Introduction:
The environment itself contributes to rheumatic musculoskeletal diseases. Among the emerging environmental factors, air pollution is one of the autoimmune disease risk factors 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 Environmental Factors Influence Rheumatic Diseases?
Numerous environmental factors are considered autoimmune disease risk factors. For example, infections can provoke a genetically predisposed immune system to attack the body tissues, causing illnesses like reactive arthritis. Smoking triggers the production of auto antibodies by increasing the citrullination of proteins. Exposure to silica dust, a crystalline form of quartz that is frequently used in mining and construction materials, has been observed to induce distinctive pulmonary inflammation in rheumatoid arthritis patients. Additionally, physical distress or infections can act as rheumatoid arthritis triggers. 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 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 Exist in Linking Air Pollution to Rheumatic Diseases?
An association between exposures to air pollutants and health conditions is difficult to assess, based on several critical biases about exposure assessments and population sampling.
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Air Quality Monitors: These are distributed in space and time across many regions, offering a definitive measure of daily exposure to different gases and particulates. This technique is susceptible to weather sensitivity. It would typically depend on the association of patient data to air quality data using zip code centroids. This is not an accurate estimate of personal exposure because patients are often relocated during their visits or travel daily, and wet deposition via rain will add noise. An individual exposure questionnaire to determine personal lifestyles and statistical models accounting for local weather patterns might be necessary for the above questions.
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Personal Devices: This method uses personal devices, from research-grade instruments to commercially available lower-cost devices. They are particulate matter measurements but give a much more accurate measure of individual exposure to indoor and outdoor air pollution. Compliance is usually restricted, and the Hawthorne effect can be said to change subjects' behavior.
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Measuring Specific Biological Markers: Most complex approaches directly measure specific biological markers in human samples, such as blood or urine. This approach may provide a high estimation of personal exposure but has certain drawbacks, such as giving only cumulative exposure measurements and incurring intrinsic costs requiring special facilities and laboratories.
Assessing the health effects of chronic or acute air pollution exposure presents challenges. Long-term exposure studies require methodologies that measure air quality over extended periods, and air sampling is 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 periods within the same group of patients, controlling for confounding factors. Conditional logistic regression is commonly used to account for time-varying confounders.
How Does Chronic Air Pollution Exposure Contribute to Rheumatoid Arthritis?
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The World Health Organization reports that exposure to air pollution significantly contributes to global mortality and morbidity. Such exposure is linked to increased risks of major cardiovascular (heart) events, pulmonary (lung) diseases, and cancer. Besides, numerous studies suggest that long-term exposure to pollutants resulting from fossil fuel combustion has a role in immune-mediated conditions. Studies established that environmental factors like 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.
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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.
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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. 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 to 30.0 μg/m3 in 2021.
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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 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 significantly impacting ILD risk.
How Does Acute Exposure to High Levels of Air Pollution Affect the Risk of Rheumatic Diseases?
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There is evidence that acute exposure to high air pollution levels increases the chance of developing certain conditions, such as myocardial infarction, stroke, asthma exacerbations, and chronic obstructive pulmonary disease exacerbations. 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.
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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.
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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. This suggests 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.
More recent studies pointed out that specific types of air pollution, such as ultrathin particles and gases, can interfere with an individual's immune system and make them vulnerable to these diseases. The precise processes underlying this phenomenon are yet unclear, but it likely involves factors that lead the individual's body to overreact, such as inflammation and stress. Scientists are working to understand these processes better and find ways to safeguard individuals from falling ill.
