Excellent new paper by Dr. Adam Shapiro, et al on the value of nasal nitric oxide (nNO) measurement for the diagnosis of PCD published in the Annals of the American Thoracic Society (ATS) last week. The summary abstract is available by clicking on the link above.

Long discussion below for those interested, but here are some highlights:

–Meta-analysis of multiple datasets (generally considered the strongest form of evidence) looking at nNO in PCD

–nNO performed as well as/better than currently used tests for PCD

–Results were limited to children over age five using velum closure maneuver (blowing against a resistor) because most of the studies included in the analysis used these restrictions (as an aside–efforts are underway to assess the reliability in children younger than age five and w/o velum closure maneuver)

–Recommendation to include nNO as a diagnostic (not just screening) test for PCD in children over five able to perform closed velum maneuver, according to validated SOPs and using chemiluminescent technology (please note, nNO measurements using portable devices–e.g. ‘MINO’–for diagnosis of PCD has not yet been validated and these devices are NOT recommended for establishing the diagnosis at this time)


This is a welcome addition to the literature on PCD diagnosis and it demonstrates, using rigorous statistical modeling and evidence-based criteria, that when performed appropriately on patients with a history compatible with PCD, nNO is a sensitive and specific diagnostic (not just screening) test for PCD. It is, in fact, statistically more reliable than most diagnostic tests currently available for PCD. This gets us one step closer to being able to officially add nNO to the matrix of tests used for PCD diagnosis, rather than limiting it to its current use–a screening test used primarily in research settings (at least in North America).

This does not mean, however, that nNO it is 100% reliable at diagnosing PCD and we know there are some PCD mutations that can produce normal/near normal nNO values (very few, affecting a very small percentage of patients so far). We do not currently have any test that can pick up 100% of all cases of PCD, nor do we have a test that can rule out PCD 100%. Like other testing options (electron microscopy, high-speed videomicroscopy and genetics) the quality of nNO testing will rely on multiple factors. For best results, highly-trained individuals using validated standard operating procedures (SOPs) on carefully calibrated equipment are essential. It can be challenging to find this level of expertise—especially since different skills are required for different tests– in a disorder as rare as PCD and expecting to find it at centers that may only ever see a handful of patients is probably not realistic. This is why many countries in Europe, the UK, the USA, Canada and Australia have opted to create centers of excellence for PCD diagnosis and care.

Even expert centers will often use a matrix approach to diagnosis, performing multiple tests for PCD and basing the diagnosis on the totality of the results, plus carefully collected patient history (probably the most important diagnostic test!). With the exception of genetic testing that shows two known PCD-causing mutations—one from each parent—almost all PCD diagnoses will require this sort of matrix approach because no single test is 100% reliable. The more positive tests, the greater the likelihood that PCD is the underlying diagnosis. The fewer positive tests, the less likely. But note that this is a spectrum. It may currently be possible to definitely confirm the diagnosis, but it is not possible to entirely rule out PCD (the obvious exception to this is if another underlying cause for symptoms is discovered)—only to suggest that it is not a likely diagnosis based on what we now know about PCD and on currently available PCD testing.

Awareness of PCD has grown exponentially in the past decade+. While this is a welcome development, it has also (in the US) contributed at times to ‘over-diagnosis.’ PCD symptoms can mimic other disorders and in preschool age children can even mimic the ‘daycare-itis’ seen in perfectly normal children. However, PCD is a genetic disorder that cannot be diagnosed on the basis of symptoms alone, any more than the diagnosis of CF would be arbitrarily given to child who didn’t gain weight and coughed a lot. In both cases, the underlying genetic defect must be established before the diagnosis can be made. We will often hear frustrated parents say, ‘my child has every symptom of PCD* and we still can’t get a confirmed diagnosis.’ With both CF and PCD, recognizing a symptom pattern associated with the disorders can help direct diagnostic investigation, but it is not enough to make the diagnosis. In these cases, the family sometimes feels strung along with no firm answer about whether PCD is the correct diagnosis. This is an incredibly difficult situation for all involved and is an example of where a test like nNO could be very helpful, providing immediate information on the likelihood of PCD, while awaiting other test results.

Getting the diagnosis right is also very important for individuals who do not have PCD, but who have been told that they do. Once a diagnosis like PCD has been established, further diagnostic testing stops. If PCD is not the correct diagnosis, this can have serious—sometimes even fatal—consequences. This is not theoretical—preventable illness, including loss of life has actually happened as the result of PCD misdiagnosis on more than one occasion. We take the issue of misdiagnosis seriously—not out of a desire to exclude anyone, but to ensure every person is getting the best, most appropriate care. For this reason, we welcome efforts to officially include nNO measurement in the PCD diagnostic arsenal.



*For some perspective on this, the top ciliary biopsy processing lab in the US once estimated that only one of every 100 biopsies they processed—all of which came from people with symptoms suggestive of PCD—actually turned out to be PCD.