Predictors of Mortality Poorly Predict Common Measures of Disease Progression in Idiopathic Pulmonary Fibrosis

Abstract

Rationale: Mortality prediction is well studied in idiopathic pulmonary fibrosis (IPF), but little is known about predictors of premortality disease progression. Identification of patients at risk for disease progression would be useful for clinical decision-making and designing clinical trials.Objectives: To develop prediction models for disease progression in IPF.Methods: In a large clinical trial cohort of patients with IPF (n = 1,113), we comprehensively screened multivariate models of candidate baseline and past-change predictors for disease progression defined by 48-week worsening of FVC, dyspnea (University of California, San Diego Shortness of Breath Questionnaire [UCSD SOBQ]), 6-minute-walk distance (6MWD), and occurrence of respiratory hospitalization, or death. Progression outcomes were modeled as appropriate, by slope change using linear regression models and time to binary outcomes using Cox proportional hazards models. Measurements and Main Results:The overall cohort experienced considerable disease progression. Top-performing prediction models did not meaningfully predict most measures of disease progression. For example, prediction modeling explained less than or equal to 1% of the observed variation in 48-week slope change in FVC, UCSD SOBQ, and 6MWD. Models performed better for binary measures of time to disease progression but were still largely inaccurate (cross-validated C statistic <0.63 for >10% decline in FVC or death, <0.68 for >20-U increase in UCSD SOBQ or death, <0.70 for >100 m decline in 6MWD or death). Models for time to respiratory hospitalization or death (C statistic <0.77) or death alone (C statistic <0.81) demonstrated acceptable discriminative performance.Conclusions: Clinical prediction models poorly predicted physiologic and functional disease progression in IPF. This is in contrast to respiratory hospitalization and mortality prediction.

Prognosis and longitudinal changes of physical activity in idiopathic pulmonary fibrosis

“…Therefore, the relatively preserved exercise capacity in our study might be biased by the fact that patients with rapid 6MWD-decline did not survive three years of observation [10]. For that same reason, the data on 6MWD-decline from other cohorts with an observation period of twelve months only, might not be comparable to our 3-year data with its calculated annual decline [27, 31, 32]. Nevertheless, our present study depicts an astonishing discrepancy between 6MWD and physical activity when studied longitudinally in patients with IPF.…”

miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis

“…Currently, IPF is the most life-threatening idiopathic disease, presenting a mortality rate that exceeds those of numerous cancers [10,13]. Although several genetic, epigenetic, and proteomic studies have been conducted to date, studies investigating miRNA regulatory networks in IPF have only recently gained significant attention [2].…”

Evaluating disease severity in idiopathic pulmonary fibrosis

“…Indeed, when incorporated within clinical prediction models, they perform better at predicting binary outcomes like respiratory hospitalisation and death than intrinsic disease progression [54]. This highlights the need for the development and validation of tools that have the potential to predict disease behaviour and risk of progression which would be useful in clinical decision-making and designing future clinical trials.…”