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Showing papers in "Rhinology in 2020"


Journal ArticleDOI
TL;DR: The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012 and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery.
Abstract: The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

2,853 citations


Journal ArticleDOI
TL;DR: There is an important fourth presenting syndrome, namely isolated sudden onset anosmia (ISOA), which should be considered highly suspicious for SARS-CoV-2, and the international community is urged to consider this presentation in current management advice.
Abstract: Background The amelioration of the current COVID pandemic relies on swift and efficient case finding as well as stringent social distancing measures. Current advice suggests that fever or new onset dry cough are the commonest presenting complaints. Methodology We present a case report and case series as well as other evidence that there is an important fourth presenting syndrome, namely isolated sudden onset anosmia (ISOA), which should be considered highly suspicious for SARS-CoV-2. Results A patient presenting with ISOA who went on to test positive for infection with COVID-19 and did not develop any further symptoms as well as a case series of similar patients although limited by the lack of reliable testing at the moment. Conclusions We posit the existence of a fourth common syndrome of COVID-19 infection: isolated sudden onset anosmia (ISOA) and urge the international community to consider this presentation in current management advice.

338 citations


Journal ArticleDOI
TL;DR: Anosmia is reported in conjunction with well-reported symptoms of coronas virus, but 1 in 6 patients with recent onset anosmia report this as an isolated symptom, which might help identify otherwise asymptomatic carriers of disease and trigger targeted testing.
Abstract: Introduction Anosmia has not been formally recognised as a symptom of COVID-19 infection. Growing anecdotal evidence suggests increasing incidence of cases of anosmia during the current pandemic, suggesting that COVID-19 may cause olfactory dysfunction. The objective was to characterise patients reporting new onset anosmia during the COVID-19 pandemic METHODOLOGY: Design: Survey of 2428 patients reporting new onset anosmia during the COVID-19 pandemic. Setting Volunteer sample of patients seeking medical advice of recent onset self-diagnosed loss of sense of smell RESULTS: 2428 surveys were completed within 7 days; 64% respondents were under 40. The majority of respondents reported onset of their anosmia in the last week. Of the cohort, 17% did not report any other symptom thought to be associated with COVID-19. In patients who reported other symptoms, 51% reported either cough or fever and therefore met current guidelines for self-isolation. Conclusions Anosmia is reported in conjunction with well-reported symptoms of coronas virus, but 1 in 6 patients with recent onset anosmia report this as an isolated symptom. This might help identify otherwise asymptomatic carriers of disease and trigger targeted testing. Further study with COVID-19 testing is required to identify the proportion of patients in whom new onset anosmia can be attributed to COVID-19.

256 citations


Journal ArticleDOI
TL;DR: The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS.
Abstract: Together with this issue of Rhinology the new European Position Paper on Rhinosinusitis and Nasal Polyps will see the light. The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 like paediatric CRS, sinus surgery, exacerbations of CRS and the prevention of CRS. EPOS2020 also involved new stakeholders, like neurologists, immunologists, pharmacists and patients and address new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestion for future research in this area and offer updated guidance for definitions and outcome measurements in research in different settings.

252 citations


Journal ArticleDOI
TL;DR: The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012 and offers updated guidance for definitions and outcome measurements in research in different settings.
Abstract: The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012(1-3). The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings.

190 citations


Journal ArticleDOI
TL;DR: Identifying the early symptoms of COVID-19 is of particular importance and is a health system priority because of the lack of current effective treatment and vaccine for the disease.
Abstract: According to WHO recommendations, everyone must protect themselves against Coronavirus disease 2019 (COVID-19), which will also protect others. Due to the lack of current effective treatment and vaccine for COVID-19, screening, rapid diagnosis and isolation of the patients are essential (1, 2). Therefore, identifying the early symptoms of COVID-19 is of particular importance and is a health system priority. Early studies from COVID-19 outbreak in China have illustrated several non-specific signs and symptoms in infected patients, including fever, dry cough, dyspnea, myalgia, fatigue, lymphopenia, and radiographic evidence of pneumonia (3, 4). Recently, a probability of association between COVID-19 and altered olfactory function has been reported in South Korea, Iran, Italy, France, UK and the United States (5-8). However, to our knowledge, the definite association between COVID-19 and anosmia has not been published.

118 citations


Journal ArticleDOI
TL;DR: This meta-analysis recommends self-isolation and testing, where possible, for patients complaining smell or taste impairment during COVID-19 pandemic in order to prevent spread of disease and proposes the inclusion of loss of smell and taste as recognized symptoms of SARS-CoV-2 in the World Health Organization and other relevant regulatory body's lists.
Abstract: Background Emerging reports suggest that new onset of smell or taste loss are potential early clinical markers of SARS-CoV-2 infection, but it remains unclear as to what extent. Therefore, the purpose of this study is to systematically assess the prevalence of self-reported altered sense of smell or taste in patients with confirmed SARS-CoV-2 infection, overcoming the limitations of individual studies by meta-analysis of pooled data. Methods The databases Medline, Embase, Web of Science, Scopus and MedRxiv's set were searched from inception to the 4th May 2020. This study was conducted following the PRISMA checklist. Results 18 studies met the eligibility criteria out of the 171 initially screened citations. The overall prevalence of alteration of the sense of smell or taste was 47% , but estimates were 31% and 67% in severe and mild-to-moderate symptomatic patients, respec- tively. The loss of smell and taste preceded other symptoms in 20% of cases and it was concomitant in 28%. Conclusions Based on this meta-analysis, we recommend self-isolation and testing, where possible, for patients complaining smell or taste impairment during COVID-19 pandemic in order to prevent spread of disease and propose the inclusion of loss of smell and taste as recognized symptoms of SARS-CoV-2 in the World Health Organization and other relevant regulatory body's lists.

96 citations


Journal ArticleDOI
TL;DR: While many patients recover quickly, some experience long-term deficits with no self-reported improvement at 6 months, and there is a high prevalence of parosmia even in those who report at least some recovery of olfactory recovery.
Abstract: INTRODUCTION: Loss of smell and taste is now recognised as amongst the most common symptoms of COVID-19 and the best predictor of COVID-19 positivity. Long term outcomes are unknown. This study aims to investigate recovery of loss of smell and the prevalence of parosmia. METHODOLOGY: 6-month follow-up of respondents to an online surgery who self-reported loss of smell at the onset of the CO- VID-19 pandemic in the UK. Information of additional symptoms, recovery of loss of smell and the development of parosmia was collected. RESULTS: 44% of respondents reported at least one other ongoing symptom at 6 months, of which fatigue (n=106) was the most prevalent. There was a significant improvement in self-rating of severity of olfactory loss where 177 patients stated they had a normal smell of smell while 12 patients reported complete loss of smell. The prevalence of parosmia is 43.1% with median interval of 2.5 months (range 0-6) from the onset of loss of smell. CONCLUSIONS: While many patients recover quickly, some experience long-term deficits with no self-reported improvement at 6 months. Furthermore, there is a high prevalence of parosmia even in those who report at least some recovery of olfactory func- tion. Longer term evaluation of recovery is required.

95 citations


Journal ArticleDOI
TL;DR: The results suggest that mechanisms of COVID-19 related olfactory dysfunction are different from those seen in an AC and may reflect, at least to some extent, a specific involvement at the level of central nervous system in some CO VID-19 patients.
Abstract: Anosmia constitutes a prominent symptom of COVID-19 However, anosmia is also a common symptom of acute colds of various origins In contrast to an acute cold, it appears from several questionnaire-based studies that in the context of COVID-19 infection, anosmia is the main rhinological symptom and is usually not associated with other rhinological symptoms such as rhinorrhoea or nasal obstruction Until now, no study has directly compared smell and taste function between COVID-19 patients and patients with other causes of upper respiratory tract infection (URTI) using valid and reliable psychophysical tests In this study, we aimed to objectively assess and compare olfactory and gustatory functions in 10 COVID-19 patients (PCR diagnosed, assessed on average 2 weeks after infection), 10 acute cold (AC) patients (assessed before the COVID-19 outbreak) and 10 healthy controls, matched for age and sex Smell performance was assessed using the extended "Sniffin' Sticks" test battery (4), while taste function was assessed using "taste strips" (5) Receiver Operating Characteristic (ROC) curves were built to probe olfactory and gustatory scores in terms of their discrimination between COVID-19 and AC patients Our results suggest that mechanisms of COVID-19 related olfactory dysfunction are different from those seen in an AC and may reflect, at least to some extent, a specific involvement at the level of central nervous system in some COVID-19 patients In the future, studies to assess the prevalence of persistent anosmia and neuroanatomical changes on MRI correlated to chemosensory function, will be useful to understand these mechanisms

85 citations


Journal ArticleDOI
TL;DR: The mix of drugs including steroids could represent a useful specific therapy to reduce the prevalence of this long-term morbidity in patients with COVID-19 related anosmia or severe hyposmia.
Abstract: BACKGROUND: The growing number of COVID-19 patients with long-lasting olfactory disorders makes it necessary to identify ef- fective treatments that enhance the spontaneous recovery of olfactory function. METHODS: Multicentre randomised case-control study that involved 18 patients with COVID-19 related anosmia or severe hyposmia for more than 30 days. Nine patients were prescribed systemic prednisone and nasal irrigation with betamethasone, ambroxol and rinazine for 15 days. The other 9, untreated, patients were used as controls. The olfactory function was evaluated with CCCRC test at 20 and 40 days from the first evaluation. RESULTS: In the control group, a median olfactory score of 20 (IQR 30) was detected at baseline. At the 20-day control there was no significant improvement in olfactory function. The improvement in olfactory performance became significant at the 40-day follow-up compared to baseline scores [60 (IQR 60) versus 20 (IQR 30)]. In the treatment group, patients had a mean olfactory score of 10 (IQR 15) at initial control. At the 20-day control, a significant im-provement in the olfactory scores, compared to the baseline, was detected [70 (IQR 40) versus 10 (IQR 15)]. Olfactory function further improved at 40 days [median score 90 (IQR 50)]. Patients in the treatment group reported significantly higher improvements of the olfactory scores than the controls at both the 20-day [40 (IQR 45) versus 10 (IQR 15)] and 40-day [60 (IQR 40) versus 30 (IQR 25)] evaluations. CONCLUSIONS: Based on the results of this study, the mix of drugs including steroids could represent a useful specific therapy to reduce the prevalence of this long-term morbidity.

71 citations


Journal ArticleDOI
TL;DR: Olfactory (± gustatory) dysfunction is indicative of COVID-19 infection and thus has important implications in the context of healthcare workers, or key workers in general, who work in close contact with others if not recognised as suffering from COVID, which leads to a potentially higher likelihood of spreading the virus.
Abstract: BACKGROUND: Healthcare workers are at the forefront of the ongoing COVID-19 pandemic and are at high risk for both the contraction and subsequent spread of virus. Understanding the role of anosmia as an early symptom of infection may improve monitoring and management of SARS-CoV2 infection. METHODOLOGY: We conducted a systematic review of the literature of SARS-CoV2 infection/COVID-19 and anosmia to help inform management of anosmia in healthcare works. We report a case series of healthcare workers, who presented with a loss of sense of smell secondary to COVID-19 infection to demonstrate management principles. RT-PCR was used to confirm COVID-19 positivity and psychophysical testing of olfaction was performed using the British version of the University of Pennsylvania Smell Identification Test, UPSIT. RESULTS: The systematic literature search returned 31 articles eligible for inclusion in the study and informed our recommendations for clinical assessment and management. All three healthcare professionals who presented with loss of sense of smell subsequently tested positive for SARS-CoV-2. Psychophysical testing of olfaction using the UPSIT confirmed mild and moderate microsmia in two, respectively, and normosmia at day 17 in one. CONCLUSIONS: Olfactory (± gustatory) dysfunction is indicative of COVID-19 infection and thus has important implications in the context of healthcare workers, or key workers in general, who work in close contact with others if not recognised as suffering from COVID. This leads to a potentially higher likelihood of spreading the virus. In conjunction with our literature review these findings have helped with creating recommendations on the assessment and management of olfactory dysfunction during the ongoing COVID-19 pandemic, both for healthcare workers and patients.

Journal ArticleDOI
TL;DR: Recommendations and relevant information are provided for rhinologists, based on the limited amount of (anecdotal) data, to guarantee high-quality patient care and adequate levels of infection prevention in the rhinology clinic.
Abstract: On March 11th 2020, the World Health Organization (WHO) declared COVID-19 pandemic, with subsequent profound impact on the entire health care system. During the COVID-19 outbreak, activities in the rhinology outpatient clinic and operation rooms are limited to emergency care only. Health care practitioners are faced with the need to perform rhinological and skull base emergency procedures in patients with a positive or unknown COVID-19 status. This article aims to provide recommendations and relevant information for rhinologists, based on the limited amount of (anecdotal) data, to guarantee high-quality patient care and adequate levels of infection prevention in the rhinology clinic.

Journal ArticleDOI
TL;DR: Although RESS alone appears to be the best option for patients with recurrent CRSwNP with asthma, these findings need to be confirmed in further studies involving more patients, longer follow-up duration and stricter standardized medication use especially the adequate steroid irrigations.
Abstract: Background Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma have poorer outcomes after functional endoscopic sinus surgery (FESS) and higher recurrence rate. The aim of present study was to investigate the long-term clinical outcomes of extended surgical strategies for patients with recurrent CRSwNP and asthma. Methods Eighty-one patients with CRSwNP and asthma were enrolled in this 5-year prospective study. They were randomly assigned to undergo FESS, radical endoscopic sinus surgery (RESS), or RESS+Draf 3 surgery. Disease severity and clinical outcomes were evaluated using symptoms scoring, endoscopic scoring system, computed tomography staging system, sinus-specific quality of life scores, tissue and peripheral blood eosinophil percentage, and pulmonary function tests. Baseline, 1-year, 3-year, and 5-year follow-up data were compared among the groups. Results RESS and RESS+Draf 3 strategies yielded better short-term (1 year) outcomes than did FESS. FESS had a higher short-term recurrence rate, although recurrence rates were similarly high (95.6 - 96.1%) in all the groups at 5 years postoperatively. RESS and RESS+Draf 3 yielded a lower long-term revision surgery rate and a longer time to recurrence post-surgery than FESS, which was negatively correlated with tissue and peripheral blood eosinophil percentage. Conclusions CRSwNP with asthma is a systemic disease that inevitably recurs. Radical surgery prolongs recurrence time and improves olfaction, rhinorrhea, and quality of life in the short-term. Combining Draf 3 with RESS did not yield better clinical outcomes than RESS alone; thus, although RESS alone appears to be the best option, these findings need to be confirmed in further studies involving more patients, longer follow-up duration and stricter standardized medication use especially the adequate steroid irrigations.

Journal ArticleDOI
TL;DR: Adult patients with CRSwNP have higher indirect costs than direct costs and this forms a substantial burden to society.
Abstract: Background European direct and indirect cost data is missing for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). This study was aimed to establish the economic burden of CRSwNP based on a Dutch cohort of patients. Methods A cross-sectional study was performed in adult patients with CRSwNP (N=115) to calculate mean annual direct medical costs and indirect costs per patient with CRSwNP. Outpatient visits, general practitioner visits, first aid visits, hospitalisation and patient travel expenses were measured with the iMTA medical consumption questionnaire. Missed workdays (absenteeism) and decreased productivity during paid work (presenteeism) or during daily life were measured with the and the iMTA productivity cost questionnaire. Results Total direct costs were €1501 per patient/year, primarily due to outpatient department visits and hospitalisation. Indirect costs were €5659 per patient/year, with productivity losses as major cost expense. Conclusion Adult patients with CRSwNP have higher indirect costs than direct costs and this forms a substantial burden to society. Total annual costs of patients with CRSwNP are estimated to be 1,9 billion/year in the Netherlands.

Journal ArticleDOI
TL;DR: This study showed that CRS has a significant wider economic burden beyond the immediate direct healthcare costs, and emphasises the need for effective treatments for these patients to reduce the disease impact.
Abstract: Introduction Chronic rhinosinusitis (CRS) is highly prevalent, affecting 11% of the population. Studies evaluating the socio-economic impact of CRS are mostly limited to the US population. Currently there is no study that has evaluated the socio-economic costs of CRS in the UK. Methods A case-control study of patients with CRS and healthy controls was conducted to investigate the wider socio-economic impact of the disease. Data on demographic and socioeconomic characteristics, out-of-pocket expenditure (OOPE), health resource utilisation, productivity losses and health-related quality of life (HRQoL) via the EQ-5D and SNOT-22 instruments, were collected from questionnaires. Results A total of 139 CRS participants and 67 control participants completed the questionnaires. The average total OOPE per patient extrapolated to a 12-month period was £304.84. Other important findings include significantly higher reported primary care interactions (4.14 vs. 1.16) as well as secondary care interactions (2.61 vs 0.4) in CRS group as compared to controls over three-months. The average total missed workdays was estimated to be 18.7 per patient per year. The estimated incremental healthcare cost of CRS per year is £16.8 billion or £2.8 billion per million inhabitants. Factors predictive of a higher OOPE include higher household occupancy and income and these accounted for only 9.7% of the total variance in total OOPEs. Other socioeconomic, demographic and HRQoL variables were not found to be predictive factors of OOPE. Conclusions This study showed that CRS has a significant wider economic burden beyond the immediate direct healthcare costs. CRS participants had a high level of healthcare service use, OOPE and productivity loss. Results from this study will add to the existing limited data both for the UK and abroad and emphasises the need for effective treatments for these patients to reduce the disease impact.

Journal ArticleDOI
TL;DR: Self-reported loss of smell and taste have greater value in controlling disease transmis- sion than psychophysical testing, which is not widely available outside of highly specialized clinics.
Abstract: There is mounting evidence that a new onset of altered sense of smell or taste is related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In order to allow patients to recognize symptoms indicative of SARS-CoV-2 infection and self-isolate at the earliest opportunity, self-reported loss of smell and taste have greater value in controlling disease transmis- sion than psychophysical testing, which is not widely available outside of highly specialized clinics.

Journal ArticleDOI
TL;DR: It is now clear that olfactory dysfunction may also be present in these patients as the only or prevalent manifestation of Covid-19, and the clinical manifestations range from asymptomatic carrier status to severe pneumonia.
Abstract: Since December 2019, a novel coronavirus SARS-CoV-2 (Covid-19) outbreak emerged in China and spread rapidly in several countries. As of April 5, 2020, 1.218.474 cases were confirmed with 65.884 deaths worldwide (1). The clinical manifestations of Covid-19 range from asymptomatic carrier status to severe pneumonia. In a study of 7,736 Covid-19 patients in China, of all the clinical symptoms, hyposmia was not reported in any patient(2). Anyway, it is now clear that olfactory dysfunction may also be present in these patients(3) as the only or prevalent manifestation(4).

Journal ArticleDOI
TL;DR: The Hopkins team published the first case report and case series as well as other evidence that isolated sudden onset anosmia (ISOA), should be considered highly suspicious for SARS-CoV-2(1).
Abstract: Since the outbreak of the pandemic, anecdotal observations have been accumulating rapidly that sudden anosmia and dysgeusia are peculiar symptoms associated with the COVID-19 infection. Prof C. Hopkins, as President of British Rhinological Society, published a letter describing "the loss of sense of smell as a marker of COVID-19 infection" and proposed that adults presenting with anosmia but no other symptoms should self-isolate for seven days. The Hopkins team published the first case report and case series as well as other evidence that isolated sudden onset anosmia (ISOA), should be considered highly suspicious for SARS-CoV-2(1). Subsequently, a larger series of 2428 patients presenting with new onset anosmia during the COVID-19 pandemic has been reported, of whom 16% report loss of sense of smell as an isolated symptom. Only 51% reported the recognized symptoms of cough or fever. A major limitation of this series however, was a lack of access to testing to confirm the COVID-19 status of the patients(2); in the 80 who had been tested 74% were positive. In the same way, the American Academy of Otolaryngology-head and neck surgery (AA0-HNS) proposed "that anosmia could be added to the list of screening tools for possible COVID-19 infection. More, they warrant serious consideration for self-isolation and testing those patients".

Journal ArticleDOI
TL;DR: EGFR exon 20 mutation is frequent in ISP and SNSCC-isp, while activation of EGFR through phosphorylation also plays an important role, indicating that a large proportion of S NSCC patients could benefit from therapy with modern EGFR inhibitors.
Abstract: Background To evaluate the involvement of EGFR signalling and HPV infection in a cohort of inverted sinonasal papilloma (ISP) and sinonasal squamous cell carcinoma (SNSCC) and their value for prognosis and clinical treatment. Methods We analysed 55 ISP, 14 SNSCC associated with ISP (SNSCC-isp) and and 60 SNSCC not associated with ISP (SNSCC-novo) for EGFR gene mutation and copy number gain, protein expression of EGFR and phosporylated EGFR (pEGFR), and HPV-infection and KRAS mutation. Findings were correlated to clinico-pathological and follow-up data. Results We found EGFR exon 20 mutations in 38% (7/18) ISP, in 50% (6/12) SNSCC-isp and in 5% (1/19) SNSCC-novo. EGFR was expressed in 92% of ISP, while pEGFR was observed in 54% (21/39). SNSCC-isp and SNSCC-novo demonstrated comparable expression of EGFR (57% and 33%) and of pEGFR (44% and 38%). We observed an inverse relation between EGFR exon 20 mutation and pEGFR expression. Four of 39 (10%) ISP carried HPV-16. Oncogenic HPV was detected in 3/12 (25%) SNSSC-isp and in 1/8 (13%) SNSCC-novo. KRAS mutations were not detected in any of the samples. HPV infection was inversely correlated with pEGFR expression but not with EGFR mutation. ISP with EGFR activation by mutation or by phosphorylation had longer ISP-free survival, however, neither EGFR exon 20 mutation, pEGFR expression nor HPV infection demonstrated prognostic value in SNSCC. Conclusions EGFR exon 20 mutation is frequent in ISP and SNSCC-isp, while activation of EGFR through phosphorylation also plays an important role. Our data indicate that a large proportion of SNSCC patients could benefit from therapy with modern EGFR inhibitors.

Journal ArticleDOI
TL;DR: To elucidate the mechanisms underlying olfactory dysfunction in COVID-19 patients, the expression of ACE2, TMPRSS2, and Furin in the respiratory mucosa, Olfactory mucosa (OM), and o aroma bulb of mouse and human tissues was investigated using immunohistochemistry and gene analyses.
Abstract: 1 To the Editor: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in numerous clinical symptoms, including a deteriorated sense of taste and smell and respiratory and digestive disorders (1). Anosmia, the loss of smell, is a common clinical feature observed in the early stages of COVID-19. SARS-CoV-2 entry into the host cell depends on several factors, including the binding of viral spike proteins to the cellular receptor angiotensin-converting enzyme 2 (ACE2) (2, 3), spike protein cleavage by the host cell enzyme, Furin (4, 5), and spike protein priming by host cell proteases such as transmembrane protease serine 2 (TMPRSS2) (2). Thus, high expression of ACE2, TMPRSS2, and Furin is thought to enhance SARS-CoV-2 entry, as well as clinical symptoms. To elucidate the mechanisms underlying olfactory dysfunction in COVID-19 patients, we investigated the expression of ACE2, TMPRSS2, and Furin in the respiratory mucosa (RM), olfactory mucosa (OM), and olfactory bulb (OB) of mouse and human tissues using immunohistochemistry and gene analyses.

Journal ArticleDOI
TL;DR: The aim of the study was to compare the characteristics of loss of smell and taste between patients with a clinical diagnosis of SARS-CoV-2 infection to patients with an RT-PCR diagnosis.
Abstract: During SARS-CoV-2 pandemic, our region (Alsace, East of France) became a Covid-19 cluster quite early in Europe. Loss of smell and taste was quickly flagged by the Ears-Nose and Throat scientific community as a potential warning signs of SARS-CoV-2 infection (1). Many patients and medical/paramedical workers with mild to moderate form of SARS-CoV-2 infection complained about their loss of sense of smell and taste to our ENT department. The aim of our study was to compare the characteristics of loss of smell and taste between patients with a clinical diagnosis of SARS-CoV-2 infection to patients with a RT-PCR diagnosis.

JournalDOI
TL;DR: The assessment of Chronic Rhinosinusitis, like any other disease, may involve multiple possible disease manifestations, including subjective patient-reported outcomes, objective disease, and physician-driven (e.g. need for systemic medications).
Abstract: The assessment of Chronic Rhinosinusitis, like any other disease, may involve multiple possible disease manifestations, including subjective patient-reported outcomes, objective disease (e.g. endoscopy or radiographic), and physician-driven (e.g. need for systemic medications). Disease control is often used as a global metric of disease burden and represents the extent to which disease manifestations are within an acceptable range. Achieving control is an important treatment goal.

Journal ArticleDOI
TL;DR: The current review provides an overview of olfactory related questionnaires and scales, highlighting the emotional and affective impact of Olfactory dysfunction and the impact on quality of life due to olfaction dysfunction.
Abstract: Purpose Although neglected by science for a long time, the sense of olfaction has received increasing attention from research areas including psychology, neuroscience, clinical medicine and nutrition. With the rise of psychophysical and neuroimaging re- search into olfaction, psychometric tools (e.g. questionnaires and scales) are the basis for the quantitative exploration of inter-in- dividual variability regarding olfactory related responses. The current systematic review is to summarize existing olfaction related questionnaires and/or scales. Methods Peer-reviewed literature on scales and questionnaires related to perception of odors were searched from online databa- ses (PubMed, Web of Science and PsycINFO). Twenty-one articles that meet the following criteria were included in the review: "hu- man species", "no physical odor stimuli" and "describing the original development of the tool", and "with specific focus on olfaction or odor related responses or behaviors". The psychometric properties, advantages and possible disadvantages were discussed. Results Existing psychometric measures focus on various aspects of olfactory related responses and behaviors, including af- fective experiences of odor perception, awareness and attitude towards olfaction, olfactory function and the quality of life change due to olfactory dysfunction, and the ability to create vivid mental odor images. While most of them have been tested to have good reliability and validity, some were relatively time-consuming due to the number of questionnaire items. Besides, although many measures have been used in clinical populations, few have provided information on the predictive validity regarding effecti- veness of clinical intervention on changes of certain responses or behaviors. Summary The current review provides an overview of olfactory related questionnaires and scales, highlighting the emotional and affective impact of olfaction and the impact on quality of life due to olfactory dysfunction. With growing interest in olfaction as an important sense, the development and use of psychometrically sound measurements in conjunction with objective assess- ments will advance our understanding of human olfaction and olfactory dysfunction. The review provides a guide for researchers and clinicians alike to select olfactory scales suitable for olfactory research with different experimental purposes and specific samples.

Journal ArticleDOI
TL;DR: ILIT was safe and effective for Japanese cedar pollinosis and the clinical effects remained for 1-2 years, and its safety was confirmed.
Abstract: Background Intralymphatic immunotherapy (ILIT) for allergic patients requires only a few intralymphatic injections of the allergen. However, the effectiveness and safety for Japanese cedar pollinosis are unclear. The objectives of this study were to clarify whether and how long ILIT is effective for pollinosis, and its safety. Methods In an open pilot investigation followed by a double-blind, placebo-controlled study, patients with Japanese cedar pollinosis received 3 intralymphatic inguinal injections of the pollen extracts before the first pollen season. The symptom medication score (SMS), nasal provocation testing and scoring visual analogue scale (VAS) were assessed after the first-third seasons. Results (1) Although mild adverse events were induced at the injected site, severe adverse events were not noted. (2) During the latter part of the first season, ILIT-treated patients (n=12) tended to show improved SMS compared to placebo-treated (n=6) without statistical significance. When assessed by nasal provocation testing and VAS scoring after the first season, the effectiveness of ILIT was significant. (3) The effects of ILIT continued until the second or third season. (4) Neither allergen-specific antibodies nor Treg/Breg cells changed in the peripheral blood. Conclusions ILIT was safe and effective for Japanese cedar pollinosis. The clinical effects remained for 1-2 years.

Journal ArticleDOI
TL;DR: Findings help in further standardizing ROT, may encourage rhinologists to more routinely evaluate retronasal olfactory abilities and pave the way for larger epidemiologic studies also in regard to food preferences and nutritional behaviour.
Abstract: BACKGROUND The olfactory system is able to detect external odours through the orthonasal- and internal odours through the retronasal route. Flavour perception strongly relies on the sense of smell and this back route. In contrast to orthonasal, retronasal olfactory tests (ROT) are less frequently applied, although testing should be recommended for several reasons. The aim of the present investigation was to propose a suitable form of ROT for home-testing (and postal distribution) and evaluate a retronasal screening test. METHODOLOGY Initially, 111 participants were tested using a 27-item version of the Candy Smell Test (CST). Fifty-four participants performed retesting, of which 25 subjects did so in a home-setting being supplied with professionally packed "candy-chains". Seven candies were chosen by means of hit rate differences in normosmics and severely hyposmics/anosmics. The 7-CST is designed in a non-forced-choice fashion with same seven flavours to choose from. RESULTS For the 27-item CST both groups (subjects performing home-testing and those performing retesting at the clinic) showed highly significant test-rest-reliabilities. The 7-CST was capable of discriminating healthy from diseased subjects when being tested in 116 healthy subjects and 47 patients suffering from olfactory dysfunction. CONCLUSION The CST is suitable for home-testing and postal distribution. The new 7-item CST can be valuable for rapidly revealing anosmics. These findings help in further standardizing ROT, may encourage rhinologists to more routinely evaluate retronasal olfactory abilities and pave the way for larger epidemiologic studies also in regard to food preferences and nutritional behaviour.

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TL;DR: It is demonstrated that subepithelial neutrophils in NP tissues had a high expression of Ki-67 and could serve as a cellular biomarker for predicting surgical outcomes in CRSwNP patients.
Abstract: Background Neutrophils present as major inflammatory cells in refractory chronic rhinosinusitis with nasal polyps (CRSwNP), regardless of the endotype. However, their role in the pathophysiology of CRSwNP remains poorly understood. We investigated factors predicting the surgical outcomes of CRSwNP patients with focus on neutrophilic localization. Methods We employed machine-learning methods such as the decision tree and random forest models to predict the surgical outcomes of CRSwNP. Immunofluorescence analysis was conducted to detect human neutrophil elastase (HNE), Bcl-2, and Ki-67 in NP tissues. We counted the immunofluorescence-positive cells and divided them into three groups based on the infiltrated area, namely, epithelial, subepithelial, and perivascular groups. Results On machine learning, the decision tree algorithm demonstrated that the number of subepithelial HNE-positive cells, Lund-Mackay (LM) scores, and endotype (eosinophilic or non-eosinophilic) were the most important predictors of surgical outcomes in CRSwNP patients. Additionally, the random forest algorithm showed that, after ranking the mean decrease in the Gini index or the accuracy of each factor, the top three ranking factors associated with surgical outcomes were the LM score, age, and number of subepithelial HNE-positive cells. In terms of cellular proliferation, immunofluorescence analysis revealed that Ki-67/HNE-double positive and Bcl-2/HNE-double positive cells were significantly increased in the subepithelial area in refractory CRSwNP. Conclusion Our machine-learning approach and immunofluorescence analysis demonstrated that subepithelial neutrophils in NP tissues had a high expression of Ki-67 and could serve as a cellular biomarker for predicting surgical outcomes in CRSwNP patients.

Journal ArticleDOI
TL;DR: This comprehensive quantitative assessment of postoperativeCSF leakage showed that obesity, perioperative radiotherapy, and high intraoperative CSF flow rate raised the risk of CSF leakage; however, a pedicled vascularized flap can ef- fectively reduce the risk.
Abstract: Background Cerebrospinal fluid (CSF) leakage is a complication that any surgeon working in the field of skull base surgery does not wish to encounter. The surgical approach to the skull base often varies, and the various sizes and locations of skull base lesions make it difficult to determine the cause of CSF leakage. However, it is useful to investigate which factors contribute to postopera- tive CSF leakage. Methods Related studies were identified by searching the following databases: PubMed/Medline, Embase, and Web of Sciences through December 2019. Random-effects models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The Newcastle-Ottawa scale was used to evaluate the quality of observational studies. Results Our search yielded 56 retrospective cohort studies involving a total of 11,826 skull base surgical procedures. The overall rate of postoperative CSF leakage was 7.2%. The effect of obesity on postoperative CSF leakage had an OR of 1.88, and the effect of perioperative radiotherapy on postoperative CSF leakage yielded an OR of 1.87. High intraoperative CSF flow rate also had a significant OR of 2.98. On the other hand, a pedicled vascularized flap efficiently reduced the risk of postoperative CSF leakage. Defect size and the presence or absence of a lumbar drain had no effect on postoperative CSF leakage. Conclusions This comprehensive quantitative assessment of postoperative CSF leakage showed that obesity, perioperative radiotherapy, and high intraoperative CSF flow rate raised the risk of CSF leakage; however, a pedicled vascularized flap can ef- fectively reduce the risk of postoperative CSF leakage.

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TL;DR: This study quantified sinus airflow in the largest set of post-FESS patients to date, to show that with increasing extensive surgery, the sinus and nasal cavity become more interconnected and functionally interdependent, and sinus ventilation is improved.
Abstract: Background Despite functional endoscopic sinus surgery (FESS) being the standard of care in medically recalcitrant chronic rhinosinusitis (CRS), its effect on sinus ventilation has not been fully characterized. Airflow simulations can help improve our understanding of how surgical strategies affect post-surgical sinus ventilation. Methods Eight postoperative sinonasal cavity models were reconstructed from a wide spectrum of CRS patients who had undergone FESS. Computational fluid dynamics modeling of steady-state, laminar, inspiratory airflow was performed. Ventilation was quantified and observed for all the sinuses in each model. Results Sinus aeration was enhanced following FESS, particularly in the maxillary and ethmoid sinuses. The degree of improvement was related to the extent of surgery performed. This finding was accentuated at a higher inhalational flow rate of 15L/min. The relationship between ostium size and corresponding sinus inflow was stronger for the maxillary and sphenoid sinuses. Maxillary inflow reached 50% in a mega-antrostomy patient, while negligible flow occurred in the frontal sinuses for except one whom had undergone a modified Lothrop procedure. Conclusions This study has quantified sinus airflow in the largest set of post-FESS patients to date, to show that with increasing extensive surgery, the sinus and nasal cavity become more interconnected and functionally interdependent. Accordingly, sinus ventilation is improved. This may have important consequences for pre- and post-surgical assessment and planning, and on predicting how drug delivery treatments and devices can be designed to target the postoperative sinuses.

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TL;DR: Omalizumab is an effective therapy option in N-ERD patients in a 9 month study period and Oral prednisolone therapy was required in one case and a repeated nasal sinus surgery in an additional case due to progression of NP.
Abstract: Background The association of acetylsalicylic acid (ASA) intolerance, chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, or chronic urticaria is known as NSAID-exacerbated respiratory disease (N-ERD). N-ERD patients often suffer from recurrent nasal polyps, severe asthma or also from urticaria. The aim of the present study was to retrospectively analyze the clinical efficacy of anti-IgE antibody treatment with omalizumab in patients with confirmed N-ERD. Methods In the open trial with patients receiving verum patients with CRSwNP, confirmed N-ERD by oral or nasal ASA challenges, asthma or chronic urticaria were included in the study. Rhinological and pulmonary parameters were evaluated before and after 3, 6 and 9 months of therapy by rhinological questionnaires (CRS VAS-scores and RSOM-31), nasal polyp (NP)-, ACT-scores and FEV1 values. Urticaria activity was monitored clinically. N-ERD patients with aspirin desensitization were included as control group (follow-up 9 months). Results In the omalizumab group 16 patients were included (10 female, 6 male, mean age 51 yrs). CRS symptoms, RSOM-31- and NP-score decreased significantly following omalizumab therapy compared to baseline. The ACT-score (MV 16.5 to 20.6) and FEV1values (MV 80 % to 89 %) improved significantly. No urticaria symptoms were reported after 3 months. Oral prednisolone therapy was required in one case and a repeated nasal sinus surgery in an additional case due to progression of NP. In the control group (8 female, 8 male, mean age 45 yrs) the NP-score was unchanged. Conclusions Omalizumab is an effective therapy option in N-ERD patients in a 9 month study period.

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TL;DR: This study adds to the growing body of evidence that many patients with N-ERD are living with uncontrolled disease which has significant impact on their quality of life and highlights the importance of patient advocacy groups in providing support to patients living with chronic disease.
Abstract: Background A subset of patients with chronic rhinosinusitis with nasal polyps and asthma have non-steroidal anti-inflammatory drug exacerbated respiratory disease (N-ERD). Typically, these patients often have more difficult to treat symptoms of both chronic rhinosinusitis and asthma. They also have higher rates of revision after endoscopic sinus surgery. In this paper we aim to include the patient's perspective of living with N-ERD. Methods In this qualitative study, three months of posts from the Samter's Society Support Group on social media were screened and analysed. Results Thematic analysis revealed eight main themes with subthemes in relation to patient interpretations when living with NERD. Main themes included symptom severity, quality of life, biological treatment options, diet, surgery, medical treatment, lack of awareness of N-ERD, conflicts between medical professionals and the importance of the support group. Conclusions This study adds to the growing body of evidence that many patients with N-ERD are living with uncontrolled disease which has significant impact on their quality of life. In addition, it has identified important themes that are relevant to know for doctors treating these patients. The results are also important for future research purposes. Finally, it has highlighted the importance of patient advocacy groups in providing support to patients living with chronic disease.