Diagnosis of primary ciliary dyskinesia: summary of the ERS Task Force report

Claudia E. Kuehni; Jane S. Lucas

doi:10.1183/20734735.008517

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Supplementary Materials

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Figure 1
Diagram of the ultrastructure of the normal ciliary axoneme in transverse section. Reproduced from [5].
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Figure 2
Electron microscopy images of defects seen in patients with primary ciliary dyskinesia. a) Outer dynein arm defect. b) Inner dynein arm and microtubular disarrangement. Reproduced and modified from [5].
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Figure 3
The role of primary care physicians, specialists and PCD diagnostic centres in diagnosing and managing patients with PCD.
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Figure 4
Algorithm for diagnostic assessment of patients for PCD proposed by the ERS Task Force. This is a simplified version of the previously published diagram; see the full Task Force report [5] for details.
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Figure 5
Further steps after diagnostic workup and management for patients with positive, highly likely, highly unlikely and inconclusive diagnostic data. MRI: magnetic resonance imaging; CT: computed tomography.

Table 1

Characteristic symptoms in patients with PCD, stratified by age^#

Neonates	Situs abnormalities Normal situs (∼47%) Situs inversus totalis (∼47%) Situs ambiguus with or without cardiac defects (∼6–12%) Neonatal respiratory distress At term with no risk factors Prolonged oxygen requirement Atelectasis on radiography Persistent rhinorrhoea Family history of PCD
Childhood	Wet cough Typically starts in infancy Persistent, year-round, doesn’t completely resolve with antibiotics Bronchiectasis Sometimes present in pre-school year Chronic rhinitis typically starts in infancy Persistent, year round even when “well” Otitis media with effusion (“glue ear”) Conductive hearing loss Variability within and between patients, normal to requiring hearing aids Mucopurulent discharge complicates ventilation tube insertion (evidence poor)
Adolescents and adults	As for children, plus Bronchiectasis Almost universal by adulthood Rhinosinusitis, variability within and between patients; symptoms might include Persistent nasal blockage and discharge Conductive hearing loss Sinusitis Anosmia Nasal polyposis Male infertility (not 100% and incidence unclear) Female fertility issues (incidence unclear)

Not all symptoms may be present. Although individual symptoms are nonspecific, the combination of symptoms is a strong indicator. The early onset and persistence of airway symptoms is typical. ^#: as hardly any of the available publications has been stratified by age, this table is mainly based on the authors’ expert opinion and will change as good epidemiological data become available; it is based mainly on the pulmonologist’s perspective, as few papers come from ENT, fertility, cardiology or neonatal services and reflect their patient mix.

Table 2

Diagnostic tests for PCD with specification of rationale, requirements for infrastructure, strengths and limitations, and contribution to the final diagnosis

Investigation	Rationale	Infrastructure required	Strengths and limitations	Contribution to final decision
nNO	Very low in most PCD patients	Chemiluminescence analyser (portable analysers are acceptable for screening) Staff trained to take measurements and interpret results according to ATS/ERS standards [21]	Sensitivity and specificity good but not 100% International measurements standards “Gold standard” (velum closure) impossible in young children Tidal breathing method as alternative in young children but healthy infants have low nNO	Screening test for patients with clinical symptoms Contributes to diagnostic decision but in isolation does not rule in or rule out PCD
HSVA
CBF	CBF can be slow or fast in some patients with PCD	High-speed video (capable of 250–500 fps) attached to high-resolution microscope Observer with extensive experience of normal and abnormal	Neither sensitive nor specific No standards for measurement or reporting	Should only be used in combination with CBP
CBP	Abnormal ciliary beating is a feature of PCD	High-speed video (capable of 250–500 fps) attached to high-resolution microscope Observer with extensive experience of normal and abnormal Accuracy improved by reanalysis following cell culture (to mitigate secondary defects)	Sensitivity excellent but specificity can be a problem due to secondary defects (e.g. infections) No standards for measurement or reporting	Contributes to diagnostic decision but in isolation does not rule in or rule out PCD
TEM	Abnormal ciliary ultrastructure is a feature of some phenotypes	Electron microscope Observer with extensive experience of normal and abnormal Analysis of sufficient cilia (e.g. 100) in transverse section from different healthy cells	Diagnostic if “hallmark” abnormalities are found Sensitivity limited, as 15–20% of patients have normal ultrastructure; not useful in isolation No standards for measurement or reporting	Confirms the diagnosis if “hallmark” abnormalities are present Does not rule out PCD if normal
Genotyping	PCD is a genetic disorder	Specialist genetic services with knowledge of the complexities of PCD Parental segregation for new mutations	Diagnostic if pathogenic biallelic mutations found No studies have investigated its role as a diagnostic test National and international standards for clinical genetic reports	Confirms diagnosis if pathogenic biallelic mutations are identified Known mutations are identified in 65% of patients with PCD Does not rule out PCD
IF staining of proteins	Specific proteins are missing from cilia	Standard pathology IF labelling Observer with extensive experience of normal and abnormal	Faster and cheaper to assess ciliary ultrastructure than TEM Antibodies not commercially available for all ciliary proteins No standards for measurement or reporting	Until Task Force report, no publications on role as a diagnostic test A recent single-centre study suggests usefulness