Objective: To investigate the association of air pollution exposure with the severity of interstitial lung disease (ILD) at diagnosis and ILD progression among patients with systemic sclerosis (SSc)-associated ILD. Methods: We conducted a retrospective two-center study of patients with SSc-associated ILD diagnosed between 2006 and 2019. Exposure to the air pollutants particulate matter of up to 10 and 2.5 µm in diameter (PM₁₀, PM_2.5), nitrogen dioxide (NO₂), and ozone (O₃) was assessed at the geolocalization coordinates of the patients’ residential address. Logistic regression models were used to evaluate the association between air pollution and severity at diagnosis according to the Goh staging algorithm, and progression at 12 and 24 months. Results: We included 181 patients, 80% of whom were women; 44% had diffuse cutaneous scleroderma, and 56% had anti-topoisomerase I antibodies. ILD was extensive, according to the Goh staging algorithm, in 29% of patients. O₃ exposure was associated with the presence of extensive ILD at diagnosis (adjusted OR: 1.12, 95% CI 1.05–1.21; p value = 0.002). At 12 and 24 months, progression was noted in 27/105 (26%) and 48/113 (43%) patients, respectively. O₃ exposure was associated with progression at 24 months (adjusted OR: 1.10, 95% CI 1.02–1.19; p value = 0.02). We found no association between exposure to other air pollutants and severity at diagnosis and progression. Conclusion: Our findings suggest that high levels of O₃ exposure are associated with more severe SSc-associated ILD at diagnosis, and progression at 24 months.

Background and aims Systemic sclerosis (SSc) is an autoimmune connective disease characterised by excessive extracellular matrix deposition and widespread skin and internal organ fibrosis including various cardiac manifestations. Heart involvement is one of the leading causes of death among patients with SSc. In this study, we aimed to assess the effect of various vasodilator treatments. Methods We used data from a national multicentric prospective study using the French SSc national database. We estimated the average treatment effect (ATE) of sildenafil, bosentan, angiotensin-converting enzyme (ACE) inhibitors and iloprost on diastolic dysfunction, altered ejection fraction <50% and pulmonary arterial hypertension (PAH) using a causal method, namely the longitudinal targeted minimum loss-based estimation, to adjust for confounding and informative censoring. Results We included 1048 patients with available data regarding treatment. Regarding sildenafil analyses, the ATE on diastolic dysfunction at 3 years was −2.83% (95% CI −4.06; −1.60, p<0.00001), and the estimated ATE on altered ejection fraction <50% was −0.88% (95% CI −1.70; −0.05, p=0.037). We did not find a significative effect on PAH. Regarding bosentan, ACE inhibitors and iloprost, none of them neither showed a significant effect on diastolic dysfunction, altered ejection fraction <50% or PAH. Conclusions Using causal methods, our study is the first and largest suggesting that sildenafil might have benefits among SSc patients regarding diastolic dysfunction and altered ejection fraction occurrence. However, further studies assessing the effect of vasodilators on heart-related outcome among SSc patients are needed to confirm those exploratory results.