Introduction

Rheumatoid arthritis (RA), mainly characterized by inflammatory joint involvement potentially leading to a progressive disability; it is considered a global public health challenge with almost 20 million prevalent cases, 1.2 million incident cases and 3.4 million disability-adjusted life years [1]. Despite our considerable knowledge of heterogeneous clinical phenotypes of RA, both genetic and environmental factors underpinning RA are not fully understood.
Specifically, it has been shown that environmental exposures (e.g. cigarette smoking, silica dust and mineral oil) may promote oxidative stress that causes bronchial and systemic inflammation, which, in turn, enhances monocytes and dendritic cells to present auto-antigens and to favour anti-citrullinated protein antibodies (ACPA) production in inducible bronchus-associated lymphoid tissue [2-6]. Thus, a failure to maintain homeostatic host-environment interactions along the lung mucosal border has been proposed as a key factor in the multifactorial pathogenesis of RA.
The role of long-term exposure to air pollution in RA development was investigated in several studies, with controversial results [7-12]. An increased risk of RA (about 30%) was found in women living within 50 meters from a trafficked road compared to women living further [7]. Similarly, in a large population-based Canadian study, RA risk was incremented for people living closer to a highway, even if exposure to specific pollutants was not found accountable [8]. A positive association was also found between particulate matter (PM)2.5/NO2 levels and the risk of developing a systemic autoimmune rheumatic disease in two different Canadian studies [9, 10]. Conversely, other studies failed to find an association between air pollution and RA susceptibility [11, 12]. A very recent metanalysis reported that long-term exposure to O3 and living near traffic roads could increase the risk of RA, while other pollutants, such as PM, didn’t seem to have an impact [13].
In addition, advances in the understanding of the potential triggers of RA flares during the disease course are also important for different reasons: to complement and improve RA management, to give the opportunity to devise preventative strategies, and to avoid disease relapse or gradual loss of drug responsiveness that substantially contributes to patient poorer health-related quality of life, disability, healthcare use and costs [14]. To date, only two studies have been published on this topic. The first is based on the Kuwait Registry for Rheumatic Diseases, describing the detrimental effects of short-term SO2 and NO2 exposure on RA disease activity, while no correlation was found for PM10, O3 and CO [15]. The second study provides evidence that exposure to high concentration of PM2.5 and NO2 was related to hospital readmission of RA patients within one year after the last discharge in Hefei (China) [16].
In the present study, we aimed to investigate whether short-term exposure (14 days) to air pollutants (PM10, PM2.5, NO2 and O3) influence disease activity indices in RA patients referring to an Academic Rheumatology Unit in Milan, North of Italy.

Materials and methods