Rhinorrhea and increased chloride secretion through the CFTR chloride channel-a systematic review

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Eisenhut, M
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2023
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Research Subject Categories::MEDICINE::Surgery::Otorhinolaryngology
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Abstract Purpose: Allergic and non-allergic rhinorrhea in the forms of acute or chronic rhinosinusitis can mean a watery nasal discharge that is disabling. Primary objective was to review the evidence supporting the hypothesis that rhinorrhea is due to increased chloride secretion through the CFTR chloride channel. Methods: The structure of the evidence review followed the EQUATOR Reporting Guidelines. Databases searched from inception to February 2022 included Pubmed, EMBASE and the Cochrane library using keywords "Rhinorrhea", "chloride", "chloride channel", "CFTR" and "randomized controlled trial". Quality assessment was according to the Oxford Centre for Evidence-based Medicine. Results: 49 articles were included. They included randomized controlled trials out of which subsets of data with the outcome of rhinorrhea on 6038 participants were analysed and in vitro and animal studies. The review revealed that drugs, which activate CFTR are associated with rhinorrhea. Viruses, which cause rhinorrhea like rhinovirus were found to activate CFTR. The chloride concentration in nasal fluid showed an increase in patients with viral upper respiratory tract infection. Increased hydrostatic tissue pressure, which is an activator of CFTR was observed in allergic upper airway inflammation. In this condition exhaled breath condensate chlorine concentration was found to be significantly increased. Drugs, which can reduce CFTR function including steroids, anti-histamines, sympathomimetic and anticholinergic drugs reduced rhinorrhea in randomized controlled trials. Conclusions: A model of CFTR activation-mediated rhinorrhea explains the effectiveness of anticholinergic, sympathomimetic, anti-histamine and steroid drugs in reducing rhinorrhea and opens up avenues for further improvement of treatment by already known specific CFTR inhibitors. Keywords: Chloride channel; Cystic fibrosis transmembrane conductance regulator; Hydrostatic interstitial tissue pressure; Rhinorrhea; Transudate; Vasodilatation. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. PubMed Disclaimer Similar articles Potentiators (specific therapies for class III and IV mutations) for cystic fibrosis. Skilton M, Krishan A, Patel S, Sinha IP, Southern KW. Cochrane Database Syst Rev. 2019 Jan 7;1(1):CD009841. doi: 10.1002/14651858.CD009841.pub3. PMID: 30616300 Free PMC article. Resveratrol ameliorates abnormalities of fluid and electrolyte secretion in a hypoxia-Induced model of acquired CFTR deficiency. Woodworth BA. Laryngoscope. 2015 Oct;125 Suppl 7(0 7):S1-S13. doi: 10.1002/lary.25335. Epub 2015 May 6. PMID: 25946147 Free PMC article. Potentiators (specific therapies for class III and IV mutations) for cystic fibrosis. Patel S, Sinha IP, Dwan K, Echevarria C, Schechter M, Southern KW. Cochrane Database Syst Rev. 2015 Mar 26;(3):CD009841. doi: 10.1002/14651858.CD009841.pub2. Update in: Cochrane Database Syst Rev. 2019 Jan 07;1:CD009841. doi: 10.1002/14651858.CD009841.pub3. PMID: 25811419 Review. Resveratrol enhances airway surface liquid depth in sinonasal epithelium by increasing cystic fibrosis transmembrane conductance regulator open probability. Zhang S, Blount AC, McNicholas CM, Skinner DF, Chestnut M, Kappes JC, Sorscher EJ, Woodworth BA. PLoS One. 2013 Nov 25;8(11):e81589. doi: 10.1371/journal.pone.0081589. eCollection 2013. PMID: 24282612 Free PMC article. CFTR chloride channel drug discovery--inhibitors as antidiarrheals and activators for therapy of cystic fibrosis. Verkman AS, Lukacs GL, Galietta LJ. Curr Pharm Des. 2006;12(18):2235-47. doi: 10.2174/138161206777585148. PMID: 16787252 Review. See all similar articles References Eccles R (2005) Understanding the symptoms of the common cold and influenza. Lancet Infect Dis 5(11):718–725 - PubMed - PMC - DOI Pfaar O, Raap U, Holz M, Hörmann K, Klimek L (2009) Pathophysiology of itching and sneezing in allergic rhinitis. Swiss Med Wkly 139(3–4):35–40 - PubMed Saint-Criq V, Gray MA (2017) Role of CFTR in epithelial physiology. Cell Mol Life Sci 74(1):93–115 - PubMed - DOI Vitzthum C, Clauss WG (1848) Fronius M (2015) Mechanosensitive activation of CFTR by increased cell volume and hydrostatic pressure but not shear stress. Biochim Biophys Acta 11 Pt A:2942–2951 Solymosi EA, Kaestle-Gembardt SM, Vadász I, Wang L, Neye N, Chupin CJ et al (2013) Chloride transport-driven alveolar fluid secretion is a major contributor to cardiogenic lung edema. Proc Natl Acad Sci U S A 110(25):E2308-23163 - PubMed - PMC - DOI Show all 49 references Publication types Systematic Review Review MeSH terms Animals Chloride Channels* Chlorides Cystic Fibrosis Transmembrane Conductance Regulator* Nasal Mucosa / metabolism Randomized Controlled Trials as Topic Sympathomimetics Substances Chloride Channels Cystic Fibrosis Transmembrane Conductance Regulator Chlorides Sympathomimetics Related information Gene Gene (GeneRIF) MedGen Protein (RefSeq) PubChem Compound (MeSH Keyword) LinkOut - more resources Full Text Sources Springer
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Eisenhut M. Rhinorrhea and increased chloride secretion through the CFTR chloride channel-a systematic review. Eur Arch Otorhinolaryngol. 2023 Oct;280(10):4309-4318. doi: 10.1007/s00405-023-08067-w. Epub 2023 Jun 20. PMID: 37338585.
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