Jonathan Rose, MD, MS

Rank

Instructor

Department

Medicine

Pulmonary and Critical Care

Authors

Jonathan A. Rose MD, MS1*; Mark P. Steele MD2*; Esteban J. Kosak Lopez MD1; Gisli Thor Axelsson MD PhD3; Andrea G. Galecio Chao, MD4; Alan Waich MD4; Katie Regan, MS5; Swati Gulati MS1; Anthony H. Maeda MD1; Sharmin Sultana MD MPH1; Claire Cutting MD1; Ann-Marcia C. Tukpah MD MPH1; Andrew J. Synn, MD6; Mary B. Rice, MD, MPH6; Hilary J. Goldberg MD1; Joyce S. Lee2; David A. Lynch MD7; Rachel K. Putman, MD, MPH1; Hiroto Hatabu MD, PhD8; Benjamin A. Raby MD, MPH1,5; David A. Schwartz MD MPH2†; Ivan O. Rosas MD4†; Gary M. Hunninghake, MD, MPH1†

Principal Investigator

Jonathan A. Rose MD, MS1

Twitter / Website

Categories

Proteins Biomarkers of Interstitial Lung Abnormalities in Relatives of Patients with Pulmonary Fibrosis

Abstract

Rationale: First-degree relatives of patients with pulmonary fibrosis (relatives) are at high risk for interstitial lung abnormalities (ILA), highlighting the need for biomarkers for risk prediction.
Methods: Relatives enrolled in two independent cohorts had protein levels measured using an aptamer-based proteomic platform. ILA was assessed with CT scans per Fleischner Society recommendations. Protein associations with ILA were assessed using regression, and 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 FDR-adjustment, including GDF15 (OR=4.9, p=0.0001), SFTPD (OR=4.3, p=0.0005), and SFTPB (OR=3.6, p=0.0006), and all remained significant after adjusting for age, sex, and smoking status. Six of seven were significant in the validation cohort. In a multivariable model, six proteins combined with basic demographics in the discovery cohort had AUC=0.92 (0.88 in validation cohort). LASSO modelling of the combined cohorts identified three proteins and age as predictors with an AUC=0.86. When applied to the combined cohorts, this simple model would reduce the need for CT 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 ILA. Our findings demonstrate the potential utility of blood biomarkers in this high-risk group and suggests molecular targets for future investigation.