title: Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography.
abstract: EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting "emphysema-dominant", "airway disease-dominant", "mixed" disease and "mild" disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2 ) and carbon dioxide (PCO2 ) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease.
authors.affiliation: Dept of Respiratory Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK Dept of Respiratory Medicine, Royal Derby Hospital, Derby, UK Both authors contributed equally.
authors.forename: Deepak R
authors.initials: DR
authors.lastname: Subramanian
authors.affiliation: Dept of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, UK Radiology Dept, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK Both authors contributed equally.
authors.forename: Sumit
authors.initials: S
authors.lastname: Gupta
authors.affiliation: EvA Study Center, Helmholtz Zentrum Muenchen and Asklepios-Klinik, Gauting, Germany.
authors.forename: Dorothe
authors.initials: D
authors.lastname: Burggraf
authors.affiliation: EvA Study Center, Helmholtz Zentrum Muenchen and Asklepios-Klinik, Gauting, Germany.
authors.forename: Suzan J
authors.initials: SJ
authors.lastname: Vom Silberberg
authors.affiliation: EvA Study Center, Helmholtz Zentrum Muenchen and Asklepios-Klinik, Gauting, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Heimbeck
authors.affiliation: EvA Study Center, Helmholtz Zentrum Muenchen and Asklepios-Klinik, Gauting, Germany.
authors.forename: Marion S
authors.initials: MS
authors.lastname: Heiss-Neumann
authors.affiliation: EvA Study Center, Helmholtz Zentrum Muenchen and Asklepios-Klinik, Gauting, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Haeussinger
authors.affiliation: Institute for Lung Health, Dept of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Newby
authors.affiliation: National Institute for Health Research, Leicester Respiratory Biomedical Research Unit, Leicester Institute for Lung Health, University Hospitals of Leicester, Leicester, UK.
authors.forename: Beverley
authors.initials: B
authors.lastname: Hargadon
authors.affiliation: Dept of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, UK Radiology Dept, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK.
authors.forename: Vimal
authors.initials: V
authors.lastname: Raj
authors.affiliation: Centre for Respiratory Medicine and Allergy, The University of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.affiliation: Centre for Respiratory Medicine and Allergy, The University of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Umme
authors.initials: U
authors.lastname: Kolsum
authors.affiliation: EvA Study Center, Helmholtz Zentrum Muenchen and Asklepios-Klinik, Gauting, Germany.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Hofer
authors.affiliation: Centre for Respiratory Medicine and Allergy, The University of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Khaled
authors.initials: K
authors.lastname: Al-Shair
authors.affiliation: Dept of Diagnostic Radiology, University Medical Center, Freiburg, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Luetzen
authors.affiliation: Dept of Pneumology, University Medical Center, Freiburg, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Prasse
authors.affiliation: Dept of Pneumology, University Medical Center, Freiburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Müller-Quernheim
authors.affiliation: Dept of Medical Sciences, University of Ferrara and Ferrara City Hospital, Ferrara, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Benea
authors.affiliation: Dept of Medical Sciences, University of Ferrara and Ferrara City Hospital, Ferrara, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Leprotti
authors.affiliation: Dept of Medical Sciences, University of Ferrara and Ferrara City Hospital, Ferrara, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: Boschetto
authors.affiliation: 2nd Dept of Respiratory Medicine, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Gorecka
authors.affiliation: 2nd Dept of Respiratory Medicine, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Nowinski
authors.affiliation: Department of Radiology and Diagnostic Imaging, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.
authors.forename: Karina
authors.initials: K
authors.lastname: Oniszh
authors.affiliation: Scientific Computing Research Unit, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Wolfgang Zu
authors.initials: WZ
authors.lastname: Castell
authors.affiliation: Scientific Computing Research Unit, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hagen
authors.affiliation: Dept of Pathophysiology, National Koranyi Institute for TB and Pulmonology, Budapest, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Barta
authors.affiliation: Dept of Tumorbiology, National Koranyi Institute for TB and Pulmonology, Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Döme
authors.affiliation: Dept of Pneumology, National Koranyi Institute for TB and Pulmonology, Budapest, Hungary.
authors.forename: Janos
authors.initials: J
authors.lastname: Strausz
authors.affiliation: Dept of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University, Marburg, Germany Member of the German Center for Lung Research (DZL).
authors.forename: Timm
authors.initials: T
authors.lastname: Greulich
authors.affiliation: Dept of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University, Marburg, Germany Member of the German Center for Lung Research (DZL).
authors.forename: Claus
authors.initials: C
authors.lastname: Vogelmeier
authors.affiliation: Dept of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University, Marburg, Germany Member of the German Center for Lung Research (DZL).
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Koczulla
authors.affiliation: Centre Nacional d'Anàlisi Genòmica, Barcelona, Spain.
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.affiliation: Member of the German Center for Lung Research (DZL) Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany Dept of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Hohlfeld
authors.affiliation: Member of the German Center for Lung Research (DZL) Dept of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.affiliation: Dept of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Mahyar
authors.initials: M
authors.lastname: Lavae-Mokhtari
authors.affiliation: EvA Study Center, Helmholtz Zentrum Muenchen and Asklepios-Klinik, Gauting, Germany Loems-EvA@gmx.de.
authors.forename: Loems
authors.initials: L
authors.lastname: Ziegler-Heitbrock
authors.affiliation: Dept of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, UK Radiology Dept, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK Both authors contributed equally.
authors.forename: Christopher
authors.initials: C
authors.lastname: Brightling
authors.affiliation: Dept of Respiratory Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK Both authors contributed equally.
authors.forename: David G
authors.initials: DG
authors.lastname: Parr
mesh_terms: D000328:Adult; D000368:Aged; D005060:Europe; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging*; D012137:Respiratory System / Q000503:physiopathology; D013147:Spirometry; D014057:Tomography, X-Ray Computed / Q000592:standards*