Air Pollution & Autoimmune Disease: Adverse Health Outcomes
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During the last century, researchers have been keen on understanding the consequences of human beings’ separation from nature, looking for links between this relationship and its impact on both the planet and on human health.1 The idea that human beings are distinct from nature, particularly in Western culture, is steeped in a complex narrative that continues to fundamentally change the health of our planet. These values form the foundation of modern anthropocentrism, a system of beliefs that places humans as separate from and superior to the non-human world. We now know that human influence can alter everything from the diversity of ecosystems and the geochemistry of the planet to the abiotic—the hydrosphere, lithosphere, and atmosphere—and that this impact can ultimately shape human health.2 Subtopics of this narrative, including climate change, the loss of biodiversity, and population growth, are as diverse as they are perceptive.3,4 For the purposes of this article, we will explore a possible clinical link between the degradation of air quality through pollution and its effect on autoimmunity.2,3,5 In light of these findings, how can clinicians work with patients to improve biotransformation and the elimination of toxicants?
Air Pollution and Immune Function
Individuals suffering from chronic respiratory allergic diseases such as asthma and allergic rhinoconjunctivitis are at particular risk from the effects of both air pollution and climate change due to increased exposure to pollen, as well as the increased concentration and distribution of air pollutants such as ozone, nitric oxide, and other volatile organic chemicals.3 The inhalation of these air pollutants has been found to cause inflammation and increased mucosal permeability within the airways, ultimately allowing increased barrier penetrance by allergens. This is mediated by oxidative stress—whereby oxidants produced by pollutants within respiratory mucosal epithelial cells trigger the release of inflammatory mediators, causing the destruction and apoptosis of respiratory mucosal cells and eventually leading to bronchial hyperreactivity.3 Allergic and inflammatory diseases may also trigger autoimmune conditions by relaxing the controls that normally eliminate newly produced, self-reactive B cells.6 Early exposure to air pollutants has also been linked to an increased risk of incident asthma, allergic rhinitis, and eczema in children.3
The reality is that we are basically swimming in a soup of toxins. We are exposed to a wide range of things, some of which we can eliminate very quickly—but a lot of others stay in our body. The idea is that those toxicants can act synergistically to cause disease in susceptible individuals.
– Robert Rountree, MD
Air pollution has become a significant concern for its serious toxicological impact, not only on the environment but also on human health.2 Large-scale human activities such as the use of industrial machinery, power-producing stations, combustion engines, and cars produce the majority of environmental pollutants.2 Six major air pollutants are studied by the World Health Organization (WHO), including particle pollution, ground-level ozone, carbon monoxide, sulfur oxides, nitrogen oxides, and lead. Pollutants with the strongest evidence for public health concern include particulate matter (PM), ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2).7,8 Chronic exposures to these chemicals may lead to chronic diseases, as they are known to have disastrous effects on all components of the environment, including living organisms like humans.2 Short-term exposure to air pollution can cause headaches, nausea, and dizziness while long-term exposure may affect the nervous,9 cardiovascular, and respiratory10 systems. Air pollution may increase the incidence of adult mortality11 and may act as a trigger for some autoimmune diseases like type 1 diabetes (T1D) and rheumatoid arthritis (RA).7,10,12
Type 1 Diabetes
The incidence and prevalence of T1D is increasing in the world, based on data from 1980-2019.13 It has been suggested that air pollution exposure may contribute to the development of T1D.14 Ambient air pollution—emitted by industries, households, cars, and trucks—is aligned with an increased risk of cardiovascular disease morbidity and mortality; patients with T1D and T2D diabetes may bear a disproportionately greater risk of cardiovascular disease associated with increases in air pollution.10 Exactly why individuals with diabetes are particularly vulnerable to the effects of ambient air pollution is poorly understood, but evidence suggests that mechanisms associated with proinflammatory responses may include chronic inflammation/oxidative stress, chronic autonomic dysfunction resulting in arterial stiffness, or imbalances in arterial vasoactive mediators.10,15 The studies detailed below explore environmental exposures and mechanisms in relation to T1D.
In 2019, in a racially and geographically diverse cohort of youth with T1D, researchers observed strong positive associations of elemental carbon (EC) average week exposures with biomarkers of inflammation, including interleukin-6 (IL-6) and C-reactive protein (hs-CRP).10 This research is significant in part because very few studies to date have examined the relationship of EC with inflammatory biomarkers, and those have been primarily conducted on healthy adults. This study is one of the first to show that a young population, which is more vulnerable to cardiovascular disease due to T1D, may be at risk for ambient air pollution–related inflammation.10
A 2020 retrospective population-based cohort study examining the association between maternal and early-life exposures to common ambient air pollutants (NO2, PM2.5, O3, and oxidant capacity [Ox]) and the incidence of pediatric diabetes in children up to six years of age found that ozone (O3) exposure during the first trimester of pregnancy was associated with an increased risk of pediatric diabetes incidence.16
WHO reports that air pollution contributed to seven million premature deaths in 2012 globally; this finding more than doubles previous estimates and confirms that air pollution is now the world’s largest single environmental health risk.17 In Poland, reports from the European Environment Agency claim that daily PM10 concentration standards are exceeded.14 The concentration of particles with a diameter lower than 10 micrometers (PM10) consisting of various elements of the organic and nonorganic matter is an acknowledged indicator of air pollution; they are also called fine particles. PM10 coarse particles can bond with various chemical compounds, heavy metals, or microorganisms and can be transferred over long distances, causing negative health effects. The prevalence of T1D in children from Poland increased 1.5 times within a five-year observation study, and researchers have begun to analyze the concentrations of PM10 and gaseous pollutants (NO2, NOx, SO2, CO) in the air and the number of new cases of T1D in children. PM10 emissions were mainly coming from roads with the greatest traffic volume. In 2020, Michalska et al found there was a relationship between the number of new cases of T1D and the annual average concentrations of PM10, SO2, and CO in ambient air.14 These results are consistent with other studies.18-20 Epidemiological evidence linking ambient air pollution to pediatric T1D diabetes remains mixed.16
A 2020 systematic review and meta-analysis found significant associations between some markers of air pollution (ozone, proximity to road traffic, and PM2.5) and RA.21 Several other studies suggest that exposure to air pollution may increase the risk of RA,7,22-23 and epidemiological evidence indicates a significant association between the risk of RA and exposure to environmental factors such as cigarette smoke, dioxin, noise, and traffic-related air pollution.7,24-25
Specifically, a 2019 nested case-control 12-year cohort database study of 1,025,340 participants in South Korea showed that a one-year exposure to carbon monoxide (CO) and ozone (O3) in adults was associated with an increased risk of RA.26 In the one-year air pollution exposure model, when researchers compared subjects who had been exposed to the lowest quartile of O3 exposure, the risk of RA increased significantly in the highest quartile of one-year ozone exposure by approximately 1.35-fold. Furthermore, when they used a two-pollutant model for CO and O3, the effect became larger than the single-pollutant model.26 These findings are largely consistent with those from previous studies on air pollution and RA, as well as a recent 2020 study in Kuwait. Here, the origin of air pollutants are oil refineries, traffic, and power plants (mostly using fossil fuels), which are thought to be sources of SO2 and NO2; NO2 and SO2 were found to be significant risk factors for RA activity, with 7% positive correlation with disease activity indices.7 These findings are largely consistent with those from other studies on air pollution.24-25,27-28
Another fascinating 2019 study examining the relationship between early-life exposure to air pollution and RA suggest the following:29
- The development of rheumatoid arthritis is sensitive to air pollution exposure in early life.
- Even a single exposure to extreme air pollution can have long-term effects.
- Exposure to London’s Great Smog during infancy increased arthritis rates in those >50 by 23.4 percentage points.29
Furthermore, these findings are consistent with those of shorter-term, correlational studies and indicate that health effects of air pollution exposure may span decades.29
Human beings depend on a healthy earth to maintain a vibrant quality of life, and while the role of protecting the environment traditionally lies outside of the health sector, we know that human health is fundamentally tied to our surroundings. Medical research continues to evolve in such a way that furthers this understanding, offering a profound opportunity to enhance both planetary health and human well-being. Furthermore, the medical community has learned a great deal over the last few decades about how toxicants affect the human body, where they originate, and how to improve our ability to detoxify.
Understanding toxicity and taking practical steps to improve biotransformation and the elimination of toxicants are essential and critical pieces in any functional medicine approach to health and well-being. Functional medicine educates clinicians about the biochemistry and genetics of biotransformation pathways, the connection between organ system dysfunction and potential toxic exposures, the laboratory evaluations necessary in working up a toxin-exposed patient, and various treatment approaches. Learn more about human health and the environment by following the links provided below.
Learn more about the connection between environmental toxins and autoimmune disease at IFM’s 2023 Annual International Conference (AIC). Expert clinician Aly Cohen, MD, FACR, will present a plenary session discussing evidence-based data on everyday chemicals that we put in, on, and around our bodies and how they contribute to diseases of the immune system. She will provide practical tips and resources to enable and empower patients to limit environmental exposures in order to prevent disease, better manage current conditions, and improve overall well-being. Dr. Cohen will also lead and concurrent session entitled A Rheumatologist’s Integrative Approach to Autoimmune Disease.
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- Seymour V. The human-nature relationship and its impact on health: a critical review. Front Public Health. 2016;4:260. doi:3389/fpubh.2016.00260
- Manisalidis I, Stavropoulou E, Stavropoulos A, Bezirtzoglou E. Environmental and health impacts of air pollution: a review. Front Public Health. 2020;8:14. doi:3389/fpubh.2020.00014
- Ray C, Ming X. Climate change and human health: a review of allergies, autoimmunity and the microbiome. Int J Environ Res Public Health. 2020;17(13):4814. doi:3390/ijerph17134814
- Sandifer PA, Sutton-Grier AE, Ward BP. Exploring connections among nature, biodiversity, ecosystem services, and human health and well-being: opportunities to enhance health and biodiversity conservation. Ecosystem Services. 2015;12:1-15. doi:1016/j.ecoser.2014.12.007
- Adami G, Pontalti M, Cattani G, et al. Association between long-term exposure to air pollution and immune-mediated diseases: a population-based cohort study. RMD Open. 2022;8(1):e002055. doi:1136/rmdopen-2021-002055
- Hampe CS. B cells in autoimmune diseases. Scientifica. 2012;215308. doi:6064/2012/215308
- Alsaber A, Pan J, Al-Herz A, Alkandary DS, Al-Hurban A, Setiya P. Influence of ambient air pollution on rheumatoid arthritis disease activity score index. Int J Environ Res Public Health. 2020;17(2):416. doi:3390/ijerph17020416
- Markozannes G, Pantavou K, Rizos EC, et al. Outdoor air quality and human health: an overview of reviews of observational studies. Environ Pollut. 2022;306:119309. doi:1016/j.envpol.2022.119309
- Zhang X, Chen X, Zhang X. The impact of exposure to air pollution on cognitive performance. Proc Natl Acad Sci U S A. 2018;115(37):9193-9197. doi:1073/pnas.1809474115
- Puett RC, Yanosky JD, Mittleman MA, et al. Inflammation and acute traffic-related air pollution exposures among a cohort of youth with type 1 diabetes. Environ Int. 2019;132:105064. doi:1016/j.envint.2019.105064
- Anderson ML. As the wind blows: the effects of long-term exposure to air pollution on mortality. J Eur Econ Assoc. 2020;18(4):1886-1927. doi:1093/jeea/jvz051
- Vojdani A. A potential link between environmental triggers and autoimmunity. Autoimmune Dis. 2014;2014:437231. doi:1155/2014/437231
- Mobasseri M, Shirmohammadi M, Amiri T, Vahed N, Hosseini Fard H, Ghojazadeh M. Prevalence and incidence of type 1 diabetes in the world: a systematic review and meta-analysis. Health Promot Perspect. 2020;10(2):98-115. doi:34172/hpp.2020.18
- Michalska M, Zorena K, Waz P, et al. Gaseous pollutants and particulate matter (PM) in ambient air and the number of new cases of type 1 diabetes in children and adolescents in the Pomeranian Voivodeship, Poland. Biomed Res Int. 2020;2020:1648264. doi:1155/2020/1648264
- Jacobs L, Emmerechts J, Mathieu C, et al. Air pollution-related prothrombotic changes in persons with diabetes. 2010;118(2):191-196. doi:1289/ehp.0900942
- Elten M, Donelle J, Lima I, et al. Ambient air pollution and incidence of early-onset paediatric type 1 diabetes: a retrospective population-based cohort study. Environ Res. 2020;184:109291. doi:1016/j.envres.2020.109291
- World Health Organization. 7 million premature deaths annually linked to air pollution. Published March 25, 2014. Accessed August 18, 2022. https://www.who.int/news/item/25-03-2014-7-million-premature-deaths-annually-linked-to-air-pollution
- Hathout EH, Beeson WL, Nahab F, Rabadi A, Thomas W, Mace JW. Role of exposure to air pollutants in the development of type 1 diabetes before and after 5 yr of age. Pediatr Diabetes. 2002;3(4):184-188. doi:1034/j.1399-5448.2002.30403.x
- Beyerlein A, Krasmann M, Thiering E. Ambient air pollution and early manifestation of type 1 diabetes. 2015;26(3):e31-e32. doi:10.1097/ede.0000000000000254
- Michalska M, Bartoszewicz M, Waz P, Kozaczuk S, Ben-Skowronek I, Zorena K. PM10 concentration and microbiological assessment of air in relation to the number of acute cases of type 1 diabetes mellitus in the Lubelskie Voivodeship. Preliminary report. Pediatr Endocrinol Diabetes Metab. 2017;23(2):70-76. doi:18544/pedm-23.02.0076
- Di D, Zhang L, Wu X, Leng R. Long-term exposure to outdoor air pollution and the risk of development of rheumatoid arthritis: a systematic review and meta-analysis. Semin Arthritis Rheum. 2020;50(2):266-275. doi:1016/j.semarthrit.2019.10.005
- Shen L, Zhang H, Zhou X, Liu R. Association between polymorphisms of interleukin 12 and rheumatoid arthritis associated biomarkers in a Chinese population. 2015;76(2):363-367. doi:10.1016/j.cyto.2015.09.007
- Solus JF, Chung CP, Oeser A, et al. Genetics of serum concentration of IL-6 and TNF-? in systemic lupus erythematosus and rheumatoid arthritis: a candidate gene analysis. Clin Rheumatol. 2015;34(8):1375-1382. doi:1007/s10067-015-2881-6
- Hart JE, Laden F, Puett RC, Costenbader KH, Karlson EW. Exposure to traffic pollution and increased risk of rheumatoid arthritis. Environ Health Perspect.2009;117(7):1065-1069. doi:1289/ehp.0800503
- De Roos AJ, Koehoorn M, Tamburic L, Davies HW, Brauer M. Proximity to traffic, ambient air pollution, and community noise in relation to incident rheumatoid arthritis. Environ Health Perspect.2014;122(10):1075-1080. doi:1289/ehp.1307413
- Shin J, Lee J, Lee J, Ha EH. Association between exposure to ambient air pollution and rheumatoid arthritis in adults. Int J Environ Res Public Health. 2019;16(7):1227. doi:3390/ijerph16071227
- Chang KH, Hsu CC, Muo CH, et al. Air pollution exposure increases the risk of rheumatoid arthritis: a longitudinal and nationwide study. Environ Int. 2016;94:495-499. doi:1016/j.envint.2016.06.008
- Jung CR, Hsieh HY, Hwang BF. Air pollution as a potential determinant of rheumatoid arthritis: a population-based cohort study in Taiwan. 2017;28(Suppl 1):S54-S59. doi:10.1097/ede.0000000000000732
- Shepherd A, Mullins JT. Arthritis diagnosis and early-life exposure to air pollution. Environ Pollut. 2019;253:1030-1037. doi:1016/j.envpol.2019.07.054