Air Pollution May Cause Rheumatoid Arthritis

Newswise — CHICAGO – Exposure to some types of air pollution, especially sulfur dioxide — one of the six most common pollutants in the United States — is associated with a somewhat increased risk of developing rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Chicago.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

Environmental factors have been connected with the development of RA, and exposure through a person’s airways is of particular interest to researchers. Researchers from Brigham and Women’s Hospital in the United States and the Karolinska Institute in Sweden recently examined whether long-term exposure to air pollution is associated with an increased risk of RA. They studied 1,330 cases of RA (as well as an additional 2,235 people without the disease) from the Swedish Epidemiological Investigation of Rheumatoid Arthritis, and 91,203 women from the US Nurses’ Health Study (among whom 762 developed RA over 30 years of follow up).

The researchers predicted exposures to several common air pollutants, classified as either gaseous (air pollution in gas form, such as carbon monoxide, sulfur dioxide and nitrogen dioxide) or particulate (air pollution that contains tiny particles, such as soot or dust), at homes of all participants based upon residential addresses. Then, they examined the association between increases in these different components of air pollution with the increased risk of developing RA. While looking at the risk associations between air pollution and RA, the researchers took into account other variables that might affect RA risk, such as age, gender, socioeconomic status, education, race, smoking ,reproductive factors, hormone use, physical activity and body mass index.

In both the Swedish and American studies, researchers found no evidence of an increased risk of RA related to particulate air pollution. “We were surprised that we did not observe evidence of an increased risk of RA with increasing levels of particulate matter, since our previous work had shown elevated risks of RA in women living close to major roads,” says lead investigator in the study, Jaime Hart, MD; instructor in medicine at Brigham and Women’s Hospital, Boston, Mass. “However, this may just mean that our predictions of particulate matter have more error than our models of the gaseous pollutants.”

In contrast, in the Swedish study, increasing exposure to the gaseous air pollutants (sulfur dioxide and oxides of nitrogen) in the 10 and 20 years prior to onset of RA were associated with an increased risk of the disease. Going from low to high exposure to sulfur dioxide, nitrogen dioxide, or nitrogen oxide were associated with an up to seven percent, 11 percent, and seven percent increased risk for RA, respectively.

These risks were higher in individuals with less than a university education, a measure of socioeconomic status, than in individuals with at least a university education. Dr. Hart explains, “This may be because individuals with a lower socioeconomic status are more likely to live in houses where more air pollution leaks in from the outside or other factors such as general health status that may make them more susceptible to the effects of air pollution.”

In the U.S. study, only exposures to sulfur dioxide were associated with modest increases in total RA risk – with a five percent increased risk for in going from low to high exposure. Given the findings among those with lower socioeconomic status in the Swedish study, Dr. Hart feels that the lack of similar findings in the Nurses’ Health Study may be because members of the NHS cohort — all trained nurses —may have relatively higher levels of socioeconomic status.

“Overall, in both studies it appeared that individuals with higher exposures to sulfur dioxide had a modestly increased risk of RA. As this is the first study to examine the effects of air pollution on RA risk, it is important to validate these findings in other studies, and in populations with a wide range of socioeconomic backgrounds,” explains Dr. Hart.

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.rheumatology.org/education. Follow the meeting on Twitter by using the official hashtag: #ACR2011.

Editor’s Notes: Jaime E. Hart, MD will present this research during the ACR Annual Scientific Meeting at the McCormick Place Convention Center at 9:15 AM on Wednesday, November 9 in Room W194b. Dr. Hart will be available for media questions and briefing at 1:30 PM on Tuesday, November 8 in the on-site press conference room, W 175C .

Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care. Also, discover the ACR’s Simple Tasks campaign, which highlights the severity of rheumatic diseases and the importance of early and appropriate referral to a rheumatologist.

Presentation Number: 2574

The Association of Ambient Air Pollution Exposures and Risk of Rheumatoid Arthritis: Results From the Swedish EIRA Case-Control Study and the US Nurses’ Health Prospective Cohort Study

Jaime E. Hart (Brigham and Women's Hospital, Boston, MA)Henrik Källberg (Karolinska Institutet, Stockholm, Sweden)Francine Laden (Harvard School of Public Health, Boston, MA)Karen H. Costenbader (Brigham and Women's Hospital, Boston, MA)Marie Holmqvist (Karolinska Institutet, Stockholm, Sweden)Lars Klareskog (Karolinska Institutet, Stockholm, Sweden)Lars Alfredsson (Institute of Environmental Medicine, Unit of Cardiovascular Epidemiology, Karolinska Institutet, Stockholm, Sweden)Elizabeth W. Karlson (Brigham and Women's Hospital, Boston, MA)

Background/Purpose: Environmental factors play an important role in the development of rheumatoid arthritis (RA), and airway exposures to environmental agents are postulated to be of special importance. We examined whether long-term exposures to ambient air pollution were associated with risk of RA in the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) Study and in the US Nurses' Health Study (NHS).

Method: We studied 1,330 incident RA cases and 2,235 controls from EIRA and 91,203 members of the NHS, among whom 762 had developed RA. Exposures to particulate matter (PM10, PM2.5) and gaseous pollutants (SO2, NO2, and NOx, in EIRA only) were predicted for all residential addresses. We examined the association of an interquartile range increase in each air pollutant with the risk of RA, and risks of seropositive (rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA)) RA phenotypes, using multivariable logistic regression for EIRA and Cox proportional hazards models for NHS. Models in EIRA were adjusted for age, gender, smoking status, and educational attainment. Models in NHS were adjusted for age, race, reproductive factors, hormone use, physical activity, body mass index, smoking status and pack-years, and individual and area level measures of socioeconomic status. As the relevant etiological time period of exposure is unknown, we examined pollution in various years before RA onset.

Result: In both studies there was no evidence for an increased risk of RA with PM10 or PM2.5 in any exposure window or with any pollutant in the year of onset, and in some cases modest inverse associations were observed. In EIRA, elevated risks with increases in SO2, NO2, and NOx in the 10th and 20th years prior to RA symptom onset were observed, particularly in models restricted to RF+ and ACPA+ phenotypes. For each interquartile range increase (2 µg/m3 for SO2, 7 µg/m3 for NO2, and 8 µg/m3 for NOx) in exposure in the 10th year prior to onset, the fully-adjusted odds ratios for ACPA+ RA (95% confidence intervals (CI)) were 1.07 (1.01-1.13), 1.11 (1.01-1.21) and 1.07 (1.00-1.14) for SO2, NO2, and NOx respectively. Results were strongest in individuals with less than a university education (Figure 1). In the NHS, only exposures to SO2 were associated with modest increases in total RA risk (fully adjusted hazard ratio (95%CI) for an interquartile range (16 µg/m3) increase in SO2 10 years prior to onset 1.05 (0.92-1.19)).

Conclusion: In EIRA, we observed elevations in the odds of developing RA and seropositive RA in individuals with higher levels of gaseous air pollution exposures, particularly SO2. These risks were strongest in those with less than a university education. In NHS, we observed modest elevations only with increasing exposures to SO2. To the best of our knowledge, this is the first study to examine the effects of air pollution on risk of RA.

Disclosure: J. E. Hart, None; H. Källberg, None; F. Laden, None; K. H. Costenbader, None; M. Holmqvist, None; L. Klareskog, None; L. Alfredsson, None; E. W. Karlson, None.