Predictors of death or lung transplant after a diagnosis of idiopathic pulmonary fibrosis: insights from the IPF-PRO Registry

Laurie Snyder,Shaun Bender,Megan L Neely,Emily O’Brien,Daniel A Culver,Scott Palmer,Robert J Kaner,Mridu Gulati,Hyun Joo Kim,Thomas Leonard,Craig S Conoscenti,Joao De Andrade,Anne S Hellkamp

doi:10.1186/s12931-019-1043-9

Abstract

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive disease with a variable clinical course and high mortality. We used data from a large national US registry of patients with IPF to investigate relationships between patient characteristics, including markers of disease severity, and mortality.MethodsThe analysis cohort comprised patients enrolled in the IPF-PRO Registry from its inception on 5 June 2014 to 26 October 2017. The primary criterion for inclusion in this registry is that patients must be diagnosed or confirmed with IPF at the enrolling centre within 6 months. Associations between patient characteristics and markers of disease severity at enrolment and mortality outcomes were investigated using univariable, multivariable and adjustment models.ResultsAmong 662 patients enrolled, 111 patients died or had a lung transplant over a follow-up period of 30 months. The probability of being free of both events at month 30 was 50.6% (95% CI: 40.0, 60.2). When patient characteristics and markers of disease severity were jointly examined in a multivariable analysis, oxygen use at rest (hazard ratio [HR] 2.44 [95% CI: 1.45, 4.10]), lower forced vital capacity (FVC) % predicted (HR 1.28 [95% CI: 1.10, 1.49] per 10% decrease) and diffusion capacity for carbon monoxide (DLco) % predicted (HR 1.25 [95% CI: 1.04, 1.51] per 10% decrease) were significantly associated with increased risk of death or lung transplant. The risk of death or lung transplant increased with increasing age in patients ≥62 years old (HR 1.18 [95% CI: 0.99, 1.40] per 5-year increase), and decreased with increasing age in patients <62 years old (HR 0.60 [95% CI: 0.39, 0.92] per 5-year increase).ConclusionsIn an observational US registry of patients with IPF, oxygen use at rest, lower FVC % predicted, and lower DLco % predicted were associated with risk of death or lung transplant. An audio podcast of the lead author discussing these data can be downloaded from: http://www.usscicomms.com/respiratory/snyder/IPF-PROsurvival1/.Trial registrationClinicalTrials.gov number: NCT01915511.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) characterised by decline in lung function and high mortality [1]
In the analysis adjusted for patient characteristics in the adjustment model, worse forced vital capacity (FVC) % predicted (HR 1.36 [95% CI: 1.18, 1.57] per 10% decrease), worse DLco % predicted (HR 1.38 [95% CI: 1.15, 1.64] per 10% decrease), and worse disease severity according to composite physiologic index (CPI) (HR 1.30 [95% CI: 1.15, 1.46] per 5-point increase) and GAP stage (HR 1.68 [95% CI: 0.95, 2.99] for II vs I; Hazard ratio (HR) 2.93 [95% CI: 1.48, 5.80] for III vs I) were significantly associated with an increased risk of death or lung transplant (Fig. 4b)
In a national US registry of patients diagnosed or confirmed with IPF at the enrolling centre within 6 months, we found that the probability of death or lung transplant over a follow-up period of 30 months, based on Kapan-Meier estimates, was approximately 50%

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) characterised by decline in lung function and high mortality [1]. IPF has a variable clinical course, but a number of patient and clinical characteristics have been shown to be predictors of mortality in single-centre reports, clinical trial data and registry studies These include older age; male sex; lower body mass index (BMI); definite usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT); low, or decline in, forced vital capacity (FVC), diffusing capacity of the lungs for Snyder et al Respiratory Research (2019) 20:105 carbon monoxide (DLco), or exercise capacity (6-min walk distance, 6MWD); use of supplemental oxygen; and a history of respiratory-related hospitalisation [4, 6,7,8,9,10,11,12,13,14]. We used data from a large national US registry of patients with IPF to investigate relationships between patient characteristics, including markers of disease severity, and mortality

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Conclusion