Pursuing Clinical Predictors and Biomarkers for Progression in ILD: Analysis of the Pulmonary Fibrosis Foundation (PFF) Registry

• Published in: Lung Vol. 202; no. 3; pp. 269 - 273
• Main Authors: Chang, Sarah E., Jia, Guiquan, Gao, Xia, Schiffman, Courtney, Gupta, Sachin, Wolters, Paul, Neighbors, Margaret
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2024; Springer Nature B.V
• Subjects: Aged; Biomarkers; Brief Report; Chemokines, CC; Chitinase-3-Like Protein 1 - blood; Clinical trials; Criteria; CXCL13 protein; Disease Progression; Epithelium; Female; Fibrosis; Humans; Idiopathic Pulmonary Fibrosis - diagnosis; Idiopathic Pulmonary Fibrosis - physiopathology; Lung - physiopathology; Lung diseases; Lung Diseases, Interstitial - diagnosis; Lung Diseases, Interstitial - physiopathology; Male; Medicine; Medicine & Public Health; Middle Aged; Osteopontin; Patients; Phenotypes; Pneumology/Respiratory System; Predictive Value of Tests; Pulmonary fibrosis; Pulmonary Fibrosis - diagnosis; Pulmonary Fibrosis - physiopathology; Pulmonary Surfactant-Associated Protein D - blood; Receptor for Advanced Glycation End Products - blood; Registries; Respiratory function; Senescence; Telomeres; Vital Capacity; Biomarkers; Idiopathic Pulmonary Fibrosis (IPF); Interstitial Lung disease (ILD); Progressive Pulmonary Fibrosis (PPF)
• ISSN: 0341-2040; 1432-1750; 1432-1750
• DOI: 10.1007/s00408-024-00694-2

Introduction Pulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry. Methods Biomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3). Results PFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low. Conclusions Our findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs.