Comparison of recommendations for the diagnosis of primary ciliary dyskinesia (PCD) by the European Respiratory Society (ERS) task force and American Thoracic Society (ATS) guideline committee
| ERS task force (2017) [6] | ATS guideline committee (2018) [7] | |
| Final guideline criteria endorsed for definitive PCD diagnosis | Biallelic pathogenic variants in PCD-associated gene or TEM hallmark ciliary ultrastructural defect. | Biallelic pathogenic variants in PCD-associated gene or TEM hallmark ciliary ultrastructural defect or low nNO level+. |
| Patients included/referred for testing | A combination of typical symptoms, possibly supported by symptom-based predictive tools such as PICADAR [12]. PICADAR score of 4 has sensitivity 0.97, specificity 0.48; score of 5 has a sensitivity of 0.90 and specificity of 0.75 [12]. | Two of four clinical features: early onset chronic wet cough, early onset chronic nasal congestion, unexplained neonatal respiratory distress or an organ laterality defect (for two key symptoms: sensitivity 0.80, specificity 0.72%; for four key symptoms: sensitivity 0.21, specificity 0.99) [15]. |
| Evidence based recommendations for the role of diagnostic tests in patients with high pre-test probability of PCD# (GRADE strength of recommendations) | ||
| Nasal nitric oxide (nNO) | nNO¶ should be used as part of the diagnostic work-up of patients >6 years (MODERATE). | Low nNO+ should be used to replace TEM and/or PCD gene testing in cooperative patients ≥5 years, when CF ruled out (CONDITIONAL). |
| Ciliary ultrastructure analysis by transmission electron microscopy (TEM) | TEM should be used as part of the diagnostic work-up (STRONG). Further diagnostic testing should be performed in patients with normal TEM if clinical history is strong (STRONG). A hallmark defect confirms diagnosis (STRONG). | TEM not evaluated as it was included in the diagnostic reference standard. |
| Genetic testing | No studies met inclusion criteria for analysis. | An extended gene panel (>12 genes) should be used to replace electron microscopy and/or standard gene panels (≤12 genes) (CONDITIONAL). |
| High speed video microscopy (HSVMA) | HSVMA should be used as part of the diagnostic work-up (WEAK). HSVMA should be repeated after ALI culture (STRONG). | HSVMA should not be used to replace electron microscopy and/or PCD gene testing (CONDITIONAL). |
| Ciliary beat frequency (CBF) | CBF alone should not be used as part of the diagnostic work-up (STRONG). | CBF alone should not be used to replace electron microscopy and/or PCD gene testing (CONDITIONAL). |
| Immunofluorescence | No studies met inclusion criteria for analysis. | Not evaluated. |
#: ERS task force evaluated specific clinical criteria to develop evidence-based recommendations for which patients should be referred for diagnostic testing, while ATS guideline committee specified criteria a priori. ¶: preferably using a chemiluminescence analyser with a velum closure technique. In children <6 years, tidal breathing should be used as part of the diagnostic work-up (weak recommendation). +: <77 nL·min−1 measured on two separate occasions with a chemiluminescence device using a standardised protocol at a PCD specialty centre. Corroborative testing with TEM and/or genetic testing should be pursued to further define PCD phenotype and genotype, which may assist in clinical prognosis and family planning. CF: cystic fibrosis; ALI: air–liquid interface.