POS0644 AIR POLLUTION IS A PREDICTOR OF POOR RESPONSE TO BIOLOGICAL THERAPIES IN CHRONIC INFLAMMATORY ARTHRITIDES

Background:There is increasingly evidence that environmental air pollution is associated with both development of chronic inflammatory arthritides (CIA). The role of air pollutants on the treatment response of CIA (including psoriatic arthritis [PsA] and ankylosing spondylitis [AS]) is still unclear.Objectives:The objective of the present study is to determine the association between the concentration of air pollutants and biological drug retention rates in CIA.Methods:We retrieved longitudinal data of patients affected by CIA on biological therapies and of the daily concentration of air pollutants in the Verona area. We designed a case-crossover study to compare the exposure to pollutants in the 30-day and 60-day periods preceding a drug switch or swap due to disease progression referent to the 30-day and 60-day periods preceding a visit with stable treatment for at least 6 months.Results:1,286 patients with CIA (888 with RA, 260 with PsA and 138 with AS) with 5,454 follow-up visits were included in the study. 13,636 daily air pollution records were retrieved. We found an exposure-dependent relationship between exposure to air pollutants and CRP serum levels in CIA. At PM10 exposures of >50 μg/m3 and >40 μg/m3 we found a 150% and 65% higher risk of having CRP above 5 mg/L respectively (OR 2.564, 95% CI 2.114-3.110 and OR 1.659, 95% CI 1.440-1.910, respectively.). If the threshold was set at >30 μg/m3 of PM10 (below the European Union health protection limit) we still found a 38% higher risk of having altered CRP (OR 1.383, 95% CI 1.206-1.588). Among CIA patients, 280 patients (21.7%) had at least 2 follow-up visits with at least one drug switch or swap due to drug inefficacy and one visit with stable treatment for at least 6 months, serving as our sample for the case-crossover study. We found that air pollutants concentrations were higher before a switch or swap due to drug inefficacy (Figure 1A). Figure 1B shows the receiver operating characteristic (ROC) curve for the prediction of switch or swap due to drug inefficacy. Discriminatory capacity of disease activity alone was the highest (AUC 0.841) but when the prediction model included the concentrations of air pollutants in the 60 days before the visit the discriminatory capacity increased (AUC 0.879).Figure 1.A) Mean concentrations of air pollutants in the 60-day period before switch or swap visit compared to the stable treatment visit. p <0.001 between all groups. B) Receiving operating characteristics (ROC) curves for the prediction of switch or swap due to drug inefficacyConclusion:We found that environmental air pollution was a determinant of poor response to biological treatment in a cohort of patients with CIA followed over a 5-year period. Intervention aimed to decrease the fossil combustion emissions might have beneficial effects on biologics persistence rate of patients with CIA.Disclosure of Interests:None declared

Endothelial Progenitor Cells as Critical Mediators of Environmental Air Pollution-Induced Cardiovascular Toxicity.

Environmental air pollution exposure is a leading cause of death worldwide, and with increasing industrialization and urbanization, its disease burden is expected to rise even further. The majority of air pollution exposure-associated deaths are linked to cardiovascular disease (CVD). Although ample research demonstrates a strong correlation between air pollution exposure and CVD risk, the mechanisms by which inhalation of polluted air affects cardiovascular health are not completely understood. Inhalation of environmental air pollution has been associated with endothelial dysfunction, which suggests that air pollution exposure impacts CVD health by inducing endothelial injury. Interestingly, recent studies demonstrate that air pollution exposure affects the number and function of endothelial progenitor cells (EPCs) - subpopulations of bone marrow-derived pro-angiogenic cells that have been shown to play an essential role in maintaining cardiovascular health. In line with their beneficial function, chronically low levels of circulating EPCs and EPC dysfunction (e.g., in diabetic patients) have been associated with vascular dysfunction, poor cardiovascular health, and increases in the severity of cardiovascular outcomes. In contrast, treatments that improve EPC number and function (e.g., exercise) have been found to attenuate cardiovascular dysfunction. Considering the critical, non-redundant role of EPCs in maintaining vascular health, air pollution exposure-induced impairments in EPC number and function could lead to endothelial dysfunction, consequently increasing the risk for CVD. This review article covers novel aspects and new mechanistic insights of the adverse effects of air pollution exposure on cardiovascular health associated with changes in EPC number and function.

Association between environmental air pollution and rheumatoid arthritis flares

Objectives Environmental air pollution has been linked to the pathogenesis of RA. Nevertheless, evidence linking higher concentrations of air pollutants with the risk of RA reactivations is missing. The objective of the present study was to determine the association between RA flares and air pollution. Methods We collected longitudinal data of patients affected by RA and of the daily concentration of air pollutants in the Verona area. We designed a case-crossover study. We compared the exposure to pollutants in the 30-day and 60-day periods preceding an arthritic flare referent to the 30-day and 60-day preceding a low-disease activity visit. Results The study included 888 patients with RA with 3396 follow-up visits; 13 636 daily air pollution records were retrieved. We found an exposure–response relationship between the concentration of air pollutants and the risk of having abnormal CRP levels. Patients exposed to greater concentrations of air pollutants were at higher risk of having CRP levels ≥5 mg/l. Concentrations of CO, NO, NO2, NOx, PM10, PM2.5 and O3 were higher in the 60-day period preceding a flare. Conclusions We found a striking association between air pollution and RA disease severity and reactivations in a cohort of patients followed over a 5-year period. The exposure to high levels of air pollutants was associated with increased CRP levels and a higher risk of experiencing a flare of arthritis. This excessive risk was evident at very low levels of exposure.