ATS 2018: Ramping up recognition of a rare lung disease


By Mardi Chapman

29 May 2018

Clinical practice guidelines for the diagnosis of primary ciliary dyskinesia (PCD) have been updated in an effort to reduce the delay in diagnosis for a rare disease that nevertheless has well defined clinical features.

Dr Adam Shapiro told ATS 2018 that PCD symptoms such as a year-round wet cough and nasal congestion from a young age (<6 months) overlapped with other paediatric conditions such as cystic fibrosis and ‘daycare-itis’.

Other key clinical features include unexplained neonatal respiratory distress and organ laterality defects.

PCD is characterised by defective mucous clearance leading to recurrent infections, bronchiectasis and respiratory failure.

While its prevalence is estimated at 1 in 10,000-30,000, it represented about 10% of adult idiopathic bronchiectasis patients.

Dr Shapiro, a paediatric pulmonologist from Montreal Children’s Hospital, said an international committee of 30 PCD experts had reviewed the evidence for key diagnostic approaches.

“No single test will accurately diagnose all forms of PCD,” Dr Shapiro said.

They found an extended gene panel of more than 12 genes in children and adults with a strong clinical phenotype for PCD offered better sensitivity and specificity than limited gene panels or the presence of ciliary defects on transmission electron microscopy (TEM).

However he emphasised that negative results from genetic testing could not rule out a diagnosis of PCD given the many genes involved. More than 41 genes have been implicated to date but the number could possibly be as high as 150.

Dr Shapiro said nasal nitric oxide (NO) measured by chemiluminescence analysers, was non-invasive, fast and inexpensive in cooperative patients from about five years of age.

Low levels of nNO <77nL/min, after CF had been ruled out, had a diagnostic sensitivity of about 98% and specificity of 96%.

“However acute viral infections can also give a false low therefore [the test] should be repeated on two separate occasions.”

Digital high-speed video microscopy with ciliary beat pattern analysis was the primary technique used in most European centres, Dr Shapiro noted.

However the panel found great uncertainty with the results from four studies and did not recommend it as a replacement for either TEM or genetic testing.

And finally the expert panel found no reviewable evidence to recommend ciliary beat frequency alone, as measured under standard 100x light microscopy.

Their proposed standard diagnostic algorithm starts with at least two of the four cardinal features.

Where there was access to nNO chemiluminescence in specialty centres for children from five years and with CF ruled out, a normal result suggested the diagnosis was unlikely to be PCD.

In patients with low levels of nNO, results should be confirmed with a repeat test before referring for genetic testing.

“Biallelic pathogenic variants in PCD-associated genes indicated a diagnosis of PCD.”

Single or no pathogenic variants could be referred for TEM, he suggested.

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