollution, at a general population level. Is there anything we can do about this? Yes, there is. We need to nudge our politicians whenever we can to enact legislation to clean up the air that we have to breathe.  I am aware that there are retrograde steps in the US to reverse some of the clean air legislation; this should be resisted. My heart goes out to people living in low- and middle-income countries who will have to wait for a generation or two to get to the point when air pollution drops to safer levels.

Why should people with MS be exposed to unnecessarily high levels of air pollution that are likely to make their MS worse? 

Why should people at high risk of getting MS, be exposed to environmental pollutants that may push them over the “autoimmune tipping point” resulting in them developing MS?

Part of our lifestyle and wellness campaign is focusing on environmental health; air pollution is one of the things that impact wellness. Our marginal gains management philosophy has just acquired another component; environmental pollution. Do you agree? 

Heydarpour  et al. Potential impact of air pollution on multiple sclerosis in Tehran, Iran. Neuroepidemiology. 2014;43(3-4):233-8.

BACKGROUND: Multiple sclerosis (MS) incidence has dramatically increased in Tehran, Iran. The health impact of air pollution in Tehran underscores the attention to a possible association to this environmental risk factor. In this study, the authors aimed to analyze the spatial distribution of prevalent MS cases and their association with the spatial patterns of air pollution.

METHODS: Patient records meeting McDonald’s criteria for definite MS diagnosis with disease onset during 2003-2013 were obtained. Next, the location of 2,188 patients was successfully geo-referenced within Tehran metropolis by geographic information system (GIS) bureau of Iran’s post office based on their phone numbers. A cluster analysis was performed using the average nearest neighbor index (ANNI) and quadrat analysis. The long-term exposures of MS patients to particulate matter (PM10), sulfur dioxide (SO2), nitrogen oxide (NO), nitrogen dioxide (NO2), and nitrogen oxides (NOx) were estimated using the previously developed land use regression models.

RESULTS: Prevalent MS cases had a clustered pattern in Tehran. A significant difference in exposure to PM10, SO2, NO2, and NOx (p < 0.001) was observed in MS cases compared with controls.

CONCLUSION: This study revealed the potential role of long-term exposure to air pollutants as an environmental risk factor in MS.

Wei et al. Short term exposure to fine particulate matter and hospital admission risks and costs in the Medicare population: time stratified, case-crossover study. BMJ. 2019 Nov 27;367:l6258. doi: 10.1136/bmj.l6258.

OBJECTIVE: To assess risks and costs of hospital admission associated with short term exposure to fine particulate matter with diameter less than 2.5 µm (PM2.5) for 214 mutually exclusive disease groups.

DESIGN: Time stratified, case-crossover analyses with conditional logistic regressions adjusted for non-linear confounding effects of meteorological variables.

SETTING: Medicare inpatient hospital claims in the United States, 2000-12 (n=95 277 169).

PARTICIPANTS: All Medicare fee-for-service beneficiaries aged 65 or older admitted to hospital.

MAIN OUTCOME MEASURES: Risk of hospital admission, number of admissions, days in hospital, inpatient and post-acute care costs, and value of statistical life (that is, the economic value used to measure the cost of avoiding a death) due to the lives lost at discharge for 214 disease groups.

RESULTS: Positive associations between short term exposure to PM2.5 and risk of hospital admission were found for several prevalent but rarely studied diseases, such as septicemia, fluid and electrolyte disorders, and acute and unspecified renal failure. Positive associations were also found between risk of hospital admission and cardiovascular and respiratory diseases, Parkinson’s disease, diabetes, phlebitis, thrombophlebitis, and thromboembolism, confirming previously published results. These associations remained consistent when restricted to days with a daily PM2.5 concentration below the WHO air quality guideline for the 24 hour average exposure to PM2.5. For the rarely studied diseases, each 1 µg/m3 increase in short term PM2.5 was associated with an annual increase of 2050 hospital admissions (95% confidence interval 1914 to 2187 admissions), 12 216 days in hospital (11 358 to 13 075), US$31m (£24m, €28m; $29m to $34m) in inpatient and post-acute care costs, and $2.5bn ($2.0bn to $2.9bn) in value of statistical life. For diseases with a previously known association, each 1 µg/m3 increase in short term exposure to PM2.5 was associated with an annual increase of 3642 hospital admissions (3434 to 3851), 20 098 days in hospital (18 950 to 21 247), $69m ($65m to $73m) in inpatient and post-acute care costs, and $4.1bn ($3.5bn to $4.7bn) in value of statistical life. 

CONCLUSIONS: New causes and previously identified causes of hospital admission associated with short term exposure to PM2.5 were found. These associations remained even at a daily PM2.5 concentration below the WHO 24 hour guideline. Substantial economic costs were linked to a small increase in short term PM2.5.

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