. 2022 Mar 31;59(3):2101181.

doi: 10.1183/13993003.01181-2021. Print 2022 Mar.

Biomarker signatures for progressive idiopathic pulmonary fibrosis

Britt Clynick^{1

2

3

4}, Tamera J Corte^{1

5

6

4}, Helen E Jo^{1

5

6}, Iain Stewart⁷, Ian N Glaspole^{8

9}, Christopher Grainge^{10

11}, Toby M Maher¹², Vidya Navaratnam^{7

13}, Richard Hubbard⁷, Peter M A Hopkins^{14

15}, Paul N Reynolds^{16

17}, Sally Chapman¹⁷, Christopher Zappala¹⁴, Gregory J Keir¹⁴, Wendy A Cooper^{5

6

18}, Annabelle M Mahar⁶, Samantha Ellis^{8

9}, Nicole S Goh^{19

20}, Emma De Jong^{2

3}, Lilian Cha^{2

3}, Dino B A Tan^{2

3}, Lucy Leigh^{10

21}, Christopher Oldmeadow^{10

21}, E Haydn Walters^{1

9

22

23

24}, R Gisli Jenkins⁷, Yuben Moodley^{25

2

3

26}

Affiliations

¹ Centre of Research Excellence in Pulmonary Fibrosis, Camperdown, Australia.
² Institute for Respiratory Health Inc., Nedlands, Australia.
³ University of Western Australia, Crawley, Australia.
⁴ These two authors are joint first authors.
⁵ The University of Sydney Central Clinical School, Camperdown, Australia.
⁶ Royal Prince Alfred Hospital, Camperdown, Australia.
⁷ NIHR Biomedical Research Centre, Respiratory Theme, University of Nottingham, Nottingham, UK.
⁸ Monash University, Clayton, Australia.
⁹ Alfred Hospital, Melbourne, Australia.
¹⁰ University of Newcastle, Callaghan, Australia.
¹¹ John Hunter Hospital, New Lambton Heights, Australia.
¹² University of Southern California, Los Angeles, CA, USA.
¹³ Nottingham University Hospitals, Nottingham, UK.
¹⁴ University of Queensland, St Lucia, Australia.
¹⁵ Prince Charles Hospital, Chermside, Australia.
¹⁶ University of Adelaide, Adelaide, Australia.
¹⁷ Royal Adelaide Hospital, Adelaide, Australia.
¹⁸ Western Sydney University, Sydney, Australia.
¹⁹ Austin Hospital, Heidelberg, Australia.
²⁰ Institute of Breathing and Sleep, Heidelberg, Australia.
²¹ Hunter Medical Research Institute, Newcastle, Australia.
²² University of Tasmania, Hobart, Australia.
²³ University of Melbourne, Parkville, Australia.
²⁴ Royal Hobart Hospital, Hobart, Australia.
²⁵ Centre of Research Excellence in Pulmonary Fibrosis, Camperdown, Australia yuben.moodley@uwa.edu.au.
²⁶ Fiona Stanley Hospital, Murdoch, Australia.

PMID: 34675050
DOI: 10.1183/13993003.01181-2021

Free article

Biomarker signatures for progressive idiopathic pulmonary fibrosis

Britt Clynick et al. Eur Respir J. 2022.

Free article

. 2022 Mar 31;59(3):2101181.

doi: 10.1183/13993003.01181-2021. Print 2022 Mar.

Authors

Affiliations

¹ Centre of Research Excellence in Pulmonary Fibrosis, Camperdown, Australia.
² Institute for Respiratory Health Inc., Nedlands, Australia.
³ University of Western Australia, Crawley, Australia.
⁴ These two authors are joint first authors.
⁵ The University of Sydney Central Clinical School, Camperdown, Australia.
⁶ Royal Prince Alfred Hospital, Camperdown, Australia.
⁷ NIHR Biomedical Research Centre, Respiratory Theme, University of Nottingham, Nottingham, UK.
⁸ Monash University, Clayton, Australia.
⁹ Alfred Hospital, Melbourne, Australia.
¹⁰ University of Newcastle, Callaghan, Australia.
¹¹ John Hunter Hospital, New Lambton Heights, Australia.
¹² University of Southern California, Los Angeles, CA, USA.
¹³ Nottingham University Hospitals, Nottingham, UK.
¹⁴ University of Queensland, St Lucia, Australia.
¹⁵ Prince Charles Hospital, Chermside, Australia.
¹⁶ University of Adelaide, Adelaide, Australia.
¹⁷ Royal Adelaide Hospital, Adelaide, Australia.
¹⁸ Western Sydney University, Sydney, Australia.
¹⁹ Austin Hospital, Heidelberg, Australia.
²⁰ Institute of Breathing and Sleep, Heidelberg, Australia.
²¹ Hunter Medical Research Institute, Newcastle, Australia.
²² University of Tasmania, Hobart, Australia.
²³ University of Melbourne, Parkville, Australia.
²⁴ Royal Hobart Hospital, Hobart, Australia.
²⁵ Centre of Research Excellence in Pulmonary Fibrosis, Camperdown, Australia yuben.moodley@uwa.edu.au.
²⁶ Fiona Stanley Hospital, Murdoch, Australia.

PMID: 34675050
DOI: 10.1183/13993003.01181-2021

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.

Trial registration: ClinicalTrials.gov NCT01134822.

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Conflict of interest statement

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.

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Biomarker signatures for progressive idiopathic pulmonary fibrosis

Affiliations

Biomarker signatures for progressive idiopathic pulmonary fibrosis

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous