Air Pollution Increases RA Activity and Flares Save

Koreans with rheumatoid arthritis (RA) showed increased disease activity and higher flare rates when exposed to relatively high levels of small atmospheric particulate matter, researchers reported.

Each 6-μg/m³ increment in particles ≤2.5 μm (PM_2.5) was associated with an 11% increase in odds for developing an RA flare (OR 1.113, 95% CI 1.017-1.218), according to Eun Bong Lee, MD, PhD, of Seoul National University College of Medicine in South Korea, and colleagues.

As well, each 10-μg/m³ increment in PM_2.5 came with a statistically significant 0.052-point increase in 28-joint Disease Activity Score (DAS28) values, the group reported in Annals of the Rheumatic Diseases.

Some other air pollutants also showed similar trends, including particles smaller than 10 μm (PM₁₀), nitrogen oxides, and ozone, which did not achieve statistical significance. Curiously, though, a negative (but not significant) association was seen between carbon monoxide levels and flare risk (OR 0.917 per 1 standard deviation [SD], P=0.092).

In an accompanying editorial, Jeffrey Sparks, MD, MMSc, of Mass General Brigham in Boston, called the study "impactful" and commented that it demonstrates that "[p]ollution now links pathogenesis and progression in RA. These findings emphasize how inhalants such as pollution may drive RA and perhaps other autoimmune processes."

Previous studies had already established that some inhalants may serve as triggers for RA. Tobacco smoking, for example, is a well-known risk factor for developing RA. Sparks noted that inhalants' apparent role in RA pathogenesis "also might in part explain risk for pulmonary manifestations of RA, such as interstitial lung disease." How much inhalants including less noticeable environmental pollutants may worsen the disease when already present, however, is less well known. Unlike smoking, which is easily asked about in clinic visits, individuals' air pollution exposure is rarely tracked and requires considerable sleuthing.

For the current study, Lee and colleagues analyzed data collected for a prospectively assembled cohort of Korean RA patients, treated from 2021 through 2024. Exposures for six air pollutants -- sulfur dioxide, nitrogen dioxide, carbon monoxide, ground-level ozone, PM_2.5, and PM₁₀ -- were extracted from environmental monitoring data for South Korea's 17 administrative regions. The researchers also looked at air quality index (AQI) values that combine levels of all major pollutants. (AQI values of 50-99 reflect "moderate" pollution and 100-plus is "unhealthy"; areas experiencing visible wildfire smoke, for example, may see AQI values approaching 400.)

Some 1,070 RA patients were studied, with an aggregate of 12,583 outpatient visits over the 4 years of follow-up. Median DAS28 score at baseline was 2.4. Most patients were taking some type of disease-modifying medication and half were on glucocorticoids, mostly at low doses.

The mean overall PM_2.5 level was 18.49 μg/m³ (SD 6.0) but this varied seasonally and by region. Values reported for the month of March were consistently higher, averaging from 18.75 to 27.75 μg/m³.

In multivariable analysis, AQI values were significantly associated with both flare risk and disease activity. Mean AQI across the 17 regions was 68.35 (SD 11.5) annually, reaching 83.70 in January and with a nadir of 51.25 in September. For each 1-SD increment in AQI, odds of developing a flare rose 11.5% (P=0.016), and mean DAS28 values increased by 0.03 points (P=0.003). Other measures of disease activity including the Clinical Disease Activity Index and swollen/tender joint counts showed the same pattern.

Analysis of individual pollutants indicated that PM_2.5 levels were the driving factor. Associations between RA outcomes and levels of the other five pollutants were close to zero for sulfur dioxide, nitrogen dioxide, and ozone; point estimates for PM₁₀ indicated a relationship with worsened disease but not as strongly as for smaller particles.

Some clinical factors appeared to mitigate the risks associated with PM_2.5: male sex, history of smoking, chronic kidney disease, and use of disease-modifying drugs and steroids. Compared with patients lacking them, these subgroups did not face the same risks for exacerbation driven by PM_2.5 exposure.

Limitations to the study included its reliance on region-level pollution averages to estimate individual exposures, and presence of pulmonary comorbidities was not included in the data. The study was conducted in Korea, which may limit its generalizability.