Significance of autoimmune disease in severe pulmonary hypertension complicating extensive pulmonary fibrosis: a prospective cohort study

Rajeev Saggar; Paresh C Giri; Chunqin Deng; Dana Johnson; Mary K McCloy; Lloyd Liang; Faisal Shaikh; Jason Hong; Richard N Channick; Shelley S Shapiro; Joseph P Lynch; John A Belperio; Samuel S Weigt; Allison L Ramsey; David J Ross; David M Sayah; Michael Y Shino; Ariss Derhovanessian; Alexander E Sherman; Rajan Saggar

doi:10.1177/20458940211011329

Significance of autoimmune disease in severe pulmonary hypertension complicating extensive pulmonary fibrosis: a prospective cohort study

Pulm Circ. 2021 May 2;11(2):20458940211011329. doi: 10.1177/20458940211011329. eCollection 2021 Apr-Jun.

Authors

Rajeev Saggar¹, Paresh C Giri², Chunqin Deng³, Dana Johnson³, Mary K McCloy⁴, Lloyd Liang⁴, Faisal Shaikh⁴, Jason Hong⁴, Richard N Channick⁴, Shelley S Shapiro⁴, Joseph P Lynch⁴, John A Belperio⁴, Samuel S Weigt⁴, Allison L Ramsey⁴, David J Ross⁵, David M Sayah⁴, Michael Y Shino⁴, Ariss Derhovanessian⁴, Alexander E Sherman⁴, Rajan Saggar⁴

Affiliations

¹ Theravance Biopharma, San Francisco, USA.
² Division of Pulmonary and Critical Care Medicine, Loma Linda University School of Medicine, Loma Linda, USA.
³ United Therapeutics Corp., Durham, USA.
⁴ David Geffen School of Medicine, University of California Los Angeles, Los Angeles, USA.
⁵ Transplant Molecular Genomics, Brisbane, USA.

Abstract

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 D_LCO (% 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.

Keywords: autoimmune disease; pulmonary fibrosis; pulmonary hypertension.