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      Optimal Management of Allergic Fungal Rhinosinusitis

      review-article
      1 , 2
      Journal of Asthma and Allergy
      Dove
      fungal, allergic, rhinosinusitis, eosinophilic, IgE, immunotherapy

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          Abstract

          Introduction

          Allergic fungal rhinosinusitis (AFRS) is a chronic disorder with significant morbidity and a high recurrence rate needing long-term follow-up. Even after its first description many decades ago, there is still considerable uncertainty about the management of this condition.

          Description

          In this chapter, we breakdown the topic “Optimal management of allergic fungal rhinosinusitis” into sub-headings in order to discuss the latest research and available literature under each topic in great detail. Every attempt has been made to incorporate the highest level of evidence that was available at the time of writing.

          Summary

          Pre-operative diagnosis and further management prior to surgery is important. Steroids help in reducing inflammation and help improve the surgical field. Surgery remains the mainstay in the management of this condition along with long-term medical management. Oral steroids are reserved for acute flare-ups in the background of associated lung concerns. Oral and topical antifungal agents have no role in the control of the disease. Biological agents are being prescribed predominantly by respiratory physician colleagues, mainly for the control of the chest-related issues rather than for sinus disease. Immunotherapy as an adjunct with surgery is promising.

          Conclusion

          AFRS is a disease with many variables and a wide range of symptomatic presentation. It takes a keen clinician to identify the disease and subsequently manage the condition. Treatment involves long-term follow-up with early detection of recurrence or flare-ups. Any of the mentioned modalities of management may be employed to effectively control the condition, and treatment protocols will have to be tailor-made to suit each individual patient. Various medications and drugs such as Manuka honey, antimicrobial photodynamic therapy, hydrogen peroxide and betadine rinses appear to be promising. More robust studies need to be undertaken to ascertain their routine use in clinical practice.

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          Most cited references71

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          Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials

          Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) generally have a high symptom burden and poor health-related quality of life, often requiring recurring systemic corticosteroid use and repeated sinus surgery. Dupilumab is a fully human monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation, and has been approved for use in atopic dermatitis and asthma. In these two studies, we aimed to assess efficacy and safety of dupilumab in patients with CRSwNP despite previous treatment with systemic corticosteroids, surgery, or both.
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            Identification and quantification of methylglyoxal as the dominant antibacterial constituent of Manuka (Leptospermum scoparium) honeys from New Zealand.

            The 1,2-dicarbonyl compounds 3-deoxyglucosulose (3-DG), glyoxal (GO), and methylglyoxal (MGO) were measured as the corresponding quinoxalines after derivatization with orthophenylendiamine using RP-HPLC and UV-detection in commercially available honey samples. Whereas for most of the samples values for 3-DG, MGO, and GO were comparable to previously published data, for six samples of New Zealand Manuka (Leptospermum scoparium) honey very high amounts of MGO were found, ranging from 38 to 761 mg/kg, which is up to 100-fold higher compared to conventional honeys. MGO was unambigously identified as the corresponding quinoxaline via photodiodearry detection as well as by means of mass spectroscopy. Antibacterial activity of honey and solutions of 1,2-dicarbonyl towards Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were analyzed using an agar well diffusion assay. Minimum concentrations needed for inhibition of bacterial growth (minimum inhibitory concentration, MIC) of MGO were 1.1 mM for both types of bacteria. MIC for GO was 6.9 mM (E. coli) or 4.3 mM (S. aureus), respectively. 3-DG showed no inhibition in concentrations up to 60 mM. Whereas most of the honey samples investigated showed no inhibition in dilutions of 80% (v/v with water) or below, the samples of Manuka honey exhibited antibacterial activity when diluted to 15-30%, which corresponded to MGO concentrations of 1.1-1.8 mM. This clearly demonstrates that the pronounced antibacterial activity of New Zealand Manuka honey directly originates from MGO.
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              The unusual antibacterial activity of medical-grade Leptospermum honey: antibacterial spectrum, resistance and transcriptome analysis.

              There is an urgent need for new, effective agents in topical wound care, and selected honeys show potential in this regard. Using a medical-grade honey, eight species of problematic wound pathogens, including those with high levels of innate or acquired antibiotic resistance, were killed by 4.0-14.8% honey, which is a concentration that can be maintained in the wound environment. Resistance to honey could not be induced under conditions that rapidly induced resistance to antibiotics. Escherichia coli macroarrays were used to determine the response of bacterial cells to a sub-lethal dose of honey. The pattern of gene expression differed to that reported for other antimicrobial agents, indicating that honey acts in a unique and multifactorial way; 78 (2%) genes were upregulated and 46 (1%) genes were downregulated more than two-fold upon exposure to the medical-grade honey. Most of the upregulated genes clustered into distinct functional regulatory groups, with many involved in stress responses, and the majority of downregulated genes encoded for products involved in protein synthesis. Taken together, these data indicate that honey is an effective topical antimicrobial agent that could help reduce some of the current pressures that are promoting antibiotic resistance.
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                Author and article information

                Journal
                J Asthma Allergy
                J Asthma Allergy
                jaa
                jaa
                Journal of Asthma and Allergy
                Dove
                1178-6965
                11 September 2020
                2020
                : 13
                : 323-332
                Affiliations
                [1 ]Medikeri’s Superspeciality ENT Center , Bangalore, India
                [2 ]Rhinology & Skull Base Surgery, St. Paul’s Sinus Center , Vancouver, BC, Canada
                Author notes
                Correspondence: Amin Javer St. Paul’s Sinus Centre , 1081 Burrard St, VancouverBC V6Z 1Y6, CanadaTel +1- 604-806-9926 Email sinusdoc@me.com
                Author information
                http://orcid.org/0000-0002-7575-7791
                http://orcid.org/0000-0003-3116-6559
                Article
                217658
                10.2147/JAA.S217658
                7494399
                32982320
                e646d7f9-a812-482d-a997-cd8ab9f68f78
                © 2020 Medikeri and Javer.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 06 May 2020
                : 13 August 2020
                Page count
                Figures: 0, Tables: 1, References: 76, Pages: 10
                Categories
                Review

                Immunology
                fungal,allergic,rhinosinusitis,eosinophilic,ige,immunotherapy
                Immunology
                fungal, allergic, rhinosinusitis, eosinophilic, ige, immunotherapy

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