title: Accuracy of diagnostic testing in primary ciliary dyskinesia.
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.
authors.affiliation: 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.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Jackson
authors.affiliation: 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.
authors.forename: Laura
authors.initials: L
authors.lastname: Behan
authors.affiliation: 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.
authors.forename: Samuel A
authors.identifier: http://orcid.org/0000-0003-1571-7410
authors.initials: SA
authors.lastname: Collins
authors.affiliation: 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.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Goggin
authors.affiliation: 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.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Adam
authors.affiliation: 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.
authors.forename: Janice L
authors.initials: JL
authors.lastname: Coles
authors.affiliation: 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.
authors.forename: Hazel J
authors.initials: HJ
authors.lastname: Evans
authors.affiliation: 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.
authors.forename: Amanda
authors.initials: A
authors.lastname: Harris
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: Lackie
authors.affiliation: 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.
authors.forename: Samantha
authors.initials: S
authors.lastname: Packham
authors.affiliation: 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.
authors.forename: Anton
authors.initials: A
authors.lastname: Page
authors.affiliation: 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.
authors.forename: James
authors.initials: J
authors.lastname: Thompson
authors.affiliation: 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.
authors.forename: Woolf T
authors.initials: WT
authors.lastname: Walker
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kuehni
authors.affiliation: 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.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Lucas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001944:Breath Tests / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D003955:Diagnostic Tests, Routine / Q000592:standards*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007619:Kartagener Syndrome / Q000175:diagnosis*; D008297:Male; D046529:Microscopy, Electron, Transmission; D018715:Microscopy, Video; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D006113:United Kingdom; D055815:Young Adult
chemical_list: D009569:Nitric Oxide