{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:49:20Z","timestamp":1782895760408,"version":"3.54.5"},"reference-count":89,"publisher":"European Respiratory Society (ERS)","issue":"181","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir Rev"],"accepted":{"date-parts":[[2026,3,27]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Primary ciliary dyskinesia (PCD) comprises a group of rare genetic disorders that primarily affect the function of motile respiratory cilia, leading to progressive sinopulmonary disease. Disease models can be used to investigate potential therapies or responses to environmental exposures. We sought to identify and describe knowledge gaps in the modelling approaches and outcome measures used in applied\n                      <jats:italic>in vitro<\/jats:italic>\n                      or\n                      <jats:italic>ex vivo<\/jats:italic>\n                      human respiratory cellular models of PCD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a scoping review of Medline and Embase (2000\u20132024), screening studies of\n                      <jats:italic>in vitro<\/jats:italic>\n                      or\n                      <jats:italic>ex vivo<\/jats:italic>\n                      human respiratory cellular models of PCD and charted modelling approaches, applications and outcome measures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 612 screened abstracts, 10 articles were included in the qualitative synthesis. The modelling approaches included primary cell culture at an air\u2013liquid interface (ALI) (n=5), spheroid culture (n=2), organoid culture (n=2) and induced pluripotent stem cell-derived ALI culture (n=1). Modelling protocols were heterogenous. Applications included 1) therapeutic gene correction or replacement applications (n=4) and therapeutic drug screening (n=1), or 2) exposure to infection (n=4), drugs (n=3) and house dust mite allergen (n=1). Outcome measures used for both model characterisation and evaluation of therapeutic interventions were inconsistent. Certain outcome measures, such as ciliary function, were reported inconsistently, which limited interpretability of findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A variety of PCD models exist but a lack of standardised characterisation hinders the reproducibility and comparability of findings. Consensus is needed on the minimum requirements for model characterisation and standardised reporting of outcome measures, which will facilitate model development for therapeutic and exposure applications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/16000617.0193-2025","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:34:51Z","timestamp":1782894891000},"page":"250193","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Utilising human cellular models of primary ciliary dyskinesia: a scoping review"],"prefix":"10.1183","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7429-4185","authenticated-orcid":false,"given":"Jonathan W.Y.","family":"Ong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Tsang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8701-9975","authenticated-orcid":false,"given":"Jane S.","family":"Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1200-0935","authenticated-orcid":false,"given":"Claire L.","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1629-8601","authenticated-orcid":false,"given":"Bruna","family":"Rubbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"2026070101300689000_35.181.250193.1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S2213-2600(21)00453-7","article-title":"The global prevalence and ethnic heterogeneity of primary ciliary dyskinesia gene variants: a genetic database analysis","volume":"10","author":"Hannah","year":"2022","journal-title":"Lancet Respir Med"},{"key":"2026070101300689000_35.181.250193.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2020.11.007"},{"key":"2026070101300689000_35.181.250193.3","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S2213-2600(19)30374-1","article-title":"Primary ciliary dyskinesia in the genomics age","volume":"8","author":"Lucas","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2026070101300689000_35.181.250193.4","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-0808"},{"key":"2026070101300689000_35.181.250193.5","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00736-2016"},{"key":"2026070101300689000_35.181.250193.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-010-1341-9"},{"key":"2026070101300689000_35.181.250193.7","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2018-212104"},{"key":"2026070101300689000_35.181.250193.8","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmad003"},{"key":"2026070101300689000_35.181.250193.9","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00745-2025"},{"key":"2026070101300689000_35.181.250193.10","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2023.102"},{"key":"2026070101300689000_35.181.250193.11","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22001"},{"key":"2026070101300689000_35.181.250193.12","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.6.715"},{"key":"2026070101300689000_35.181.250193.13","doi-asserted-by":"crossref","first-page":"e91702","DOI":"10.1172\/jci.insight.91702","article-title":"Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography","volume":"2","author":"Solomon","year":"2017","journal-title":"JCI Insight"},{"key":"2026070101300689000_35.181.250193.14","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0118OC"},{"key":"2026070101300689000_35.181.250193.15","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2013.79"},{"key":"2026070101300689000_35.181.250193.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36735-z"},{"key":"2026070101300689000_35.181.250193.17","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.14.1.8534481"},{"key":"2026070101300689000_35.181.250193.18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3390\/jcm9113753","article-title":"A revised protocol for culture of airway epithelial cells as a diagnostic tool for primary ciliary dyskinesia","volume":"9","author":"Coles","year":"2020","journal-title":"J Clin Med"},{"key":"2026070101300689000_35.181.250193.19","doi-asserted-by":"publisher","DOI":"10.1080\/000164800750001116"},{"key":"2026070101300689000_35.181.250193.20","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02300-2021"},{"key":"2026070101300689000_35.181.250193.21","doi-asserted-by":"publisher","DOI":"10.1378\/chest.10-0175"},{"key":"2026070101300689000_35.181.250193.22","doi-asserted-by":"crossref","unstructured":"Willems T , Jorissen M . Sequential monolayer-suspension culture of human airway epithelial cells. J Cyst Fibros 2004; Suppl. 2, 53\u201354. doi:10.1016\/j.jcf.2004.05.011","DOI":"10.1016\/j.jcf.2004.05.011"},{"key":"2026070101300689000_35.181.250193.23","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00471.2016"},{"key":"2026070101300689000_35.181.250193.24","doi-asserted-by":"crossref","first-page":"104730","DOI":"10.1016\/j.isci.2022.104730","article-title":"Engineering rotating apical-out airway organoid for assessing respiratory cilia motility","volume":"25","author":"Wijesekara","year":"2022","journal-title":"iScience"},{"key":"2026070101300689000_35.181.250193.25","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202052058"},{"key":"2026070101300689000_35.181.250193.26","doi-asserted-by":"publisher","DOI":"10.1016\/J.STEM.2020.09.017"},{"key":"2026070101300689000_35.181.250193.27","doi-asserted-by":"publisher","DOI":"10.3390\/cells12111467"},{"key":"2026070101300689000_35.181.250193.28","doi-asserted-by":"crossref","unstructured":"Aromataris E , Lockwood C , Porritt K , et al. JBI Manual for Evidence Synthesis. Adelaide, JBI, 2024.","DOI":"10.46658\/JBIMES-24-01"},{"key":"2026070101300689000_35.181.250193.29","doi-asserted-by":"publisher","DOI":"10.7326\/M18-0850"},{"key":"2026070101300689000_35.181.250193.30","doi-asserted-by":"crossref","first-page":"L468","DOI":"10.1152\/ajplung.00208.2022","article-title":"Antigen stasis and airway nitrosative stress in human primary ciliary dyskinesia","volume":"326","author":"Gaston","year":"2024","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026070101300689000_35.181.250193.31","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1378\/chest.13-0159","article-title":"Ciliated cultures from patients with primary ciliary dyskinesia do not produce nitric oxide or inducible nitric oxide synthase during early infection","volume":"144","author":"Smith","year":"2013","journal-title":"Chest"},{"key":"2026070101300689000_35.181.250193.32","doi-asserted-by":"crossref","first-page":"14453","DOI":"10.1038\/s41598-023-41577-5","article-title":"Azithromycin promotes proliferation, and inhibits inflammation in nasal epithelial cells in primary ciliary dyskinesia","volume":"13","author":"Varenyiova","year":"2023","journal-title":"Sci Rep"},{"key":"2026070101300689000_35.181.250193.33","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00612-2017"},{"key":"2026070101300689000_35.181.250193.34","doi-asserted-by":"publisher","DOI":"10.3390\/cells11121957"},{"key":"2026070101300689000_35.181.250193.35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000422"},{"key":"2026070101300689000_35.181.250193.36","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103539"},{"key":"2026070101300689000_35.181.250193.37","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00455-2020"},{"key":"2026070101300689000_35.181.250193.38","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb1298"},{"key":"2026070101300689000_35.181.250193.39","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01769-2023"},{"key":"2026070101300689000_35.181.250193.40","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00176608"},{"key":"2026070101300689000_35.181.250193.41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906850106"},{"key":"2026070101300689000_35.181.250193.42","doi-asserted-by":"publisher","DOI":"10.1242\/dev.177428"},{"key":"2026070101300689000_35.181.250193.43","doi-asserted-by":"crossref","unstructured":"Fulcher ML , Randell SH . Human nasal and tracheo-bronchial respiratory epithelial cell culture. In: Randell SH , Fulcher ML , eds. Epithelial Cell Culture Protocols, 2nd Edn. Totowa, NJ, Humana Press, 2013; pp. 109\u2013121.","DOI":"10.1007\/978-1-62703-125-7_8"},{"key":"2026070101300689000_35.181.250193.44","doi-asserted-by":"publisher","DOI":"10.1159\/000092672"},{"key":"2026070101300689000_35.181.250193.45","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2008.110940"},{"key":"2026070101300689000_35.181.250193.46","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-002-0562-y"},{"key":"2026070101300689000_35.181.250193.47","doi-asserted-by":"publisher","DOI":"10.1007\/BF00463582"},{"key":"2026070101300689000_35.181.250193.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.082."},{"key":"2026070101300689000_35.181.250193.49","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247125"},{"key":"2026070101300689000_35.181.250193.50","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018100300"},{"key":"2026070101300689000_35.181.250193.51","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1293"},{"key":"2026070101300689000_35.181.250193.52","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.stemcr.2015.11.010","article-title":"Directed induction of functional multi-ciliated cells in proximal airway epithelial spheroids from human pluripotent stem cells","volume":"6","author":"Konishi","year":"2016","journal-title":"Stem Cell Rep"},{"key":"2026070101300689000_35.181.250193.53","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00725-2019"},{"key":"2026070101300689000_35.181.250193.54","unstructured":"Batista Leite S , Cipriano M , Carpi D , et al. Establishing the Scientific Validity of Complex In Vitro Models: Results of a EURL ECVAM Survey. Luxembourg, Publications Office of the European Union, 2021."},{"key":"2026070101300689000_35.181.250193.55","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1177\/2472555220923332","article-title":"Recommended guidelines for developing, qualifying, and implementing complex in vitro models (CIVMs) for drug discovery","volume":"25","author":"Ekert","year":"2020","journal-title":"SLAS Discov"},{"key":"2026070101300689000_35.181.250193.56","unstructured":"Organisation for Economic Co-operation and Development . Guidance Document for Describing Non-Guideline In Vitro Test Methods. Paris, OECD Publishing, 2017."},{"key":"2026070101300689000_35.181.250193.57","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0378-4274(02)00493-9","article-title":"Validation and acceptance of new and revised tests: a flexible but transparent process","volume":"140\u2013141","author":"Zeiger","year":"2003","journal-title":"Toxicology Letters"},{"key":"2026070101300689000_35.181.250193.58","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01441-2023"},{"key":"2026070101300689000_35.181.250193.59","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201607-1351oc"},{"key":"2026070101300689000_35.181.250193.60","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01809-2017"},{"key":"2026070101300689000_35.181.250193.61","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":"2026070101300689000_35.181.250193.62","unstructured":"Organisation for Economic Co-operation and Development . Guidance Document on the Validation and International Acceptance of New or Updated Test Methods for Hazard Assessment. Paris, OECD Publishing, 2005."},{"key":"2026070101300689000_35.181.250193.63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089675"},{"key":"2026070101300689000_35.181.250193.64","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00749-2015"},{"key":"2026070101300689000_35.181.250193.65","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-78"},{"key":"2026070101300689000_35.181.250193.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2019.01.036"},{"key":"2026070101300689000_35.181.250193.67","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00039412"},{"key":"2026070101300689000_35.181.250193.68","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01090-2016"},{"key":"2026070101300689000_35.181.250193.69","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2444"},{"key":"2026070101300689000_35.181.250193.70","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/S2213-2600(18)30236-4","article-title":"Tropism, replication competence, and innate immune responses of influenza virus: an analysis of human airway organoids and ex-vivo bronchus cultures","volume":"6","author":"Hui","year":"2018","journal-title":"Lancet Respir Med"},{"key":"2026070101300689000_35.181.250193.71","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1806308115"},{"key":"2026070101300689000_35.181.250193.72","doi-asserted-by":"crossref","first-page":"102254","DOI":"10.1016\/j.nantod.2024.102254","article-title":"Functioning human lung organoids model pulmonary tissue response from carbon nanomaterial exposures","volume":"56","author":"Issa","year":"2024","journal-title":"Nano Today"},{"key":"2026070101300689000_35.181.250193.73","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.gendis.2015.04.001","article-title":"Bmi-1: at the crossroads of physiological and pathological biology","volume":"2","author":"Bhattacharya","year":"2015","journal-title":"Genes Dis"},{"key":"2026070101300689000_35.181.250193.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.07.007"},{"key":"2026070101300689000_35.181.250193.75","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0479OC"},{"key":"2026070101300689000_35.181.250193.76","first-page":"e63882","article-title":"Generation of airway epithelial cell air\u2013liquid interface cultures from human pluripotent stem cells","volume":"184","author":"Berical","year":"2022","journal-title":"J Vis Exp"},{"key":"2026070101300689000_35.181.250193.77","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00950-2019"},{"key":"2026070101300689000_35.181.250193.78","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1164\/rccm.202406-1110RL","article-title":"Airway disease modeling with gene-edited human basal cell transplantation","volume":"211","author":"Berical","year":"2025","journal-title":"Am J Respir Crit Care Med"},{"key":"2026070101300689000_35.181.250193.79","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2016.1219832"},{"key":"2026070101300689000_35.181.250193.80","doi-asserted-by":"crossref","first-page":"4923","DOI":"10.3390\/ijms22094923","article-title":"Properties of non-aminoglycoside compounds used to stimulate translational readthrough of PTC mutations in primary ciliary dyskinesia","volume":"22","author":"Dabrowski","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2026070101300689000_35.181.250193.81","doi-asserted-by":"publisher","DOI":"10.1126\/science.adf5489"},{"key":"2026070101300689000_35.181.250193.82","doi-asserted-by":"crossref","first-page":"100798","DOI":"10.1016\/j.gim.2023.100798","article-title":"Pathogenic variants in CLXN encoding the outer dynein arm docking-associated calcium-binding protein calaxin cause primary ciliary dyskinesia","volume":"25","author":"Hjeij","year":"2023","journal-title":"Genet Med"},{"key":"2026070101300689000_35.181.250193.83","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1016\/j.gim.2022.07.019","article-title":"Biallelic DAW1 variants cause a motile ciliopathy characterized by laterality defects and subtle ciliary beating abnormalities","volume":"24","author":"Leslie","year":"2022","journal-title":"Genet Med"},{"key":"2026070101300689000_35.181.250193.84","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/s41591-019-0730-x","article-title":"A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance","volume":"26","author":"Chivukula","year":"2020","journal-title":"Nat Med"},{"key":"2026070101300689000_35.181.250193.85","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.3390\/ijms23031749","article-title":"PCD genes\u2013from patients to model organisms and back to humans","volume":"23","author":"Niziolek","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026070101300689000_35.181.250193.86","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.3390\/cells8121614","article-title":"Rare human diseases: model organisms in deciphering the molecular basis of primary ciliary dyskinesia","volume":"8","author":"Poprzeczko","year":"2019","journal-title":"Cells"},{"key":"2026070101300689000_35.181.250193.87","doi-asserted-by":"crossref","first-page":"102134","DOI":"10.1016\/j.pupt.2022.102134","article-title":"Inhaled delivery of a lipid nanoparticle encapsulated messenger RNA encoding a ciliary protein for the treatment of primary ciliary dyskinesia","volume":"75","author":"Woo","year":"2022","journal-title":"Pulm Pharmacol Ther"},{"key":"2026070101300689000_35.181.250193.88","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41419-022-05010-5","article-title":"Dnah9 mutant mice and organoid models recapitulate the clinical features of patients with PCD and provide an excellent platform for drug screening","volume":"13","author":"Zheng","year":"2022","journal-title":"Cell Death Dis"},{"key":"2026070101300689000_35.181.250193.89","doi-asserted-by":"publisher","DOI":"10.1172\/JCI175824"}],"container-title":["European Respiratory Review"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/16000617.0193-2025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:35:16Z","timestamp":1782894916000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/16000617.0193-2025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":89,"journal-issue":{"issue":"181","published-online":{"date-parts":[[2026,7,1]]},"published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1183\/16000617.0193-2025"],"URL":"https:\/\/doi.org\/10.1183\/16000617.0193-2025","relation":{},"ISSN":["0905-9180","1600-0617"],"issn-type":[{"value":"0905-9180","type":"print"},{"value":"1600-0617","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]}}}