Discussion
Both PCD and PID are part of the spectrum of suppurative lung diseases
that describes individuals with persistent productive cough, recurrent
pneumonia, and often bronchiectasis [3]. The PCD diagnostic testing
guidelines acknowledge the importance of considering immunodeficiency
testing especially when initial PCD genetic testing is not
confirmatory[4]. Our cases further emphasize this recommendation, as
both children presented with clinical symptoms that were consistent with
PCD and with initial low nNO levels but were both later confirmed to
have the same specific immunodeficiency.
The APDS1 is a primary immunodeficiency syndrome resulting from
autosomal dominant heterozygous pathogenic variants. Affected
individuals typically have abnormal lymphocyte subsets and develop
recurrent sinopulmonary infections and often bronchiectasis. Other
features include chronic diarrhea, recurrent viral infections and
lymphadenopathy, as was noted in our second case, a clinical feature not
routinely observed in PCD. Clinical features of PCD often overlap with
those of PID. Organ laterality abnormalities and unexplained neonatal
respiratory distress are more specific but not universal presentations
of PCD and thus cannot always be used to differentiate from
immunodeficiency. In individuals >5 years and with PCD, nNO
values are persistently low [5] and thus the normalization in our
first case was not consistent with a diagnosis of PCD. Confirmatory
genetic testing and if needed ciliary EM studies following initial low
nNO testing is recommended. When this testing fails to confirm a
diagnosis of PCD, the differential should be expanded to include
immunodeficiency while nNO testing continues to be repeated.
These two cases are the first reports of APDS1 presenting as PCD with
initial low nNO testing; however other immunodeficiencies presentations
have been reported in a similar manner including GATA2, RAG1, and
polysaccharide antibody deficiency [2, 6]. These cases represent
notable exceptions as there is evidence that nNO testing does have the
ability to distinguish between PCD and many other cases of PID[6]
and is still a useful diagnostic test, as illustrated in our first case
in which the normalization of values prompted further work-up.
In conclusion, clinical features associated with PCD may overlap with
PID and thus careful considerations are needed until a specific disease
is confirmed. Nasal nitric oxide testing is a useful diagnostic tool in
the work-up of individuals suspected to have PCD, but positive results
need to be further confirmed with either genetic testing or ciliary EM.
When PCD confirmatory testing is not conclusive, repeat nNO testing over
time while considering an alternative diagnosis is strongly recommended.