Disease progression in idiopathic pulmonary fibrosis with mild physiological impairment: analysis from the Australian IPF registry

Helen E Jo,Christopher Zappala,Tamera J Corte,Sally Chapman,E Haydn Walters,Ian Glaspole,Samantha Ellis,Annabelle Mahar,Wendy Cooper,Paul Reynolds,Yuben Moodley,Heather Allan,Sacha Macansh,Nicole Goh,Greg Keir,Peter Hopkins,Christopher Grainge

doi:10.1186/s12890-018-0575-y

Abstract

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrosing lung disease of unknown cause. The advent of anti-fibrotic medications known to slow disease progression has revolutionised IPF management in recent years. However, little is known about the natural history of IPF patients with mild physiological impairment. We aimed to assess the natural history of these patients using data from the Australian IPF Registry (AIPFR).MethodsUsing our cohort of real-world IPF patients, we compared FVC criteria for mild physiological impairment (FVC ≥ 80%) against other proposed criteria: DLco ≥ 55%; CPI ≤40 and GAP stage 1 with regards agreement in classification and relationship with disease outcomes. Within the mild cohort (FVC ≥ 80%), we also explored markers associated with poorer prognosis at 12 months.ResultsOf the 416 AIPFR patients (mean age 70.4 years, 70% male), 216 (52%) were classified as ‘mild’ using FVC ≥ 80%. There was only modest agreement between FVC and DLco (k = 0.30), with better agreement with GAP (k = 0.50) and CPI (k = 0.48). Patients who were mild had longer survival, regardless of how mild physiologic impairment was defined. There was, however, no difference in the annual decline in FVC% predicted between mild and moderate-severe groups (for all proposed criteria). For patients with mild impairment (n = 216, FVC ≥ 80%), the strongest predictor of outcomes at 12 months was oxygen desaturation on a 6 min walk test.ConclusionIPF patients with mild physiological impairment have better survival than patients with moderate-severe disease. Their overall rate of disease progression however, is comparable, suggesting that they are simply at different points in the natural history of IPF disease.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrosing lung disease of unknown cause
Logistic regression assessing a composite end-point of death or disease progression at 12 months was performed in patients with mild impairment (FVC ≥ 80%) at baseline, to determine markers associated with poorer shortterm prognosis in this group
In our cohort of IPF patients from the Australian IPF Registry, we demonstrate that a significant proportion of IPF patients have mild physiological impairment; though this proportion varied depending on the criteria and threshold used to define mild impairment

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrosing lung disease of unknown cause. The advent of anti-fibrotic medications known to slow disease progression has revolutionised IPF management in recent years. Little is known about the natural history of IPF patients with mild physiological impairment. Idiopathic pulmonary fibrosis (IPF), a progressive fibrosing interstitial lung disease (ILD) of unknown cause, results in respiratory failure and death. The two most commonly used composite scores are the composite physiological index (CPI) [14] and the GAP (gender, age and physiology) stage [15] While both individual physiologic measurements and composite scores predict mortality, the ability of each to distinguish differences in disease progression among those with mild disease from those more significantly affected remains unknown. The FVC has been used as a clinical trial endpoint, and by funding authorities worldwide to limit access to anti-fibrotic medications

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