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Diagnostic Testing of Patients Suspected of Primary Ciliary Dyskinesia

Wendy A. Stannard^1,, Mark A. Chilvers^1,*, Andrew R. Rutman¹, Chris D. Williams¹ and Chris O'Callaghan¹

¹ Division of Child Health, Department of Infection, Immunity, and Inflammation, and Institute of Lung Health, University of Leicester, and Leicester Royal Infirmary, Leicester, United Kingdom

Correspondence and requests for reprints should be addressed to Professor Chris O'Callaghan, M.D., Ph.D., Division of Child Health, Institute of Lung Health, Department of Infection, Immunity, and Inflammation, University of Leicester, Robert Kilpatrick Clinical Sciences Building, P.O. Box 65, Leicester Royal Infirmary, Leicester LE2 7LX, UK. E-mail: ajb64{at}le.ac.uk

Rationale: Electron microscopy (EM) of ciliated epithelium is widely used to diagnose primary ciliary dyskinesia (PCD). Ciliary beat frequency (CBF) has been used to screen samples to determine whether EM is indicated. Beat pattern analysis has been advocated as an additional diagnostic test. Neither has been subject to formal review.

Objectives: To determine the ability of CBF and beat pattern analysis to predict EM-diagnosed PCD.

Methods: CBF calculation and beat pattern analysis, using high-speed video microscopy, and EM were performed on nasal tissue from 371 patients consecutively referred to the Leicester Royal Infirmary for diagnostic assessment for PCD. With EM as the "gold standard," receiver operating characteristic (ROC) curves were constructed and sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were calculated for CBF less than 11 Hz, ciliary dyskinesia score equal to or exceeding 2, at least 90% of ciliated edges beating dyskinetically, and an immotility index equal to or exceeding 10%.

Measurements and Main Results: PCD was excluded in 270 patients and confirmed in 70 by EM. The sensitivity, specificity, PPV, and NPV for CBF less than 11 Hz were 87.1, 77.2, 50.0, and 95.8%, respectively. These values were higher for ciliary dyskinesia scores equal to or exceeding 2 (92.5, 97.6, 91.2, and 98.0%) and when at least 90% of ciliated edges were dyskinetic (97.1, 95.3, 84.6, and 99.2%). ROCs confirmed that the ciliary dyskinesia score and percentage of dyskinetic edges were superior screening indices compared with CBF and the immotility index.

Conclusions: The use of CBF alone to screen which biopsies should have EM will result in a significant number of missed diagnoses. Ciliary beat pattern analysis is a more sensitive and specific test for PCD with higher PPV and NPV.

Key Words: cilia • primary ciliary dyskinesia • bronchiectasis • ciliary beat pattern • sinusitis

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Electron microscopy of ciliated epithelium, is widely used to diagnose primary ciliary dyskinesia. Ciliary beat frequency (CBF) has been used to screen samples to determine whether electron microscopy is indicated and ciliary beat pattern analysis has been advocated as an additional test. Neither test has been subject to formal review. What This Study Adds to the Field The use of CBF alone to screen for biopsies requiring further assessment by electron microscopy will result in missed diagnoses.