Pulmonary arterial hypertension associated with exposure to toxic rapeseed oil.

Aims: Toxic oil syndrome (TOS) was one of the first described forms of drug-induced pulmonary arterial hypertension (PAH). Its long-term clinical evolution remains poorly understood. The objectives of the present study were to provide new clinical, pathological and genetic insights into TOS-associated PAH (TOS-PAH), and to evaluate its long-term outcomes. Methods: Patients diagnosed with TOS-PAH and included in the Spanish Registry of PAH (REHAP) were prospectively analysed. Results: 59 new cases were diagnosed between 1997 and 2025 (63% female; median age 47 years), including several in the past two decades. The median interval between TOS exposure and PAH diagnosis was 270.8 months (interquartile range (IQR) 204.9-398.0). Patients diagnosed in earlier periods were younger, with more advanced functional impairment and more severe haemodynamics. In contrast, recent cohorts showed a higher prevalence of cardiovascular and respiratory comorbidities. No significant differences were observed in overall or transplant-free survival across decades (p=0.677). Median transplantation-free survival was 97.2 months (IQR 64.2-199.4). Three patients achieved complete haemodynamic resolution. Genetic testing was negative in all evaluated patients. Pathological findings were comparable with those observed in other PAH forms, with some cases with significant venous remodelling. Conclusions: TOS-PAH remains a distinct clinical entity, with new cases diagnosed decades after toxic exposure. Despite differences in presentation over time, its long-term clinical course appears similar to that of other PAH types.