Evidence map›Paper›PMID 39884764›Full record

ArticleThe European respiratory journal2025

Protein biomarkers of interstitial lung abnormalities in relatives of patients with pulmonary fibrosis.

Jonathan A Rose, Mark P Steele, Esteban J Kosak Lopez, Gisli Thor Axelsson, Andrea G Galecio Chao, Alan Waich, Katie Regan, Swati Gulati, Anthony H Maeda, Sharmin Sultana and 13 more

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PubMed Full text at PMC Publisher
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Article in The European respiratory journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Jonathan A RosePulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID https://orcid.org/0000-0003-3024-8309
Mark P SteeleDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Esteban J Kosak LopezPulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Gisli Thor AxelssonLandspitali University Hospital, Division of Internal Medicine, Reykjavik, Iceland.
Andrea G Galecio ChaoPulmonary Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA.
Alan WaichPulmonary Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA.
Katie ReganDivision of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Swati GulatiPulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Anthony H MaedaPulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Sharmin SultanaPulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Claire CuttingPulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Ann-Marcia C TukpahPulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Andrew J SynnPulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Mary B RicePulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID https://orcid.org/0000-0003-2538-391X
Hilary J GoldbergPulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Joyce S LeeDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
David A LynchRadiology, National Jewish Health, Denver, CO, USA.
Rachel K PutmanPulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID https://orcid.org/0000-0002-8027-7450
Hiroto HatabuDepartment of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID https://orcid.org/0000-0003-1436-2988
Benjamin A RabyPulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
David A SchwartzDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Ivan O RosasPulmonary Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA.
Gary M HunninghakePulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA ghunninghake@bwh.harvard.edu.

Funding

Harvard Clinical and Translational Science CenterUM1TR004408 · NCATS · HARVARD MEDICAL SCHOOL · PI Lindsey Robert Baden, Lee Marshall Nadler · 2023 to 2026
$43.3M
RESPIRATORY RESEARCHT32HL007633 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI George R Washko · 1985 to 2026
$14.9M
Systems Biology of Airway DiseaseP01HL132825 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WEISS, SCOTT T · 2016 to 2020
$12.6M
Targeting early events in MUC5B-driven lung injury and fibrosisP01HL162607 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI David Albert Schwartz · 2023 to 2026
$12.4M
The Boston Lung Cancer Survival CohortU01CA209414 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI David C Christiani · 2017 to 2026
$12.2M
Clinical Genetics and Screening for Pulmonary FibrosisR01HL130974 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GARY MATTHEW HUNNINGHAKE, Benjamin Alexander Raby · 2016 to 2026
$10.0M
Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung AbnormalitiesR01HL135142 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI MICHAEL H. CHO, GARY MATTHEW HUNNINGHAKE · 2017 to 2026
$7.7M
The Integrative Genomics of Acute Asthma ControlR01HL118455 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI MILLSTEIN, JOSHUA, RABY, BENJAMIN ALEXANDER · 2014 to 2024
$6.5M
Interstitial Lung Abnormalities: Defining the Phenotype, Causes, and Consequences.R01HL111024 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI HUNNINGHAKE, GARY MATTHEW · 2013 to 2022
$6.4M
A National iPS Cell Network with Deep Phenotyping for Translational ResearchU01TR001810 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GILAD, YOAV, KOTTON, DARRELL N. · 2016 to 2020
$4.4M
Preclinical Pulmonary Fibrosis, an opportune rare disease cohortUH3HL151865 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI SCHWARTZ, DAVID ALBERT · 2022 to 2025
$4.3M
A Randomized Controlled Trial of Home Air Purification for Eosinophilic COPDR01ES031252 · NIEHS · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI RICE, MARY B · 2020 to 2025
$3.8M
BLRD VA I01 BX005295NCATS NIH HHS U01 TR001810NCATS NIH HHS UM1 TR004408NCI NIH HHS R01 CA203636NCI NIH HHS U01 CA209414NHLBI NIH HHS K08 HL140087NHLBI NIH HHS K08 HL173562NHLBI NIH HHS P01 HL132825NHLBI NIH HHS P01 HL162607NHLBI NIH HHS R01 HL111024NHLBI NIH HHS R01 HL118455NHLBI NIH HHS R01 HL130974NHLBI NIH HHS R01 HL135142NHLBI NIH HHS R01 HL149836NHLBI NIH HHS R01 HL158668NHLBI NIH HHS T32 HL007633NHLBI NIH HHS U01 HL133232NHLBI NIH HHS UG3 HL151865NHLBI NIH HHS UH3 HL151865NIEHS NIH HHS R01 ES031252
6 · The paper itself

Abstract

rationaleFirst-degree relatives of patients with pulmonary fibrosis (referred to here as relatives) are at high risk for interstitial lung abnormalities (ILA), highlighting the need for biomarkers for risk prediction. We aimed to identify blood proteins associated with and predictive of ILA among relatives of patients with pulmonary fibrosis.

methodsRelatives enrolled in two independent cohorts had protein levels measured using an aptamer-based proteomic platform. ILA were assessed with computed tomography scans as per Fleischner Society recommendations. Protein associations with ILA were assessed using regression. Significant proteins were used with clinical variables to detect ILA.

resultsOf 237 relatives from two independent cohorts, 26% had ILA. Seven proteins were associated with ILA in the discovery cohort after false discovery rate adjustment, and all remained significant after adjusting for age, gender and smoking status. Six of the seven proteins were significantly associated in the validation cohort, including growth differentiation factor 15, surfactant protein D and surfactant protein B. In a multivariable model, six proteins combined with basic demographics in the discovery cohort had an area under the curve of 0.92 (0.88 in the validation cohort). Least absolute shrinkage and selection operator modelling identified three proteins and age as predictors, with an area under the curve of 0.89 in the validation cohort. When applied to the combined cohorts, this simple model would reduce the need for computed tomography imaging in one of every three relatives screened.

conclusionPeripheral blood proteins are associated with ILA in relatives of patients with pulmonary fibrosis and can be used to detect them. Our findings demonstrate the potential use of blood biomarkers in this high-risk group and suggest molecular targets for future investigation.

Indexed as

Blood ProteinsLung Diseases, InterstitialPulmonary FibrosisAdultAgedBiomarkersCohort StudiesFamilyFemaleHumansMaleMiddle AgedProteomicsPulmonary Surfactant-Associated Protein DTomography, X-Ray ComputedBiomarkersBlood ProteinsPulmonary Surfactant-Associated Protein D

Identifiers

PMID39884764
PMCPMC12138028

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.