MORPHOLOGICAL INDICES ASSOCIATED WITH PULMONARY HYPERTENSION AND MORTALITY PREDICTION IN INTERSTITIAL LUNG DISEASE

TOPIC: Diffuse Lung Disease TYPE: Original Investigations PURPOSE: Pulmonary hypertension (PH) is common in interstitial lung disease (ILD) and associated with increased morbidity and mortality. PH detected by echocardiography (ECHO) impacts survival in patients with ILD. The mortality association of other surrogate indices of PH, such as clinical, serologic, histopathologic, and radiographic biomarkers, remains unclear. METHODS: The Indiana University (IRB#11488) and University of Chicago ILD (IRB#17-1617) databases were screened to identify patients with histopathologic specimens obtained from lung biopsies or at the time of lung transplantation from 2006-2019. Demographic, clinical, serologic, radiographic and histopathologic data were obtained from the electronic medical record (EMR). Pulmonary artery: aorta (PA/A) ratio was evaluated on computed tomography (CT) scans. Morphological indices of PH were deemed present upon identification of any of the following parameters: (a) PA/A >0.9 on CT; (b) right ventricular systolic pressure >40 mmHg on ECHO; (c) NT-proBNP >300pg/uL; or (d) pulmonary vasculopathy on histology. Patients with any of these PH indices were compared to those without. Six-minute walk distance (6MWD) was also assessed. Transplant-free survival was analyzed using Cox regression models. RESULTS: 568 patients with ILD and lung biopsies (idiopathic pulmonary fibrosis, n=260, connective tissue disease-ILD, n=75, hypersensitivity pneumonitis, n=102, interstitial pneumonia with autoimmune features, n=80, and other ILDs, n=51) were identified. Morphological PH indices were present in 71% (n=401). These patients had lower forced vital capacity (FVC, 59% vs 65%; P<0.001), lower diffusing capacity (DLCO, 44% vs 50%; P<0.001), shorter 6MWD (320m vs 356m; P=0.002), more frequently required supplemental oxygen (65% vs 46%; P<0.001), and had greater prevalence of CT honeycombing (52% vs 34%; P<0.001) when compared to those without.In unadjusted analyses, all morphological PH indices assessed predicted mortality. In contrast, only the PA/A ratio and histologic pulmonary vasculopathy remained predictive in fully adjusted models that accounted for age, sex, FVC, DLCO, ILD subtype, BMI, immunosuppression, smoking, hypothyroidism, and coronary artery disease. 6MWD >450m, and PH index absence remained predictive of improved survival (HR=0.55; 95%CI=0.34-0.89; P=0.016; and HR=0.74; 95%CI=0.56-0.98; P=0.039, respectively) in fully adjusted analyses. Presence of PA/A >0.9 combined with a 6MWD<450m predicted the highest risk for mortality in ILD (HR=2.31; 95%CI=1.83-2.92; P<0.001). CONCLUSIONS: Radiologic and histopathologic indices of PH are comparatively stronger predictors of survival than ECHO in patients with ILD. CLINICAL IMPLICATIONS: PH-associated indices on CT and 6MWD could be valuable surrogates in identifying patients with the highest mortality risk for earlier intervention in ILD. DISCLOSURES: Advisory Committee Member relationship with Genentech Please note: 2019 Added 04/26/2021 by Ayodeji Adegunsoye, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Boehringer Ingelheim Please note: 2018-2021 Added 04/29/2021 by Ayodeji Adegunsoye, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2018-2021 Added 04/29/2021 by Ayodeji Adegunsoye, source=Web Response, value=Honoraria Consultant relationship with Genentech Please note: 2018-2020 Added 04/29/2021 by Ayodeji Adegunsoye, source=Web Response, value=Consulting fee No relevant relationships by Remzi Bag, source=Web Response No relevant relationships by Linda Bocanegra-English, source=Web Response Consultant relationship with Boehringer Ingelheim Please note: 12 months Added 04/20/2021 by Ryan Boente, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Veracyte Please note: $1001 - $5000 by Jonathan Chung, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $1001 - $5000 by Jonathan Chung, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: $1001 - $5000 by Jonathan Chung, source=Web Response, value=Honoraria Advisory Committee Member relationship with Riverain Please note: current Added 06/02/2021 by Jonathan Chung, source=Web Response, value=Consulting fee No relevant relationships by john donatelli, source=Web Response No relevant relationships by Aliya Husain, source=Web Response No relevant relationships by Cathryn Lee, source=Web Response No relevant relationships by Steven Montner, source=Web Response No relevant relationships by Kavitha Selvan, source=Web Response No relevant relationships by Danielle Stahlbaum, source=Web Response PI relationship with Boehringer-Ingelheim Please note: >$100000 by Mary Strek, source=Web Response, value=Grant/Research Support PI relationship with Galapagos Please note: $70,000-100,00 Added 05/03/2021 by Mary Strek, source=Web Response, value=Grant/Research Support PI relationship with Novartis Please note: $5001 - $20000 by Mary Strek, source=Web Response, value=Grant/Research Support Removed 05/03/2021 by Mary Strek, source=Web Response Endpoint Adjudication Committee Member relationship with Fibrogen Please note: $1-$1000 by Mary Strek, source=Web Response, value=Honoraria No relevant relationships by Rekha Vij, source=Web Response