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Jonathan Rose, MD, MS







Pulmonary and Clinical Care Medicine


Jonathan A. Rose MD*, MS; Gisli Thor Axelsson MD PhD; Esteban J. Kosak Lopez MD; Maria A. Planchart Ferretto MD; Anthony H. Maeda MD; Maria F. Perez Garcia MD; Nikkola E. Carmichael MS, PhD; Katie Regan, MS; Swati Gulati MS; Andrew J. Synn, MD; Mary B. Rice, MD, MPH; Hilary J. Goldberg MD; Rachel K. Putman, MD, MPH; Hiroto Hatabu MD, PhD; Benjamin A. Raby MD, MPH; Ivan O. Rosas MD; Gary M. Hunninghake, MD, MPH

Principal Investigator

Jonathan A. Rose


Proteomic Profile of Interstitial Lung Abnormalities in Relatives of Patients with Pulmonary Fibrosis


Rationale: While protein biomarkers were found to be associated with interstitial lung abnormalities (ILA) in the general population and in smokers, these results have not been validated in relatives of patients with pulmonary fibrosis (relatives), a group at highest risk to develop ILA and interstitial lung disease (ILD).

Methods: Relatives enrolled in the CGS-PF study had ILA assessed per Fleischner Society recommendations on prone volumetric chest computed tomography scans (CT). Peripheral blood proteins were measured in plasma using DNA aptamers through the SomaScan proteomics assay targeting over 7,000 proteins. The association of individual proteins with ILA was assessed in an unbiased fashion, and the top ten proteins in the AGES-Reykjavik study were assessed using multivariable logistic regression. P-values below 0.05 were considered significant and Bonferroni adjustment was used when appropriate.

Results: Of the 84 participants with plasma samples available, 28 (33%) had ILA and 56 (77%) were without ILA. The top three proteins associated with ILA in this cohort were GDF15 (p=4.7×10-6), SFTPD (p=2.5×10-5), and SFTPB (p=7.6×10-4). Of the top 10 proteins found in the AGES-Reykjavik study, 3 associations replicated in this cohort after correction for multiple hypothesis testing (p-values are Bonferroni-adjusted): GDF15 (OR 3.2 [1.8-5.8], p=0.001), SFTPB (OR 2.7 [1.5-4.7], p=0.006], and SCGB3A1 (OR 2.1 [1.3-3.6], p=0.049). Effect estimates were similar to the findings in the AGES-Reykjavik cohort, and after adjusting for covariates, GDF15 and SFTPB remained statistically associated with ILA.

Conclusion: Despite the small sample size, there is evidence for an association between peripheral blood plasma measures of GDF15, and for replication of GDF15, SFTPB, and SCG3A1 with ILA in relatives of patients with pulmonary fibrosis. In addition to highlighting important pathways suggested by these secreted proteins, if validated, these findings may help to improve risk prediction and could suggest important targets for therapeutic intervention.

Clinical Implications

Interstitial lung abnormalities (ILA) are incidental imaging findings consistent with interstitial lung disease (ILD), and have been associated with adverse consequences including increased mortality. Family members of patients with pulmonary fibrosis are at the highest risk of developing ILA and ILD. Identifying peripheral proteins associated with ILA in this population In addition to highlighting important pathways suggested by these secreted proteins, may allow us to develop an easily-accessible biomarker to predict those family members at highest risk of developing disease. It may also help identify important targets for therapeutic intervention.