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

Abstract

Background: The association of autoimmune disease (AI) with transplant-free survival in the setting of severe Group 3 Pulmonary Hypertension (PH) and extensive Pulmonary Fibrosis (PF) remains unclear. Methods: We report cases of severe PH [mean pulmonary artery pressure (mPAP) >35mmHg and right ventricular (RV) dysfunction] and extensive PF after pulmonary arterial hypertension (PAH)-specific therapy. We used multivariate regression to determine the clinical variables associated with transplant-free survival. Results: Of 286 screened patients, 55 demonstrated severe PH and extensive PF 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 FVC [absolute] (1.9+0.7 versus 2.9+1.1 liters), 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 year (71+8.2% versus 28.6+11.9%), and 5 year (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 PH diagnosis (HR 1.23 [CI 1.03-1.47]; p=0.02) and presence of AI (HR 0.26 [CI 0.10-0.70]; p<0.01). Gas exchange was not adversely affected by parenteral prostacyclin therapy. Conclusions: In the setting of severe Group 3 PH and extensive PF treated with PAH-specific therapy, AI is independently associated with increased transplant-free survival. PH/PF associated with AI should be considered in future clinical trials of PAH-specific therapy in Group 3 PH.

Hydroxychloroquine on the Pulmonary Vascular Diseases in Interstitial Lung Disease: Immunologic Effects, and Virus Interplay

“…The PVD may be found in any stage of the course of CTD-ILD or autoimmune disease-related ILDs with or without fibrosing [ 23 , 24 ]. Meanwhile, the PVD, in the late course of lupus with PF-ILD, was life-threatening [ 25 , 26 ]. In the recent Chiu et al study, they found that (20/150, 22%) with HCQ use and (17/150, 11.3%) with PAH in the 150 patients had ILD (33/150, 33% fibrotic predominant, PF-ILD) [ 2 ].…”

Pathogenesis, clinical features, and phenotypes of pulmonary hypertension associated with interstitial lung disease: A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative ‐ Group 3 Pulmonary Hypertension

“…In patients with SSc presenting with ILD and PH, there is no association between the extent of ILD on imaging and the severity of pulmonary hemodynamics 52 . In one study, patients with pulmonary fibrosis and PH associated with an autoimmune disease had increased survival after the administration of PAH‐targeted therapy, compared with ILD‐PH patients without autoimmune disease 53 . On the contrary, no apparent physiologic differences in response to pulmonary vasodilator treatment were found comparing SSc‐ILD with PH patients and SSc‐PAH 54 patients.…”

“…52 In one study, patients with pulmonary fibrosis and PH associated with an autoimmune disease had increased survival after the administration of PAH‐targeted therapy, compared with ILD‐PH patients without autoimmune disease. 53 On the contrary, no apparent physiologic differences in response to pulmonary vasodilator treatment were found comparing SSc‐ILD with PH patients and SSc‐PAH 54 patients. This latter study also found that patients with SSc‐ILD associated with PH had worse survival than SSc‐PAH patients, albeit they have better survival than IPF patients with associated PH.…”

“…Even though ILD-PH associated with autoimmune disease is not an established phenotype, the argument for differentiating it hinges on the difference in its clinical behavior and prognosis 55 compared to ILD-PH without autoimmune disease. 53 Post-tuberculosis PH It is estimated that there were 155 million survivors of tuberculosis alive in 2020, many of whom will meet the criteria for post-tuberculosis lung disease (PTBLD). 56 PTBLD is currently defined as "Evidence of chronic respiratory abnormality, with or without symptoms, attributable at least in part to previous tuberculosis."…”

“…The three phenomena are associated with varying degrees of inflammation. Even though ILD‐PH associated with autoimmune disease is not an established phenotype, the argument for differentiating it hinges on the difference in its clinical behavior and prognosis 55 compared to ILD‐PH without autoimmune disease 53 …”