The association of
autoimmune disease (AI) with transplant-free survival in the setting of severe Group 3
pulmonary hypertension and extensive
pulmonary fibrosis remains unclear. We report cases of severe
pulmonary hypertension (mean pulmonary artery pressure ≥35 mmHg and
right ventricular dysfunction) and extensive
pulmonary fibrosis after
pulmonary arterial hypertension-specific
therapy. We used multivariate regression to determine the clinical variables associated with transplant-free survival. Of 286 screened patients, 55 demonstrated severe
pulmonary hypertension and extensive
pulmonary fibrosis and were treated with parenteral
prostacyclin therapy. The (+)AI subgroup (n = 34), when compared to the (-)AI subgroup (n = 21), was more likely to be female (77% versus 19%) and younger (58.7 ± 12.1 versus 66.0 ± 10.7 years), and revealed lower forced vital capacity (absolute) (1.9 ± 0.7 versus 2.9 ± 1.1 L), higher DLCO (% predicted) (31.1 ± 15.2 versus 23.2 ± 8.0), and increased unadjusted transplant-free survival (1 year (84.6 ± 6.3% versus 45 ± 11.1%)), 3 years (71 ± 8.2% versus 28.6 ± 11.9%), and 5 years (47.6 ± 9.6% versus 6.4 ± 8.2%); (p = 0.01)). Transplant-free survival was unchanged after adjusting for age and gender. The pulmonary hemodynamic profiles improved after parenteral
prostacyclin therapy, independent of AI status. The baseline variables associated with mortality included age at
pulmonary hypertension diagnosis (heart rate (HR) 1.23 (confidence interval (CI) 1.03-1.47); p = 0.02) and presence of AI (HR 0.26 (confidence interval (CI) 0.10-0.70); p < 0.01). Gas exchange was not adversely affected by parenteral
prostacyclin therapy. In the setting of severe Group 3
pulmonary hypertension and extensive
pulmonary fibrosis treated with
pulmonary arterial hypertension-specific
therapy, AI is independently associated with increased transplant-free survival.
Pulmonary hypertension/
pulmonary fibrosis associated with AI should be considered in future clinical trials of
pulmonary arterial hypertension-specific
therapy in Group 3
pulmonary hypertension.