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.