Running Title: Rheumatoid arthritis and short-term pollutants exposure

RHEUMATOID ARTHRITIS ACTIVITY AND SHORT-TERM EXPOSURE TO AIR POLLUTANTS IN METROPOLITAN AREAS IN THE NORTH OF ITALY

Francesca Ingegnoli ^1,2, ORCID 0000-0002-6727-1273, @IngegnoliFra

Tania Ubiali ¹,

Tommaso Schioppo ^1,2, ORCID 0000-0001-8359-5131

Valentina Longo ¹,

Antonella Murgo ¹,

Orazio De Lucia ¹, ORCID 0000-0003-2304-6661

Ennio Giulio Favalli ¹, ORCID 0000-0003-1471-6467

Simona Iodice ³,

Valentina Bollati ^2,3, ORCID 0000-0002-0370-9598

Roberto Caporali ^1,2, ORCID 0000-0001-9300-6169

¹Division of Clinical Rheumatology, ASST Pini-CTO, Milano, Italy

²Dept of Clinical Sciences & Community Health, Research Center for Adult and Pediatric Rheumatic Diseases, Research Center for Environmental Health, Università degli Studi di Milano, Milano, Italy

³EPIGET – Epidemiology, Epigenetics and Toxicology Lab, Dept of Clinical Sciences & Community Health, Università degli Studi di Milano, Milano, Italy

Corresponding author :

Francesca Ingegnoli

Department of Clinical Sciences and Community Health,

Division of Clincal Rheumatology, ASST Pini-CTO, Università degli Studi di Milano,

Piazza Cardinal Ferrari 1, 20122 Milano, Italy

Tel: +39 02 5829 6456

Fax: +39 02 5829 6804

E-mail: francesca.ingegnoli@unimi.it

ABSTRACT

Background. Rheumatoid arthritis (RA) flare is related to an increased joint damage, disability and healthcare use. The impact of short-term air pollution exposure on RA activity is still a matter of debate. We investigated in a cross-sectional study whether short-term exposure to particulate matter (PM)₁₀, PM_2.5, nitrogen dioxide (NO₂) and ozone (O₃) affected RA disease activity.

Methods. 422 consecutive RA patients resident in Lombardy, North of Italy were studied. Air pollutant concentrations, estimated by Regional Environmental Protection Agency (Lombardy – Italy) at municipality resolution, were used to assign short-term exposure from the day of visit back to 14 days.

Results . Sparse punctual significant negative associations emerged between PM₁₀, PM_2.5, NO₂ and RA disease activity, whereas positive associations were observed for O₃. Moreover, patients were stratified according to their ongoing Disease Modifying anti-Rheumatic Drugs (DMARDs) treatment: no DMARDs (n=25), conventional synthetic - csDMARDs (n=108), and biological or targeted synthetic b/tsDMARDs (n=289). At visit, an inverse association was observed in the b/tsDMARDs group between PM_2.5 and Disease Activity Score on 28 joints (DAS28) (-0.047±0.020, p =0.023), a positive tendency in the no-DMARD group (0.125±0.070, p =0.075) and no association for csDMARDs group (0.042±0.039, p =0.288). The association between O₃ the day before the visit and DAS28 was positive only in the b/tsDMARDs group (0.038±0.009,p <0.001).

Conclusion. The impact of air pollution short-term exposure seems minimally clinical relevant, as the scattered significant differences were observed. Further evidence is needed to elucidate determinants of RA flare and the implications for management.