PURPOSE: Rationale: Currently used surrogate makers of progression of disease in patients with idiopathic pulmonary fibrosis (IPF) have inherent limitations which hamper their use as endpoints in clinical trials and in clinical practice. Progression of fibrosis as assessed by high-resolution computed tomography (HRCT) may be a more direct surrogate marker for IPF, but semi-quantitative assessment by experienced radiologists is limited by significant intra- and interobserver variability. Objective: To evaluate the value of Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER), a novel tool developed at Mayo Clinic, Rochester, MN in characterizing the extent of fibrotic changes and independently predicting outcomes based on progression of these fibrotic changes on serial HRCT.
METHODS: Retrospective cohort study of IPF patients followed in the Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN. Consecutive patients diagnosed with IPF from January, 2005 to December, 2010 and having at least 2 HRCT within 4 to 14 months and appropriate clinical and follow-up data were included in the study. CALIPER analysis was conducted to determine extent of various tissue-types (reticular, groundglass and honeycomb) using validated lung signatures. Cox proportional hazards regression was used to examine the influence on survival of percent change of various HRCT patterns.
RESULTS: Sixty patients were included in the study (mean age 72.3 +/- 6.9 years). Median survival from 2nd HRCT was 2.1 years. After adjustment for gender, smoking history (pack-years), time interval between HRCT and baseline percent predicted FVC and DLCO, longitudinal changes in the extent of reticular infiltrates (HR=1.73 (1.2-2.51), p=0.003) and overall fibrosis (combination of reticular, groundglass and honeycomb infiltrates) (HR=1.72 (1.20-2.47), p=0.003) as assessed by CALIPER analysis were independent predictors of survival.
CONCLUSIONS: Longitudinal changes in fibrotic infiltrates as assessed by CALIPER are predictive of outcomes in patients with IPF. .
CLINICAL IMPLICATIONS: CALIPER could represent a novel tool in the management of patients with IPF and serve as a marker of progression of disease in IPF clinical trials.
DISCLOSURE: The following authors have nothing to disclose: Teng Moua, Sushravya Raghunath, Srinivasan Rajagopalan, Ronald Karwoski, Brian Bartholmai, Jay Ryu, Richard Robb, Fabien Maldonado
Computer-Aided Lung Informatics for pathology Evaluation and rating (CALIPER) is a computed-tomography-based technology that provides qualitative and quantitative assessment of different tissue types for diffuse parenchymal lung diseases based on validated lung signatures.