Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort

Jamie L. Todd; Megan L. Neely; Robert Overton; Hillary Mulder; Jesse Roman; Joseph A. Lasky; Joao A. De Andrade; Mridu Gulati; Howard Huang; Thomas B. Leonard; Christian Hesslinger; Imre Noth; John A. Belperio; Kevin R. Flaherty; Scott M. Palmer; Hyun J Kim

doi:10.1007/s00408-021-00505-y

Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort

Jamie L. Todd, Megan L. Neely, Robert Overton, Hillary Mulder, Jesse Roman, Joseph A. Lasky, Joao A. De Andrade, Mridu Gulati, Howard Huang, Thomas B. Leonard, Christian Hesslinger, Imre Noth, John A. Belperio, Kevin R. Flaherty, Scott M. Palmer, Hyun J Kim

Pulmonary, Allergy, Critical Care and Sleep Medicine

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease with a variable clinical course. Biomarkers that predict patient outcomes are needed. We leveraged data from 300 patients in the multicenter IPF-PRO Registry to determine associations between circulating proteins and the composite outcome of respiratory death or lung transplant. Plasma collected at enrollment was analyzed using aptamer-based proteomics (1305 proteins). Over a median follow-up of 30.4 months, there were 76 respiratory deaths and 26 lung transplants. In unadjusted univariable analyses, 61 proteins were significantly associated with the outcome (hazard ratio > 2 or < 0.5, corrected p ≤ 0.05). In multivariable analyses, a set of 4 clinical measures and 47 unique proteins predicted the probability of respiratory death or lung transplant with an optimism-corrected C-index of 0.76. Our results suggest that select circulating proteins strongly associate with the risk of mortality in patients with IPF and confer information independent of clinical measures.

Original language	English (US)
Pages (from-to)	11-18
Number of pages	8
Journal	Lung
Volume	200
Issue number	1
DOIs	https://doi.org/10.1007/s00408-021-00505-y
State	Published - Feb 1 2022

Bibliographical note

Funding Information:
We thank the principal investigators and enrolling centers in the IPF-PRO Registry. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment for development of this article. Writing support was provided by Elizabeth Ng and Wendy Morris of Fleishman-Hillard, London, UK, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. Boehringer Ingelheim was given the opportunity to review the article for medical and scientific accuracy as well as intellectual property considerations.

Funding Information:
The authors have reported to Lung the following conflicts of interest: JLT, MLN, RO, HM and SMP are employees of the Duke Clinical Research Institute, which was funded by Boehringer Ingelheim Pharmaceuticals, Inc to conduct this research. JR reports grants and personal fees from Boehringer Ingelheim and grants from Genentech, Galapagos, Syneos Health, Bellerophon Therapeutics, FibroGen, and the National Institutes of Health. JAL reports personal fees from Biogen, Boehringer Ingelheim, Galecto, Roche/Genentech and Veracyte. JAdA reports personal fees from Boehringer Ingelheim. MG reports personal fees, non-financial support, and other support from the France Foundation; grants, non-financial support and other support from Boehringer Ingelheim and the Pulmonary Fibrosis Foundation; and personal fees from Genentech. HH is on a speaker panel for Boehringer Ingelheim. IN reports personal fees from Boehringer Ingelheim, Genentech, and ImmuneWorks. JAB has no disclosures. KRF reports grants and personal fees from Boehringer Ingelheim and Roche/Genentech and personal fees from FibroGen, Sanofi, Genzyme, and Veracyte. TBL was an employee of Boehringer Ingelheim at the time this study was conducted. CH is an employee of Boehringer Ingelheim.

Publisher Copyright:
© 2022, The Author(s).

Keywords

Biomarkers
Interstitial lung diseases
Observational study
Proteomics

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Multicenter Study
Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00408-021-00505-y

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Todd, J. L., Neely, M. L., Overton, R., Mulder, H., Roman, J., Lasky, J. A., De Andrade, J. A., Gulati, M., Huang, H., Leonard, T. B., Hesslinger, C., Noth, I., Belperio, J. A., Flaherty, K. R., Palmer, S. M., & Kim, H. J. (2022). Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort. Lung, 200(1), 11-18. https://doi.org/10.1007/s00408-021-00505-y

Todd, JL, Neely, ML, Overton, R, Mulder, H, Roman, J, Lasky, JA, De Andrade, JA, Gulati, M, Huang, H, Leonard, TB, Hesslinger, C, Noth, I, Belperio, JA, Flaherty, KR, Palmer, SM & Kim, HJ 2022, 'Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort', Lung, vol. 200, no. 1, pp. 11-18. https://doi.org/10.1007/s00408-021-00505-y

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title = "Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort",

abstract = "Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease with a variable clinical course. Biomarkers that predict patient outcomes are needed. We leveraged data from 300 patients in the multicenter IPF-PRO Registry to determine associations between circulating proteins and the composite outcome of respiratory death or lung transplant. Plasma collected at enrollment was analyzed using aptamer-based proteomics (1305 proteins). Over a median follow-up of 30.4 months, there were 76 respiratory deaths and 26 lung transplants. In unadjusted univariable analyses, 61 proteins were significantly associated with the outcome (hazard ratio > 2 or < 0.5, corrected p ≤ 0.05). In multivariable analyses, a set of 4 clinical measures and 47 unique proteins predicted the probability of respiratory death or lung transplant with an optimism-corrected C-index of 0.76. Our results suggest that select circulating proteins strongly associate with the risk of mortality in patients with IPF and confer information independent of clinical measures.",

keywords = "Biomarkers, Interstitial lung diseases, Observational study, Proteomics",

author = "Todd, {Jamie L.} and Neely, {Megan L.} and Robert Overton and Hillary Mulder and Jesse Roman and Lasky, {Joseph A.} and {De Andrade}, {Joao A.} and Mridu Gulati and Howard Huang and Leonard, {Thomas B.} and Christian Hesslinger and Imre Noth and Belperio, {John A.} and Flaherty, {Kevin R.} and Palmer, {Scott M.} and Kim, {Hyun J}",

note = "Funding Information: We thank the principal investigators and enrolling centers in the IPF-PRO Registry. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment for development of this article. Writing support was provided by Elizabeth Ng and Wendy Morris of Fleishman-Hillard, London, UK, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. Boehringer Ingelheim was given the opportunity to review the article for medical and scientific accuracy as well as intellectual property considerations. Funding Information: The authors have reported to Lung the following conflicts of interest: JLT, MLN, RO, HM and SMP are employees of the Duke Clinical Research Institute, which was funded by Boehringer Ingelheim Pharmaceuticals, Inc to conduct this research. JR reports grants and personal fees from Boehringer Ingelheim and grants from Genentech, Galapagos, Syneos Health, Bellerophon Therapeutics, FibroGen, and the National Institutes of Health. JAL reports personal fees from Biogen, Boehringer Ingelheim, Galecto, Roche/Genentech and Veracyte. JAdA reports personal fees from Boehringer Ingelheim. MG reports personal fees, non-financial support, and other support from the France Foundation; grants, non-financial support and other support from Boehringer Ingelheim and the Pulmonary Fibrosis Foundation; and personal fees from Genentech. HH is on a speaker panel for Boehringer Ingelheim. IN reports personal fees from Boehringer Ingelheim, Genentech, and ImmuneWorks. JAB has no disclosures. KRF reports grants and personal fees from Boehringer Ingelheim and Roche/Genentech and personal fees from FibroGen, Sanofi, Genzyme, and Veracyte. TBL was an employee of Boehringer Ingelheim at the time this study was conducted. CH is an employee of Boehringer Ingelheim. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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doi = "10.1007/s00408-021-00505-y",

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T1 - Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort

AU - Todd, Jamie L.

AU - Neely, Megan L.

AU - Overton, Robert

AU - Mulder, Hillary

AU - Roman, Jesse

AU - Lasky, Joseph A.

AU - De Andrade, Joao A.

AU - Gulati, Mridu

AU - Huang, Howard

AU - Leonard, Thomas B.

AU - Hesslinger, Christian

AU - Noth, Imre

AU - Belperio, John A.

AU - Flaherty, Kevin R.

AU - Palmer, Scott M.

AU - Kim, Hyun J

N1 - Funding Information: We thank the principal investigators and enrolling centers in the IPF-PRO Registry. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment for development of this article. Writing support was provided by Elizabeth Ng and Wendy Morris of Fleishman-Hillard, London, UK, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. Boehringer Ingelheim was given the opportunity to review the article for medical and scientific accuracy as well as intellectual property considerations. Funding Information: The authors have reported to Lung the following conflicts of interest: JLT, MLN, RO, HM and SMP are employees of the Duke Clinical Research Institute, which was funded by Boehringer Ingelheim Pharmaceuticals, Inc to conduct this research. JR reports grants and personal fees from Boehringer Ingelheim and grants from Genentech, Galapagos, Syneos Health, Bellerophon Therapeutics, FibroGen, and the National Institutes of Health. JAL reports personal fees from Biogen, Boehringer Ingelheim, Galecto, Roche/Genentech and Veracyte. JAdA reports personal fees from Boehringer Ingelheim. MG reports personal fees, non-financial support, and other support from the France Foundation; grants, non-financial support and other support from Boehringer Ingelheim and the Pulmonary Fibrosis Foundation; and personal fees from Genentech. HH is on a speaker panel for Boehringer Ingelheim. IN reports personal fees from Boehringer Ingelheim, Genentech, and ImmuneWorks. JAB has no disclosures. KRF reports grants and personal fees from Boehringer Ingelheim and Roche/Genentech and personal fees from FibroGen, Sanofi, Genzyme, and Veracyte. TBL was an employee of Boehringer Ingelheim at the time this study was conducted. CH is an employee of Boehringer Ingelheim. Publisher Copyright: © 2022, The Author(s).

PY - 2022/2/1

Y1 - 2022/2/1

N2 - Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease with a variable clinical course. Biomarkers that predict patient outcomes are needed. We leveraged data from 300 patients in the multicenter IPF-PRO Registry to determine associations between circulating proteins and the composite outcome of respiratory death or lung transplant. Plasma collected at enrollment was analyzed using aptamer-based proteomics (1305 proteins). Over a median follow-up of 30.4 months, there were 76 respiratory deaths and 26 lung transplants. In unadjusted univariable analyses, 61 proteins were significantly associated with the outcome (hazard ratio > 2 or < 0.5, corrected p ≤ 0.05). In multivariable analyses, a set of 4 clinical measures and 47 unique proteins predicted the probability of respiratory death or lung transplant with an optimism-corrected C-index of 0.76. Our results suggest that select circulating proteins strongly associate with the risk of mortality in patients with IPF and confer information independent of clinical measures.

AB - Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease with a variable clinical course. Biomarkers that predict patient outcomes are needed. We leveraged data from 300 patients in the multicenter IPF-PRO Registry to determine associations between circulating proteins and the composite outcome of respiratory death or lung transplant. Plasma collected at enrollment was analyzed using aptamer-based proteomics (1305 proteins). Over a median follow-up of 30.4 months, there were 76 respiratory deaths and 26 lung transplants. In unadjusted univariable analyses, 61 proteins were significantly associated with the outcome (hazard ratio > 2 or < 0.5, corrected p ≤ 0.05). In multivariable analyses, a set of 4 clinical measures and 47 unique proteins predicted the probability of respiratory death or lung transplant with an optimism-corrected C-index of 0.76. Our results suggest that select circulating proteins strongly associate with the risk of mortality in patients with IPF and confer information independent of clinical measures.

KW - Biomarkers

KW - Interstitial lung diseases

KW - Observational study

KW - Proteomics

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U2 - 10.1007/s00408-021-00505-y

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SP - 11

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JF - Lung

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ER -

Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

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