{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:57:45Z","timestamp":1792166265184,"version":"4.4.0"},"reference-count":108,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,11]],"date-time":"2021-09-11T00:00:00Z","timestamp":1631318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary ciliary dyskinesia (PCD) is a rare genetic ciliopathy in which mucociliary clearance is disturbed by the abnormal motion of cilia or there is a severe reduction in the generation of multiple motile cilia. Lung damage ensues due to recurrent airway infections, sometimes even resulting in respiratory failure. So far, no causative treatment is available and treatment efforts are primarily aimed at improving mucociliary clearance and early treatment of bacterial airway infections. Treatment guidelines are largely based on cystic fibrosis (CF) guidelines, as few studies have been performed on PCD. In this review, we give a detailed overview of the clinical studies performed investigating PCD to date, including three trials and several case reports. In addition, we explore precision medicine approaches in PCD, including gene therapy, mRNA transcript and read-through therapy.<\/jats:p>","DOI":"10.3390\/ijms22189834","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T21:45:57Z","timestamp":1631483157000},"page":"9834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["Current and Future Treatments in Primary Ciliary Dyskinesia"],"prefix":"10.3390","volume":"22","author":[{"given":"Tamara","family":"Paff","sequence":"first","affiliation":[{"name":"Department of Paediatric Pulmonology, Emma Children\u2019s Hospital, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heymut","family":"Omran","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, University Childrens\u2019s Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim G.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Danish PCD Centre, Danish Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Righospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric G.","family":"Haarman","sequence":"additional","affiliation":[{"name":"Department of Paediatric Pulmonology, Emma Children\u2019s Hospital, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ajhg.2016.11.019","article-title":"Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects","volume":"100","author":"Paff","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.ajhg.2018.03.025","article-title":"Mutations in C11orf70 Cause Primary Ciliary Dyskinesia with Randomization of Left\/Right Body Asymmetry Due to Defects of Outer and Inner Dynein Arms","volume":"102","author":"Hjeij","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/humu.10057","article-title":"Mutations of RPGR in X-linked retinitis pigmentosa (RP3)","volume":"19","author":"Vervoort","year":"2002","journal-title":"Hum. Mutat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1086\/318802","article-title":"Identification of the gene for oral-facial-digital type I syndrome","volume":"68","author":"Ferrante","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.ajhg.2019.09.022","article-title":"De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy with Hydrocephalus and Randomization of Left\/Right Body Asymmetry","volume":"105","author":"Wallmeier","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4418","DOI":"10.1038\/ncomms5418","article-title":"MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia","volume":"5","author":"Boon","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e002686","DOI":"10.1161\/CIRCGEN.119.002686","article-title":"Randomization of Left-right Asymmetry and Congenital Heart Defects: The Role of DNAH5 in Humans and Mice","volume":"12","author":"Wallmeier","year":"2019","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13630-014-0010-9","article-title":"Situs inversus and ciliary abnormalities: 20 years later, what is the connection?","volume":"4","author":"Pennekamp","year":"2015","journal-title":"Cilia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"gaab009","DOI":"10.1093\/molehr\/gaab009","article-title":"Motility of efferent duct cilia aids passage of sperm cells through the male reproductive system","volume":"27","author":"Aprea","year":"2021","journal-title":"Mol. Hum. Reprod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41572-020-0209-6","article-title":"Motile ciliopathies","volume":"6","author":"Wallmeier","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2002359","DOI":"10.1183\/13993003.02359-2020","article-title":"Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia","volume":"58","author":"Shoemark","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1164\/rccm.201803-0548OC","article-title":"Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype","volume":"199","author":"Davis","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1002\/humu.22957","article-title":"Systematic Analysis of CCNO Variants in a Defined Population: Implications for Clinical Phenotype and Differential Diagnosis","volume":"37","author":"Amirav","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/ng.2961","article-title":"Mutations in CCNO result in congenital mucociliary clearance disorder with reduced generation of multiple motile cilia","volume":"46","author":"Wallmeier","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1164\/rccm.200811-1731OC","article-title":"Lung function in patients with primary ciliary dyskinesia: A cross-sectional and 3-decade longitudinal study","volume":"181","author":"Marthin","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1007\/s11136-017-1564-y","article-title":"The patient\u2019s experience of primary ciliary dyskinesia: A systematic review","volume":"26","author":"Behan","year":"2017","journal-title":"Qual. Life Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1183\/09031936.00051509","article-title":"Health-related quality of life and unmet needs in patients with primary ciliary dyskinesia","volume":"35","author":"Pifferi","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1080\/17476348.2017.1360770","article-title":"Clinical care of children with primary ciliary dyskinesia","volume":"11","author":"Lucas","year":"2017","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1183\/09031936.97.10102376","article-title":"Longitudinal study of lung function in a cohort of primary ciliary dyskinesia","volume":"10","author":"Ellerman","year":"1997","journal-title":"Eur. Respir. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1183\/09031936.00176608","article-title":"Primary ciliary dyskinesia: A consensus statement on diagnostic and treatment approaches in children","volume":"34","author":"Barbato","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1183\/09031936.93.01020161","article-title":"The clinical effect and the effect on the ciliary motility of oral N-acetylcysteine in patients with cystic fibrosis and primary ciliary dyskinesia","volume":"1","author":"Stafanger","year":"1988","journal-title":"Eur. Respir. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Paff, T., Daniels, J.M., Weersink, E.J., Lutter, R., Vonk Noordegraaf, A., and Haarman, E.G. (2017). A randomised controlled trial on the effect of inhaled hypertonic saline on quality of life in primary ciliary dyskinesia. Eur. Respir. J., 49.","DOI":"10.1183\/13993003.01770-2016"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S2213-2600(20)30058-8","article-title":"Efficacy and safety of azithromycin maintenance therapy in primary ciliary dyskinesia (BESTCILIA): A multicentre, double-blind, randomised, placebo-controlled phase 3 trial","volume":"8","author":"Kobbernagel","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1183\/09031936.00073911","article-title":"Management of primary ciliary dyskinesia in European children: Recommendations and clinical practice","volume":"39","author":"Strippoli","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1602514","DOI":"10.1183\/13993003.02514-2016","article-title":"Hypertonic saline in patients with primary ciliary dyskinesia: On the road to evidence-based treatment for a rare lung disease","volume":"49","author":"Kuehni","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kobbernagel, H.E., Buchvald, F.F., Haarman, E.G., Casaulta, C., Collins, S.A., Hogg, C., Kuehni, C.E., Lucas, J.S., Omran, H., and Quittner, A.L. (2016). Study protocol, rationale and recruitment in a European multi-centre randomized controlled trial to determine the efficacy and safety of azithromycin maintenance therapy for 6 months in primary ciliary dyskinesia. BMC Pulm. Med., 16.","DOI":"10.1186\/s12890-016-0261-x"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1801040","DOI":"10.1183\/13993003.01040-2018","article-title":"Lung function in patients with primary ciliary dyskinesia: An iPCD Cohort study","volume":"52","author":"Halbeisen","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1701659","DOI":"10.1183\/13993003.01659-2017","article-title":"Growth and nutritional status, and their association with lung function: A study from the international Primary Ciliary Dyskinesia Cohort","volume":"50","author":"Goutaki","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Crowley, S., Azevedo, I., Boon, M., Bush, A., Eber, E., Haarman, E., Karadag, B., K\u00f6tz, K., Leigh, M., and Moreno-Gald\u00f3, A. (2020). Access to medicines for rare diseases: Beating the drum for primary ciliary dyskinesia. ERJ Open Res., 6.","DOI":"10.1183\/23120541.00377-2020"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ardura-Garcia, C., Goutaki, M., Carr, S.B., Crowley, S., Halbeisen, F.S., Nielsen, K.G., Pennekamp, P., Raidt, J., Thouvenin, G., and Yiallouros, P.K. (2020). Registries and collaborative studies for primary ciliary dyskinesia in Europe. ERJ Open Res., 6.","DOI":"10.1183\/23120541.00005-2020"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Piatti, G., De Santi, M.M., Farolfi, A., Zuccotti, G.V., D\u2019Auria, E., Patria, M.F., Torretta, S., Consonni, D., and Ambrosetti, U. (2020). Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia. BMC Pediatr., 20.","DOI":"10.1186\/s12887-020-02062-4"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1378\/chest.07-2812","article-title":"Structural and functional lung disease in primary ciliary dyskinesia","volume":"134","author":"Santamaria","year":"2008","journal-title":"Chest"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/qjmed\/hcy166","article-title":"N-acetylcysteine (NAC) in COPD: Benefits often lost in trials","volume":"112","author":"Moitra","year":"2019","journal-title":"QJM"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12931-016-0500-y","article-title":"Pharmacological investigation on the anti-oxidant and anti-inflammatory activity of N-acetylcysteine in an ex vivo model of COPD exacerbation","volume":"18","author":"Cazzola","year":"2017","journal-title":"Respir. Res."},{"key":"ref_35","first-page":"73","article-title":"No penetration of orally administered N-acetylcysteine into bronchoalveolar lavage fluid","volume":"70","author":"Cotgreave","year":"1987","journal-title":"Eur. J. Respir. Dis."},{"key":"ref_36","first-page":"721","article-title":"The in Vitro Reduction in Viscosity of Human Tracheobronchial Secretions by Acetylcysteine","volume":"90","author":"Sheffner","year":"1964","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12931-019-1042-x","article-title":"Effect of N-acetylcysteine on exacerbations of bronchiectasis (BENE): A randomized controlled trial","volume":"20","author":"Qi","year":"2019","journal-title":"Respir. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S2213-2600(13)70286-8","article-title":"Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): A randomised, double-blind placebo-controlled trial","volume":"2","author":"Zheng","year":"2014","journal-title":"Lancet Respir. Med."},{"key":"ref_39","first-page":"Cd007168","article-title":"Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis","volume":"2013","author":"Tam","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jcf.2014.08.008","article-title":"Long-term treatment with oral N-acetylcysteine: Affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial","volume":"14","author":"Conrad","year":"2015","journal-title":"J. Cyst. Fibros."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1056\/NEJMoa043891","article-title":"Mucus clearance and lung function in cystic fibrosis with hypertonic saline","volume":"354","author":"Donaldson","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.rmed.2004.05.006","article-title":"Evaluation of nebulised hypertonic saline (7%) as an adjunct to physiotherapy in patients with stable bronchiectasis","volume":"99","author":"Kellett","year":"2005","journal-title":"Respir. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S1097-2765(01)00286-6","article-title":"The CF salt controversy: In vivo observations and therapeutic approaches","volume":"8","author":"Tarran","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1164\/ajrccm.156.1.9512074","article-title":"Rheology of cystic fibrosis sputum after in vitro treatment with hypertonic saline alone and in combination with recombinant human deoxyribonuclease I","volume":"156","author":"King","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_45","first-page":"Cd001506","article-title":"Nebulised hypertonic saline for cystic fibrosis","volume":"9","author":"Wark","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1186\/s13063-019-3766-9","article-title":"A 2 \u00d7 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52\u2009weeks in adults with bronchiectasis: A protocol for the CLEAR clinical trial","volume":"20","author":"Bradley","year":"2019","journal-title":"Trials"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.rmed.2011.12.021","article-title":"The long term effect of inhaled hypertonic saline 6% in non-cystic fibrosis bronchiectasis","volume":"106","author":"Nicolson","year":"2012","journal-title":"Respir. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/ppul.25206","article-title":"Effectiveness of hypertonic saline nebulization in airway clearance in children with non-cystic fibrosis bronchiectasis: A randomized control trial","volume":"56","author":"Anuradha","year":"2021","journal-title":"Pediatr. Pulmonol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lucas, J.S., Barbato, A., Collins, S.A., Goutaki, M., Behan, L., Caudri, D., Dell, S., Eber, E., Escudier, E., and Hirst, R.A. (2017). European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur. Respir. J., 49.","DOI":"10.1183\/13993003.01090-2016"},{"key":"ref_50","first-page":"Cd001127","article-title":"Dornase alfa for cystic fibrosis","volume":"3","author":"Yang","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1378\/chest.113.5.1329","article-title":"Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I. rhDNase Study Group","volume":"113","author":"Barker","year":"1998","journal-title":"Chest"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1164\/ajrccm.154.2.8756815","article-title":"Short-term recombinant human DNase in bronchiectasis. Effect on clinical state and in vitro sputum transportability","volume":"154","author":"Wills","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1016\/j.rmed.2007.05.014","article-title":"Long-term use of nebulized human recombinant DNase1 in two siblings with primary ciliary dyskinesia","volume":"101","author":"Clifton","year":"2007","journal-title":"Respir. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/(SICI)1099-0496(199901)27:1<59::AID-PPUL11>3.0.CO;2-D","article-title":"DNase treatment in primary ciliary dyskinesia--assessment by nocturnal pulse oximetry","volume":"27","author":"Brinkhorst","year":"1999","journal-title":"Pediatr. Pulmonol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/ppul.1950200509","article-title":"Clinical benefit from nebulized human recombinant DNase in Kartagener\u2019s syndrome","volume":"20","author":"Desai","year":"1995","journal-title":"Pediatr. Pulmonol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Marthin, J.K., Lucas, J.S., Boon, M., Casaulta, C., Crowley, S., Destouches, D.M.S., Eber, E., Escribano, A., Haarman, E., and Hogg, C. (2021). International BEAT-PCD consensus statement for infection prevention and control for primary ciliary dyskinesia in collaboration with ERN-LUNG PCD Core Network and patient representatives. ERJ Open Res., 7.","DOI":"10.1183\/13993003.congress-2021.PA2061"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1093.e1","DOI":"10.1016\/j.cmi.2015.08.020","article-title":"A longitudinal study of lung bacterial pathogens in patients with primary ciliary dyskinesia","volume":"21","author":"Alanin","year":"2015","journal-title":"Clin. Microbiol. Infect"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1164\/rccm.201409-1672OC","article-title":"Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype","volume":"191","author":"Davis","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1164\/rccm.200303-365OC","article-title":"Primary ciliary dyskinesia: Diagnostic and phenotypic features","volume":"169","author":"Noone","year":"2004","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1002\/ppul.22984","article-title":"Multicenter analysis of body mass index, lung function, and sputum microbiology in primary ciliary dyskinesia","volume":"49","author":"Maglione","year":"2014","journal-title":"Pediatr. Pulmonol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.rmed.2017.08.028","article-title":"Clinical impact of Pseudomonas aeruginosa colonization in patients with Primary Ciliary Dyskinesia","volume":"131","author":"Weigert","year":"2017","journal-title":"Respir. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1479972318787919","DOI":"10.1177\/1479972318787919","article-title":"Variation in treatment strategies for the eradication of Pseudomonas aeruginosa in primary ciliary dyskinesia across European centers","volume":"16","author":"Crowley","year":"2019","journal-title":"Chron. Respir. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1901472","DOI":"10.1183\/13993003.01472-2019","article-title":"Primary ciliary dyskinesia patients have the same P. aeruginosa clone in sinuses and lungs","volume":"55","author":"Arndal","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Lucas, J.S., Gahleitner, F., Amorim, A., Boon, M., Brown, P., Constant, C., Cook, S., Crowley, S., Destouches, D.M.S., and Eber, E. (2019). Pulmonary exacerbations in patients with primary ciliary dyskinesia: An expert consensus definition for use in clinical trials. ERJ Open Res., 5.","DOI":"10.1183\/23120541.00147-2018"},{"key":"ref_65","first-page":"CD006682","article-title":"Duration of intravenous antibiotic therapy in people with cystic fibrosis","volume":"9","author":"Abbott","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"i1","DOI":"10.1136\/thx.2010.136119","article-title":"British Thoracic Society guideline for non-CF bronchiectasis","volume":"65","author":"Pasteur","year":"2010","journal-title":"Thorax"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1128\/CMR.00078-09","article-title":"Mechanisms of action and clinical application of macrolides as immunomodulatory medications","volume":"23","author":"Kanoh","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1164\/ajrccm.157.6.9710075","article-title":"Improvement of survival in patients with diffuse panbronchiolitis treated with low-dose erythromycin","volume":"157","author":"Kudoh","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1164\/rccm.201802-0215OC","article-title":"Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis. The OPTIMIZE Randomized Trial","volume":"198","author":"Kloster","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_70","first-page":"Cd002203","article-title":"Macrolide antibiotics for cystic fibrosis","volume":"11","author":"Southern","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1001\/jama.2013.1937","article-title":"Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: The BAT randomized controlled trial","volume":"309","author":"Altenburg","year":"2013","journal-title":"Jama"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/S0140-6736(12)60953-2","article-title":"Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): A randomised, double-blind, placebo-controlled trial","volume":"380","author":"Wong","year":"2012","journal-title":"Lancet"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.2169\/internalmedicine.51.6617","article-title":"Two cases of primary ciliary dyskinesia with different responses to macrolide treatment","volume":"51","author":"Kido","year":"2012","journal-title":"Intern. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.2169\/internalmedicine.49.3453","article-title":"Primary ciliary dyskinesia that responded to long-term, low-dose clarithromycin","volume":"49","author":"Yoshioka","year":"2010","journal-title":"Intern. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1702221","DOI":"10.1183\/13993003.02221-2017","article-title":"Are inhaled corticosteroids prescribed rationally in primary ciliary dyskinesia?","volume":"51","author":"Dehlink","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1007\/s004310050843","article-title":"Primary ciliary dyskinesia: Evolution of pulmonary function","volume":"157","author":"Hellinckx","year":"1998","journal-title":"Eur. J. Pediatrics"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1183\/09031936.98.11061389","article-title":"Airway response of children with primary ciliary dyskinesia to exercise and beta2-agonist challenge","volume":"11","author":"Phillips","year":"1998","journal-title":"Eur. Respir. J."},{"key":"ref_78","first-page":"CD001915","article-title":"Inhaled corticosteroids for cystic fibrosis","volume":"7","author":"Welch","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1183\/09031936.00068810","article-title":"Agenesis of paranasal sinuses and nasal nitric oxide in primary ciliary dyskinesia","volume":"37","author":"Pifferi","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1111\/jpc.12791","article-title":"Presentation of primary ciliary dyskinesia in children: 30 years\u2019 experience","volume":"51","author":"Hosie","year":"2015","journal-title":"J. Paediatr. Child Health"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/alr.21873","article-title":"Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia","volume":"7","author":"Alanin","year":"2017","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1288\/00005537-199311000-00010","article-title":"A treatment for primary ciliary dyskinesia: Efficacy of functional endoscopic sinus surgery","volume":"103","author":"Parsons","year":"1993","journal-title":"Laryngoscope"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1177\/1945892420933175","article-title":"Sinus Development and Pneumatization in a Primary Ciliary Dyskinesia Cohort","volume":"35","author":"Pappa","year":"2021","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1136\/thoraxjnl-2015-207891","article-title":"Clinical characteristics, functional respiratory decline and follow-up in adult patients with primary ciliary dyskinesia","volume":"72","author":"Bassinet","year":"2017","journal-title":"Thorax"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Bequignon, E., Dupuy, L., Zerah-Lancner, F., Bassinet, L., Honor\u00e9, I., Legendre, M., Devars du Mayne, M., Escabasse, V., Crestani, B., and Ma\u00eetre, B. (2019). Critical Evaluation of Sinonasal Disease in 64 Adults with Primary Ciliary Dyskinesia. J. Clin. Med., 8.","DOI":"10.3390\/jcm8050619"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1183\/13993003.00736-2016","article-title":"Clinical manifestations in primary ciliary dyskinesia: Systematic review and meta-analysis","volume":"48","author":"Goutaki","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00405-010-1341-9","article-title":"ENT manifestations in patients with primary ciliary dyskinesia: Prevalence and significance of otorhinolaryngologic co-morbidities","volume":"268","author":"Sommer","year":"2011","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ijporl.2017.11.005","article-title":"Hearing loss in children with primary ciliary dyskinesia","volume":"104","author":"Kreicher","year":"2018","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ijporl.2016.08.011","article-title":"A longitudinal evaluation of hearing and ventilation tube insertion in patients with primary ciliary dyskinesia","volume":"89","author":"Andersen","year":"2016","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1542\/peds.102.5.1161","article-title":"Language of early- and later-identified children with hearing loss","volume":"102","author":"Sedey","year":"1998","journal-title":"Pediatrics"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1001\/archoto.2010.183","article-title":"Otologic features in children with primary ciliary dyskinesia","volume":"136","author":"Coste","year":"2010","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1016\/j.ijporl.2012.07.011","article-title":"Middle ear ventilation in children with primary ciliary dyskinesia","volume":"76","author":"Wolter","year":"2012","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Chhin, B., Negre, D., Merrot, O., Pham, J., Tourneur, Y., Ressnikoff, D., Jaspers, M., Jorissen, M., Cosset, F.L., and Bouvagnet, P. (2009). Ciliary beating recovery in deficient human airway epithelial cells after lentivirus ex vivo gene therapy. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000422"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1164\/rccm.200603-370OC","article-title":"Mutations of DNAI1 in primary ciliary dyskinesia: Evidence of founder effect in a common mutation","volume":"174","author":"Zariwala","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/gt.2013.79","article-title":"Restoring ciliary function to differentiated primary ciliary dyskinesia cells with a lentiviral vector","volume":"21","author":"Ostrowski","year":"2014","journal-title":"Gene Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1165\/rcmb.2009-0118OC","article-title":"Conditional deletion of dnaic1 in a murine model of primary ciliary dyskinesia causes chronic rhinosinusitis","volume":"43","author":"Ostrowski","year":"2010","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/nm.2860","article-title":"Gene therapy rescues cilia defects and restores olfactory function in a mammalian ciliopathy model","volume":"18","author":"McIntyre","year":"2012","journal-title":"Nat. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1097\/MOH.0b013e328302c807","article-title":"Recent advances in gene therapy for severe congenital immunodeficiency diseases","volume":"15","author":"Sokolic","year":"2008","journal-title":"Curr. Opin. Hematol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1136\/jmedgenet-2015-103539","article-title":"Gene editing of DNAH11 restores normal cilia motility in primary ciliary dyskinesia","volume":"53","author":"Lai","year":"2016","journal-title":"J. Med Genet."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1165\/rcmb.2015-0353OC","article-title":"DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes","volume":"55","author":"Dougherty","year":"2016","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1164\/rccm.201301-0059CI","article-title":"Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease","volume":"188","author":"Knowles","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/humu.23403","article-title":"Diagnostic yield of a targeted gene panel in primary ciliary dyskinesia patients","volume":"39","author":"Paff","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"10282","DOI":"10.1073\/pnas.152337699","article-title":"Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia","volume":"99","author":"Bartoloni","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/mt.2011.248","article-title":"Restoration of the dystrophin-associated glycoprotein complex after exon skipping therapy in Duchenne muscular dystrophy","volume":"20","author":"Cirak","year":"2012","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.nmd.2014.11.011","article-title":"European Medicines Agency review of ataluren for the treatment of ambulant patients aged 5 years and older with Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin gene","volume":"25","author":"Haas","year":"2015","journal-title":"Neuromuscul. Disord."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S2213-2600(14)70100-6","article-title":"Ataluren for the treatment of nonsense-mutation cystic fibrosis: A randomised, double-blind, placebo-controlled phase 3 trial","volume":"2","author":"Kerem","year":"2014","journal-title":"Lancet Respir. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1080\/13543784.2020.1828862","article-title":"ELX-02: An investigational read-through agent for the treatment of nonsense mutation-related genetic disease","volume":"29","author":"Kerem","year":"2020","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"609","DOI":"10.3389\/fphar.2020.00609","article-title":"Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors","volume":"11","author":"Joskova","year":"2020","journal-title":"Front. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9834\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:00:59Z","timestamp":1760166059000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,11]]},"references-count":108,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22189834"],"URL":"https:\/\/doi.org\/10.3390\/ijms22189834","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,11]]}}}