TY - JOUR
T1 - Predicting outcomes in idiopathic pulmonary fibrosis using automated computed tomographic analysis
AU - Jacob, Joseph
AU - Bartholmai, Brian J.
AU - Rajagopalan, Srinivasan
AU - Van Moorsel, Coline H.M.
AU - Van Es, Hendrik W.
AU - Van Beek, Frouke T.
AU - Struik, Marjolijn H.L.
AU - Kokosi, Maria
AU - Egashira, Ryoko
AU - Brun, Anne Laure
AU - Nair, Arjun
AU - Walsh, Simon L.F.
AU - Cross, Gary
AU - Barnett, Joseph
AU - De Lauretis, Angelo
AU - Judge, Eoin P.
AU - Desai, Sujal
AU - Karwoski, Ronald
AU - Ourselin, Sebastien
AU - Renzoni, Elisabetta
AU - Maher, Toby M.
AU - Altmann, Andre
AU - Wells, Athol U.
N1 - Funding Information:
J.J. was supported by Wellcome Trust Clinical Research Career Development Fellowship 209553/Z/17/Z. A.A. was supported by the Medical Research Council (grant MR/L016311/1). The work was supported by the National Institute of Health Research Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. S.O. was partially funded by the National Institute for Health Research, University College London Hospitals Biomedical Research Centre.
Publisher Copyright:
Copyright © 2018 by the American Thoracic Society.
PY - 2018/9/15
Y1 - 2018/9/15
N2 - Rationale: Quantitative computed tomographic (CT) measures of baseline disease severity might identify patients with idiopathic pulmonary fibrosis (IPF) with an increased mortality risk. We evaluated whether quantitative CT variables could act as a cohort enrichment tool in future IPF drug trials. Objectives: To determine whether computer-derived CT measures, specifically measures of pulmonary vessel-related structures (VRSs), can better predict functional decline and survival in IPF and reduce requisite sample sizes in drug trial populations. Methods: Patients with IPF undergoing volumetric noncontrast CT imaging at the Royal Brompton Hospital, London, and St. Antonius Hospital, Utrecht, were examined to identify pulmonary function measures (including FVC) and visual and computer-derived (CALIPER [Computer-Aided Lung Informatics for Pathology Evaluation and Rating] software) CT features predictive of mortality and FVC decline. The discovery cohort comprised 247 consecutive patients, with validation of results conducted in a separate cohort of 284 patients, all fulfilling drug trial entry criteria. Measurements and Main Results: In the discovery and validation cohorts, CALIPER-derived features, particularly VRS scores, were among the strongest predictors of survival and FVC decline. CALIPER results were accentuated in patients with less extensive disease, outperforming pulmonary function measures. When used as a cohort enrichment tool, a CALIPER VRS score greater than 4.4% of the lung was able to reduce the requisite sample size of an IPF drug trial by 26%. Conclusions: Our study has validated a new quantitative CT measure in patients with IPF fulfilling drug trial entry criteria-the VRS score-that outperformed current gold standard measures of outcome. When used for cohort enrichment in an IPF drug trial setting, VRS threshold scores can reduce a required IPF drug trial population size by 25%, thereby limiting prohibitive trial costs. Importantly, VRS scores identify patients in whom antifibrotic medication prolongs life and reduces FVC decline.
AB - Rationale: Quantitative computed tomographic (CT) measures of baseline disease severity might identify patients with idiopathic pulmonary fibrosis (IPF) with an increased mortality risk. We evaluated whether quantitative CT variables could act as a cohort enrichment tool in future IPF drug trials. Objectives: To determine whether computer-derived CT measures, specifically measures of pulmonary vessel-related structures (VRSs), can better predict functional decline and survival in IPF and reduce requisite sample sizes in drug trial populations. Methods: Patients with IPF undergoing volumetric noncontrast CT imaging at the Royal Brompton Hospital, London, and St. Antonius Hospital, Utrecht, were examined to identify pulmonary function measures (including FVC) and visual and computer-derived (CALIPER [Computer-Aided Lung Informatics for Pathology Evaluation and Rating] software) CT features predictive of mortality and FVC decline. The discovery cohort comprised 247 consecutive patients, with validation of results conducted in a separate cohort of 284 patients, all fulfilling drug trial entry criteria. Measurements and Main Results: In the discovery and validation cohorts, CALIPER-derived features, particularly VRS scores, were among the strongest predictors of survival and FVC decline. CALIPER results were accentuated in patients with less extensive disease, outperforming pulmonary function measures. When used as a cohort enrichment tool, a CALIPER VRS score greater than 4.4% of the lung was able to reduce the requisite sample size of an IPF drug trial by 26%. Conclusions: Our study has validated a new quantitative CT measure in patients with IPF fulfilling drug trial entry criteria-the VRS score-that outperformed current gold standard measures of outcome. When used for cohort enrichment in an IPF drug trial setting, VRS threshold scores can reduce a required IPF drug trial population size by 25%, thereby limiting prohibitive trial costs. Importantly, VRS scores identify patients in whom antifibrotic medication prolongs life and reduces FVC decline.
KW - Idiopathic pulmonary fibrosis
KW - Pulmonary vessels
KW - Quantitative computed tomographic imaging
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U2 - 10.1164/rccm.201711-2174OC
DO - 10.1164/rccm.201711-2174OC
M3 - Article
C2 - 29684284
AN - SCOPUS:85051187177
SN - 1073-449X
VL - 198
SP - 767
EP - 776
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 6
ER -