Quantitative computed tomography–derived clusters: Redefining airway remodeling in asthmatic patients - 01/03/14
, Ruth Hartley, MBChB, MRCS a, Umair T. Khan, MBChB a, Amisha Singapuri, BSc a, Beverly Hargadon, RGN a, William Monteiro, MSc a, Ian D. Pavord, DM, FRCP a, Ana R. Sousa, PhD c, Richard P. Marshall, PhD, MRCP c, Deepak Subramanian, MD, MRCP d, David Parr, MD, FRCP d, James J. Entwisle, MBBS, FRCR e, Salman Siddiqui, PhD, MRCP a, Vimal Raj, MBBS, FRCR b, Christopher E. Brightling, PhD, FRCP aAbstract |
Background |
Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)–assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms.
Objectives |
The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes.
Methods |
Sixty-five asthmatic patients and 30 healthy subjects underwent detailed clinical, physiologic characterization and quantitative CT analysis. Factor and cluster analysis techniques were used to determine 3 novel, quantitative, CT-based asthma phenotypes.
Results |
Patients with severe and mild-to-moderate asthma demonstrated smaller mean right upper lobe apical segmental bronchus (RB1) lumen volume (LV) in comparison with healthy control subjects (272.3 mm3 [SD, 112.6 mm3], 259.0 mm3 [SD, 53.3 mm3], 366.4 mm3 [SD, 195.3 mm3], respectively; P = .007) but no difference in RB1 wall volume (WV). Air trapping measured based on mean lung density expiratory/inspiratory ratio was greater in patients with severe and mild-to-moderate asthma compared with that seen in healthy control subjects (0.861 [SD, 0.05)], 0.866 [SD, 0.07], and 0.830 [SD, 0.06], respectively; P = .04). The fractal dimension of the segmented airway tree was less in asthmatic patients compared with that seen in control subjects (P = .007). Three novel, quantitative, CT-based asthma clusters were identified, all of which demonstrated air trapping. Cluster 1 demonstrates increased RB1 WV and RB1 LV but decreased RB1 percentage WV. On the contrary, cluster 3 subjects have the smallest RB1 WV and LV values but the highest RB1 percentage WV values. There is a lack of proximal airway remodeling in cluster 2 subjects.
Conclusions |
Quantitative CT analysis provides a new perspective in asthma phenotyping, which might prove useful in patient selection for novel therapies.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, airway remodeling, distal airway, CT, quantitative imaging, phenotypes, cluster analysis, fractal analysis
Abbreviations used : ATS, BSA, CT, Dav, De, Dsc, Dsce, FRC, HU, ICC, LA, LV, MLD E/I, Pi10, Po20, RB1, ROI, RV, TLC, VI, VI−850 E-I, VI−850/−950 E-I, WA, WV
Plan
| ☆ | This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Supported in part by GlaxoSmithKline, Wellcome Trust Senior Fellowship, and the Airway Disease Predicting Outcomes through Patient Specific Computational Modelling (AirPROM) project (funded through FP7 EU grant). This article presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health. |
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| Disclosure of potential conflict of interest: I. D. Pavord has received research support from, consulting fees from, and travel fees from GlaxoSmithKline (GSK); is a board member for and has consultancy arrangements with Almirall, AstraZeneca, Boehringer Ingelheim, 220 GSK, MSD, Schering-Plough, Novartis, Dey, and Napp; and has received one or more payments for lecturing from or is on the speakers' bureau for AstraZeneca, Boehringer Ingelheim, GSK, Boston Scientific, and Aerocrine. R. P. Marshall is employed by and owns stock/stock options in GSK. D. Subramanian has received one or more payments for lecturing from or is on the speakers' bureau for GSK and has received one or more payments for travel/accommodations/meeting expenses from Talecris Biopharmaceuticals and GSK. D. Parr has consultancy arrangements with and has received one or more payments for lecturing from or is on the speakers' bureau for GRIFOLS/TALECRIS and has received one or more payments for travel/accommodations/meeting expenses from Boehringer Ingelheim. S. Siddiqui is a board member for Teva; has received small-airway research grants from Chiesi; has received one or more payments for lecturing from the European Respiratory Society and in EAACI symposia/PG courses and for lectures organized by Chiesi and GSK and in dry powder inhaler industry symposia; and has received one or more payments for the development of educational presentations for GSK (airway physiology course educational grants). C. E. Brightling has been supported by one or more grants from the Wellcome Trust and GSK; is a Board member for MedImmune, Novartis, Chiesi, and Amgen; and has consultancy arrangements with MedImmune, Roche, and Chiesi. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 133 - N° 3
P. 729 - mars 2014 Retour au numéro
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