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 |
CBF: ciliary beat frequency; CBP: ciliary beat pattern; ATS: American Thoracic Society; fps: frames per second.