Accuracy of Clinical Phenotype for Diagnosing Adults With Primary Ciliary Dyskinesia.

Abstract

Primary ciliary dyskinesia (PCD) is a heterogenous disease that is difficult to diagnose. Investigations for PCD are recommended with an appropriate phenotype of 4 key PCD clinical criteria: (1) year-round wet cough from before 6 months of age, (2) year-round nasal congestion from before 6 months of age, (3) neonatal respiratory distress at term birth, (4) an organ laterality defect, or a combination thereof. Accuracy of these symptoms was validated in children, but has not been explored robustly in adults. Among adults referred for possible PCD, what is the diagnostic accuracy of the 4 key PCD clinical criteria, additional PCD-related clinical features, and nasal nitric oxide measurement for identifying definite PCD? This retrospective analysis explored patients 18 years of age or older, referred for possible PCD between 2013 and 2024. All underwent nasal nitric oxide (nNO) measurement and key PCD clinical criteria were collected systematically, but were modified for year-round wet cough or nasal congestion since early childhood. Additional PCD-related features (sinusitis, otitis in adulthood, infertility or subfertility, and PCD family history) were collected. Those with ≥ 2 key PCD clinical criteria or low nNO (< 77 nL/min) underwent PCD genetic testing, transmission electron microscopy testing, or both. Of 156 referred adults, 41 participants (26%) demonstrated definite PCD, 6 participants (4%) demonstrated probable PCD, and 109 participants (70%) were unlikely to have PCD. Sensitivity and specificity for ≥ 2 of 4 key PCD clinical criteria were 95% and 88%, respectively, and 73% and 85% for ≥ 2 of 4 additional PCD-related features. Addition of infertility or subfertility to the 4 key PCD clinical criteria (5 features total) improved diagnostic accuracy, such that the presence of ≥ 2 of 5 features increased sensitivity to 100%, although specificity slightly decreased to 84%. nNO o < 77 nL/min also showed high diagnostic accuracy, with 88% sensitivity and 98% specificity for adults having PCD. Our results show that the key PCD clinical criteria, with the addition of infertility or subfertility and nNO measurement, have high diagnostic accuracy for PCD in adults. Clinicians should assess these features in adults and screen for PCD with nNO when available.