{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:09:52Z","timestamp":1787771392956,"version":"build-2784847793"},"reference-count":10,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000736","name":"University of East Anglia","doi-asserted-by":"publisher","award":["Proof of Concept fund"],"award-info":[{"award-number":["Proof of Concept fund"]}],"id":[{"id":"10.13039\/501100000736","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ENT UK","award":["Foundation Grant [000022]"],"award-info":[{"award-number":["Foundation Grant [000022]"]}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"crossref","award":["Academic Clinical Fellowship"],"award-info":[{"award-number":["Academic Clinical Fellowship"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["Strategic Programme Gut Microbes and Health [Grant numbers BB\/R012490\/1, BBS\/E\/F\/000PR10353, BBS\/E\/F\/000PR10355)"],"award-info":[{"award-number":["Strategic Programme Gut Microbes and Health [Grant numbers BB\/R012490\/1, BBS\/E\/F\/000PR10353, BBS\/E\/F\/000PR10355)"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Chronic Rhinosinusitis (CRS) affects approximately 1 in 10 UK adults and impacts quality of life quality of life significantly. Response to treatment may be driven by individual CRS endotypes and therefore work to delineate biomarker clusters that may separate responders from non-responders is needed. The ongoing MACRO three-arm parallel-group trial randomises adult CRS patients to endoscopic sinus surgery, macrolide therapy or placebo.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Aim<\/jats:title>\n<jats:p>This study aims to correlate CRS endotypes with clinical parameters from the ongoing MACRO trial, including olfactory function and outcomes in terms of response to treatment using core biomarkers sets.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Adult CRS patients enrolled into the MACRO trial will be recruited from participating UK otorhinolaryngology departments. Nasal tissue samples and swabs will be obtained in theatre or clinic from patients randomised to all three trial arms. Nasal tissue will be analysed with multiplex electrochemiluminescence for 32 cytokines including IL-5, IL-13, IgE and periostin. Bacterial swabs will be analysed using illumina miSeq 16S amplicon sequencing. Mean expression for each biomarker will be reported for treatment responder and non-responder groups. Correlation of biomarkers with MACRO trial outcome data such as endoscopic evaluation scores and quality-of-life improvement scores will be reported.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>Defining clear endotypes in CRS will contribute to refining patient pathways for the efficient use of clinical resources. This work may lay the groundwork for future studies to predict which patients might respond to medical or surgical therapy.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0289407","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T17:37:47Z","timestamp":1690997867000},"page":"e0289407","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring Endotypes in Chronic Rhinosinusitis (ExpRess): Protocol for a cohort study"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4320-0961","authenticated-orcid":true,"given":"Shyam Ajay","family":"Gokani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Jefferson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Gavrilovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falk","family":"Hildebrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Wileman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Hopkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-3236","authenticated-orcid":true,"given":"Carl","family":"Philpott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"issue":"1","key":"pone.0289407.ref001","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":"RE Gliklich","year":"1995","journal-title":"Otolaryngol Head Neck Surg"},{"issue":"7","key":"pone.0289407.ref002","article-title":"JAK2 Phosphorylation Signals and Their Associated Cytokines Involved in Chronic Rhinosinusitis with Nasal Polyps and Correlated with Disease Severity","volume":"11","author":"YT Lin","year":"2021","journal-title":"Biomolecules"},{"issue":"1","key":"pone.0289407.ref003","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1177\/0194599817737967","article-title":"Periostin as a Biomarker for Nasal Polyps in Chronic Rhinosinusitis","volume":"158","author":"AZ Maxfield","year":"2018","journal-title":"Otolaryngol Head Neck Surg"},{"key":"pone.0289407.ref004","first-page":"CD011994","article-title":"Systemic and topical antibiotics for chronic rhinosinusitis","volume":"4","author":"K Head","year":"2016","journal-title":"Cochrane Database Syst Rev"},{"issue":"3","key":"pone.0289407.ref005","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/alr.22249","article-title":"Patterns of olfactory dysfunction in chronic rhinosinusitis identified by hierarchical cluster analysis and machine learning algorithms","volume":"9","author":"JC Morse","year":"2019","journal-title":"Int Forum Allergy Rhinol"},{"issue":"1","key":"pone.0289407.ref006","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/s13063-019-3314-7","article-title":"Clarithromycin and endoscopic sinus surgery for adults with chronic rhinosinusitis with and without nasal polyps: study protocol for the MACRO randomised controlled trial","volume":"20","author":"C Philpott","year":"2019","journal-title":"Trials"},{"issue":"1","key":"pone.0289407.ref007","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s40168-022-01365-1","article-title":"LotuS2: an ultrafast and highly accurate tool for amplicon sequencing analysis","volume":"10","author":"E \u00d6zkurt","year":"2022","journal-title":"Microbiome"},{"issue":"1","key":"pone.0289407.ref008","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s40168-021-01012-1","article-title":"Much ado about nothing? Off-target amplification can lead to false-positive bacterial brain microbiome detection in healthy and Parkinson\u2019s disease individuals","volume":"9","author":"JR Bedarf","year":"2021","journal-title":"Microbiome"},{"issue":"2","key":"pone.0289407.ref009","doi-asserted-by":"crossref","first-page":"e055603","DOI":"10.1136\/bmjopen-2021-055603","article-title":"Observational retrospective study calculating health service costs of patients receiving surgery for chronic rhinosinusitis in England, using linked patient-level primary and secondary care electronic data","volume":"12","author":"CS Clarke","year":"2022","journal-title":"BMJ Open"},{"issue":"6","key":"pone.0289407.ref010","first-page":"420","article-title":"Antibiotic usage in chronic rhinosinusitis: analysis of national primary care electronic health records","volume":"57","author":"C Hopkins","year":"2019","journal-title":"Rhinology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0289407","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T17:38:14Z","timestamp":1690997894000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0289407"}},"subtitle":[],"editor":[{"given":"Sethu Thakachy","family":"Subha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,8,2]]},"references-count":10,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0289407","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,2]]}}}