Biomarker signatures for progressive idiopathic pulmonary fibrosis

Britt Clynick; Tamera J Corte; Helen E Jo; Iain Stewart; Ian N Glaspole; Christopher Grainge; Toby M Maher; Vidya Navaratnam; Richard Hubbard; Peter M A Hopkins; Paul N Reynolds; Sally Chapman; Christopher Zappala; Gregory J Keir; Wendy A Cooper; Annabelle M Mahar; Samantha Ellis; Nicole S Goh; Emma De Jong; Lilian Cha; Dino B A Tan; Lucy Leigh; Christopher Oldmeadow; E Haydn Walters; R Gisli Jenkins; Yuben Moodley

doi:10.1183/13993003.01181-2021

Biomarker signatures for progressive idiopathic pulmonary fibrosis

Eur Respir J. 2022 Mar 31;59(3):2101181. doi: 10.1183/13993003.01181-2021. Print 2022 Mar.

Authors

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

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Australia
Biomarkers
Humans
Idiopathic Pulmonary Fibrosis* / diagnosis
Idiopathic Pulmonary Fibrosis* / genetics
Prospective Studies
Proteomics
Retrospective Studies

Biomarker signatures for progressive idiopathic pulmonary fibrosis

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