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

Abstract

Background: Idiopathic 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.

Methods: The 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.

Results: Among 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).

Conclusions: In 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 registration: ClinicalTrials.gov number: NCT01915511 .

Fig. 1

Kaplan-Meier estimate of time from enrolment in the IPF-PRO Registry to death or lung transplant

Fig. 2

Spline transformation for patient age at enrolment. Orange line and band show predicted 1-year event rate with 95% CI from the model including age, oxygen use at rest, oxygen use with activity, FVC % predicted and DLco % predicted. Observed (Kaplan-Meier) rates are from age groups defined in 5-year intervals. Group age ranges and patient numbers are: ≤60 years (n = 76), 61–65 years (n = 99), 66–70 years (n = 175), 71–75 years (n = 165), 75–80 years (n = 103) and >80 years (n = 44)

Fig. 3

Associations between patient characteristics and death or lung transplant in (a) univariable models, b a multivariable model, and (c) an adjustment model

Fig. 4

Associations between markers of disease severity and death or lung transplant in (a) univariable models and (b) a model adjusted for patient characteristics

Fig. 5

Joint association between patient characteristics and disease severity markers, and death or lung transplant