Primary Ciliary Dyskinesia (PCD) is a clinically heterogeneous rare genetic disease that affects motile cilia. There is, at this time, no single definitive test for PCD that is both sensitive and specific. Guidelines have been developed, which include algorithms for establishing the diagnosis, noting the limitations for each individual test. The purpose of this study is to provide real-world evidence of the implementation of the strategies proposed by the American Thoracic Society (ATS) to diagnose PCD. Methods: This was a retrospective, observational, single-center cohort study of patients referred for suspected PCD to Boston Children's Hospital (BCH), one of the few Centers of Excellence endorsed by the PCD Foundation. Demographic, clinical, genetic, and imaging data were collected through a detailed review of the electronic medical record. The diagnosis of PCD was made according to the recommendations by the ATS Clinical Practice Guideline. Results: Between 2008-2019, a total of 304 patients were referred to the BCH PCD clinic. A pulmonologist referred 80.3% of the patients in the cohort. 110 (36.2%) patients had at least two or more clinical features suggestive of PCD. Of those, 50 (45.4%) had nasal nitric oxide levels (nNO) less than 77 nl/min. Median nasal nitric oxide (nNO) of patients with 2 or more clinical features and nNO < 77 nl/min was 18.2 nl/min (IQR 11.7, 38.9). Additionally, genetic sequencing was performed in 55 patients. Definitive positive results were seen in 7 (12.7%) patients, 6 of whom had at least 2 PCD features and nNO <77 (Figure 1A). 29 (52.7%) subjects had genotypes not definitive for PCD [one pathogenic / variant of unknown significance (VUS)]. Genetic testing was negative for the remaining 19 (34.5%). Finally, 194 patients had less than two key clinical features of PCD. Of these, 28 (14.4%) had low nNO, 10 (7.8%) had genotypes not definitive for PCD, and 3 (1.5%) had recognized ciliary structure defect (Figure 1B). Conclusion: We report, for the first time, real-world implementation of the ATS recommendations for the diagnosis of PCD. A confirmed diagnosis of PCD was established in 16.8% of referred patients. 31 (10%) patients who are referred to an expert center for the diagnosis of PCD do not fulfill the diagnostic criteria established by the ATS guidelines. However, these patients cannot be discarded entirely as many have partial clinical or laboratory evidence of disease.
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