RT Journal Article
SR Electronic
T1 Longitudinal prediction of outcome in idiopathic pulmonary fibrosis using automated CT analysis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 493544
DO 10.1101/493544
A1 Joseph Jacob
A1 Brian J. Bartholmai
A1 Coline H.M. van Moorsel
A1 Srinivasan Rajagopalan
A1 Anand Devaraj
A1 Hendrik W. van Es
A1 Teng Moua
A1 Frouke T. van Beek
A1 Ryan Clay
A1 Marcel Veltkamp
A1 Maria Kokosi
A1 Angelo de Lauretis
A1 Eoin P. Judge
A1 Teresa Burd
A1 Tobias Peikert
A1 Ronald Karwoski
A1 Fabien Maldonado
A1 Elisabetta Renzoni
A1 Toby M. Maher
A1 Andre Altmann
A1 Athol U. Wells
YR 2018
UL http://biorxiv.org/content/early/2018/12/13/493544.abstract
AB AIMS To evaluate computer-derived (CALIPER) CT variables against FVC change as potential drug trials endpoints in IPF.METHODS 71 Royal Brompton Hospital (discovery cohort) and 23 Mayo Clinic Rochester and 24 St Antonius Hospital Nieuwegein IPF patients (validation cohort) were analysed. Patients had two CTs performed 5-30 months apart, concurrent FVC measurements and were not exposed to antifibrotics (to avoid confounding of mortality relationships from antifibrotic use). Cox regression analyses (adjusted for patient age and gender) evaluated outcome for annualized FVC and CALIPER vessel-related structures (VRS) change and examined the added prognostic value of thresholded VRS changes beyond standard FVC change thresholds.RESULTS Change in VRS was a stronger outcome predictor than FVC decline when examined as continuous variables, in discovery and validation cohorts. When FVC decline (≥10%) and VRS thresholds were examined together, the majority of VRS change thresholds independently predicted outcome, with no decrease in model fit. When analysed as co-endpoints, a VRS threshold of ≥0·40 identified 30% more patients reaching an endpoint than a ≥10% FVC decline threshold alone.CONCLUSIONS Change in VRS is a strong predictor of outcome in IPF and can increase power in future drug trials when used as a co-endpoint alongside FVC change.Ethics committee approval Approval for this study of clinically indicated CT and pulmonary function data was obtained from Liverpool Research Ethics Committee (Reference: 14/NW/0028) and the Institutional Ethics Committee of the Royal Brompton Hospital, Mayo Clinic Rochester and St. Antonius Hospital, Nieuwegein. Informed patient consent was not required.Take home message Change in the vessel-related structures, a computer-derived CT variable, is a strong predictor of outcome in idiopathic pulmonary fibrosis and can increase power in future drug trials when used as a co-endpoint alongside forced vital capacity change.