A four-year study links higher PM2.5 exposure to worsening rheumatoid arthritis, with prolonged pollution exposure showing the clearest association with flare risk.
Study: Effects of air pollution on disease activity in patients with rheumatoid arthritis. Image Credit: MDGRPHCS / Shutterstock
In a recent study published in Annals of the Rheumatic Diseases, researchers examined the associations between ambient air pollution and disease activity and flare occurrence among patients with rheumatoid arthritis (RA).
RA is a chronic, systemic autoimmune disease characterized by polyarticular joint inflammation and other extra-articular manifestations. Autoantibody production, genetics, protein modification, environmental exposures, and mucosal inflammation contribute to its pathogenesis. In particular, environmental factors play a crucial role in RA onset and exacerbation.
Particulate matter, including PM10 and the finer PM2.5 fraction, can enter the respiratory tract, induce oxidative stress, and promote systemic inflammation. In line with this, epidemiological studies have demonstrated associations between air pollution and a higher RA risk. Nevertheless, the effects of air pollution on RA disease activity remain understudied.
About the study
In the present study, researchers examined the longitudinal association between air pollutants and disease activity in RA patients. South Korean RA patients treated at a tertiary medical center between January 2021 and December 2024 were included. Patients with fewer than three outpatient visits or six months of follow-up were excluded. Patients were followed up until the last outpatient visit, death, or December 31, 2024, whichever occurred first.
Data on clinical, demographic, and socioeconomic characteristics as well as serological status, concomitant medications, and smoking were collected at baseline. Further, C-reactive protein (CRP), physician and patient global assessment, disease-modifying anti-rheumatic drug (DMARD) use, 28-tender joint count (TJC-28), 28-swollen joint count (SJC-28), and glucocorticoid dose were evaluated at each visit.
Further, data on monthly average levels of six air pollutants, sulfur dioxide, ozone, carbon monoxide, PM10, nitrogen dioxide, and PM2.5, were obtained and matched to patients' residential areas across 17 administrative regions. In addition, climate data, such as humidity and temperature, were obtained. The study’s outcomes were flare occurrence, SJC-28, TJC-28, clinical disease activity index (CDAI), and disease activity score using 28-joint count and CRP (DAS28-CRP).
Flare occurrence was defined as an increase in DAS28-CRP of> 0.6 points from the previous visit, or> 1.2 points from baseline. Logistic and linear generalized estimating equations were used to evaluate the associations between air pollution and disease activity (SJC-28, TJC-28, CDAI, and DAS28-CRP) and flare occurrence. Analyses were adjusted for age, sex, serological status, smoking status, DMARD use, glucocorticoid dose, humidity, temperature, insurance type, and area deprivation index.
Subgroup analyses were conducted based on age, smoking status, sex, baseline SJC-28, baseline TJC-28, baseline concomitant medications, and comorbidities. A case-crossover sensitivity analysis was performed to further investigate the association between air pollution and flare among patients with at least one flare during the study period.
Findings
The study included 1,070 RA patients with 12,583 outpatient visits between 2021 and 2024. On average, patients were aged 61.3 years and had RA for 9.1 years. About 86.2% of subjects were female, 83.4% used conventional synthetic DMARDs, and 50.7% used glucocorticoids. Air pollution was generally higher in spring and winter, and showed regional differences. In total, 1,278 flare events occurred in 604 patients over 3,235 person-years of follow-up.
This corresponded to an incidence rate (IR) of 39.5 flare occurrences per 100 person-years. The highest and lowest monthly ratios of flare occurrences to outpatient visits were recorded in January and April, respectively. PM2.5 levels were significantly associated with a higher risk of flares. PM10 and ozone levels showed positive but non-significant associations with flare risk. Higher PM2.5 levels were significantly associated with higher SJC-28, TJC-28, CDAI, and DAS28-CRP.
Further, SJC-28 increased with higher ozone levels, while DAS28-CRP increased with greater PM10 levels. Among air pollutants, only PM2.5 showed significant associations with all disease activity parameters. Females and nonsmokers exhibited a more pronounced association between PM2.5 and DAS28-CRP. Moreover, patients with higher baseline TJC-28 showed a relatively greater increase in DAS28-CRP with increasing PM2.5 levels, although evidence for an interaction was weaker than for sex and smoking status.
Sensitivity analysis yielded results consistent with the main analysis. Short-term increases in PM2.5 were not associated with an immediate increase in flare risk, whereas associations became more pronounced when cumulative exposure extended beyond approximately two weeks, suggesting sustained exposure may be more relevant than brief pollution peaks.
The researchers cautioned that pollution exposure was estimated from residential-area measurements rather than individual exposure, potentially leading to exposure misclassification and residual confounding. The exclusively Korean cohort may also limit generalizability, and although several associations were statistically significant, effect sizes were relatively modest, and most participants had well-controlled RA.
Conclusions
Taken together, the study observed a significant association between air pollution and disease activity in RA patients, with PM2.5 showing the most consistent and strongest association with flare occurrence. Women and nonsmokers with RA showed stronger associations between PM2.5 and DAS28-CRP, while those with higher baseline TJC-28 showed a relatively greater increase in disease activity.
These results have significant implications for public health and support efforts to improve air quality, although further studies are needed to determine whether such improvements can reduce RA disease activity and flare risk.
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