Ciliary Videomicroscopy: A Long Beat from the European Respiratory Society Guidelines to the Recognition as a Confirmatory Test for Primary Ciliary Dyskinesia
[en] Primary ciliary dyskinesia (PCD) is a rare inherited ciliopathy in which respiratory cilia are stationary or dyskinetic. The clinical presentation of PCD is highly non-specific since it includes infections and disorders of the upper (otitis and rhinosinusitis) and lower (neonatal respiratory distress, bronchitis, pneumonia and bronchiectasis) airways, starting in early life. Clinical exami- nation alone does not allow a PCD diagnosis, which relies on several concordant tests, since none are sensitive or specific enough alone. Despite being the most sensitive and specific test to diagnose PCD, digital high-speed videomicroscopy (DHSV) is not sufficiently standardized, preventing its use with complete confidence as a confirmatory diagnostic test for PCD, or its inclusion in a diagnostic algorithm. Since the 2017 ERS recommendations for PCD diagnosis, three main issues remain to be solved in order to optimize DHSV ciliary beating evaluation: the problem in defining an accu- rate sensitivity and specificity as there is no gold standard method to diagnose all PCD cases, a lack of standardization in the operating procedure for processing respiratory samples, and in the choice of measured parameters (self-operating or not). The development of new automated analysis approaches is promising and will require full clinical validation.
Disciplines :
Pediatrics
Author, co-author :
Bricmont, Noémie ; Université de Liège - ULiège > Département des sciences cliniques > Pédiatrie cardiologique et pneumologique
Alexandru, Mihaela; ENT Department, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Saclay, Hôpital Bicêtre, 94270 Le Kremlin-Bicêtre, France
Bruno, Louis; Institut Mondor de Recherche Biomédicale INSERM-UPEC UMR 955, CNRS ERL7000, 94010 Créteil, France
Papon, Jean-François; ENT Department, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Saclay, Hôpital Bicêtre, 94270 Le Kremlin-Bicêtre, France
KEMPENEERS, Céline ; Centre Hospitalier Universitaire de Liège - CHU > Département de Pédiatrie > Service de pédiatrie
Language :
English
Title :
Ciliary Videomicroscopy: A Long Beat from the European Respiratory Society Guidelines to the Recognition as a Confirmatory Test for Primary Ciliary Dyskinesia
Barbato, A.; Frischer, T.; Kuehni, C.E.; Snijders, D.; Azevedo, I.; Baktai, G.; Bartoloni, L.; Eber, E.; Escribano, A.; Haarman, E.; et al. Primary ciliary dyskinesia: A consensus statement on diagnostic and treatment approaches in children. Eur. Respir. J. 2009, 34, 1264–1276. [CrossRef] [PubMed]
Guichard, C.; Harricane, M.-C.; Lafitte, J.-J.; Godard, P.; Zaegel, M.; Tack, V.; Lalau, G.; Bouvagnet, P. Axonemal Dynein Intermediate-Chain Gene (DNAI1) Mutations Result in Situs Inversus and Primary Ciliary Dyskinesia (Kartagener Syndrome). Am. J. Hum. Genet. 2001, 68, 1030–1035. [CrossRef]
Sleigh, M.A. Kartagener’s syndrome, ciliary defects and ciliary function. Eur. J. Respir. Dis. Suppl. 1983, 127, 157–161. [PubMed]
Vanaken, G.-J.; Bassinet, L.; Boon, M.; Mani, R.; Honoré, I.; Papon, J.F.; Cuppens, H.; Jaspers, M.; Lorent, N.; Coste, A.; et al. Infertility in an adult cohort with primary ciliary dyskinesia: Phenotype–gene association. Eur. Respir. J. 2017, 50, 1700314. [CrossRef]
Lucas, J.S.; Barbato, A.; Collins, S.A.; Goutaki, M.; Behan, L.; Caudri, D.; Dell, S.; Eber, E.; Escudier, E.; Hirst, R.A.; et al. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur. Respir. J. 2017, 49, 1601090. [CrossRef]
Rayner, C.F.; Rutman, A.; Dewar, A.; Greenstone, M.A.; Cole, P.J.; Wilson, R. Ciliary disorientation alone as a cause of primary ciliary dyskinesia syndrome. Am. J. Respir. Crit. Care Med. 1996, 153, 1123–1129. [CrossRef]
Coste, A.; Millepied, M.-C.; Chapelin, C.; Reinert, P.; Poron, F.; Boucherat, M.; Escudier, E. Incidence of Primary Ciliary Dyskinesia in Children with Recurrent Respiratory Diseases. Ann. Otol. Rhinol. Laryngol. 1997, 106, 854–858. [CrossRef]
Santamaria, F.; de Santi, M.M.; Grillo, G.; Sarnelli, P.; Caterino, M.; Greco, L. Ciliary motility at light microscopy: A screening technique for ciliary defects. Acta Paediatr. 1999, 88, 853–857. [CrossRef] [PubMed]
Jorissen, M.; Willems, T.; Van Der Schueren, B.; Verbeken, E.; De Boeck, K. Ultrastructural expression of primary ciliary dyskinesia after ciliogenesis in culture. Acta Otorhinolaryngol. Belg. 2000, 54, 343–356.
Toskala, E.; Haataja, J.; Shirasaki, H.; Rautiainen, M. Culture of cells harvested with nasal brushing: A method for evaluating ciliary function. Rhinol. J. 2005, 43, 121–124.
Pifferi, M.; Montemurro, F.; Cangiotti, A.M.; Ragazzo, V.; Di Cicco, M.; Vinci, B.; Vozzi, G.; Macchia, P.; Boner, A.L. Simplified cell culture method for the diagnosis of atypical primary ciliary dyskinesia. Thorax 2009, 64, 1077–1081. [CrossRef] [PubMed]
Pedersen, H.; Mygind, N. Absence of axonemal arms in nasal mucosa cilia in Kartagener’s syndrome. Nat. Cell Biol. 1976, 262, 494–495. [CrossRef]
Afzelius, B.A. A human syndrome caused by immotile cilia. Science 1976, 193, 317–319. [CrossRef] [PubMed]
Rossman, C.M.; Forrest, J.B.; Lee, R.M.; Newhouse, A.F.; Newhouse, M.T. The dyskinetic cilia syndrome; abnormal ciliary motility in association with abnormal ciliary ultrastructure. Chest 1981, 80, 860–865.
Chilvers, M.A.; O’Callaghan, C. Analysis of ciliary beat pattern and beat frequency using digital high speed imaging: Comparison with the photomultiplier and photodiode methods. Thorax 2000, 55, 314–317. [CrossRef]
Stannard, W.A.; Chilvers, M.; Rutman, A.R.; Williams, C.; O’Callaghan, C.L. Diagnostic Testing of Patients Suspected of Primary Ciliary Dyskinesia. Am. J. Respir. Crit. Care Med. 2010, 181, 307–314. [CrossRef] [PubMed]
Adam, E.C.; Mitchell, B.S.; Schumacher, D.U.; Grant, G. Pseudomonas aeruginosa II lectin stops human ciliary beating: Therapeutic implications of fucose. Am. J. Respir. Crit. Care Med. 1997, 155, 2102–2104. [CrossRef]
Feldman, C.; Anderson, R.; Cockeran, R.; Mitchell, T.; Cole, P.; Wilson, R. The effects of pneumolysin and hydrogen peroxide, alone and in combination, on human ciliated epithelium in vitro. Respir. Med. 2002, 96, 580–585. [CrossRef]
Fliegauf, M.; Sonnen, A.F.-P.; Kremer, B.; Henneke, P. Mucociliary Clearance Defects in a Murine In Vitro Model of Pneumococcal Airway Infection. PLoS ONE 2013, 8, e59925. [CrossRef]
Min, Y.-G.; Oh, S.J.; Won, T.-B.; Kim, Y.M.; Shim, W.S.; Rhee, C.-S.; Min, J.-Y.; Dhong, H.-J. Effects of staphylococcal enterotoxin on ciliary activity and histology of the sinus mucosa. Acta Otolaryngol. 2006, 126, 941–947. [CrossRef]
Dresdner, R.D.; Wong, L.B. Measurement of ciliary beat frequency using high-speed video microscopy. Biomed. Sci. Instrum. 1984, 20, 37–46. [PubMed]
Chilvers, M.; Rutman, A.; O’Callaghan, C. Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia. J. Allergy Clin. Immunol. 2003, 112, 518–524. [CrossRef]
Kempeneers, C.; Seaton, C.; Espinosa, B.G.; Chilvers, M. Ciliary functional analysis: Beating a path towards standardization. Pediatr. Pulmonol. 2019, 54, 1627–1638. [CrossRef] [PubMed]
Thomas, B.; Rutman, A.; O’Callaghan, C. Disrupted ciliated epithelium shows slower ciliary beat frequency and increased dyskinesia. Eur. Respir. J. 2009, 34, 401–404. [CrossRef]
Papon, J.-F.; Bassinet, L.; Cariou-Patron, G.; Zerah-Lancner, F.; Vojtek, A.-M.; Blanchon, S.; Crestani, B.; Amselem, S.; Coste, A.; Housset, B.; et al. Quantitative analysis of ciliary beating in primary ciliary dyskinesia: A pilot study. Orphanet J. Rare Dis. 2012, 7, 78. [CrossRef]
Raidt, J.; Wallmeier, J.; Hjeij, R.; Onnebrink, J.G.; Pennekamp, P.; Loges, N.T.; Olbrich, H.; Häffner, K.; Dougherty, G.W.; Omran, H.; et al. Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia. Eur. Respir. J. 2014, 44, 1579–1588. [CrossRef]
Blanchon, S.; Legendre, M.; Bottier, M.; Tamalet, A.; Montantin, G.; Collot, N.; Faucon, C.; Dastot, F.; Copin, B.; Clement, A.; et al. Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia. J. Med. Genet. 2019, 57, 237–244. [CrossRef] [PubMed]
Schünemann, H.J.; Oxman, A.D.; Brozek, J.; Glasziou, P.; Jaeschke, R.; Vist, G.E.; Williams, J.W., Jr.; Kunz, R.; Craig, J.; Montori, V.M.; et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ 2008, 336, 1106–1110. [CrossRef]
Rubbo, B.; Shoemark, A.; Jackson, C.L.; Hirst, R.; Thompson, J.; Hayes, J.; Frost, E.; Copeland, F.; Hogg, C.; O’Callaghan, C.; et al. Accuracy of High-Speed Video Analysis to Diagnose Primary Ciliary Dyskinesia. Chest 2019, 155, 1008–1017. [CrossRef]
Shapiro, A.J.; Leigh, M.W.; Omran, H.; Lavergne, V.; Knowles, M.R. Errors in Methodology Affect Diagnostic Accuracy of High-Speed Videomicroscopy Analysis in Primary Ciliary Dyskinesia. Chest 2019, 156, 1032–1033. [CrossRef]
Shoemark, A.; Rubbo, B.; Haarman, E.; Hirst, R.A.; Hogg, C.; Jackson, C.L.; Nielsen, K.G.; Papon, J.-F.; Robinson, P.; Walker, W.T.; et al. The Controversies and Difficulties of Diagnosing Primary Ciliary Dyskinesia. Am. J. Respir. Crit. Care Med. 2020, 201, 120–122. [CrossRef]
Shapiro, A.J.; Davis, S.D.; Polineni, D.; Manion, M.; Rosenfeld, M.; Dell, S.D.; Chilvers, M.A.; Ferkol, T.W.; Zariwala, M.A.; Sagel, S.D.; et al. Diagnosis of Primary Ciliary Dyskinesia. An Official American Thoracic Society Clinical Practice Guideline. Am. J. Respir. Crit. Care Med. 2018, 197, e24–e39. [CrossRef]
Clary-Meinesz, C.; Mouroux, J.; Cosson, J.; Huitorel, P.; Blaive, B. Influence of external pH on ciliary beat frequency in human bronchi and bronchioles. Eur. Respir. J. 1998, 11, 330–333. [CrossRef]
Luk, C.K.; Dulfano, M.J. Effect of pH, Viscosity and Ionic-Strength Changes on Ciliary Beating Frequency of Human Bronchial Explants. Clin. Sci. 1983, 64, 449–451. [CrossRef] [PubMed]
Van de Donk, H.J.; Zuidema, J.; Merkus, F.W. The influence of the pH and osmotic pressure upon tracheal ciliary beat frequency as determined with a new photo-electric registration device. Rhinology 1980, 18, 93–104.
Stanek, A.; Brambrink, A.M.; Latorre, F.; Bender, B.; Kleemann, P.P. Effects of normobaric oxygen on ciliary beat frequency of human respiratory epithelium. Br. J. Anaesth. 1998, 80, 660–664. [CrossRef]
Rusznak, C.; Devalia, J.; Lozewicz, S.; Davies, R. The assessment of nasal mucociliary clearance and the effect of drugs. Respir. Med. 1994, 88, 89–101. [CrossRef]
Jiao, J.; Meng, N.; Wang, H.; Zhang, L. The effects of vitamins C and B12 on human nasal ciliary beat frequency. BMC Complement. Altern. Med. 2013, 13, 110. [CrossRef]
Yasuda, M.; Inui, T.-A.; Hirano, S.; Asano, S.; Okazaki, T.; Inui, T.; Marunaka, Y.; Nakahari, T. Intracellular Cl− Regulation of Ciliary Beating in Ciliated Human Nasal Epithelial Cells: Frequency and Distance of Ciliary Beating Observed by High-Speed Video Microscopy. Int. J. Mol. Sci. 2020, 21, 4052. [CrossRef]
Jackson, C.; Goggin, P.M.; Lucas, J.S. Ciliary Beat Pattern Analysis Below 37◦ C May Increase Risk of Primary Ciliary Dyskinesia Misdiagnosis. Chest 2012, 142, 543–544. [CrossRef]
Jackson, C.; Behan, L.; Collins, S.A.; Goggin, P.M.; Adam, E.C.; Coles, J.L.; Evans, H.J.; Harris, A.; Lackie, P.; Packham, S.; et al. Accuracy of diagnostic testing in primary ciliary dyskinesia. Eur. Respir. J. 2016, 47, 837–848. [CrossRef] [PubMed]
Bricmont, N.; Benchimol, L.; Poirrier, A.-L.; Boboli, H.; Seghaye, M.-C.; Louis, R.; Lefebvre, P.; Louis, B.; Papon, J.-F.; Kempeneers, C. The influence of the conservation of respiratory epithelial samples on ciliary functional analysis. Eur. Respir. J. Sep. 2020, 56, 1888. [CrossRef]
Bricmont, N.; Benchimol, L.; Poirrier, A.-L.; Grignet, C.; Seaton, C.; Chilvers, M.A.; Seghaye, M.-C.; Louis, R.; Lefebvre, P.; Kempeneers, C. Nasal Brushing Sampling and Processing using Digital High Speed Ciliary Videomicroscopy—Adaptation for the COVID-19 Pandemic. J. Vis. Exp. 2020, 10, e61949. [CrossRef]
Hirst, R.A.; Jackson, C.; Coles, J.L.; Williams, G.; Rutman, A.; Goggin, P.M.; Adam, E.C.; Page, A.; Evans, H.J.; Lackie, P.M.; et al. Culture of Primary Ciliary Dyskinesia Epithelial Cells at Air-Liquid Interface Can Alter Ciliary Phenotype but Remains a Robust and Informative Diagnostic Aid. PLoS ONE 2014, 9, e89675. [CrossRef]
Nikolaizik, W.; Hahn, J.; Bauck, M.; Weber, S. Comparison of ciliary beat frequencies at different temperatures in young adults. ERJ Open Res. 2020, 6, 00477–02020. [CrossRef]
Reula, A.; Pitarch-Fabregat, J.; Milara, J.; Cortijo, J.; Mata-Roig, M.; Milian, L.; Armengot, M. High-Speed Video Microscopy for Primary Ciliary Dyskinesia Diagnosis: A Study of Ciliary Motility Variations with Time and Temperature. Diagnnostics 2021, 11, 1301. [CrossRef]
Lee, D.D.H.; Petris, A.; Hynds, R.E.; O’Callaghan, C. Ciliated Epithelial Cell Differentiation at Air-Liquid Interface Using Commercially Available Culture Media. Methods Mol. Biol. 2020, 2109, 275–291. [CrossRef]
Coles, J.L.; Thompson, J.; Horton, K.L.; Hirst, R.A.; Griffin, P.; Williams, G.M.; Goggin, P.; Doherty, R.; Lackie, P.M.; Harris, A.; et al. A Revised Protocol for Culture of Airway Epithelial Cells as a Diagnostic Tool for Primary Ciliary Dyskinesia. J. Clin. Med. 2020, 9, 3753. [CrossRef]
Horani, A.; Ferkol, T.W. Advances in the Genetics of Primary Ciliary Dyskinesia: Clinical Implications. Chest 2018, 154, 645–652. [CrossRef] [PubMed]
Sisson, J.H.; Stoner, J.A.; Ammons, B.A.; Wyatt, T.A. All-digital image capture and whole-field analysis of ciliary beat frequency. J. Microsc. 2003, 211, 103–111. [CrossRef]
Smith, C.M.; Djakow, J.; Free, R.C.; Djakow, P.; Lonnen, R.; Williams, G.; Pohunek, P.; Hirst, R.A.; Easton, A.J.; Andrew, P.W.; et al. ciliaFA: A research tool for automated, high-throughput measurement of ciliary beat frequency using freely available software. Cilia 2012, 1, 14. [CrossRef] [PubMed]
Armengot, M.; Bonet, M.; Carda, C.; Gómez, M.J.; Milara, J.; Mata, M.; Cortijo, J. Development and Validation of a Method of Cilia Motility Analysis for the Early Diagnosis of Primary Ciliary Dyskinesia. Acta Otorrinolaringol. 2012, 63, 1–8. [CrossRef] [PubMed]
Dimova, S.; Maes, F.; Brewster, M.E.; Jorissen, M.; Noppe, M.; Augustijns, P. High-speed digital imaging method for ciliary beat frequency measurement. J. Pharm. Pharmacol. 2010, 57, 521–526. [CrossRef] [PubMed]
Bottier, M.; Blanchon, S.; Pelle, G.; Bequignon, E.; Isabey, D.; Coste, A.; Escudier, E.; Grotberg, J.; Papon, J.F.; Filoche, M.; et al. A new index for characterizing micro-bead motion in a flow induced by ciliary beating: Part I, experimental analysis. PLoS Comput. Biol. 2017, 13, e1005605. [CrossRef]
Bottier, M.; Fernández, M.P.; Pelle, G.; Isabey, D.; Louis, B.; Grotberg, J.; Filoche, M. A new index for characterizing micro-bead motion in a flow induced by ciliary beating: Part II, modeling. PLoS Comput. Biol. 2017, 13, e1005552. [CrossRef]
Feriani, L.; Juenet, M.; Fowler, C.J.; Bruot, N.; Chioccioli, M.; Holland, S.M.; Bryant, C.E.; Cicuta, P. Assessing the Collective Dynamics of Motile Cilia in Cultures of Human Airway Cells by Multiscale DDM. Biophys. J. 2017, 113, 109–119. [CrossRef] [PubMed]
Cerbino, R.; Trappe, V. Differential Dynamic Microscopy: Probing Wave Vector Dependent Dynamics with a Microscope. Phys. Rev. Lett. 2008, 100, 188102. [CrossRef] [PubMed]
Chioccioli, M.; Feriani, L.; Kotar, J.; Bratcher, P.E.; Cicuta, P. Phenotyping ciliary dynamics and coordination in response to CFTR-modulators in Cystic Fibrosis respiratory epithelial cells. Nat. Commun. 2019, 10, 1–11. [CrossRef] [PubMed]
