New Studies Link Air Pollution, Particularly Fine... : Neurology Today - LWW Journals

New Studies Link Air Pollution, Particularly Fine Particulat... : Neurology Today

Article In Brief
Researchers behind two new papers have found associations between exposure to air pollution and neurodegenerative conditions and stroke, with one study showing that pollution may significantly increase a person's risk of experiencing a stroke within the first five days of exposure. And as climate change affects weather patterns, air pollution events like those experienced in large swaths of the US this summer are expected to be more common. Two new papers published online ahead of print in Neurology add to the growing body of evidence of the association between air pollution, particularly fine particular matter (PM2.5), and stroke and neurodegenerative conditions. Although links have been long been established between air pollution and respiratory disease, cardiovascular disease, and certain cancers, less is known about how air pollution may contribute to neurologic disease. With climate change leading to different weather patterns, the prevalence of drought, and smoke from wildfires, air pollution events like those experienced in large swaths of the US this summer are expected to be more common. As polluting emissions from the use of fossil fuels continue, the need to better understand the associations between pollution and neurologic disease and any opportunities for mitigation are increasingly important, experts told Neurology Today. One study, published Sept. 27, found that exposure to air pollution may significantly increase a person's risk of experiencing a stroke within the first five days of exposure. The global meta-analysis included more than 110 observational or interventional studies examining the correlation between short-term exposure to air pollutants and ischemic stroke, involving more than 18 million stroke cases, and found that the risk of stroke increased by nearly 30 percent in people exposed to nitrogen dioxide up to five days prior to their stroke. The risk increased for other pollutants as well, including carbon monoxide (26 percent), sulfur dioxide (15 percent), and ozone exposure (5 percent). Pollutant exposure also increased the risk of dying from a stroke by 60 percent in the case of sulfur dioxide and 33 percent in the case of nitrogen dioxide. Exposure to PM2.5 particles, which are less than 2.5 microns in diameter, was associated with a 15 percent increased risk of stroke, the study found. “To our knowledge, this is the most updated and comprehensive systematic review and meta-analysis since 2015, that was conducted to accommodate the rapidly growing literature in the last nine years, included all the air pollutants as well as explored its impact on stroke incidence and related mortality,” wrote the authors, led by Ahmad Tubasi, a researcher with the faculty of medicine at the University of Jordan. “The association between particulate matter, gaseous pollutants and the incidence and mortality of stroke demonstrates a notable temporal link.”

“Given that stroke is one of the leading causes of morbidity and mortality both in the United States and globally, and that air pollution is such a prevalent exposure, improving air quality standards could have a very significant impact.”—DR. MARIANTHI-ANNA KIOUMOURTZOGLOU

The authors also noted that the overall association between exposure to pollutants and stroke incidence may in fact be underestimated in the meta-analysis, given that existing literature suggests that approximately 50 percent of patients with stroke do not seek care until one day after experiencing their initial symptoms. In the second study, published Oct. 26 in Neurology, investigators from Barrow Neurological Institute and Washington University in St. Louis assessed the nationwide geographic relationship between Parkinson's disease (PD) and air pollution, particularly PM2.5, finding that the relative risk for incident PD increased by 24 percent when comparing zip+4 neighborhoods with the lowest to the highest quartile of PM2.5 throughout the US. The authors, led by Brittany Krzyzanowski, PhD, an assistant professor at Barrow Neurological Institute in Phoenix, conducted a population-based analysis of Medicare beneficiaries aged 66 to 90 in 2009, coded to US counties and zip code+4 neighborhoods. Among more than 21 million Medicare beneficiaries that year, 89,390 had incident PD. Using innovative geographic analytic techniques, they found the association between PM2.5 and PD varied in strength by region. The strongest link between PM2.5 and incident PD was in the Rocky Mountain region, particularly Lake County, CO, and its surrounding counties. They observed a weaker association between PM2.5 and incident PD in a PD hot spot in the Mississippi-Ohio River Valley. The area, which includes parts of Tennessee and Kentucky, has a 19 percent greater risk for PD compared with the rest of the country. The relative weakness of that association was likely because of a “plateau effect,” the authors noted, as that region has some of the highest levels of particulate matter in the nation. “People in the Rocky Mountain region overall have a lower risk of PD, which is why the association between PM2.5 and incident PD in that area stands out. In the Rocky Mountains, moving from one neighborhood with low air pollution to a different neighborhood with higher air pollution yields a very noticeable increase in risk,” Dr. Krzyzanowski said. “But, in fact, the ‘hot spot’ in the Mississippi-Ohio River Valley is a major point of interest because these associations are harder to detect with our geographic methods. That's because at the higher ends of air pollution, risk seems to plateau, so the geographic methods we used will not identify as strong of a relationship in areas with both high incidence of PD and high levels of PM2.5 like the southeast/south central part of the nation. The fact that we were still able to see this association despite the plateau effect is remarkable.” Going forward, Dr. Krzyzanowski plans to dive deeper into the neurotoxic roles of individual subcomponents of air pollution. Specifically, one thing that comes to mind is the value of subcomponent analyses. “PM2.5 is made up of a variety of different subcomponents—including heavy metals and combustion particles from vehicle exhaust,” she explained. “Air pollution is not the same everywhere—the subcomponents of particulate matter vary based on the region and source. Since PD incidence also varies by region, that captured our interest. Some subcomponents of air pollution could be more neurotoxic than others.”

A Growing Consensus
Both of the two studies build on other recent research strongly suggesting a connection between air pollution and neurologic disease, including a 2020 study in Lancet Planetary Health that found that exposure to annual mean PM2.5 in the US is significantly associated with an increased hazard of first hospital admission with PD and Alzheimer's disease (AD) and related dementias, and a February 2023 study in Stroke, which found an association between long-term exposure to common air pollutants, even at levels below national limits, and higher all-cause 30-day readmissions after ischemic stroke. “Within the last several years, we have seen an increasing number of publications and supporting data to suggest that certain forms of air pollution play some role in neurodegenerative disease as well as stroke,” said Briana De Miranda, PhD, assistant professor of neurology at the University of Alabama-Birmingham Heersink School of Medicine, whose laboratory studies the effects of environmental toxicants in the risk for PD and related neurodegenerative conditions. “Especially in a condition like PD, where the majority of the population is idiopathic, without a known family history or genetic mutation, there is an inherent question as to how much disease risk is being caused by an environmental exposure. This paper emphasizes that the environment can impact chronic neurologic disease pretty significantly, especially in diseases for which the risk increases as we age.” Marianthi-Anna Kioumourtzoglou, MSPH, ScD, associate professor of environmental health sciences at the Columbia University Mailman School of Public Health, also published investigations into links between air pollution and neurologic disease, including a 2021 paper in the journal Environmental Research on PD aggravation in association with fine particle components in New York State and a 2017 study in Environmental Health Perspectives on the relationship between long-term exposure to PM2.5 and time to first hospitalization for PD, AD and dementia. “Their findings are very similar to ours; when fine particulate matter pollution goes up, incident cases of PD also go up,” she says. “This new study is very comprehensive, with more than 21 million Medicare enrollees, in theory capturing most Americans over 65 and most incident cases of PD.”

Consistent With Other Studies
The fact that the stroke meta-analysis selected for only ischemic stroke is a particular strength, said Erin Kulick, PhD, MPH, assistant professor of epidemiology and biostatistics at Temple University College of Public Health, an epidemiologist with a background in both neuroepidemiology and environmental health sciences whose research focuses on environmental and social determinants of brain aging. “A lot of the existing literature looks at all-cause strokes rather than focusing on specific types, but we believe that different types of stroke may manifest differently in the face of exposures to air pollutants. Many people in the field think that ischemic stroke has the strongest association with air pollution. Being able to pull together such a large body of existing studies really solidifies that this is a true relationship—that air pollution, especially in the short term, is a big trigger for stroke.” Although the effect size might not appear extremely large at the individual level, air pollution is such a prevalent exposure that at a population level these factors ultimately have an extremely significant impact, Dr. Kioumourtzoglou said. “Given that stroke is one of the leading causes of morbidity and mortality both in the United States and globally, and that air pollution is such a prevalent exposure, improving air quality standards could have a very significant impact.”

Impact on Neurologic Practice
The substantial literature connecting air pollution with neurologic disease should influence neurologic practice, said Dr. De Miranda. “Getting an environmental history on a patient is important. Just as we have standards for clinical assessments, it would be good for leading organizations within neurology to develop a standard assessment for environmental exposures as well, both for clinical practice and for future research. It would be helpful if we could start gathering all this data on all our patients to the extent we can measure it. We need more studies that monitor as many environmental factors as we can. A lot of our environmental exposure studies come from surveys and self-reporting, and we know there are limitations to the accuracy of that data, so having monitoring systems that integrate from biological health research to environmental health research would also be helpful.” “I think there is enough evidence at this point that we need to start thinking of these environmental factors such as air pollution as another risk factor for neurologic disease and including them in how we assess and counsel our patients,” Dr. Kulick agreed. “Even in the last five to 10 years, we have seen many more acute situations of air pollution, such as with the wildfires that affected so much of the US this past year, and we've also seen the effects of long-term exposure to lower levels of air pollution. Air pollution is becoming an ubiquitous exposure that we all experience on any given day.” How can neurologists advise their patients to mitigate these risks? “At the individual level, we are developing more and more tools to help us with that,” Dr. De Miranda noted. “You can filter your water and your air and monitor some of what's in your air. Home air purifiers are much more widely available than they were pre-pandemic, which could be especially beneficial for people who live in areas with a high burden of pollution.” In June, amid the summer wildfires, the US Department of State's global air quality monitoring and climate resilience lead, Stephanie Christel Meredith, posted a public article about her own experience with low-cost air-quality sensors and room air cleaners. “The results showed the benefits of what I tell people to do every day—close your windows and doors and run your room air cleaner—to help mitigate their exposure,” she wrote. “In less than 30 minutes, the Air Quality Index (AQI) in my office dropped more than 60 points. My windows were closed to begin with, but this dropped air pollution in the room from 170 AQI to 108. Still not great, but a big improvement in a short amount of time. Over the next two hours, I watched it drop into moderate levels and stay there.” Another tool commonly used since the COVID-19 pandemic is the N95 mask. “Most people now have them at home and are used to wearing them,” said Dr. Kulick. “These definitely reduce risk of airborne exposures and are one easy way your patients can protect themselves, particularly if they live in high-exposure areas or during times of particularly poor air quality. Even if they don't think they are at high individual risk—my family and I wore masks this summer when the air quality was so bad—and I would definitely suggest that.” Air-quality apps such as Plume Lab also can give real-time information as to the level of immediate risk from air pollution. Of course, there is only so much that can be done at the individual level and in doctor-patient interactions to mitigate the impact of air pollution exposure. “It is essential from a policy perspective that we incorporate environmental concerns into our advocacy efforts to improve the burden of neurologic disease as well as other health impacts, such as cancer and heart disease,” said Dr. De Miranda. “Are we harming our ability to live a long health span because we are living in extremely polluted environments?” She cited research from University of Montana neuropathologist Lilian Caldern-Garcidueas, MD, PhD, including a 2020 paper in Environmental Research that found early signs of AD beginning in childhood in Mexico City, one of the most polluted cities in the world. Youth in that city have lifetime exposures to PM2.5 and ozone (O3) well above standards for safe exposure. The study reviewed 134 consecutive autopsies of young people who died at age 30 or younger and found that they could stage AD progression in 99.25 percent of them. “Even in young people who had died from non-neurologic causes, there was amyloid plaque in their brains,” Dr. De Miranda said. “A major concern is that as more people spend their whole lives living with air pollution, could we see the onset of neurodegenerative disease at younger and younger ages?” And as with so many aspects of public health, systemic inequities play a key role in the impact of air pollution on neurologic disease, as people from lower socioeconomic groups and marginalized backgrounds are more likely to live in environmentally contaminated areas with more pollution, have less economic freedom to leave higher-risk areas or jobs that expose them to more air pollution (such as farm laborers and delivery workers forced to work outside during the summer wildfires), and are less able to afford mitigation resources such as air purifiers. Many people are surprised when they learn about the effects of air pollution on neurodegeneration, said Dr. Kioumourtzoglou, but she pointed out that major papers on the topic started being published by 2009. “There needs to be better dissemination of this information to the public,” she said “It needs to be much clearer and in simpler terms, and much more widespread. Ultimately, addressing the neurologic risks as well as the other health risks of air pollution primarily comes down to local, state, and federal policies. While there are mitigation steps that individuals can take, for the most part, this exposure is involuntary.”

Disclosures
None of the individuals interviewed had disclosures.