[en] Primary ciliary dyskinesia is an inherited disorder in which respiratory cilia are stationary, or beat in a slow or dyskinetic manner, leading to impaired mucociliary clearance and significant sinopulmonary disease. One diagnostic test is ciliary functional analysis using digital high-speed video microscopy (DHSV), which allows real-time analysis of complete ciliary function, comprising ciliary beat frequency (CBF) and ciliary beat pattern (CBP). However, DHSV lacks standardization. In this paper, the current knowledge of DHSV ciliary functional analysis is presented, and recommendations given for a standardized protocol for ciliary sample collection and processing. A proposal is presented for a quantitative and qualitative CBP evaluation system, to be used to develop international consensus agreement, and future DHSV research areas are identified.
Disciplines :
Pediatrics Cardiovascular & respiratory systems
Author, co-author :
KEMPENEERS, Céline ; Centre Hospitalier Universitaire de Liège - CHU > Département de Pédiatrie > Service de pédiatrie
Seaton, Claire; University of British Columbia and British Columbia Children’s Hospital, Vancouver, British Columbia, Canada > Division of Respirology, Department of Pediatrics
Garcia Espinosa, Bernardo; University of British Columbia and British Columbia Children’s Hospital, Vancouver, British Columbia, Canada > Division of Respirology, Department of Pediatrics
Chilvers, Mark A.; University of British Columbia and British Columbia Children’s Hospital, Vancouver, British Columbia, Canada > Division of Respirology, Department of Pediatrics
Language :
English
Title :
Ciliary functional analysis: Beating a path towards standardization.
Publication date :
October 2019
Journal title :
Pediatric Pulmonology
ISSN :
8755-6863
eISSN :
1099-0496
Publisher :
John Wiley & Sons, Hoboken, United States - New York
Lucas JS, Gahleitner F, Amorim A, et al. Pulmonary exacerbations in patients with primary ciliary dyskinesia: an expert consensus definition for use in clinical trials. ERJ Open Res. 2019;5:00147-02018.
Djakow J, O'Callaghan C. Primary ciliary dyskinesia. Breathe. 2014;10:122-133.
Lucas JS, Barbato A, Collins SA, et al. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur Respir J. 2017;49:1601090.
Shapiro AJ, Davis SD, Polineni 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.
Rubbo B, Shoemark A, Jackson CL, et al. Accuracy of high-speed video analysis to diagnose primary ciliary dyskinesia. Chest. 2019;155(5):1008-1017.
Horani A, Ferkol TW. Advances in the Genetics of Primary Ciliary Dyskinesia. Chest. 2018;154:645-652.
Boon M, Jorissen M, Proesmans M, et al. Primary ciliary dyskinesia, an orphan disease. Eur J Pediatr. 2013;172:151-162.
Chilvers MA, 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.
Jackson CL, Behan L, Collins SA, et al. Accuracy of diagnostic testing in primary ciliary dyskinesia. Eur Respir J. 2016;47:837-848.
Stannard WA, Chilvers MA, Rutman AR, et al. Diagnostic testing of patients suspected of primary ciliary dyskinesia. Am J Respir Crit Care Med. 2010;181:307-314.
Papon JF, Bassinet L, Cariou-Patron G, et al. Quantitative analysis of ciliary beating in primary ciliary dyskinesia: a pilot study. Orphanet J Rare Dis. 2012;7:78.
Lucas JS, Evans HJ, Haarman EG, et al. Exploring the art of ciliary beating: the benefits of high-speed video analysis. Chest. 2017;152:1348-1349.
Bush A, Hogg C. The answer is cilia, whatever the question may be! Ann Transl Med. 2018;6:S32-S32.
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.
Chilvers MA, O'Callaghan C. Local mucociliary defence mechanisms. Paediatr Respir Rev. 2000;1:27-34.
Wyatt TA, Sisson JH, Von Essen SG, et al. Exposure to hog barn dust alters airway epithelial ciliary beating. Eur Respir J. 2008;31:1249-1255.
Raidt J, Wallmeier J, Hjeij R, et al. Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia. Eur Respir J. 2014;44:1579-1588.
Shapiro AJ, Chilvers MA, Davis SD, et al. Nasal Nitric Oxide and Ciliary Videomicroscopy: Tests Used for Diagnosing Primary Ciliary Dyskinesia. In: Davis SD, Eber E, Koumbourlis AC, eds. Diagnostic Tests in Pediatric Pulmonology: Applications and Interpretation. New York City, USA: Humana Press; 2014:55-72
Kempeneers C, Seaton C, Chilvers MA. Variation of ciliary beat pattern in three different beating planes in healthy subjects. Chest. 2017;151:993-1001.
Werner C, Onnebrink JG, Omran H. Diagnosis and management of primary ciliary dyskinesia. Cilia. 2015;4:2.
Lucas JS, Paff T, Goggin P, et al. Diagnostic methods in primary ciliary dyskinesia. Paediatr Respir Rev. 2016;18:8-17.
Kouis P, Hadjisavvas A, Middleton N, et al. The effect of l-arginine on ciliary beat frequency in PCD patients, non-PCD respiratory patients and healthy controls. Pulm Pharmacol Ther. 2018;48:15-21.
Gilain L, Zahm JM, Pierrot D, et al. Nasal epithelial cell culture as a tool in evaluating ciliary dysfunction. Acta Otolaryngol. 1993;113:772-776.
Bernstein JM, Hard R, Cui ZD, et al. Human adenoidal organ culture: a model to study nontypable Haemophilus influenzae (NTHI) and other bacterial interactions with nasopharyngeal mucosa—implications in otitis media. Otolaryngol Head Neck Surg. 1990;103:784-791.
Yoshitsugu M, Rautiainen M, Matsune S, et al. Effect of exogenous ATP on ciliary beat of human ciliated cells studied with differential interference microscope equipped with high speed video. Acta Otolaryngol. 1993;113:655-659.
Ballenger JJ. Experimental effect of cigarette smoke on human respiratory cilia. N Engl J Med. 1960;263:832-835.
Yager JA, Ellman H, Dulfano MJ. Human ciliary beat frequency at three levels of the tracheobronchial tree. Am Rev Respir Dis. 1980;121:661-665.
Rutland J, Griffin WM, Cole PJ. Human ciliary beat frequency in epithelium from intrathoracic and extrathoracic airways. Am Rev Respir Dis. 1982;125:100-105.
Clary-Meinesz C, Mouroux J, Huitorel P, et al. Ciliary beat frequency in human bronchi and bronchioles. Chest. 1997;111:692-697.
Clary-Meinesz CF, Cosson J, Huitorel P, et al. Temperature effect on the ciliary beat frequency of human nasal and tracheal ciliated cells. Biol Cell. 1992;76:335-338.
Roth Y, Aharonson EF, Teichtahl H, et al. Human in vitro nasal and tracheal ciliary beat frequencies: comparison of sampling sites, combined effect of medication, and demographic relationships. Ann Otol Rhinol Laryngol. 1991;100:378-384.
Low PM, Luk CK, Dulfano MJ, et al. Ciliary beat frequency of human respiratory tract by different sampling techniques. Am Rev Respir Dis. 1984;130:497-498.
MacCormick J, Robb I, Kovesi T, et al. Optimal biopsy techniques in the diagnosis of primary ciliary dyskinesia. J Otolaryngol. 2002;31:13-17.
Rutland J, Dewar A, Cox T, et al. Nasal brushing for the study of ciliary ultrastructure. J Clin Pathol. 1982;35:357-359.
Rusznak C, Devalia JL, Lozewicz S, et al. The assessment of nasal mucociliary clearance and the effect of drugs. Respir Med. 1994;88:89-101.
Stokes AB, Kieninger E, Schögler A, et al. Comparison of three different brushing techniques to isolate and culture primary nasal epithelial cells from human subjects. Exp Lung Res. 2014;40:327-332.
Amirav I, Mussaffi H, Roth Y, et al. A reach-out system for video microscopy analysis of ciliary motions aiding PCD diagnosis. BMC Res Notes. 2015;8:71.
Chilvers MA, Rutman A, O'Callaghan C. Functional analysis of cilia and ciliated epithelial ultrastructure in healthy children and young adults. Thorax. 2003;58:333-338.
Rutland J, Griffin W, Cole P. Nasal brushing and measurement of ciliary beat frequency. An in vitro method for evaluating pharmacologic effects on human cilia. Chest. 1981;80:865-867.
Lai PS, Liang L, Cibas ES, et al. Alternate methods of nasal epithelial cell sampling for airway genomic studies. J Allergy Clin Immunol. 2015;136:1120-1123.
Rutland J, Cole PJ. Noninvasive sampling of nasal cilia for measurement of beat frequency and study of ultrastructure. Lancet. 1980;2:564-565.
Hanson FN, Wesselius LJ. Effect of bronchial brush size on cell recovery. Am Rev Respir Dis. 1987;136:1450-1452.
Sato M, Honda M, Sagawa M, et al. The efficacy of cell collection devices with a cytologic brush depends on the diameter of the bristles, not on the diameter of the brush. J Bronchol. 2002;9:177-181.
Michaelson ED, Serafind SM. Quantitative differences in the cellular yield of two bronchial brushes. Am Rev Respir Dis. 1975;112:267-268.
Chilvers MA, McKean M, Rutman A, et al. The effects of coronavirus on human nasal ciliated respiratory epithelium. Eur Respir J. 2001;18:965-970.
Carson JL, Collier AM, Hu SS. Acquired ciliary defects in nasal epithelium of children with acute viral upper respiratory infections. N Engl J Med. 1985;312:463-468.
Wong JYW, Rutman A, O'Callaghan C. Recovery of the ciliated epithelium following acute bronchiolitis in infancy. Thorax. 2005;60:582-587.
Smith CM, Kulkarni H, Radhakrishnan P, et al. Ciliary dyskinesia is an early feature of respiratory syncytial virus infection. Eur Respir J. 2014;43:485-496.
Iida H, Matsuura S, Shirakami G, et al. Differential effects of intravenous anesthetics on ciliary motility in cultured rat tracheal epithelial cells. Can J Anaesth. 2006;53:242-249.
Christopher AB, Ochoa S, Krushansky E, et al. The effects of temperature and anesthetic agents on ciliary function in murine respiratory epithelia. Front Pediatr. 2014;2:111.
Ingels KJ, Nijziel MR, Graamans K, et al. Influence of cocaine and lidocaine on human nasal cilia. Beat frequency and harmony in vitro. Arch Otolaryngol Head Neck Surg. 1994;120:197-201.
Verra F, Escudier E, Pinchon MC, et al. Effects of local anaesthetics (lidocaine) on the structure and function of ciliated respiratory epithelial cells. Biol Cell. 1990;69:99-105.
Matsuura S, Shirakami G, Iida H, et al. The effect of sevoflurane on ciliary motility in rat cultured tracheal epithelial cells: a comparison with isoflurane and halothane. Anesth Analg. 2006;102:1703-1708.
Robertson A, Stannard W, Passant C, et al. What effect does isoflurane have upon ciliary beat pattern: an in vivo study. Clin Otolaryngol Allied Sci. 2004;29:157-160.
Raphael JH, Selwyn DA, Mottram SD, et al. Effects of 3 MAC of halothane, enflurane and isoflurane on cilia beat frequency of human nasal epithelium in vitro. Br J Anaesth. 1996;76:116-121.
Raphael JH, Strupish J, Selwyn DA, et al. Recovery of respiratory ciliary function after depression by inhalation anaesthetic agents: an in vitro study using nasal turbinate explants. Br J Anaesth. 1996;76:854-859.
Jiao J, Meng N, Zhang L. The effect of topical corticosteroids, topical antihistamines, and preservatives on human ciliary beat frequency. ORL J Otorhinolaryngol Relat Spec. 2014;76:127-136.
An F, Xing L, Zhang Z, et al. Effects of histamine on ciliary beat frequency of ciliated cells from guinea pigs nasal mucosa. Eur Arch Otorhinolaryngol. 2015;272:2839-2845.
Ong HX, Traini D, Ballerin G, et al. Combined inhaled salbutamol and mannitol therapy for mucus hyper-secretion in pulmonary diseases. AAPS J. 2014;16:269-280.
Yaghi A, Zaman A, Dolovich MB. The direct effect of hyperosmolar agents on ciliary beating of human bronchial epithelial cells. J Aerosol Med Pulm Drug Deliv. 2012;25:88-95.
Devalia JL, Sapsford RJ, Rusznak C, et al. The effects of salmeterol and salbutamol on ciliary beat frequency of cultured human bronchial epithelial cells, in vitro. Pulm Pharmacol. 1992;5:257-263.
Kanthakumar K, Cundell DR, Johnson M, et al. Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin. Br J Pharmacol. 1994;112:493-498.
Toledo AC, Arantes-Costa FM, Macchione M, et al. Salbutamol improves markers of epithelial function in mice with chronic allergic pulmonary inflammation. Respir Physiol Neurobiol. 2011;177:155-161.
Uz U, Chen B, Palmer JN, et al. Effects of thymoquinone and montelukast on sinonasal ciliary beat frequency. Am J Rhinol Allergy. 2014;28:122-125.
Smith CM, Radhakrishnan P, Sikand K, et al. The effect of ethanol and acetaldehyde on brain ependymal and respiratory ciliary beat frequency. Cilia. 2013;2:5.
Pagliuca G, Rosato C, Martellucci S, et al. Cytologic and functional alterations of nasal mucosa in smokers: temporary or permanent damage? Otolaryngol Head Neck Surg. 2015;152:740-745.
Simet SM, Sisson JH, Pavlik JA, et al. Long-term cigarette smoke exposure in a mouse model of ciliated epithelial cell function. Am J Respir Cell Mol Biol. 2010;43:635-640.
Luk CK, Dulfano MJ. Effect of pH, viscosity and ionic-strength changes on ciliary beating frequency of human bronchial explants. Clin Sci (Lond). 1983;64:449-451.
van de Donk HJ, Zuidema J, Merkus FW. 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 AM, Latorre F, et al. Effects of normobaric oxygen on ciliary beat frequency of human respiratory epithelium. Br J Anaesth. 1998;80:660-664.
Kay RJ, Moate RM, Bray I, et al. Cultured rat trachea as a model for the study of ciliary abundance: the effect of oxygen. Anesthesiology. 2002;97:275-277.
Ballenger JJ, Orr MF. Quantitative measurement of human ciliary activity. Ann Otol Rhinol Laryngol. 1963;72:31-39.
Mercke U. The influence of varying air humidity on mucociliary activity. Acta Otolaryngol. 1975;79:133-139.
Clary-Meinesz C, Mouroux J, Cosson J, et al. Influence of external pH on ciliary beat frequency in human bronchi and bronchioles. Eur Respir J. 1998;11:330-333.
Sutto Z, Conner GE, Salathe M. Regulation of human airway ciliary beat frequency by intracellular pH. J Physiol. 2004;560:519-532.
Salathe M. Regulation of mammalian ciliary beating. Annu Rev Physiol. 2007;69:401-422.
Smith CM, Hirst RA, Bankart MJ, et al. Cooling of cilia allows functional analysis of the beat pattern for diagnostic testing. Chest. 2011;140:186-190.
O'Callaghan C, Achaval M, Forsythe I, et al. Brain and respiratory cilia: the effect of temperature. Biol Neonate. 1995;68:394-397.
Green A, Smallman LA, Logan AC, et al. The effect of temperature on nasal ciliary beat frequency. Clin Otolaryngol Allied Sci. 1995;20:178-180.
Konietzko N, Nakhosteen JA, Mizera W, et al. Ciliary beat frequency of biopsy samples taken from normal persons and patients with various lung diseases. Chest. 1981;80:855-857.
Mwimbi XKMS, Muimo R, Green MW, et al. Making human nasal cilia beat in the cold: a real time assay for cell signalling. Cell Signal. 2003;15:395-402.
Mercke U. The influence of temperature on mucociliary activity. Temperature range 40 degrees C to 50 degrees C. Acta Otolaryngol. 1974;78:253-258.
Lindemann J, Leiacker R, Rettinger G, et al. Nasal mucosal temperature during respiration. Clin Otolaryngol Allied Sci. 2002;27:135-139.
Mercke U, Hakansson CH, Toremalm NG. The influence of temperature on mucociliary activity. Temperature range 20 degrees C-40 degrees C. Acta Otolaryngol. 1974;78:444-450.
Jackson CL, Goggin PM, Lucas JS. Ciliary beat pattern analysis below 37°C may increase risk of primary ciliary dyskinesia misdiagnosis. Chest. 2012;142:543-544.
Sanderson MJ, Dirksen ER. Quantification of ciliary beat frequency and metachrony by high-speed digital video. Methods Cell Biol. 1995;47:289-297.
Ishijima S. High-speed video microscopy of flagella and cilia. Methods Cell Biol. 1995;47:239-243.
Centonze Frohlich V. Phase contrast and differential interference contrast (DIC) microscopy. j Vis Exp. 2008;6:844.
Hirst RA, Jackson CL, Coles JL, 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.
Sisson JH, Stoner J, Ammons B, et al. All-digital image capture and whole-field analysis of ciliary beat frequency. J Microsc. 2003;211:103-111.
Cole R. Live-cell imaging. Cell Adh Migr. 2014;8:452-459.
Horani A, Brody SL, Ferkol TW, et al. CCDC65 mutation causes primary ciliary dyskinesia with normal ultrastructure and hyperkinetic cilia. PLoS One. 2013;8:e72299.
Bleeker JD, Hoeksema PE. A simple method of measure the ciliary beat rate of respiratory epithelium. Acta Otolaryngol. 1971;71:426-429.
Rossman CM, Lee RM, Forrest JB, et al. Nasal ciliary ultrastructure and function in patients with primary ciliary dyskinesia compared with that in normal subjects and in subjects with various respiratory diseases. Am Rev Respir Dis. 1984;129:161-167.
O'Callaghan C, Smith K, Wilkinson M, et al. Ciliary beat frequency in newborn infants. Arch Dis Child. 1991;66:443-444.
Selwyn DA, Gyi A, Raphael JH, et al. A perfusion system for in vitro measurement of human cilia beat frequency. Br J Anaesth. 1996;76:111-115.
Sanderson MJ, Dirksen ER. A versatile and quantitative computer-assisted photoelectronic technique used for the analysis of ciliary beat cycles. Cell Motil. 1985;5:267-292.
Nasr G, Schoevaert D, Marano F, et al. Progress in the measurement of ciliary beat frequency by automated image analysis: application to mammalian tracheal epithelium. Anal Cell Pathol. 1995;9:165-177.
Sanderson MJ. High-speed digital microscopy. Methods. 2000;21:325-334.
O'Callaghan C, Rutman A, Williams G, et al. Ciliated conical epithelial cell protrusions point towards a diagnosis of primary ciliary dyskinesia. Respir Res. 2018;19:125.
Sommer JU, Gross S, Hormann K, et al. Time-dependent changes in nasal ciliary beat frequency. Eur Arch Otorhinolaryngol. 2010;267:1383-1387.
Lee RM, Rossman CM, O'Brodovich H. Assessment of postmortem respiratory ciliary motility and ultrastructure. Am Rev Respir Dis. 1987;136:445-447.
Chilvers MA, 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.
Armengot M, Bonet M, Carda C, et al. Development and validation of a method of cilia motility analysis for the early diagnosis of primary ciliary dyskinesia. Acta Otorrinolaringol Esp. 2012;63:1-8.
Smith CM, Djakow J, Free RC, et al. ciliaFA: a research tool for automated, high-throughput measurement of ciliary beat frequency using freely available software. Cilia. 2012;1:14.
Mantovani G, Pifferi M, Vozzi G. Automated software for analysis of ciliary beat frequency and metachronal wave orientation in primary ciliary dyskinesia. Eur Arch Otorhinolaryngol. 2010;267:897-902.
Dimova S, Maes F, Brewster ME, et al. High-speed digital imaging method for ciliary beat frequency measurement. J Pharm Pharmacol. 2005;57:521-526.
Feriani L, Juenet M, Fowler CJ, et al. Assessing the collective dynamics of motile cilia in cultures of human airway cells by multiscale DDM. Biophys J. 2017;113:109-119.
Olm MK, Kögler JE, Macchione M, et al. Primary ciliary dyskinesia: evaluation using cilia beat frequency assessment via spectral analysis of digital microscopy images. J Appl Physiol. 2011;111:295-302.
Yi WJ, Park KS, Lee CH, et al. Correlation between ciliary beat frequency and metachronal wave disorder using image analysis method. Med Biol Eng Comput. 2003;41:481-485.
Rhee CS, Min YG, Lee CH, et al. Ciliary beat frequency in cultured human nasal epithelial cells. Ann Otol Rhinol Laryngol. 2001;110:1011-1016.
Rossman CM, Forrest JB, Lee RM, et al. The dyskinetic cilia syndrome. Ciliary motility in immotile cilia syndrome. Chest. 1980;78:580-582.
Rossman CM, Forrest JB, Lee RM, et al. The dyskinetic cilia syndrome: abnormal ciliary motility in association with abnormal ciliary ultrastructure. Chest. 1981;80:860-865.
Rossman CM, Lee RM, Forrest JB, et al. Nasal cilia in normal man, primary ciliary dyskinesia and other respiratory diseases: analysis of motility and ultrastructure. Eur J Respir Dis Suppl. 1983;127:64-70.
Komatani-Tamiya N, Daikoku E, Takemura Y, et al. Procaterol-stimulated increases in ciliary bend amplitude and ciliary beat frequency in mouse bronchioles. Cell Physiol Biochem. 2012;29:511-522.
Armengot M, Milara J, Mata M, et al. Cilia motility and structure in primary and secondary ciliary dyskinesia. Am J Rhinol Allergy. 2010;24:175-180.
Shoemark A, Moya E, Hirst RA, et al. High prevalence of CCDC103 p.His154Pro mutation causing primary ciliary dyskinesia disrupts protein oligomerisation and is associated with normal diagnostic investigations. Thorax. 2018;73:157-166.
Greenstone M, Rutman A, Dewar A, et al. Primary ciliary dyskinesia: cytological and clinical features. Q J Med. 1988;67:405-423.
Knowles MR, Ostrowski LE, Leigh MW, et al. Mutations in RSPH1 cause primary ciliary dyskinesia with a unique clinical and ciliary phenotype. Am J Respir Crit Care Med. 2014;189:707-717.
Castleman VH, Romio L, Chodhari R, et al. Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities. Am J Hum Genet. 2009;84:197-209.
Daniels MLA, Leigh MW, Davis SD, et al. Founder mutation in RSPH4A identified in patients of Hispanic descent with primary ciliary dyskinesia. Hum Mutat. 2013;34:1352-1356.
Olbrich H, Schmidts M, Werner C, et al. Recessive HYDIN mutations cause primary ciliary dyskinesia without randomization of left-right body asymmetry. Am J Hum Genet. 2012;91:672-684.
Panizzi JR, Becker-Heck A, Castleman VH, et al. CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms. Nat Genet. 2012;44:714-719.
Knowles MR, Leigh MW, Carson JL, et al. Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure. Thorax. 2012;67:433-441.
Wallmeier J, Boon M, Mutairi D, et al. Mutations in CCNO and MCIDAS lead to a mucociliary clearance disorder due to reduced generation of multiple motile cilia. Mol Cell Pediatr. 2015;2:A15.
Boon M, Wallmeier J, Ma L, et al. MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia. Nat Commun. 2014;5:4418.
Bonnefoy S, Watson CM, Kernohan KD, et al. Biallelic mutations in LRRC56, encoding a protein associated with intraflagellar transport, cause mucociliary clearance and laterality defects. Am J Hum Genet. 2018;103:727-739.
Fadaee-Shohada MJ, Hirst RA, Rutman A, et al. The behaviour of both Listeria monocytogenes and rat ciliated ependymal cells is altered during their coculture. PLoS One. 2010;5:e10450.
Bottier M, Blanchon S, Pelle G, et al. A new index for characterizing microbead motion in a flow induced by ciliary beating: part I, experimental analysis. PLoS Comput Biol. 2017;13:1-19.
Sears PR, Thompson K, Knowles MR, et al. Human airway ciliary dynamics. Am J Physiol Lung Cell Mol Physiol. 2013;304:L170-L183.
Quinn SP, Zahid MJ, Durkin JR, et al. Automated identification of abnormal respiratory ciliary motion in nasal biopsies. Sci Transl Med. 2015;7:299ra124-299ra124.
Leigh MW, Hazucha MJ, Chawla KK, et al. Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. Ann Am Thorac Soc. 2013;10:574-581.
Iongh RU, de, Rutland J. Ciliary defects in healthy subjects, bronchiectasis, and primary ciliary dyskinesia. Am J Respir Crit Care Med. 1995;151:1559-1567.
Schwabe GC, Hoffmann K, Loges NT, et al. Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused by DNAH11 mutations. Hum Mutat. 2008;29:289-298.
O'Callaghan C, Rutman A, Williams GM, et al. Inner dynein arm defects causing primary ciliary dyskinesia: repeat testing required. Eur Respir J. 2011;38:603-607.
Hirst RA, Rutman A, Williams G, et al. Ciliated air-liquid cultures as an aid to diagnostic testing of primary ciliary dyskinesia. CHEST J. 2010;138:1441-1447.
Jorissen M, Van der Schueren B, Van den Berghe H, Cassiman JJ. Ciliogenesis in cultured human nasal epithelium. ORL J Otorhinolaryngol Relat Spec. 1990;52:368-374.
Jorissen M, Willems T, Van der Schueren B. Ciliary function analysis for the diagnosis of primary ciliary dyskinesia: advantages of ciliogenesis in culture. Acta Otolaryngol. 2000;120:291-295.
Boon M, Smits A, Cuppens H, et al. Primary ciliary dyskinesia: critical evaluation of clinical symptoms and diagnosis in patients with normal and abnormal ultrastructure. Orphanet J Rare Dis. 2014;9:11.
Pifferi M, Montemurro F, Cangiotti AM, et al. Simplified cell culture method for the diagnosis of atypical primary ciliary dyskinesia. Thorax. 2009;64:1077-1081.
Pifferi M, Bush A, Montemurro F, et al. Rapid diagnosis of primary ciliary dyskinesia: cell culture and soft computing analysis. Eur Respir J. 2013;41:960-965.
