External validation and longitudinal application of the DO-GAP index to individualise survival prediction in idiopathic pulmonary fibrosis

Abhimanyu Chandel; Christopher S King; Rosalinda V Ignacio; Jean Pastre; Oksana A Shlobin; Vikramjit Khangoora; Shambhu Aryal; Alan Nyquist; Anju Singhal; Kevin R Flaherty; Steven D Nathan

doi:10.1183/23120541.00124-2023

External validation and longitudinal application of the DO-GAP index to individualise survival prediction in idiopathic pulmonary fibrosis

ERJ Open Res. 2023 May 9;9(3):00124-2023. doi: 10.1183/23120541.00124-2023. eCollection 2023 May.

Affiliations

¹ Department of Pulmonary and Critical Care, Walter Reed National Military Medical Center, Bethesda, MD, USA.
² Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, VA, USA.
³ Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
⁴ Service de Pneumologie et Soins Intensifs, Hôpital Européen Georges Pompidou, APHP, Paris, France.
⁵ Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA.

Abstract

Background: The Distance-Oxygen-Gender-Age-Physiology (DO-GAP) index has been shown to improve prognostication in idiopathic pulmonary fibrosis (IPF) compared to the Gender-Age-Physiology (GAP) score. We sought to externally validate the DO-GAP index compared to the GAP index for baseline risk assessment in patients with IPF. Additionally, we evaluated the utility of serial change in the DO-GAP index in predicting survival.

Methods: We performed an analysis of patients with IPF from the Pulmonary Fibrosis Foundation-Patient Registry (PFF-PR). Discrimination and calibration of the two models were assessed to predict transplant-free survival and IPF-related mortality. Joint longitudinal time-to-event modelling was utilised to individualise survival prediction based on DO-GAP index trajectory.

Results: There were 516 patients with IPF from the PFF-PR with available demographics, pulmonary function tests, 6-min walk test data and outcomes included in this analysis. The DO-GAP index (C-statistic: 0.73) demonstrated improved discrimination in discerning transplant-free survival compared to the GAP index (C-statistic: 0.67). DO-GAP index calibration was adequate, and the model retained predictive accuracy to identify IPF-related mortality (C-statistic: 0.74). The DO-GAP index was similarly accurate in the subset of patients taking antifibrotic medications. Serial change in the DO-GAP index improved model discrimination (cross-validated area under the curve: 0.83) enabling the personalised prediction of disease trajectory in individual patients.

Conclusion: The DO-GAP index is a simple, validated, multidimensional score that accurately predicts transplant-free survival in patients with IPF and can be adapted longitudinally in individual patients. The DO-GAP may also find use in studies of IPF to risk stratify patients and possibly as a clinical trial end-point.