{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:53:21Z","timestamp":1789977201107,"version":"4.0.1"},"reference-count":50,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2018,6,15]],"date-time":"2018-06-15T00:00:00Z","timestamp":1529020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"OptiNose US"},{"name":"OptiNose US"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jacionline.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Allergy and Clinical Immunology"],"published-print":{"date-parts":[[2019,1]]},"DOI":"10.1016\/j.jaci.2018.06.010","type":"journal-article","created":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T08:38:04Z","timestamp":1529397484000},"page":"126-134.e5","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":103,"title":["NAVIGATE II: Randomized, double-blind trial of the exhalation delivery system with fluticasone for nasal polyposis"],"prefix":"10.1016","volume":"143","author":[{"given":"Donald A.","family":"Leopold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Elkayam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Messina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette","family":"Kosik-Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per G.","family":"Djupesland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramy A.","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jaci.2018.06.010_bib1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.jaci.2011.08.004","article-title":"Chronic rhinosinusitis: epidemiology and medical management","volume":"128","author":"Hamilos","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.06.010_bib2","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/j.1398-9995.2011.02646.x","article-title":"Chronic rhinosinusitis in Europe\u2014an underestimated disease. A\u00a0GA2LEN study","volume":"66","author":"Hastan","year":"2011","journal-title":"Allergy"},{"key":"10.1016\/j.jaci.2018.06.010_bib3","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/all.13042","article-title":"Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample","volume":"72","author":"Hirsch","year":"2017","journal-title":"Allergy"},{"key":"10.1016\/j.jaci.2018.06.010_bib4","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1002\/lary.21847","article-title":"Health state utility values in patients undergoing endoscopic sinus surgery","volume":"121","author":"Soler","year":"2011","journal-title":"Laryngoscope"},{"key":"10.1016\/j.jaci.2018.06.010_bib5","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/S0194-59989570152-4","article-title":"The health impact of chronic sinusitis in patients seeking otolaryngologic care","volume":"113","author":"Gliklich","year":"1995","journal-title":"Otolaryngol Head Neck Surg"},{"key":"10.1016\/j.jaci.2018.06.010_bib6","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11882-015-0540-2","article-title":"The etiology and pathogenesis of chronic rhinosinusitis: a review of current hypotheses","volume":"15","author":"Lam","year":"2015","journal-title":"Curr Allergy Asthma Rep"},{"issue":"suppl\u00a01","key":"10.1016\/j.jaci.2018.06.010_bib7","first-page":"S22","article-title":"International consensus statement on allergy and rhinology: rhinosinusitis","volume":"6","author":"Orlandi","year":"2016","journal-title":"Int Forum Allergy Rhinol"},{"key":"10.1016\/j.jaci.2018.06.010_bib8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhino12.000","article-title":"European position paper on rhinosinusitis and nasal polyps 2012","volume":"50","author":"Fokkens","year":"2012","journal-title":"Rhinol Suppl"},{"key":"10.1016\/j.jaci.2018.06.010_bib9","doi-asserted-by":"crossref","first-page":"1503.e1","DOI":"10.1016\/j.jaci.2014.03.022","article-title":"Biology of nasal polyposis","volume":"133","author":"Stevens","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.06.010_bib10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.otc.2016.08.006","article-title":"Refractory chronic rhinosinusitis with nasal polyposis","volume":"50","author":"Hull","year":"2017","journal-title":"Otolaryngol Clin North Am"},{"key":"10.1016\/j.jaci.2018.06.010_bib11","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1097\/00005537-200404000-00022","article-title":"Origin of nasal polyps: an endoscopic autopsy study","volume":"114","author":"Larsen","year":"2004","journal-title":"Laryngoscope"},{"key":"10.1016\/j.jaci.2018.06.010_bib12","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.otc.2009.01.002","article-title":"Surgical management of polyps in the treatment of nasal airway obstruction","volume":"42","author":"Becker","year":"2009","journal-title":"Otolaryngol Clin North Am"},{"key":"10.1016\/j.jaci.2018.06.010_bib13","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/j.jaci.2010.02.020","article-title":"Oral steroids and doxycycline: two different approaches to treat nasal polyps","volume":"125","author":"Van Zele","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.06.010_bib14","doi-asserted-by":"crossref","first-page":"293","DOI":"10.7326\/0003-4819-154-5-201103010-00003","article-title":"Treatment of chronic rhinosinusitis with nasal polyposis with oral steroids followed by topical steroids: a randomized trial","volume":"154","author":"Vaidyanathan","year":"2011","journal-title":"Ann Intern Med"},{"key":"10.1016\/j.jaci.2018.06.010_bib15","doi-asserted-by":"crossref","first-page":"50","DOI":"10.2500\/ar.2016.7.0142","article-title":"Avascular necrosis after oral corticosteroids in otolaryngology: case report and review of the literature","volume":"7","author":"Kennedy","year":"2016","journal-title":"Allergy Rhinol (Providence)"},{"key":"10.1016\/j.jaci.2018.06.010_bib16","doi-asserted-by":"crossref","first-page":"j1415","DOI":"10.1136\/bmj.j1415","article-title":"Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study","volume":"357","author":"Waljee","year":"2017","journal-title":"BMJ"},{"key":"10.1016\/j.jaci.2018.06.010_bib17","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1177\/0194599810391852","article-title":"Cost burden of chronic rhinosinusitis: a claims-based study","volume":"144","author":"Bhattacharyya","year":"2011","journal-title":"Otolaryngol Head Neck Surg"},{"key":"10.1016\/j.jaci.2018.06.010_bib18","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/alr.21315","article-title":"The fate of chronic rhinosinusitis sufferers after maximal medical therapy","volume":"4","author":"Baguley","year":"2014","journal-title":"Int Forum Allergy Rhinol"},{"key":"10.1016\/j.jaci.2018.06.010_bib19","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1089\/jamp.2011.0924","article-title":"Nasal deposition and clearance in man: comparison of a bidirectional powder device and a traditional liquid spray pump","volume":"25","author":"Djupesland","year":"2012","journal-title":"J Aerosol Med Pulm Drug Deliv"},{"key":"10.1016\/j.jaci.2018.06.010_bib20","first-page":"69","article-title":"Videoendoscopic analysis of nasal steroid distribution","volume":"37","author":"Weber","year":"1999","journal-title":"Rhinology"},{"key":"10.1016\/j.jaci.2018.06.010_bib21","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/alr.21769","article-title":"Defining appropriateness criteria for endoscopic sinus surgery during management of uncomplicated adult chronic rhinosinusitis: a RAND\/UCLA appropriateness study","volume":"6","author":"Rudmik","year":"2016","journal-title":"Int Forum Allergy Rhinol"},{"key":"10.1016\/j.jaci.2018.06.010_bib22","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/lary.26391","article-title":"Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis","volume":"127","author":"DeConde","year":"2017","journal-title":"Laryngoscope"},{"key":"10.1016\/j.jaci.2018.06.010_bib23","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1002\/lary.20653","article-title":"Long-term outcomes from the English national comparative audit of surgery for nasal polyposis and chronic rhinosinusitis","volume":"119","author":"Hopkins","year":"2009","journal-title":"Laryngoscope"},{"key":"10.1016\/j.jaci.2018.06.010_bib24","series-title":"XHANCE [package insert]","year":"2017"},{"key":"10.1016\/j.jaci.2018.06.010_bib25","doi-asserted-by":"crossref","first-page":"419","DOI":"10.4193\/Rhin09.024","article-title":"Effective treatment of mild-to-moderate nasal polyposis with fluticasone delivered by a novel device","volume":"47","author":"Vlckova","year":"2009","journal-title":"Rhinology"},{"key":"10.1016\/j.jaci.2018.06.010_bib26","doi-asserted-by":"crossref","first-page":"292","DOI":"10.4193\/Rhino09.178","article-title":"Preliminary efficacy of fluticasone delivered by a novel device in recalcitrant chronic rhinosinusitis","volume":"48","author":"Hansen","year":"2010","journal-title":"Rhinology"},{"issue":"suppl","key":"10.1016\/j.jaci.2018.06.010_bib27","doi-asserted-by":"crossref","first-page":"AB253","DOI":"10.1016\/j.jaci.2016.12.815","article-title":"Intranasal fluticasone propionate delivered by exhalation delivery system (FLU-EDS) versus Flonase nasal spray and Flovent HFA: a randomized comparison of bioavailability","volume":"139","author":"Messina","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.06.010_bib28","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1365-2273.1995.tb00007.x","article-title":"Efficacy of topical corticosteroid powder for nasal polyps: a double-blind, placebo-controlled study of budesonide","volume":"20","author":"Lildholdt","year":"1995","journal-title":"Clin Otolaryngol Allied Sci"},{"key":"10.1016\/j.jaci.2018.06.010_bib29","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/j.1749-4486.2009.01975.x","article-title":"A pilot study of the SNOT 22 score in adults with no sinonasal disease","volume":"34","author":"Gillett","year":"2009","journal-title":"Clin Otolaryngol"},{"key":"10.1016\/j.jaci.2018.06.010_bib30","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/j.1749-4486.2009.01995.x","article-title":"Psychometric validity of the 22-item Sinonasal Outcome Test","volume":"34","author":"Hopkins","year":"2009","journal-title":"Clin Otolaryngol"},{"key":"10.1016\/j.jaci.2018.06.010_bib31","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jmpt.2003.11.003","article-title":"Assessing the clinical significance of change scores recorded on subjective outcome measures","volume":"27","author":"Hurst","year":"2004","journal-title":"J Manipulative Physiol Ther"},{"issue":"suppl","key":"10.1016\/j.jaci.2018.06.010_bib32","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1016\/j.jpain.2009.01.258","article-title":"Patient global impression of change scores within the context of a chronic pain rehabilitation program","volume":"10","author":"Ferguson","year":"2009","journal-title":"J Pain"},{"key":"10.1016\/j.jaci.2018.06.010_bib33","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.sleep.2004.07.006","article-title":"Psychometric properties of the Medical Outcomes Study Sleep measure","volume":"6","author":"Hays","year":"2005","journal-title":"Sleep Med"},{"key":"10.1016\/j.jaci.2018.06.010_bib34","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/00005650-199206000-00002","article-title":"The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection","volume":"30","author":"Ware","year":"1992","journal-title":"Med Care"},{"key":"10.1016\/j.jaci.2018.06.010_bib35","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1001\/archotol.1997.01900110025004","article-title":"The development of the Rhinosinusitis Disability Index","volume":"123","author":"Benninger","year":"1997","journal-title":"Arch Otolaryngol Head Neck Surg"},{"key":"10.1016\/j.jaci.2018.06.010_bib36","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1046\/j.1365-2222.2000.00932.x","article-title":"Efficacy and tolerability of fluticasone propionate nasal drops 400 microgram once daily compared with placebo for the treatment of bilateral polyposis in adults","volume":"30","author":"Keith","year":"2000","journal-title":"Clin Exp Allergy"},{"key":"10.1016\/j.jaci.2018.06.010_bib37","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1046\/j.1365-2222.2000.00695.x","article-title":"Dose-related efficacy and tolerability of fluticasone propionate nasal drops 400 microg once daily and twice daily in the treatment of bilateral nasal polyposis: a placebo-controlled randomized study in adult patients","volume":"30","author":"Penttila","year":"2000","journal-title":"Clin Exp Allergy"},{"key":"10.1016\/j.jaci.2018.06.010_bib38","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1016\/j.jaci.2005.07.027","article-title":"Efficacy and safety of mometasone furoate nasal spray in nasal polyposis","volume":"116","author":"Small","year":"2005","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.06.010_bib39","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1080\/00016480500452566","article-title":"The efficacy and\u00a0safety of once-daily mometasone furoate nasal spray in nasal polyposis: a\u00a0randomized, double-blind, placebo-controlled study","volume":"126","author":"Stj\u00e4rne","year":"2006","journal-title":"Acta Otolaryngol"},{"key":"10.1016\/j.jaci.2018.06.010_bib40","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1001\/archotol.132.2.179","article-title":"A\u00a0randomized controlled trial of mometasone furoate nasal spray for the treatment of nasal polyposis","volume":"132","author":"Stj\u00e4rne","year":"2006","journal-title":"Arch Otolaryngol Head Neck Surg"},{"key":"10.1016\/j.jaci.2018.06.010_bib41","doi-asserted-by":"crossref","first-page":"117","DOI":"10.2500\/ajra.2014.28.4026","article-title":"Nasal deposition of ciclesonide nasal aerosol and mometasone aqueous nasal spray in allergic rhinitis patients","volume":"28","author":"Emanuel","year":"2014","journal-title":"Am J Rhinol Allergy"},{"key":"10.1016\/j.jaci.2018.06.010_bib42","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1089\/jamp.2014.1180","article-title":"Nasal deposition of HFA-beclomethasone, aqueous fluticasone propionate and aqueous mometasone furoate in allergic rhinitis patients","volume":"28","author":"Leach","year":"2015","journal-title":"J Aerosol Med Pulm Drug Deliv"},{"key":"10.1016\/j.jaci.2018.06.010_bib43","first-page":"CD011996","article-title":"Intranasal steroids versus placebo or no intervention for chronic rhinosinusitis","author":"Chong","year":"2016","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1016\/j.jaci.2018.06.010_bib44","doi-asserted-by":"crossref","DOI":"10.1002\/alr.22141","article-title":"EXHANCE-12: 1-year study of the exhalation delivery system with fluticasone (EDS-FLU) in chronic rhinosinusitis","author":"Palmer","year":"2018","journal-title":"Int Forum Allergy Rhinol"},{"key":"10.1016\/j.jaci.2018.06.010_bib45","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1001\/jama.2015.19330","article-title":"Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial","volume":"315","author":"Bachert","year":"2016","journal-title":"JAMA"},{"key":"10.1016\/j.jaci.2018.06.010_bib46","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jaci.2011.07.056","article-title":"Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis","volume":"128","author":"Gevaert","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.06.010_bib47","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jaci.2012.07.047","article-title":"Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma","volume":"131","author":"Gevaert","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.06.010_bib48","unstructured":"Djupesland P, Messina J, Mahmoud R. Novel nasal exhalation delivery system (EDS) may produce beneficial activity independent of delivered drug in inflammatory nasal diseases and migraine via exhaled CO2 and mucosal pH changes. Presented at: 62nd Annual Meeting of the American Rhinologic Society; September 16-17, 2016; San Diego, Calif."},{"key":"10.1016\/j.jaci.2018.06.010_bib49","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jaip.2017.05.028","article-title":"Nasal carbon dioxide used as needed in the symptomatic treatment of seasonal allergic rhinitis","volume":"6","author":"Casale","year":"2018","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"suppl","key":"10.1016\/j.jaci.2018.06.010_bib50","doi-asserted-by":"crossref","first-page":"S136","DOI":"10.1016\/j.jaci.2008.12.503","article-title":"Carbon dioxide inhibits mast cell degranulation and histamine release","volume":"123","author":"Durham","year":"2009","journal-title":"J Allergy Clin Immunol"}],"container-title":["Journal of Allergy and Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091674918308637?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091674918308637?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T09:17:39Z","timestamp":1758791859000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0091674918308637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["S0091674918308637"],"URL":"https:\/\/doi.org\/10.1016\/j.jaci.2018.06.010","relation":{},"ISSN":["0091-6749"],"issn-type":[{"value":"0091-6749","type":"print"}],"subject":[],"published":{"date-parts":[[2019,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"NAVIGATE II: Randomized, double-blind trial of the exhalation delivery system with fluticasone for nasal polyposis","name":"articletitle","label":"Article Title"},{"value":"Journal of Allergy and Clinical Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jaci.2018.06.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.","name":"copyright","label":"Copyright"}]}}