Accuracy of diagnostic testing in primary ciliary dyskinesia

Claire L Jackson; Laura Behan; Samuel A Collins; Patricia M Goggin; Elizabeth C Adam; Janice L Coles; Hazel J Evans; Amanda Harris; Peter Lackie; Samantha Packham; Anton Page; James Thompson; Woolf T Walker; Claudia Kuehni; Jane S Lucas

doi:10.1183/13993003.00749-2015

Accuracy of diagnostic testing in primary ciliary dyskinesia

Eur Respir J. 2016 Mar;47(3):837-48. doi: 10.1183/13993003.00749-2015. Epub 2015 Dec 2.

Authors

Affiliations

¹ Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK Clinical and Experimental Sciences Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK Both authors contributed equally.
² Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK Clinical and Experimental Sciences Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK NIHR Southampton Respiratory Biomedical Research Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK Department of Applied Psychology, University College Cork, Cork, Ireland Both authors contributed equally.
³ Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK Clinical and Experimental Sciences Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK NIHR Southampton Respiratory Biomedical Research Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁴ Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK Biomedical Imaging Unit, University of Southampton Faculty of Medicine and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁵ Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK Clinical and Experimental Sciences Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK.
⁶ Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK NIHR Southampton Respiratory Biomedical Research Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁷ Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK Clinical and Experimental Sciences Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK Biomedical Imaging Unit, University of Southampton Faculty of Medicine and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁸ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
⁹ Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK Clinical and Experimental Sciences Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK NIHR Southampton Respiratory Biomedical Research Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK jlucas1@soton.ac.uk.

Abstract

Diagnosis of primary ciliary dyskinesia (PCD) lacks a "gold standard" test and is therefore based on combinations of tests including nasal nitric oxide (nNO), high-speed video microscopy analysis (HSVMA), genotyping and transmission electron microscopy (TEM). There are few published data on the accuracy of this approach.Using prospectively collected data from 654 consecutive patients referred for PCD diagnostics we calculated sensitivity and specificity for individual and combination testing strategies. Not all patients underwent all tests.HSVMA had excellent sensitivity and specificity (100% and 93%, respectively). TEM was 100% specific, but 21% of PCD patients had normal ultrastructure. nNO (30 nL·min(-1) cut-off) had good sensitivity and specificity (91% and 96%, respectively). Simultaneous testing using HSVMA and TEM was 100% sensitive and 92% specific.In conclusion, combination testing was found to be a highly accurate approach for diagnosing PCD. HSVMA alone has excellent accuracy, but requires significant expertise, and repeated sampling or cell culture is often needed. TEM alone is specific but misses 21% of cases. nNO (≤30 nL·min(-1)) contributes well to the diagnostic process. In isolation nNO screening at this cut-off would miss ∼10% of cases, but in combination with HSVMA could reduce unnecessary further testing. Standardisation of testing between centres is a future priority.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Breath Tests / methods*
Child
Child, Preschool
Diagnostic Tests, Routine / standards*
Female
Genotype
Humans
Infant
Infant, Newborn
Kartagener Syndrome / diagnosis*
Male
Microscopy, Electron, Transmission
Microscopy, Video
Middle Aged
Nitric Oxide / analysis*
ROC Curve
Sensitivity and Specificity
United Kingdom
Young Adult

Substances

Nitric Oxide

Grants and funding

WT_/Wellcome Trust/United Kingdom