{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T04:33:19Z","timestamp":1769315599827,"version":"3.49.0"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,2,22]],"date-time":"2020-02-22T00:00:00Z","timestamp":1582329600000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01DC013588"],"award-info":[{"award-number":["R01DC013588"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Ketotifen is a second\u2010generation noncompetitive H1\u2010antihistamine and mast\u2010cell stabilizer. It is commonly used to treat or prevent allergic conjunctivitis, asthma, chronic urticaria, anaphylaxis, mast\u2010cell, and other allergic\u2010type disorders. However, it has never been studied in aspirin\u2010exacerbated respiratory disease (AERD), an aggressive phenotype of chronic rhinosinusitis with nasal polyps, where the mast cell plays a prominent role its pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human sinonasal epithelial cells were grown at an air\u2010liquid interface (ALI). Ketotifen powder was dissolved in saline to make 4 test solutions at 1.04, 2.08, 10.4, and 20.8 \u00b5g\/mL. Control (saline) or ketotifen solution was added apically to ALI cultures from tissue of 5 unique patients, and ciliary beat frequency (CBF) changes were recorded. Lactate dehydrogenase was measured at 24 and 48 hours to estimate long\u2010term cellular toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Apical application of ketotifen at all concentrations was neither ciliotoxic nor ciliostimulatory, with no change in CBF over a period of 15 minutes after application. Cellular toxicity for all concentrations at 24 and 48 hours after application was &lt;3% and &lt;7%, respectively, that of lysed cultures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Topical application of ketotifen to an in vitro model of sinonasal epithelium is safe, as evaluated by CBF and lactate dehydrogenase. Ketotifen is neither ciliotoxic nor ciliostimulatory, and no long\u2010term cellular toxicity was observed. Ketotifen may have promise as a topical nasal rinse in the treatment of AERD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22461","type":"journal-article","created":{"date-parts":[[2020,2,22]],"date-time":"2020-02-22T12:18:58Z","timestamp":1582373938000},"page":"265-270","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["In vitro safety of ketotifen as a topical nasal rinse"],"prefix":"10.1002","volume":"10","author":[{"given":"Vasiliki","family":"Triantafillou","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery University of Pennsylvania  Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4426-2718","authenticated-orcid":false,"given":"Ivy W.","family":"Maina","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery University of Pennsylvania  Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1365-9130","authenticated-orcid":false,"given":"Neil N.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery University of Pennsylvania  Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles C. L.","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery University of Pennsylvania  Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Papagiannopoulos","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery University of Pennsylvania  Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Kohanski","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery University of Pennsylvania  Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery University of Pennsylvania  Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James N.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery University of Pennsylvania  Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nithin D.","family":"Adappa","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery University of Pennsylvania  Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noam A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery University of Pennsylvania  Philadelphia PA"},{"name":"Corporal Michael J. Crescenz Veterans Administration Medical Center  Philadelphia PA"},{"name":"Monell Chemical Senses Center  Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John V.","family":"Bosso","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery University of Pennsylvania  Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,22]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2012.33.3541"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2016.06.004"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.08.020"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21202"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22036"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599816640723"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1325618"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2003-0071OC"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.09.025"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(91)90238-J"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000438605"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/108076803762718132"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02074654"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12672"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1976.tb08614.x"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000473"},{"issue":"6","key":"e_1_2_5_18_1","first-page":"CD009566","article-title":"Topical antihistamines and mast cell stabilisers for treating seasonal and perennial allergic conjunctivitis","author":"Castillo M","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2013.10.003"},{"key":"e_1_2_5_20_1","first-page":"1","article-title":"Efficacy and tolerability of ketotifen in the treatment of seasonal allergic conjunctivitis: comparison between ketotifen 0.025% and 0.05% eye drops","author":"Leonardi A","year":"2018","journal-title":"Ocul Immunol Inflamm"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.32.6.684"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)62951-1"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199040030-00006"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2018.1560478"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2014.28.4092"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.20018"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2009.23.3398"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21953"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2007.21.3029"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64240"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(97)00059-8"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2818.2003.01209.x"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-202184"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2003.00765.x"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000114531"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/08958370802555898"},{"key":"e_1_2_5_37_1","first-page":"915","article-title":"The role of the respiratory mucosa in health and disease","volume":"50","author":"Hilding AC","year":"1967","journal-title":"Minn Med"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2006.20.2904"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otc.2012.06.006"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21966"},{"key":"e_1_2_5_41_1","volume-title":"Nasal Absorption Enhancement: Relevance to Nasal Drug Delivery. Drug Absorption Enhancement, Concept, Possibilities, Limitations and Trends","author":"Verhoef JC","year":"1994"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1177\/00034894061150S904"},{"issue":"3","key":"e_1_2_5_43_1","first-page":"127","article-title":"The effects of nasal drops and their additives on human nasal mucociliary clearance","volume":"20","author":"Donk HJ","year":"1982","journal-title":"Rhinology"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/00020840-200502000-00005"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2003.07.005"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.64.4.546"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(97)00060-4"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-3659(02)00363-2"}],"container-title":["International Forum of Allergy &amp; Rhinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Falr.22461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alr.22461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alr.22461","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alr.22461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T18:38:50Z","timestamp":1694025530000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/alr.22461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2]]},"references-count":47,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["10.1002\/alr.22461"],"URL":"https:\/\/doi.org\/10.1002\/alr.22461","archive":["Portico"],"relation":{},"ISSN":["2042-6976","2042-6984"],"issn-type":[{"value":"2042-6976","type":"print"},{"value":"2042-6984","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2]]},"assertion":[{"value":"2019-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}