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Adding to previous studies implicating on-the-job exposure to silica dust as a risk factor for rheumatoid arthritis (RA), new research now finds dozens of other occupational inhalants that also appear to contribute to RA development.

Comparison of 4,033 cases of new-onset RA with 6,485 matched controls in Swedish registries indicated that exposure to any of 32 gases or dust types raised the odds of incident RA by 21% (95% CI 11-33), according to Lars Alfredsson, PhD, of Karolinska Institutet in Stockholm, and colleagues.

These agents ranged from synthetic fiber dust to volatile organic chemicals. Odds ratios for individual substances approached or topped 2.0 for some, including fungicides, insecticides, and asbestos, as well as silica dust, the researchers .

Other substances strongly linked (OR >1.5) with incident RA included gasoline engine exhaust, welding fumes, organic solvents, and carbon monoxide.

Cases were diagnosed from 1996 to 2017. Controls in the study were taken from general population registries and matched to cases by age, sex, and area of residence.

The risk seemed to be concentrated in the RA subtype featuring anti-citrullinated protein/peptide antibody (ACPA), about two-thirds of the study's cases. Whereas 26 of the 32 agents showed positive and statistically significant associations with ACPA-positive RA, less than one-third were clearly linked to ACPA-negative disease. (After for multiple comparisons, 17 of the substances were still significantly linked to ACPA-positive RA while none were for ACPA-negative disease.)

"Our study supports a general link between occupational inhalable agents and risk of RA, with clear restriction towards ACPA-positive rather than ACPA-negative RA and with higher [odds ratios] for risk in men than in women," Alfredsson and colleagues wrote. Odds ratios by sex were 1.66 for men versus 1.13 among women.

"We also observed an exposure-response relationship, in which the risk of ACPA-positive RA increased either with an increased duration or with an increased number of exposed agents," the group added. Odds for developing ACPA-positive RA were nearly tripled for individuals exposed to at least five of the candidate inhalants, relative to controls. Risks were also considerably higher for people with at least 8 years of exposure to such agents.

As well, risks were still greater for individuals who smoked and who had gene variants previously found to be associated with RA. The odds ratio for ACPA-positive RA reached 18.2 (95% CI 11.8-28.2) for smokers with a genetic predisposition and any exposure to a candidate inhalant. Smoking by itself, without genetic vulnerability or any inhalant exposure, was associated with ACPA-positive RA with an odds ratio of 2.63 (95% CI 2.57-4.40).

The study follows others examining occupational risks for RA, including one that found unexpectedly high rates of RA among coal miners and other examining a wider range of mining jobs. Those types of jobs are predominantly held by men, however, whereas most RA cases occur in women. By looking at inhalant exposures instead of job types, this new study may shed more light on women's occupational risks.

In , two U.S.-based researchers applauded the study for providing "several important implications regarding RA pathogenesis and prevention."

Not only does the study expand the range of workplace exposures that may precipitate RA, but it demonstrated a "positive relationship ... between dose and duration" of exposure, which "provide further support for a true association between these agents and RA," wrote Vanessa Kronzer, MD, of the Mayo Clinic in Rochester, Minnesota, and Jeffrey Sparks, MD, MMSc, of Brigham and Women's Hospital in Boston.

"Indeed, several specific public policy implications directly follow from the results of this study," they continued. These include new regulations limiting public exposure (i.e., not just in the workplace) to carbon monoxide and engine exhaust, as well as workplace rules to mitigate exposures there. And, "public health initiative[s] should continue to reduce cigarette smoking," Kronzer and Sparks wrote.

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