Accuracy of High-Speed Video Analysis to Diagnose Primary Ciliary Dyskinesia

Abstract

BACKGROUND: Diagnosis of primary ciliary dyskinesia (PCD) relies on a combination of tests. High-speed video microscopy analysis (HSVA) is widely used to contribute to the diagnosis. It can be analyzed on the day of diagnostic consultation, but the qualitative analyses are subjective. Diagnostic accuracy and reliability of assessing ciliary function have not been robustly evaluated. We aimed to establish the accuracy of HSVA to diagnose PCD compared with a combination of tests, and to assess the interobserver reliability of HSVA analysis. METHODS: We randomly selected and anonymized archived videos from 120 patients seen at three UK PCD centers. Three experienced scientists independently reviewed six videos per patient, using a standardized proforma, blinded to diagnostic and clinical data. We compared study outcomes with two references: (1) a combination of diagnostic tests in accordance with the European Respiratory Society PCD diagnostic guidelines and (2) original clinical outcome determined by all available diagnostic tests. RESULTS: HSVA had excellent sensitivity and specificity to diagnose PCD: (1) 100% and 96%, respectively, compared with ERS guidelines, and (2) 96% and 91% compared with diagnostic outcomes. There was high interobserver agreement for "PCD-positive" outcomes (k ¼ 0.7). CONCLUSIONS: Specialist scientists accurately diagnosed PCD using HSVA, with high interobserver agreement. HSVA can be reliably used to counsel patients and commence treatment on the day of testing while awaiting confirmatory investigations.

Sperm defects in primary ciliary dyskinesia and related causes of male infertility

“…Nasal nitric oxide gas is reduced in most patients with PCD [10]. Analysis of the respiratory epithelium by nasal brushing can be used for identification of ciliary structural defects by transmission electron microscopy (TEM) [113,118] and defects of the ciliary beat pattern and frequency can be identified by high-speed video microscopy analysis (HSVMA) [107]. HSVMA has excellent sensitivity and specificity for PCD and particular beat patterns have been linked to specific ultrastructural defects [15].…”

Ciliary functional analysis: Beating a path towards standardization

“…Currently, there is no single gold standard test which will diagnose every patient with PCD, and international guidelines recommend a panel of a variety of tests to diagnose PCD . According to the European Respiratory Society (ERS) guidelines, hallmark ciliary ultrastructural defects assessed by transmission electron microscopy (TEM) and bi‐allelic mutations in known PCD causing genes can confirm a diagnosis, but will miss the diagnosis in between 15%‐30% of patients with PCD. Ciliary functional analysis using digital high‐speed video microscopy (DHSV) is used internationally as part of the diagnosis of patients suspected of having PCD .…”

“…However, this may be an over‐estimation of diagnostic accuracy: DHSV was either compared with incomplete reference standards (mainly TEM alone), or to a reference standard including DHSV. A recent retrospective cohort study reported an excellent sensitivity (100%) and specificity (96%) for DHSV to diagnose PCD against the ERS guidelines, but cases with normal TEM or genotyping may not have been identified.…”

“…Being the most sensitive test to diagnose PCD, DHSV is invaluable in difficult cases, and the results are available the day of testing (TEM and genetic results may take months to be available) . However, DHSV is a challenging method, with some limitations: …”

“…A lack of standardization and precise operating procedures for processing and analyzing samples using DHSV …”