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Clinical Trial
. 2016 Sep 15;194(6):711-8.
doi: 10.1164/rccm.201508-1546OC.

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

Brett Ley  1 , Williamson Z Bradford  2 , Eric Vittinghoff  3 , Derek Weycker  4 , Roland M du Bois  5 , Harold R Collard  1
Affiliations
Clinical Trial

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

Brett Ley et al. Am J Respir Crit Care Med. .

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.

Keywords: 6-minute-walk distance; dyspnea; forced vital capacity; hospitalization; interstitial lung disease.

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Figures

Figure 1.
Figure 1.
Study design. 6MWD = 6-minute-walk distance; 6MWT = 6-minute-walk test; BMI = body mass index; DlCO = diffusing capacity of the lung for carbon monoxide; RH = respiratory hospitalization; UCSD SOBQ = University of California, San Diego Shortness of Breath Questionnaire.
Figure 2.
Figure 2.
Mean ± SE disease progression per week by Gender-Age-Physiology stage at study baseline. FVC change is in percent predicted per week, UCSD SOBQ change is in units per week, and 6MWD change is in meters per week. 6MWD = 6-minute-walk distance; UCSD SOBQ = University of California, San Diego Shortness of Breath Questionnaire.
Figure 3.
Figure 3.
Mean ± SE change in FVC % predicted per week categorized by past change in FVC % predicted over the previous 24 weeks.
Figure 4.
Figure 4.
Kaplan–Meier curves for 48-week respiratory hospitalization (Resp hosp) or death stratified by baseline Gender-Age-Physiology (GAP) stage.
See this image and copyright information in PMC

Comment in

References

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