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Since the onset of the COVID-19 pandemic, incidences of loss of smell and taste have increased substantially and, whereas many of these recover within a few weeks, in about 5% of all cases of COVID-19, olfactory dysfunction persists for many months or years. During the recovery process, many experience parosmia, which is a condition in which everyday aromas become distorted and usually evoke a sense of disgust. Previous work has shown that a set of highly potent odorants in coffee can trigger these distortions. They fall into clusters of thiols, disulphides and pyrazines, and many (but not all) of these compounds are products of the Maillard reaction. In this work, we investigated another Maillard system and asked whether any of the Maillard-derived trigger molecules from coffee were also reported to be triggers in grilled chicken. GC-olfactometry was carried out by four participants and one non-parosmic expert to assess all the odour-active compounds in grilled chicken. Results revealed that indeed six triggers were found in common with coffee – all derived from the Maillard reaction. We postulate that the same few compounds may be responsible for distortions in many roasted, grilled and fried foods, and recommend that those suffering from parosmia avoid highly cooked foods.

Harsha H Kariyawasam,1– 3 Louisa K James,4 Simon B Gane2,3 1Department of Specialist Allergy and Clinical Immunology, Royal National ENT Hospital, University College London Hospitals NHS Foundation Trust, London, UK; 2Department of Rhinology, Royal National ENT Hospital, University College London Hospitals NHS Foundation Trust, London, UK; 3UCL Ear Institute , University College London, London, UK; 4Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UKCorrespondence: Harsha H Kariyawasam Email harsha.kariyawasam@nhs.netAbstract: In September 2019, The Lancet published details of two large Phase III double-blind placebo-controlled studies (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52) confirming the clinical efficacy of the biologic dupilumab in simultaneously blocking both IL-4/IL-13 signalling in chronic rhinosinusitis with nasal polyps (CRSwNP). The studies demonstrated that dupilumab (Dupixent®, Sanofi and Regeneron) 300mg subcutaneously administered was clinically effective when added for patients with moderate to severe CRSwNP already maintained on the standard intranasal steroid mometasone furoate. Duration of treatment ranged from injections either 2 weekly for 24 weeks (SINUS-24) or every 2 weeks for 52 weeks or finally every 2 weeks for 24 weeks stepping down thereafter to every 4 weeks for a further 28 weeks (SINUS-52). Rapid improvements in all important parameters of disease burden were seen with such improvement maintained even where the frequency of injections was decreased. In patients with co-existent asthma, lung function and asthma control scores improved. This is consistent with the one airway hypothesis of shared T2 inflammatory programmes driving both disease syndromes. The studies formed the basis for FDA registration and clinical launch in the US, and EMA approval in Europe. Dupilumab presents a significant new treatment option in an area of urgent unmet therapeutic need in CRSwNP. Should dupilumab prove to be as effective in the real-life clinical environment as it has been in the studies, then a paradigm shift from sinonasal surgery to medical treatment of CRSwNP may need to occur in the ENT community. Questions in relation to best patient selection, combined upper and lower airway therapeutic pathways, long-term safety along with health economics and cost constraints ought now to be addressed.Keywords: inflammation, sinusitis, monoclonal antibody, therapeutics, biologic

Background Aspirin – exacerbated respiratory disease can prove difficult to control. Oral aspirin desensitization is effective, but has adverse effects and may not be cardio-protective at the high doses needed.Objective To examine the effectiveness of aspirin administered in lower doses via the nose.Methods An audit of 121 patients with aspirin exacerbated respiratory disease (AERD), 105 of whom were treated with intranasal lysine aspirin in gradually increasing doses following positive lysine aspirin challenge.Results Treatment was associated with subjective symptomatic improvement or stabilization in 60 of 78 patients at 3 months and 19 of 27 at 12 months. Nasal inspiratory peak flow, olfaction, exhaled and nasal nitric oxide levels were significantly improved (p < 0.05 for all). Patients with positive skin prick tests and those with later onset (>40 years) AERD improved more than non-atopics and those with early onset AERD.Asthma outcomes over 1 year were assessed by questionnaire in 22 patients on lysine aspirin and in 20 who were positive on challenge but who either refused treatment or took it only briefly (less than or equal to 3 months). There was a significant decrease in emergency visits (p = 0.0182), hospitalization (p = 0.0074) and oral steroid use (p = 0.004) in those on nasal lysine aspirin for a year.Gastrointestinal side effects occurred in 3.8%, lower than those reported for oral aspirin therapy. Conclusions and Clinical Relevance This form of therapy might reduce the need for expensive monoclonal antibodies in AERD patients. Keywords: Aspirin exacerbated respiratory disease, Lysine aspirin, Nasal polyposis, Late onset asthma

In persistent chronic rhinosinusitis (CRS), conventional treatment is often insufficient. Long-term, low-dose administration of macrolides has been suggested as a treatment option. The MACS (Macrolides in chronic rhinosinusitis) study is a randomized placebo- controlled trial evaluating the efficacy of azithromycin (AZM) in CRS. We describe a group of patients with recalcitrant CRS with and without nasal polyps unresponsive to optimal medical and (in 92% also) surgical treatment. Patients were treated with AZM or placebo. AZM was given for 3 days at 500 mg during the first week, followed by 500 mg per week for the next 11 weeks. Patients were monitored until 3 months post-therapy. The assessments included Sino-Nasal Outcome Test-22 (SNOT-22), a Patient Response Rating Scale, Visual Analogue Scale (VAS), Short Form-36 (SF-36), rigid nasal endoscopy, peak nasal inspiratory flow (PNIF), Sniffin' Sticks smell tests and endoscopically guided middle meatus cultures. Sixty patients with a median age of 49 years were included. Fifty per cent had asthma and 58% had undergone revision sinus surgery. In the SNOT-22, Patient Response Rating Scale, VAS scores and SF-36, no significant difference between the AZM and the placebo groups was demonstrated. Nasal endoscopic findings, PNIF results, smell tests and microbiology showed no relevant significant differences between the groups either. At the investigated dose of AZM over 3 months, no significant benefit was found over placebo. Possible reasons could be disease severity in the investigated group, under-dosage of AZM and under-powering of the study. Therefore, more research is urgently required.