The article WAidid suggests this week, "European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia: a guideline review", was published last month on the Archives of Disease in Childhood - Education and Practice.

SUMMARY

Primary ciliary dyskinesia (PCD) is a rare genetic condition with a prevalence of 1:10 000 -20 000 live births. It is a phenotypically and genetically heterogeneous disorder of ciliary structure and function and affects the lungs, nose, sinuses, ears and fertility.

The European Respiratory Society (ERS) previously published a consensus statement in 2009, providing a detailed review of the aetiology, presentation, diagnosis and management of PCD. In 2016, an ERS Task Force developed a guideline to provide evidence-based recommendations for the diagnosis of PCD. No single feature is specific for PCD. The use of combinations of symptoms and signs should be used, when considering referral for PCD testing. A persistent wet cough is always found, with one or more of: persistent rhinitis, chronic middle ear disease, history of neonatal respiratory distress, situs inversus totalis, heterotaxy, and congenital cardiac defects, siblings or extended family of patients with PCD who have the above symptoms. Predictive tools, such as the Primary Ciliary Dyskinesia Rule (PICADAR) score, are helpful: patients with symptoms of PCD and PICADAR score ≥5 should be referred for PCD testing.

The PCD tests available are highly specialised and should be performed and interpreted only by specialists in PCD diagnostic centres.

• nNO measurement in children over 6 years of age. It is the measurement of the expired NO from one nostril and is highly accurate, when done via a stationary chemiluminescence analyser using velum closure breathing technique. It is relatively easy to perform, non-invasive and affordable; there are no agreed cut-off values; it is not sufficiently accurate to rule in or out PCD in isolation.
• High-speed video microscopy analysis (HSVA). It is performed on a sample of respiratory epithelium, taken by nasal or lower airway brushings, in patients free of an acute respiratory tract infection for 4–6 weeks. It records the high-speed ciliary beat frequency (CBF) and beat pattern: CBF may be slow, normal or increased in PCD, depending on the genotype; the air-liquid interface culture improves diagnostic accuracy. If the results are inconclusive and there is a strong clinical suspicion, a brushing should be repeated. HSVA requires experienced observers and is not sufficiently standardized to rule PCD in or out by itself.
• Transmission electron microscopy (TEM). It is used to look for ciliary ultrastructure defects. There are some hallmark ciliary ultrastructure defects for PCD, even though some rare genetic PCD subtypes have normal TEM findings. If the ciliary ultrastructure defects are consistent with PCD, no further testing is needed, but, if normal, further testing should be undertaken, if the clinical history is strong. This test is technically demanding and requires experienced personnel to perform and interpret the findings.
• Genetic testing. It is not recommended as part of initial diagnostic testing: it is currently carried out in research setting or in limited clinical settings, such as in case of inconclusive diagnosis. Mutations in more than 30 genes have been reported. Genetic testing can be used to confirm a diagnosis, but does not help rule it out. There is a good relation between TEM and genotype, but genotype-clinical phenotype correlation is not yet well known. Genetic testing, if positive, is helpful for genetic counselling.
• This is not a routine clinical test, but its role is developing.

Not all patients need to go through all steps. The algorithm proposed by ERS Task Force helps classifying patients as PCD positive, PCD highly likely and PCD highly unlikely. A subgroup will continue to have an inconclusive outcome using currently available diagnostic tests.

The authors concluded underlying some issues: to continue investigating patients with a wet cough and refer appropriately to tertiary centres; to remember the constellation of signs and symptoms suggestive of PCD, although no single feature is specific for PCD; to use a scoring tool like PICADAR; to use the 2017 CHEST guideline for the management of children with wet cough; to ensure clinical follow-up to all patients with strong PCD phenotype but an ‘inconclusive’ diagnostic test. The authors, also, highlighted the importance of stopping the saccharin test and pulmonary radioaerosol mucociliary clearance, and the necessity of further studies, investigating the accuracy and place of genetic testing and immunofluorescence as diagnostic tools.

AUTHOS: Rebecca Amy Dalrymple; Priti Kenia.