Longitudinal Blood Transcriptomic Changes Predict Lung Function Decline in Idiopathic Pulmonary Fibrosis. Longitudinal Blood Transcriptomic Changes Predict Lung Function Decline in Idiopathic Pulmonary Fibrosis

The Rationale: Molecular markers of disease activity that are predictive of forced vital capacity (FVC) progression in idiopathic pulmonary fibrosis are needed. Objectives: Develop a predictor using longitudinal within-patient gene expression differences (ΔGE) in peripheral blood mononuclear cells (PBMC) to predict of FVC progression. Methods: Patients in the training cohort (n=74) experiencing ≥10% relative reduction in FVC% of predicted over 12 months were categorized as progressors in contrast to the remaining stable patients. Baseline to 4-month within-patient ΔGE were correlated with FVC status. FVC-predictor genes were prioritized by two-group comparison with FDR4 years prior to screening or if there was a diagnosis of collagen-vascular disorder, FEV1/FVC <0.60, evidence of active infection at screening, or comorbid conditions other than IPF likely to result in death within one year. Subjects underwent protocol-directed visits every 4 months after the baseline (0 visit) for a minimum of 1 year, establishing four transcriptome sampling timepoints. Registry patients with PBMC gene expression (GE) sampling and pulmonary function tests (PFT) over at least two time points were included in each cohort. Informed consent was obtained from all participants. The study protocol was reviewed by the institutional review board of each participating center.