Discussion
Disease activity in our Italian cohort of RA patients was not significantly affected by short-term air pollutants exposure in urban and peri-urban areas in Lombardy region in the North of Italy. Notably, scattered statistical significant associations were observed between short-term exposure to outdoor air pollutants (PM10, PM2.5, NO2, and O3) and RA activity, but the changes observed did not reach the minimal clinically important difference [20].
A clear comparison with the purpose of establishing whether a difference exists between our results and the two existing studies on this topic is not feasible [15, 16]. Firstly, our RA population includes all consecutive patients referring to the Rheumatology outpatient clinics and the disease activity was low between remission and low disease activity (see table 1). By contrast, in the study of Wu, hospital re-admissions within one year were considered, thus suggesting more severe flares of disease [16], while the Kuwaiti Colleagues described an association between DAS28, clinical disease activity index (CDAI), NO2 and SO2 using data from their national registry [15]. This latter study, as well as our results, provided very small variations in outcome measure (i.e. disease activity), which, even if statistically significant, did not reach the minimal clinically important difference [20].
Furthermore, accurate measurement of the household and workplace air pollution was not included in all these studies. These findings are consistent with studies on cigarette smoking exposure that is recognized as one of the most influencing environmental factors for RA susceptibility, but there is no evidence of its influence in a very short time on disease activity [21]. Moreover, our results are in line with those on systemic lupus erythematosus disease activity and short-term air pollution exposure [22].
Notably, strength of our study was to consider different therapeutic approaches as a potential confounding factor. Therapy seems partially able to influence the relationship between short-term air pollution exposure and RA disease activity. It should be noted that this result is limited to PM2.5 levels and DAS28 at the day of the visit and O3 levels and disease activity scores (DAS28 and SDAI) for several days with respect to the three groups of therapies.
Some limitations of our study have to be mentioned. This is a single center study and data are limited to our tertiary referral center. In addition, we could not measure all real life exposures, even those related to daily activities that can also affect results.
As already mentioned, much of our current understanding of the impact of air pollution on RA pathobiological events has been derived from long-term retrospective studies using registries or administrative databases or in vitro studies [4, 5, 13]. Although the environment seems to play a crucial role in inducing autoimmunity by favouring disease onset, it seems barely relevant to disease activity once the loss of tolerance is established in rheumatologic disorders.
In conclusion, despite the strong in vitro evidence that particulate matter enhances the inflammatory pathways, the evidence of this effect in real-life RA patients is less impressive. The role of short-term exposure to air pollutants as a potential contextual factor has not yet clarified. Further research shall help further elucidate determinants of RA flare and the implications for disease management.