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

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.Electronic supplementary materialThe online version of this article (10.1186/s12890-018-0575-y) contains supplementary material, which is available to authorized users.

Efficacy and safety of nintedanib in patients with advanced idiopathic pulmonary fibrosis

“…In our analyses, HRQL at baseline, assessed using the SGRQ total score, was worse in patients in the INSTAGE trial than in the INPULSIS trials. Previous studies have also shown that patients with IPF who have more advanced disease based on % predicted values for FVC and/or DLco have worse symptoms, worse exercise capacity, and worse HRQL [27][28][29]. In both the INPUL-SIS and INSTAGE trials, changes in SGRQ total score over 24 weeks were small, consistent with previous studies showing that small changes in FVC are not associated with meaningful changes in the patient-reported outcomes commonly used in patients with IPF [30,31].…”

Eligibility for anti‐fibrotic treatment in idiopathic pulmonary fibrosis depends on the predictive equation used for pulmonary function testing

“…The often arbitrary percentage predicted value that divides ‘normal’ and ‘abnormal’ or stages of disease are now questionable as they can easily be altered by using a different reference equation; it is highly likely that certain equations will show better and worse predicted values in one disease and not another, leading to a question of which equation is ‘best’. Despite the differences demonstrated between equations, none performed substantially better than any other in predicting mortality; however, we did demonstrate that TLco better predicts all‐cause survival than FVC and FEV 1 /FVC …”

“…Despite the differences demonstrated between equations, none performed substantially better than any other in predicting mortality; however, we did demonstrate that TLco better predicts all-cause survival than FVC and FEV 1 /FVC. 22,40 As a result of this work, we developed an automated reference table whereby a patient's demographics can be inserted and the %predicted values will be calculated for the reference equations included in this paper (Supplementary Information). This is not an exhaustive list; however, it may be useful for clinicians who treat IPF in a Caucasian population.…”

“…A retrospective cross‐sectional analysis of reference equation variability was performed by calculating %predicted results from all PFT for patients aged over 18 years at a single institution (John Hunter Hospital, JHH) from April 2005 to April 2017 (20 378 tests) (Appendix S5 in Supplementary Information). A second similar analysis was performed on 545 tests from the AIPFR, a national registry collating longitudinal data from patients with IPF since 2012 . All patient records were de‐identified.…”

“…Major Australian ILD centres were surveyed to identify reference equations in use; in addition, other published equations applicable to a Caucasian population were studied ( 21,22 All patient records were de-identified. Ethical approval and waiver and consent were obtained from Hunter New England and Sydney Local Health District Ethics Review Committee (RPAH Zone); approval numbers X17-0255 and LNR/17/ RPAH/378, LNRSSA/17/RPAH/430.…”