Abstract
Background Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers have the potential for guiding management in clinical practice. We assessed the prognostic role of serum biomarkers in three independent IPF cohorts: Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE).
Methods In the AIPFR cohort, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. LASSO (least absolute shrinkage and selection operator) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at 1 year in the AIPFR cohort, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in the PROFILE cohort. Four significantly replicating biomarkers were aggregated into a progression index model based on tertiles of circulating concentrations.
Results 189 participants were included in the AIPFR cohort, 205 participants from the TLF cohort and 122 participants from the PROFILE cohort. Differential biomarker expression was observed by ELISA and replicated for osteopontin, matrix metallopeptidase-7, intercellular adhesion molecule-1 and periostin for those with a progressor phenotype at 1 year. Proteomic data did not replicate. The progression index in the AIPFR, TLF and PROFILE cohorts predicted risk of progression, mortality and progression-free survival. A statistical model incorporating the progression index demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP (gender, age and physiology) score model alone in all cohorts, and significantly so within the incidence-based TLF and PROFILE cohorts.
Conclusion A panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.
Abstract
Pathobiologically relevant circulatory biomarkers were found to be associated with IPF progression and mortality, and a statistical model incorporating these markers into a progression index score showed improved prognostication across all outcomes https://bit.ly/37L0oMl
Footnotes
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Conflict of interest: B. Clynick has nothing to disclose.
Conflict of interest: T.J. Corte reports grants, personal fees and nonfinancial support from Boehringer Ingelheim, grants and personal fees from Roche, grants from Galapagos, Actelion and Bayer, outside the submitted work.
Conflict of interest: H.E. Jo reports other (travel support and lecture fees) from Boehringer Ingelheim and Roche, outside the submitted work.
Conflict of interest: I. Stewart has nothing to disclose.
Conflict of interest: I.N. Glaspole reports personal fees for advisory board work from Boehringer Ingelheim and Roche, outside the submitted work.
Conflict of interest: C. Grainge reports personal fees for advisory board work from Boehringer Ingelheim and Roche, outside the submitted work.
Conflict of interest: T.M. Maher reports grants, personal fees and nonfinancial support from UCB, grants and personal fees from GlaxoSmithKline and AstraZeneca, personal fees from Boehringer Ingelheim, Roche, Bayer, Prometic, Samumed, Galapagos, Celgene, Indalo, Pliant, Blade Therapeutics, Respivant, Novartis and Bristol-Myers Squibb, other (stock options) from Apellis, outside the submitted work.
Conflict of interest: V. Navaratnam has nothing to disclose.
Conflict of interest: R. Hubbard has nothing to disclose.
Conflict of interest: P.M.A. Hopkins has nothing to disclose.
Conflict of interest: P.N. Reynolds has nothing to disclose.
Conflict of interest: S. Chapman reports personal fees for advisory board work from Boehringer Ingelheim and Roche, outside the submitted work.
Conflict of interest: C. Zappala has nothing to disclose.
Conflict of interest: G.J. Keir has nothing to disclose.
Conflict of interest: W.A. Cooper has nothing to disclose.
Conflict of interest: A.M. Mahar has nothing to disclose.
Conflict of interest: S. Ellis has nothing to disclose.
Conflict of interest: N.S. Goh reports grants from the National Health Medical Research Council (NHMRC) (APP1066128, APP114776) and the Centre of Research Excellence in Pulmonary Fibrosis (CRE-PF), Australia (NHMRC GNT116371; 2017-2021), during the conduct of the study; the PROFILE study was funded by the Medical Research Council (G0901226) and GlaxoSmithKline R&D (CRT114316).
Conflict of interest: E. De Jong has nothing to disclose.
Conflict of interest: L. Cha has nothing to disclose.
Conflict of interest: D.B.A. Tan has nothing to disclose.
Conflict of interest: L. Leigh has nothing to disclose.
Conflict of interest: C. Oldmeadow has nothing to disclose.
Conflict of interest: E.H. Walters has nothing to disclose.
Conflict of interest: R.G. Jenkins reports other (sponsored research agreements) from AstraZeneca, Biogen and Galecto, outside the submitted work; is on advisory boards for Boehringer Ingelheim, NuMedii, Promedior and Redex; reports lecture fees and consultancy for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Heptares, Pliant and Roche; and is a trustee for Action for Pulmonary Fibrosis.
Conflict of interest: Y. Moodley reports personal fees for advisory board work from Boehringer Ingelheim and Roche, outside the submitted work.
Support statement: The study is supported by the National Health Medical Research Council (NHMRC) grants (APP1147776 and APP1066128) and the Centre of Research Excellence in Pulmonary Fibrosis (GNT116371; supported by the NHMRC, Lung Foundation Australia and industry sponsors including: Boehringer Ingelheim, Roche Products Pty Ltd, Galapagos and Bristol-Myers Squibb Australia). Lung Foundation Australia has established the Australian Idiopathic Pulmonary Fibrosis Registry with the generous support of unrestricted educational grant from Foundation Partners Roche Products Pty Ltd and Boehringer Ingelheim. The PROFILE study was funded by the Medical Research Council (G0901226) and GlaxoSmithKline R&D (CRT114316), and was sponsored by Nottingham University and the Royal Brompton and Harefield NHS Foundation Trust. Additionally, R.G. Jenkins is supported by an NIHR Research Professorship (RP-2017-08-ST2-014); T.M. Maher is supported by a National Institute for Health Research Clinician Scientist Fellowship (CS-2013-13-017). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received April 25, 2021.
- Accepted August 3, 2021.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
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