Protein Biomarkers of Interstitial Lung Abnormalities in Relatives of Patients With Pulmonary Fibrosis

Authors

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
Claire Cutting
Ann-Marcia C Tukpah
Andrew J Synn
Mary B Rice
Hilary J Goldberg
Joyce S Lee
David A Lynch
Rachel K Putman
Hiroto Hatabu
Benjamin A Raby
David A Schwartz
Ivan O Rosas
Gary M Hunninghake

Language

English

Publication Date

6-1-2025

Journal

European Respiratory Journal

DOI

10.1183/13993003.01349-2024

PMID

39884764

PMCID

PMC12138028

PubMedCentral® Posted Date

6-5-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Rationale: First-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.

Methods: Relatives 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.

Results: Of 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.

Conclusion: Peripheral 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.

Keywords

Humans, Male, Female, Biomarkers, Middle Aged, Aged, Tomography, X-Ray Computed, Lung Diseases, Interstitial, Pulmonary Fibrosis, Proteomics, Adult, Cohort Studies, Family, Blood Proteins, Pulmonary Surfactant-Associated Protein D

Published Open-Access

no

Recommended Citation

Rose, Jonathan A; Steele, Mark P; Kosak Lopez, Esteban J; et al., "Protein Biomarkers of Interstitial Lung Abnormalities in Relatives of Patients With Pulmonary Fibrosis" (2025). Faculty and Staff Publications. 4750.
https://digitalcommons.library.tmc.edu/baylor_docs/4750