With all the research being done with PCD, it is important for pulmonologists to be aware of the latest findings so as not to use outdated methods for diagnosing and treating PCD.  “Rapid Advances in Primary Ciliary Dyskinesia Research: A Brief Update for Pulmonologists,” published in the January 15, 2019 issue of American Journal of Respiratory and Critical Care Medicine, credits “recent efforts by the NIH-funded Genetic Diseases of Mucociliary Clearance Consortium (GDMCC), the international PCD Cohort, and the PCD Foundation have dramatically accelerated the pace of discovery.”  The authors point to three recent findings of which pulmonologists should be aware.

The first of which is that diagnosis should no longer rely solely on electron microscopy (EM).  Research shows that about 30% of PCD patients can have a normal EM, and that 15-20% of patients diagnosed using EM actually don’t have PCD.  To accurately diagnose PCD, it is essential that the patient have two of the following four clinical criteria:

  • A history of respiratory distress requiring supplemental oxygen in a newborn at full term.
  • Organ reversal or other laterality defect (heterotaxy).
  • Chronic, year-round, daily rhinorrhea (nasal congestion) beginning in the first year of life and/or have chronic sinusitis.
  • Chronic, year-round, daily wet cough and/or bronchiectasis.


Along with:

  • Definitively diagnostic genotype
  • Electron Microscopy (EM)
  • High-speed video microscopy (HSVM)
  • And/or nasal nitric oxide (nNO) results


Recently published ATS Guidelines for diagnosing PCD demonstrate that nNO values lower than 77 nl/min in patients over 5 years old, with a compatible clinical picture (as above) and where cystic fibrosis (CF) has been ruled out is 98% effective in diagnosing PCD.  nNo is also greater than 99.9% effective for ruling out PCD, again in patients over 5 years old where CF is ruled out.  The one exception to this when the patient has the rare RSPH1 mutation, where nNO levels can be normal. As gene discovery continues, it is possible that additional genes will be associated with higher nNO levels, so where there is high suspicion for PCD, nNO level alone should not be used to rule PCD out.

The authors also note that caution should be used when interpreting EMs that show absent or defective inner dynein arms (IDA) alone, as many times these test are read, incorrectly, as positive for PCD. IDA defects alone must be seen on multiple biopsies to be considered diagnostic, and ideally, if PCD is suspected, the patient should be seen at a PCD Foundation accredited center, at least initially.

The second refers to the article we shared two weeks ago by Davis and coworkers, which demonstrated the value of genetic information in PCD.  It can be helpful with diagnosis for patients under 5 years old, as well as for genetic counseling.  However, genetic testing isn’t necessarily conclusive, as it is estimated that only 75% of the PCD-related genes have been identified. What’s more, it is not uncommon for test results to return variants of unknown significance, which means just that – variants on the genes are found, but the significance is not yet known or understood.  There also seems to be a relationship between genotype and phenotype and there is likely to one day be treatment based on genotype, like there is in CF.  They mention one of the limitations in the Davis paper that with over 40 genotypes the sample size for each subgroup in their study was small.

The third is the necessity for a patient registry to help provide analysis over a PCD patient’s lifetime.  We would learn more about PCD progression and develop better management plans.  They do note that these registries are in the works.