Abstract
RationalePeripheral blood biomarkers are needed to identify and determine the extent of idiopathic pulmonary fibrosis (IPF). Current physiologic and radiographic prognostic indicators diagnose IPF too late in the course of disease. We hypothesize that peripheral blood biomarkers will identify disease in its early stages, and facilitate monitoring for disease progression.MethodsGene expression profiles of peripheral blood RNA from 130 IPF patients were collected on Agilent microarrays. Significance analysis of microarrays (SAM) with a false discovery rate (FDR) of 1% was utilized to identify genes that were differentially-expressed in samples categorized based on percent predicted DLCO and FVC.Main Measurements and ResultsAt 1% FDR, 1428 genes were differentially-expressed in mild IPF (DLCO >65%) compared to controls and 2790 transcripts were differentially- expressed in severe IPF (DLCO >35%) compared to controls. When categorized by percent predicted DLCO, SAM demonstrated 13 differentially-expressed transcripts between mild and severe IPF (< 5% FDR). These include CAMP, CEACAM6, CTSG, DEFA3 and A4, OLFM4, HLTF, PACSIN1, GABBR1, IGHM, and 3 unknown genes. Principal component analysis (PCA) was performed to determine outliers based on severity of disease, and demonstrated 1 mild case to be clinically misclassified as a severe case of IPF. No differentially-expressed transcripts were identified between mild and severe IPF when categorized by percent predicted FVC.ConclusionsThese results demonstrate that the peripheral blood transcriptome has the potential to distinguish normal individuals from patients with IPF, as well as extent of disease when samples were classified by percent predicted DLCO, but not FVC.
Highlights
Idiopathic Pulmonary Fibrosis (IPF) is categorized as an interstitial lung disease (ILD) and is the most common subtype of idiopathic interstitial pneumonias (IIP) comprising nearly 71% of the total cases [1]
These results demonstrate that the peripheral blood transcriptome has the potential to distinguish normal individuals from patients with IPF, as well as extent of disease when samples were classified by percent predicted DLCO, but not forced vital capacity (FVC)
Study Populations One hundred thirty peripheral blood RNA specimens were collected from individuals enrolled in either the Interstitial Lung Disease (ILD) or the Familial Pulmonary Fibrosis (FPF) Programs conducted at National Jewish Health and Duke University
Summary
Idiopathic Pulmonary Fibrosis (IPF) is categorized as an interstitial lung disease (ILD) and is the most common subtype of idiopathic interstitial pneumonias (IIP) comprising nearly 71% of the total cases [1]. Prognostic indicators of IPF include progressive deterioration of clinical symptoms such as dyspnea, pulmonary function, and extent of disease on high-resolution chest CT [3,4,5,6,7]. While dyspnea scores have been used as a predictor of survival in IPF patients [8], it remains an ambiguous prognostic indicator since it is highly subjective. Pulmonary function tests such as diffusing capacity for carbon monoxide (DLCO) and forced vital capacity (FVC) have been utilized as predictive indicators [9,10]. Biomarkers that measure disease stage and activity would be of benefit in understanding the effects of novel treatments, disease progression, and the design of clinical trials with homogenous placebo and treatment groups
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