Jessica Rademacher1, Sabine Dettmer2, Jan Fuge3, Jens Vogel-Claussen2, Hoen-Oh Shin2, Anand Shah4, Paula Inês Pedro5, Rob Wilson4, Tobias Welte1, Frank Wacker2, Michael R Loebinger4, Felix C Ringshausen1. 1. Department of Respiratory Medicine, Hannover Medical School, Biomedical Research in End-stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany. 2. Department of Radiology, Hannover Medical School, Biomedical Research in End-stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany. 3. Biomedical Research in End-stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany. 4. Host Defence Unit, Department of Respiratory Medicine, Royal Brompton and Harefield NHS Foundation Trust, National Heart and Lung Institute, Imperial College London, London, United Kingdom. 5. Department of Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom.
Abstract
BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder which requires a complex diagnostic workup. Thus, an easy and widely available screening method would be helpful to identify patients who need a further diagnostic workup for PCD. OBJECTIVES: The aim of the study was to develop and validate a computed tomography (CT) score for PCD to facilitate etiological diagnosis in adults with bronchiectasis. METHOD: Chest CTs from 121 adults with bronchiectasis were scored for bronchiectasis morphology, distribution, and associated findings. Patients with and without the etiological diagnosis of PCD (46 and 75, respectively) were compared. Significantly, different imaging findings (p < 0.05) in univariate analysis were considered for multivariate analysis. Distinct findings were used to build the score. Based on this score, receiver operating characteristic (ROC) curve analysis was performed. The score was validated with 2 independent cohorts, another cohort from the same institution with 56 patients (28 with PCD) and an external cohort from another referral center with 172 patients (86 with PCD). RESULTS: The following parameters predicted PCD in adults with bronchiectasis and were included in the score with weighting according to their regression coefficients: 2 points were given for predominance in the middle/lower lobe, 2 points for tree-in-bud pattern, 2 points for atelectasis or prior resection of a middle/lower lobe, and 3 points for absence of emphysema and fibrosis. Situs inversus was only observed in subjects with PCD (Kartagener syndrome) and, thus, was not used in the primary ciliary dyskinesia computed tomography (PCD-CT) score as group comparisons could not be performed. ROC curve analysis revealed an area under the curve (AUC) of 0.90 (95% CI 0.85-0.96). Youden index was the highest at a threshold of >6 with a sensitivity of 83% and a specificity of 83%. In the validation cohorts, ROC curve analysis confirmed the performance of the score with an AUC of 0.83 (95% CI 0.72-0.94) in the first validation cohort and 0.79 (95% CI 0.73-0.86) in the external validation cohort. CONCLUSIONS: The PCD-CT score provides the first validated CT score for PCD and helps physicians in identifying adult bronchiectasis patients who require further diagnostic workup. Key message: The PCD-CT score provides the first validated CT score to assist physicians in identifying adult bronchiectasis patients who require a further diagnostic workup for PCD. It potentially improves earlier recognition of this rare and underdiagnosed disease.
BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder which requires a complex diagnostic workup. Thus, an easy and widely available screening method would be helpful to identify patients who need a further diagnostic workup for PCD. OBJECTIVES: The aim of the study was to develop and validate a computed tomography (CT) score for PCD to facilitate etiological diagnosis in adults with bronchiectasis. METHOD: Chest CTs from 121 adults with bronchiectasis were scored for bronchiectasis morphology, distribution, and associated findings. Patients with and without the etiological diagnosis of PCD (46 and 75, respectively) were compared. Significantly, different imaging findings (p < 0.05) in univariate analysis were considered for multivariate analysis. Distinct findings were used to build the score. Based on this score, receiver operating characteristic (ROC) curve analysis was performed. The score was validated with 2 independent cohorts, another cohort from the same institution with 56 patients (28 with PCD) and an external cohort from another referral center with 172 patients (86 with PCD). RESULTS: The following parameters predicted PCD in adults with bronchiectasis and were included in the score with weighting according to their regression coefficients: 2 points were given for predominance in the middle/lower lobe, 2 points for tree-in-bud pattern, 2 points for atelectasis or prior resection of a middle/lower lobe, and 3 points for absence of emphysema and fibrosis. Situs inversus was only observed in subjects with PCD (Kartagener syndrome) and, thus, was not used in the primary ciliary dyskinesia computed tomography (PCD-CT) score as group comparisons could not be performed. ROC curve analysis revealed an area under the curve (AUC) of 0.90 (95% CI 0.85-0.96). Youden index was the highest at a threshold of >6 with a sensitivity of 83% and a specificity of 83%. In the validation cohorts, ROC curve analysis confirmed the performance of the score with an AUC of 0.83 (95% CI 0.72-0.94) in the first validation cohort and 0.79 (95% CI 0.73-0.86) in the external validation cohort. CONCLUSIONS: The PCD-CT score provides the first validated CT score for PCD and helps physicians in identifying adult bronchiectasis patients who require further diagnostic workup. Key message: The PCD-CT score provides the first validated CT score to assist physicians in identifying adult bronchiectasis patients who require a further diagnostic workup for PCD. It potentially improves earlier recognition of this rare and underdiagnosed disease.
Authors: Timothy R Aksamit; Anne E O'Donnell; Alan Barker; Kenneth N Olivier; Kevin L Winthrop; M Leigh Anne Daniels; Margaret Johnson; Edward Eden; David Griffith; Michael Knowles; Mark Metersky; Matthias Salathe; Byron Thomashow; Gregory Tino; Gerard Turino; Betsy Carretta; Charles L Daley Journal: Chest Date: 2016-11-23 Impact factor: 9.410
Authors: Bruna Rubbo; Amelia Shoemark; Claire L Jackson; Robert Hirst; James Thompson; Joseph Hayes; Emily Frost; Fiona Copeland; Claire Hogg; Christopher O'Callaghan; Isabel Reading; Jane S Lucas Journal: Chest Date: 2019-02-28 Impact factor: 9.410
Authors: Adam J Shapiro; Stephanie D Davis; Deepika Polineni; Michele Manion; Margaret Rosenfeld; Sharon D Dell; Mark A Chilvers; Thomas W Ferkol; Maimoona A Zariwala; Scott D Sagel; Maureen Josephson; Lucy Morgan; Ozge Yilmaz; Kenneth N Olivier; Carlos Milla; Jessica E Pittman; M Leigh Anne Daniels; Marcus Herbert Jones; Ibrahim A Janahi; Stephanie M Ware; Sam J Daniel; Matthew L Cooper; Lawrence M Nogee; Billy Anton; Tori Eastvold; Lynn Ehrne; Elena Guadagno; Michael R Knowles; Margaret W Leigh; Valery Lavergne Journal: Am J Respir Crit Care Med Date: 2018-06-15 Impact factor: 21.405
Authors: Margaret W Leigh; Jessica E Pittman; Johnny L Carson; Thomas W Ferkol; Sharon D Dell; Stephanie D Davis; Michael R Knowles; Maimoona A Zariwala Journal: Genet Med Date: 2009-07 Impact factor: 8.822
Authors: Sara Lonni; James D Chalmers; Pieter C Goeminne; Melissa J McDonnell; Katerina Dimakou; Anthony De Soyza; Eva Polverino; Charlotte Van de Kerkhove; Robert Rutherford; John Davison; Edmundo Rosales; Alberto Pesci; Marcos I Restrepo; Antoni Torres; Stefano Aliberti Journal: Ann Am Thorac Soc Date: 2015-12
Authors: James D Chalmers; Stefano Aliberti; Eva Polverino; Montserrat Vendrell; Megan Crichton; Michael Loebinger; Katerina Dimakou; Ian Clifton; Menno van der Eerden; Gernot Rohde; Marlene Murris-Espin; Sarah Masefield; Eleanor Gerada; Michal Shteinberg; Felix Ringshausen; Charles Haworth; Wim Boersma; Jessica Rademacher; Adam T Hill; Timothy Aksamit; Anne O'Donnell; Lucy Morgan; Branislava Milenkovic; Leandro Tramma; Joao Neves; Rosario Menendez; Perluigi Paggiaro; Victor Botnaru; Sabina Skrgat; Robert Wilson; Pieter Goeminne; Anthony De Soyza; Tobias Welte; Antoni Torres; J Stuart Elborn; Francesco Blasi Journal: ERJ Open Res Date: 2016-01-20
Authors: Panayiotis Kouis; Myrofora Goutaki; Florian S Halbeisen; Ifigeneia Gioti; Nicos Middleton; Israel Amirav; Angelo Barbato; Laura Behan; Mieke Boon; Nagehan Emiralioglu; Eric G Haarman; Bulent Karadag; Cordula Koerner-Rettberg; Romain Lazor; Michael R Loebinger; Bernard Maitre; Henryk Mazurek; Lucy Morgan; Kim Gjerum Nielsen; Heymut Omran; Ugur Özçelik; Mareike Price; Andrzej Pogorzelski; Deborah Snijders; Guillaume Thouvenin; Claudius Werner; Zorica Zivkovic; Claudia E Kuehni; Panayiotis K Yiallouros Journal: Respir Res Date: 2019-09-18
Authors: Helene E Kobbernagel; Frederik F Buchvald; Eric G Haarman; Carmen Casaulta; Samuel A Collins; Claire Hogg; Claudia E Kuehni; Jane S Lucas; Heymut Omran; Alexandra L Quittner; Claudius Werner; Kim G Nielsen Journal: BMC Pulm Med Date: 2016-07-22 Impact factor: 3.317