Aims Patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotic medication and patients with non-IPF fibrosing lung disease often demonstrate rates of annualised forced vital capacity (FVC) decline within the range of measurement variation (5.0%–9.9%). We examined whether change in visual CT variables could help confirm whether marginal FVC declines represented genuine clinical deterioration rather than measurement noise.
Methods In two IPF cohorts (cohort 1: n=103, cohort 2: n=108), separate pairs of radiologists scored paired volumetric CTs (acquired between 6 and 24 months from baseline). Change in interstitial lung disease, honeycombing, reticulation, ground-glass opacity extents and traction bronchiectasis severity was evaluated using a 5-point scale, with mortality prediction analysed using univariable and multivariable Cox regression analyses. Both IPF populations were then combined to determine whether change in CT variables could predict mortality in patients with marginal FVC declines.
Results On univariate analysis, change in all CT variables except ground-glass opacity predicted mortality in both cohorts. On multivariate analysis adjusted for patient age, gender, antifibrotic use and baseline disease severity (diffusing capacity for carbon monoxide), change in traction bronchiectasis severity predicted mortality independent of FVC decline. Change in traction bronchiectasis severity demonstrated good interobserver agreement among both scorer pairs. Across all study patients with marginal FVC declines, change in traction bronchiectasis severity independently predicted mortality and identified more patients with deterioration than change in honeycombing extent.
Conclusions Change in traction bronchiectasis severity is a measure of disease progression that could be used to help resolve the clinical importance of marginal FVC declines.
- idiopathic pulmonary fibrosis
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Correction notice This article has been corrected since it was published Online First. A typo in an author name has been amended.
Contributors JJ, LA, AJP, BG, GC, JB, CJB, MGJ, FvB, CHvM, MV, TB, WvE, SRD, EJ, MK, RS, SB, NM, AA and AUW were involved in either the acquisition or the analysis or interpretation of data for the study. JJ, LA, AA and AUW were also involved in the conception and design of the study. All authors revised the work for important intellectual content and gave the final approval for the version to be published. All authors agreed to be accountable for all aspects of the work and in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. None of the material has been published or is under consideration elsewhere, including the internet.
Funding JJ was supported by a Wellcome Trust Clinical Research Career Development Fellowship (209553/Z/17/Z). AA holds an MRC eMedLab Medical Bioinformatics Career Development Fellowship. This work was supported by the Medical Research Council (grant number MR/L016311/1). This project has received funding from the European Union's Horizon 2020 research and innovation program (grant agreement number 666992). CJB and MGJ were supported by the National Institute for Health Research Biomedical Research Centre at the University of Southampton.
Competing interests JJ reports personal fees from Boehringer Ingelheim outside the current work. AUW reports personal fees from Intermune, Boehringer Ingelheim, Gilead, MSD, Roche, Bayer and Chiesi outside the submitted work. SRD reports personal fees from Boehringer Ingelheim outside the submitted work. Work by CHMM, HWE, FTB and MV was supported by ZonMW TopZorg Care (grant number 842002001).
Patient consent for publication Not required.
Ethics approval Approval for this study of clinically indicated CT and pulmonary function data at the Royal Brompton Hospital was obtained from the Liverpool Research Ethics Committee (reference: 14/NW/0028) and the institutional ethics committee of University College London. Informed patient consent was not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data for the validation cohort of the study are available upon reasonable request.
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