Introduction
The development and worsening of rheumatic musculoskeletal diseases (RMDs) are significantly influenced by the environment. Among the emerging environmental factors, air pollution has been shown to contribute to the onset of autoimmune diseases and, more recently, has been linked to an increased risk of reactivating inflammatory conditions. Detecting airborne environmental pollution involves employing various methods, each with its own set of advantages and limitations. This article explores the impact of air pollution on RMDs and delves into the methods used to study the connection between exposure to air pollution and RMDs.
How Do Various Environmental Factors Contribute to the Development and Exacerbation of Autoimmune and Rheumatic Diseases?
Numerous environmental factors have been linked to the emergence of autoimmunity. For instance, infections can activate a genetically predisposed immune system, leading to conditions such as reactive arthritis. Similarly, smoking can provoke the production of autoantibodies by causing the citrullination of proteins. Exposure to silica dust, a crystalline derivative of quartz commonly found in construction materials and mining, has been observed to induce a distinctive pulmonary inflammation in rheumatoid arthritis patients. Additionally, physical distress or infections can reawaken dormant rheumatic diseases. Furthermore, there is a growing body of evidence connecting environmental air pollution to the development of autoimmune diseases and an increased risk of disease exacerbation.
Air pollution represents a significant global health threat, and mounting research suggests its role in elevating the occurrence of rheumatic musculoskeletal diseases (RMDs). This review delves into the impact of airborne environmental pollution on various rheumatic diseases. Additionally, it explores prevalent methods for evaluating air pollution and examines how chronic and acute exposure affect the likelihood of developing a rheumatic disease.
What Challenges Are Involved in Assessing the Link Between Air Pollution Exposure and Its Impact on Rheumatic Musculoskeletal Diseases (RMDs)?
Assessing the link between air pollution exposure and health outcomes can pose significant challenges, primarily due to biases related to exposure assessment and population selection.
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One approach involves the use of air quality monitors. These monitors are strategically placed across regions, providing detailed daily exposure data for various pollutants, both gaseous and particulate. However, this method can introduce misclassification bias and is influenced by weather conditions. It typically relies on linking patient data to air quality data based on zip code centroids, which may not accurately represent personal exposure due to factors like patient relocation and commuting. Moreover, wet deposition caused by rain can affect data accuracy. To address these issues, questionnaires on personal exposure and lifestyle habits, along with statistical models that consider weather conditions, can be employed.
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Another method utilizes personal devices, ranging from research-grade instruments to more affordable commercial options. These devices primarily measure particulate matter (PM) but offer a more precise estimate of personal exposure, accounting for both indoor and outdoor air pollution. However, compliance can be limited, and the Hawthorne effect may alter subjects' behavior.
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A more complex approach involves directly measuring specific biological markers in human samples, such as blood or urine. This method offers high precision in estimating personal exposure but has limitations, including providing only cumulative exposure measurements and incurring intrinsic costs, necessitating specialized facilities and laboratories.
Assessing the health effects of chronic or acute air pollution exposure presents its own challenges. Long-term exposure studies require methodologies that measure air quality over extended periods, with air sampling being the primary option. However, systematic measurements of airborne pollutants began relatively recently, limiting our ability to estimate lifelong exposure accurately. Most studies use time windows as proxies for long-term exposure, potentially leading to misclassification. For studying acute exposure effects, a case-crossover design is employed to investigate transient changes in disease risk factors, particularly for acute-onset diseases. This design involves comparing different time periods within the same group of patients, controlling for confounding factors. Conditional logistic regression is commonly used to account for time-varying confounders.
What Are the Underlying Mechanisms Through Which Chronic Exposure to Air Pollution Contributes to Immune-Mediated Diseases Like Rheumatoid Arthritis (RA)?
The World Health Organization reports that air pollution exposure is a significant factor contributing to global mortality and morbidity. Such exposure is linked to increased risks of major cardiovascular (heart) events, pulmonary (lung) diseases, and cancer. Moreover, there is a growing body of evidence suggesting that chronic exposure to pollutants from fossil fuel combustion plays a role in immune-mediated conditions. Studies indicate that environmental factors, including airborne pollutants, can trigger the immune system. Preclinical research has demonstrated that exposure to heavy metals, fine particulate matter (PM), and gaseous pollutants can harm lymphocytes and stimulate the production of pro-inflammatory cytokines and autoantibodies.
One prominent example of this association is the connection between silica dust exposure and rheumatoid arthritis (RA). Patients with RA appear to be more susceptible to silica dust exposure, which can lead to pulmonary inflammation similar to synovitis. Recent research has highlighted the interplay between occupational exposure, smoking, genetics, and the risk of developing anticitrullinated protein antibodies (ACPA)-positive RA. Interestingly, even exposure to hard rock substances like uranium, zircon, and gold has been linked to a higher risk of RA. Chronic exposure to fine PM is also associated with an elevated risk of RA and other immune-mediated diseases.
Chronic exposure to PM 2.5 concentrations exceeding 20.0 μg/m3 (Micrograms per cubic meter) is linked to a 13.0 percent higher risk of autoimmune diseases, particularly RA. Notably, many industrialized regions worldwide exceed this annual PM 2.5 concentration limit, such as the Po Valley in Northern Italy, where levels reached 25.0–30.0 μg/m3 in 2021.
Beyond RA, air pollution has been shown to impact other immune-mediated diseases, including systemic lupus erythematosus (SLE) and systemic sclerosis. Silica dust exposure is associated with both SLE and systemic sclerosis, promoting pro-inflammatory cytokines, enhancing T cell responses, reducing regulatory T cells, increasing oxidative stress, and causing apoptosis (programmed cell death). Additionally, air pollution contributes to comorbidities in patients with inflammatory rheumatic musculoskeletal diseases, such as interstitial lung disease (ILD), with specific PM 2.5 components having a significant impact on ILD risk.
How Does Acute Exposure to High Levels of Air Pollution Affect the Risk of Rheumatic Musculoskeletal Diseases (RMDs)?
Acute exposure to high levels of air pollutants has been linked to increased risks of conditions such as myocardial infarction, stroke, asthma exacerbations, and chronic obstructive pulmonary disease exacerbations, among others. This acute exposure can stimulate the immune system, leading to a pro-inflammatory state, as indicated by elevated C-reactive protein levels during highly polluted days.
Recent research has also revealed the acute impact of air pollution on the reactivation of various rheumatic musculoskeletal diseases (RMDs). For instance, studies involving patients with rheumatoid arthritis (RA) demonstrated an exposure-response relationship between air pollutant concentrations and abnormal C-reactive protein levels, along with an increased risk of arthritis flares among those exposed to higher pollutant concentrations. Similar findings were observed in patients with inflammatory arthritis, where acute exposure to air pollution was associated with changes in disease-modifying anti-rheumatic drug usage. Furthermore, acute exposure to pollutants was linked to reactivations of psoriasis and lupus.
Notably, an acute detrimental effect of air pollution was also observed in seemingly non-inflammatory conditions like osteoporotic fractures. While the impact of chronic air pollution exposure on bone health is supported by research, the acute effect on fracture risk is less straightforward to explain. However, studies have found a short-term relationship between air pollution exposure and hip fragility fractures, particularly in older individuals, suggesting that acute exposure might contribute to chronic damage that accumulates over time, which could also be relevant for RMDs and the risk of disease flares.
Conclusion
Air pollution and climate change are significant challenges that can make individuals ill and even lead to fatalities. They are associated with illnesses that affect one's muscles and joints, such as rheumatoid arthritis (RA). They may also exacerbate other conditions in which the individual's body attacks itself. Inhaling polluted air can rapidly worsen these illnesses. Recent research indicates that specific forms of air pollution, such as tiny particles and gasses, can disrupt the individual's immune system and increase their susceptibility to these illnesses. The exact mechanisms behind this phenomenon are not yet fully understood, but it likely involves factors that lead the individual's body to react excessively, such as inflammation and stress. Scientists are actively working to gain a better understanding of these processes and find ways to safeguard individuals from falling ill.
