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