A Comprehensive Approach for the Diagnosis of Primary Ciliary Dyskinesia-Experiences from the First 100 Patients of the PCD-UNIBE Diagnostic Center

Loretta Müller; Sibel T Savas; Stefan A Tschanz; Andrea Stokes; Anaïs Escher; Mirjam Nussbaumer; Marina Bullo; Claudia E Kuehni; Sylvain Blanchon; Andreas Jung; Nicolas Regamey; Beat Haenni; Martin Schneiter; Jonas Ingold; Elisabeth Kieninger; Carmen Casaulta; Philipp Latzin; On Behalf Of The Swiss Pcd Research Group

doi:10.3390/diagnostics11091540

A Comprehensive Approach for the Diagnosis of Primary Ciliary Dyskinesia-Experiences from the First 100 Patients of the PCD-UNIBE Diagnostic Center

Diagnostics (Basel). 2021 Aug 25;11(9):1540. doi: 10.3390/diagnostics11091540.

Authors

Loretta Müller^{1

2}, Sibel T Savas^{1

2}, Stefan A Tschanz³, Andrea Stokes^{1

2}, Anaïs Escher^{1

2}, Mirjam Nussbaumer^{1

2}, Marina Bullo^{1

2}, Claudia E Kuehni^{1

4}, Sylvain Blanchon⁵, Andreas Jung⁶, Nicolas Regamey⁷, Beat Haenni³, Martin Schneiter^{3

8}, Jonas Ingold³, Elisabeth Kieninger^{1

2}, Carmen Casaulta^{1

2}, Philipp Latzin^{1

2}, On Behalf Of The Swiss Pcd Research Group

Affiliations

¹ Division of Paediatric Respiratory Medicine and Allergology, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
² Department of BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland.
³ Institute of Anatomy, University of Bern, 3012 Bern, Switzerland.
⁴ Institute of Social and Preventive Medicine, University of Bern, 3012 Bern, Switzerland.
⁵ Pediatric Pulmonology and Cystic Fibrosis Unit, Service of Pediatrics, Department Woman-Mother-Child, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland.
⁶ Division of Respiratory Medicine, University Children's Hospital Zurich, 8032 Zurich, Switzerland.
⁷ Division of Paediatric Pulmonology, Children's Hospital Lucerne, 6000 Lucerne, Switzerland.
⁸ Institute of Applied Physics, University of Bern, 3012 Bern, Switzerland.

Abstract

Primary ciliary dyskinesia (PCD) is a rare genetic disease characterized by dyskinetic cilia. Respiratory symptoms usually start at birth. The lack of diagnostic gold standard tests is challenging, as PCD diagnostics requires different methods with high expertise. We founded PCD-UNIBE as the first comprehensive PCD diagnostic center in Switzerland. Our diagnostic approach includes nasal brushing and cell culture with analysis of ciliary motility via high-speed-videomicroscopy (HSVM) and immunofluorescence labeling (IF) of structural proteins. Selected patients undergo electron microscopy (TEM) of ciliary ultrastructure and genetics. We report here on the first 100 patients assessed by PCD-UNIBE. All patients received HSVM fresh, IF, and cell culture (success rate of 90%). We repeated the HSVM with cell cultures and conducted TEM in 30 patients and genetics in 31 patients. Results from cell cultures were much clearer compared to fresh samples. For 80 patients, we found no evidence of PCD, 17 were diagnosed with PCD, two remained inconclusive, and one case is ongoing. HSVM was diagnostic in 12, IF in 14, TEM in five and genetics in 11 cases. None of the methods was able to diagnose all 17 PCD cases, highlighting that a comprehensive approach is essential for an accurate diagnosis of PCD.

Keywords: air-liquid interface cell culture; airways; ciliopathy; high-speed videomicroscopy; immunofluorescence; transmission electron microscopy.

Abstract

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