Primary Ciliary Dyskinesia: Practical Pearls for Diagnosis

Primary ciliary dyskinesia (PCD), a dysfunction of the motile cilia, is not diagnosed only in childhood, as previously thought.¹ Some patients are not diagnosed with the rare genetic disease until they are adults.² Because PCD is so rare (1 in 20,000 live births), clinicians may not be aware of its many manifestations, including chronic upper and lower respiratory distress, infertility in men and women, hearing loss, bronchiectasis, and abnormal placement of the internal organs.^1,3

Recent guidelines set forth by an interdisciplinary panel of pediatric and adult pulmonologists, cardiologists, geneticists, neonatologists, radiologists, and pediatric otolaryngologists assembled by the American Thoracic Society (ATS) sought to demystify the disease by addressing 4 main questions on PCD diagnosis.^1,4 The ATS outlined the 4main clinical features that clinicians should consider before ordering tests for PCD⁴:

• Year-round wet or productive cough
• Nonseasonal daily rhinosinusitis
• The need for >24 hours of supplemental oxygen as a neonate
• Laterality defects of the internal organs

The sensitivity and specificity of having 2 of these features are 80% and 72%, respectively.⁴ The sensitivity and specificity are 21% and 99%, respectively, if all 4 features are present.⁴

Genetics of PCD Diagnosis

Thus far, 40 genes have been identified as causative for PCD.³ As such, the ATS recommended that clinicians opt for genetic testing for PCD because tests that rely on biopsy, ciliary beat pattern (CBP), and high-speed video microscopy (HSVM) depend on the skill of the individuals administering the tests. The sensitivity of genetic panels can have a somewhat wide range, with a 12-gene test yielding a sensitivity of 71.9% and the 32 gene-panel yielding a sensitivity of 93.9%.⁴ Now that genetic panels can produce more definitive results, they have supplanted tests such as transmission electron microscopy, which frequently resulted in false positives and false negatives.⁴  

Nasal Nitric Oxide Testing

In adults and cooperative children ≥5 years who have 2 of the 4 criteria for PCD, the ATS recommended conditionally that low levels of nasal nitric oxide (nNO) could be used to diagnose PCD.⁴ The nNO screenings are more readily available than are more extensive laboratory tests and are less expensive. Despite the convenience of obtaining quick results, the ATS cautioned that while the test itself yielded reasonably accurate results, the overall body of evidence is low.⁴ Repeat tests are necessary because sinusitis or acute viral infections may render low nNO levels.⁴

CBP

Because of the lack of robust evidence and the paucity of testing centers with expertise, the ATS recommended against diagnosing PCD by studying the CBP with HSVM.⁴ Many of the centers that use HSVM do so for research and not diagnostic purposes because HSVM may help them better understand the mechanisms that cause PCD.⁴

Ciliary Waveform Analysis Using Light Microscopy

The ATS also did not recommend using ciliary waveform analysis.⁴ Few centers in the United States perform the test and the results are not often accurate.⁴ Furthermore, the evidence base does not include the ciliary waveform analysis without the use of HSVM, which does not correspond with current reference points for diagnosing PCD.⁴

The ATS recommended that clinicians not favor one test over another, but rather use them in a series of algorithmic steps to diagnose PCD.⁴