Accuracy of high-speed video microscopy to diagnose primary ciliary dyskinesia

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disease that impairs motility of cilia. Diagnosis relies on a combination of tests and final decision by multidisciplinary team (MDT). High-speed video microscopy (HSVM) is an important contribution to diagnostic testing, and is the only test that examines cilia motility on the day of patients’ appointment. No study has assessed the accuracy of HSVM. We hypothesised that scientists experienced in cilia assessment by HSVM would accurately diagnose PCD using HSVM alone compared to MDT diagnosis. Methods: We used 720 archived videos from 120 patients referred to three UK PCD diagnostic services in 2015-17. One scientist from each PCD centre reviewed videos, blinded to diagnostic and clinical data, and scored them for final diagnosis using a standardised proforma. We compared the final scoring for each scientist to: a) a report containing final diagnosis from the MDT decision, and b) diagnostic criteria provided in the 2017 ERS PCD diagnostic guidelines. Results: Sensitivity and specificity were: a) 96.1% and 100% respectively when compared to MDT decision, and b) 95.7% and 100% respectively when compared to ERS guidelines criteria. Inter-rater reliability between the three scientists was substantial (k=0.7) for ‘PCD positive’, and moderate (k=0.44) for ‘PCD highly unlikely’. Conclusions: Specialist scientists accurately diagnosed PCD using HSVM analysis, with high inter-observer agreement. HSVM can be used to reliably counsel patients on their likely diagnosis on the same day as clinic appointment and inform clinicians on initiation of treatment while confirmatory investigations are conducted. Funding: NIHR Research for Patient Benefit grant