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Differentiation of Idiopathic Pulmonary Fibrosis from Connective Tissue Disease-Related Interstitial Lung Disease Using Quantitative Imaging

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Differentiation of Idiopathic Pulmonary Fibrosis from Connective Tissue Disease-Related Interstitial Lung Disease Using Quantitative Imaging Journal of Clinical Medicine Article Differentiation of Idiopathic Pulmonary Fibrosis from Connective Tissue Disease-Related Interstitial Lung Disease Using Quantitative Imaging Jonathan H. Chung 1,*, Ayodeji Adegunsoye 2, Brenna Cannon 3, Rekha Vij 2, Justin M. Oldham 4, Christopher King 5, Steven M. Montner 1, Prahasit Thirkateh 6, Scott Barnett 7, Ronald Karwoski 8, Brian J. Bartholmai 9 , Mary Strek 2 and Steven D. Nathan 7 1 Department of Radiology, The University of Chicago Medicine, Chicago, IL 60637, USA; [email protected] 2 Department of Medicine, The University of Chicago Medicine, Chicago, IL 60637, USA; [email protected] (A.A.); [email protected] (R.V.); [email protected] (M.S.) 3 Inova Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, VA 22042, USA; [email protected] 4 Department of Medicine, The University of California Davis, Sacramento, CA 95616, USA; [email protected] 5 Advanced Lung Disease and Transplant Clinic, Inova Fairfax Hospital, Falls Church, VA 22042, USA; [email protected] 6 Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA; [email protected] 7 Inova Heart and Vascular Institute, Inova Fairfax Hospital, Falls Church, VA 22042, USA; Citation: Chung, J.H.; Adegunsoye, [email protected] (S.B.); [email protected] (S.D.N.) A.; Cannon, B.; Vij, R.; Oldham, J.M.; 8 Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55902, USA; King, C.; Montner, S.M.; Thirkateh, P.; [email protected] Barnett, S.; Karwoski, R.; et al. 9 Department of Radiology, Mayo Clinic, Rochester, MN 55902, USA; [email protected] Differentiation of Idiopathic * Correspondence: [email protected]; Tel.: +1-888-824-0200 Pulmonary Fibrosis from Connective Tissue Disease-Related Interstitial Abstract: A usual interstitial pneumonia (UIP) imaging pattern can be seen in both idiopathic Lung Disease Using Quantitative pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD). Imaging. J. Clin. Med. 2021, 10, 2663. The purpose of this multicenter study was to assess whether quantitative imaging data differ between https://doi.org/10.3390/jcm10122663 IPF and CTD-ILD in the setting of UIP. Patients evaluated at two medical centers with CTD-ILD or IPF and a UIP pattern on CT or pathology served as derivation and validation cohorts. Chest CT data Academic Editor: Francisco Dasí were quantitatively analyzed including total volumes of honeycombing, reticulation, ground-glass Received: 30 March 2021 opacity, normal lung, and vessel related structures (VRS). VRS was compared with forced vital Accepted: 4 June 2021 capacity percent predicted (FVC%) and percent predicted diffusing capacity of the lungs for carbon Published: 17 June 2021 monoxide (DLCO%). There were 296 subjects in total, with 40 CTD-ILD and 85 IPF subjects in the derivation cohort, and 62 CTD-ILD and 109 IPF subjects in the validation cohort. VRS was greater Publisher’s Note: MDPI stays neutral in IPF across the cohorts on univariate (p < 0.001) and multivariable (p < 0.001–0.047) analyses. with regard to jurisdictional claims in VRS was inversely correlated with DLCO% in both cohorts on univariate (p < 0.001) and in the published maps and institutional affil- derivation cohort on multivariable analysis (p = 0.003) but not FVC%. Total volume of normal lung iations. was associated with DLCO% (p < 0.001) and FVC% (p < 0.001–0.009) on multivariable analysis in both cohorts. VRS appears to have promise in differentiating CTD-ILD from IPF. The underlying pathophysiological relationship between VRS and ILD is complex and is likely not explained solely by lung fibrosis. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Keywords: connective tissue disease; idiopathic pulmonary fibrosis; usual interstitial pneumonia; This article is an open access article image interpretation; computer-assisted; multidetector computed tomography distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). J. Clin. Med. 2021, 10, 2663. https://doi.org/10.3390/jcm10122663 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, 2663 2 of 10 J. Clin. Med. 2021, 10, x FOR PEER REVIEW 2 of 10 1. Introduction 1. IntroductionIdiopathic pulmonary fibrosis (IPF) is the most common form of the idiopathic in- terstitialIdiopathic pneumonias pulmonary as fibrosis well as (IPF) the mostis the most common common cause form of of pulmonary the idiopathic fibrosis inter- in most populations.stitial pneumonias Previously, as well discerningas the most common the exact cause diagnosis of pulmonary was thought fibrosis to in be most largely pop- academic givenulations. that Previously, management discerning of most the typesexact diagnosis of pulmonary was thought fibrosis to was be largely similar. academic However, with thegiven recent that management availability ofof antifibroticmost types of agents pulmonary for IPF fibrosis as well was as datasimilar. showing However, that with immuosup- pressionthe recent in availability IPF is associated of antifibrotic with worse agents outcomes, for IPF as anwell accurate as data diagnosis showing that in the im- setting of pulmonarymuosuppression fibrosis in IPF has is become associated essential with wo [1rse–3 ].outcomes, an accurate diagnosis in the setting of pulmonary fibrosis has become essential [1–3]. The imaging and histological correlate in IPF is a pattern that has been termed usual The imaging and histological correlate in IPF is a pattern that has been termed usual interstitialinterstitial pneumonitis pneumonitis (UIP). (UIP). However, However, a UI aP UIPpattern pattern can also can be also seen be with seen connective with connective tissuetissue disease-related disease-related interstitial interstitial lung lung diseas diseasee (CTD-ILD), (CTD-ILD), particularly particularly with rheumatoid with rheumatoid arthritis.arthritis. This This is isespecially especially problematic problematic in cases in of cases CTD of that CTD present that initially present as initiallyILD, in the as ILD, in theabsence absence of systemic of systemic manifestations manifestations [4,5] and, [4,5 ]therefore, and, therefore, mimic IPF. mimic Although IPF. Although there are there are certaincertain CT findings findings that that are are suggestive suggestive of of CTD- CTD-ILDILD in inthe the setting setting of UIP, of UIP, these these specific specific find- ingsfindings are presentare present in ain minority a minority of of cases cases [ 6[6–8].–8]. In addition, HRCT HRCT interpretation interpretation is gen- is generally hamperederally hampered by substantial by substantial inter-reader inter-reader variation variation [[9–11].9–11]. An An auto automatedmated tool tool that that could could reli- ablyreliably analyze analyze complex complex imaging imaging ILD ILD data data from from chest chest CT CT scans scans and and provide provide decisiondecision support tosupport favor to a specificfavor a specific diagnosis diagnosis would would be highly be highly valuable, valuable, particularly particularly outside outside of of academic centersacademic where centers there where is athere lower is a level lower of level ILD of expertise ILD expertise in chest in chest imaging imaging interpretation. interpre- tation. The quantitative imaging tool known as Computer-Aided Lung Informatics for Pathology The quantitative imaging tool known as Computer-Aided Lung Informatics for Pa- Evaluationthology Evaluation and Rating and (CALIPER)Rating (CALIPER) has been has repeatedly been repeatedly shown shown to predict to predict patient patient outcomes and hasoutcomes been associated and has been with associated pulmonary with function pulmonary [12–19 function]. A CALIPER [12–19]. quantitative A CALIPER variablequanti- strongly associatedtative variable with strongly patient associated prognosis with across pati multipleent prognosis diagnoses across is vessel-relatedmultiple diagnoses structure is (VRS) volumevessel-related (Figures structure1 and2 ).(VRS) In the volume anatomic (Figures segmentation 1 and 2). processIn the anatomic of the CALIPER segmentation software, the vessel-relatedprocess of the structuresCALIPER software, are detected the vessel-r and extractedelated structures algorithmically are detected for the and purpose extracted of exclusion ofalgorithmically these branching for structuresthe purpose from of exclusion the other of parenchymal these branching feature structures classification from the (such other as normal lung,parenchymal ground-glass feature opacity, classificati or reticularon (such densities)as normal oflung, the grou volumetricnd-glass data. opacity, Surprisingly, or reticu- the VRS haslar densities) been shown of the to volumetric be an independent data. Surprisi markerngly, the of patientVRS has outcomes been shown in to ILD be an [12 inde-,17,19]. Since CTD-ILDpendent marker has superior of patient survival outcomes compared in ILD [12,17,19]. to IPF, we Since postulated CTD-ILD that has VRSsuperior as measured sur- by CALIPERvival compared may beto IPF, able we to differentiatepostulated that CTD-ILD VRS as measured from IPF by even CALIPER in the setting may be of able UIP to [ 6,20–22]. differentiate CTD-ILD from IPF even in the setting of UIP [6,20–22]. The purpose of this The purpose of
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