Validation of the questionnaire of olfactory disorders (QOD) for the Brazilian population.

BACKGROUND: The incidence of olfactory disorders has increased in recent years, mainly related to COVID-19 infection. In Brazil, over 37 million cases of COVID-19 have been reported, and approximately 10 % of those cases continue to experience olfactory disorders for more than one month. Despite the significant negative impact on well-being, there is currently no validated instrument to assess how olfactory disorders impact the quality of life in Brazil. OBJECTIVES: This study aimed to validate the Questionnaire of Olfactory Disorders (QOD) for Brazilian Portuguese. METHODS: The authors first performed translation, back-translation, expert review, pre-testing, psychometric evaluation and cultural adaptation of the English version of the questionnaire. To assure linguistic and conceptual equivalence of the translated questionnaire, 126 participants from two Brazilian states and varying degrees of olfactory loss answered the QOD and the World Health Organization Quality of Life bref (WHOQOL-bref) questionnaires. The University of Pennsylvania Smell Identification Test (UPSIT®) was used to quantify the olfactory loss. Furthermore, to evaluate the reliability of the Portuguese version a test-retest was performed on a subgroup of patients. The authors observed a high Cronbach's alpha (α = 0.86) for internal consistency of the quality of Life (QOD-QOL) statements. FINDINGS: As expected, there was a negative correlation between QOD-QOL and UPSIT® (Spearman's ρ = -0.275, p = 0.002), since QOL score increases and UPSIT® score decreases with worsening of olfactory function. Correlations were moderate between QOD-QOL and WHOQOL-bref mean (Spearman's ρ = -0.374, p < 0.001) and weak to moderate between the QOD-QOL and Visual Analog Scale of the QOD regarding professional life, leisure, and private life (Spearman's ρ = -0.316, p = 0.000; Spearman's ρ = -0.293, p = 0.001; Spearman's ρ = -0.261, p = 0.004; respectively). CONCLUSION: In conclusion, the authors have demonstrated a high internal consistency and validity of the Brazilian Portuguese version of the QOD for evaluating the quality of life in individuals with olfactory disorders.

Intranasal insulin for COVID-19-related smell loss.

BACKGROUND: Quantitative (hyposmia and anosmia) and qualitative (phantosmia and parosmia) olfactory disorders are common consequences of COVID-19 infection found in more than 38% of patients even months after resolution of acute disease. SARS-CoV-2 has tropism for angiotensin-converting enzyme 2 (ACE2) in the respiratory system, suggesting that it is the mechanism of damage to the olfactory neuroepithelium and of involvement at the central nervous system. The olfactory bulb is the organ with the highest insulin uptake in the central nervous system. Insulin increases the production of Growth Factors (GF); therefore, in this study, the administration of intranasal insulin is proposed as a viable treatment for olfactory disturbances. The aim of this study was to obtain improvement in olfaction after 4 weeks of intranasal insulin administration in a group of patients presenting chronic olfactory disturbances secondary to COVID-19 infection, quantified using the Threshold, Discrimination, and Identification (TDI) score based on the Sniffin Sticks®. METHODS: Experimental, longitudinal, prolective and prospective study of patients with a previous diagnosis of COVID-19 in the last 3-18 months and who persisted with anosmia or hyposmia. The sample size was calculated with "satulator". The intervention was performed from January to May 2022. Throughout four appointments, a baseline olfactory measurement was obtained using the TDI score based on the Sniffin Sticks® test. In the first three appointments, Gelfoam® cottonoids soaked in 40 IU of NPH insulin were placed on the nasal roof of each nostril for 15 min. Descriptive statistics, student's paired t test and a multiple linear regression were utilized to ascertain statistical significance of the outcome on the TDI score obtained on the fourth and final appointment. RESULTS: 27 patients were included in the study. Table 1 summarizes the sample characteristics. The results exhibit that 93% of the sample had an improvement. The initial mean TDI score was 67% (63-71) compared to the final mean of 83% (80-86, p < 0.01). TDI subsection analysis is shown in Table 2. There was no significant difference in pre-intervention and post-intervention glucose measurements after the intranasal insulin administration. CONCLUSIONS: The administration of intranasal insulin has promising results, pointing towards an alternative of treatment for chronic olfactory disturbances secondary to neuroepithelial damage caused by upper respiratory tract infections. Furthermore, this is the first study to use a three-point assessment of olfaction in post-COVID-19 patients, while using the Sniffin Sticks® TDI score adapted to Latin Spanish.

Olfactory and taste disorders in COVID-19: a cross-sectional study in primary health care

SUMMARY OBJECTIVE: The objective of this study was to describe the occurrence of self-reported olfactory and taste disorders in non-hospitalized Brazilian adults who presented severe acute respiratory syndrome-related coronavirus 2 infection symptoms and attended primary health care. METHODS: This cross-sectional study was based on a routine standardized diagnostic screening questionnaire applied in a Brazilian primary care facility. The olfactory and taste disorder occurrence was compared between severe acute respiratory syndrome-related coronavirus 2-positive and severe acute respiratory syndrome-related coronavirus 2-negative cases and described by age and sex. RESULTS: Severe acute respiratory syndrome-related coronavirus 2-positive patients had a higher proportion of self-reported olfactory and taste disorders, as compared with severe acute respiratory syndrome-negative (50.7%, vs. 20.6%, p<0.0001). Of all individuals with self-reported olfactory and taste disorder cases, 69% presented both olfactory and taste impairments, 13% olfactory only, and 17% taste only. In severe acute respiratory syndrome-related coronavirus 2-positive cases, the frequency of olfactory and taste disorders was significantly higher among females as compared with males (71% vs. 34%). Additionally, people with olfactory and taste disorders were significantly younger in the severe acute respiratory syndrome-related coronavirus 2-positive group. CONCLUSION: Self-reported olfactory and taste disorders are highly common among non-hospitalized severe acute respiratory syndrome-related coronavirus 2-positive Brazilian people who attended the Family Health Care Unit. The co-occurrence of both self-reported olfactory and taste disorders was more frequent than self-reported olfactory or taste disorders alone.

Performance of a cost-effective olfactory test to evaluate hyposmia in Parkinson's disease patients / Desempenho de um teste de olfato de bom custo-benefício na avaliação de hiposmia em pacientes com doença de Parkinson

Abstract Background Parkinson's disease (PD) causes motor and non-motor symptoms such as hyposmia, which is evaluated through olfactory tests in the clinical practice. Objective To assess the feasibility of using the modified Connecticut Chemosensory Clinical Research Center (mCCCRC) olfactory test and to compare its performance with the Sniffin' Sticks-12 (SS-12, Burghart Messtechnik GmbH, Wedel, Germany) test. Methods A transversal case-control study in which the patients were divided into the PD group (PDG) and the control group (CG). The cost and difficulty in handling substances to produce the mCCCRC test kits were evaluated. Sociodemographic characteristics, smoking habits, past coronavirus disease 2019 (COVID-19) infections, self-perception of odor sense, and cognition through the Montreal Cognitive Assessment (MoCA) were also evaluated. The PDG was scored by part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III) and the Hoehn and Yahr Scale (H&Y) scale. Correlations were assessed through the Spearman rank correlation coefficient test (ρ, or rho). Results The mCCCRC test was easily manufactured and handled at a cost ten times lower compared with the SS-12. The groups (PDG: n= 34; CG: n= 38) were similar in terms of age, sex, level of schooling, smoking habits, and history of COVID-19. The tests results showed moderate correlation (rho = 0.65; p< 0.0001). The CG presented better cognitive performance and scored better in both tests (p< 0.0001). There was a tendency for a negative correlation with age, but good correlation with the MoCA (p= 0.0029). The results of the PDG group showed no correlation with olfactory results and motor performance or disease duration. The self-perception of hyposmia was low in both groups. Conclusion The mCCCRC is an easy-to-apply and inexpensive method that demonstrated a similar performance to that of the SS-12 in evaluating olfaction in PD patients and healthy controls.

Resumo Antecedentes A doença de Parkinson (DP) cursa com sintomas motores e não motores como a hiposmia, que é avaliada por diferentes testes olfativos na prática clínica. Objetivo Avaliar a viabilidade do teste olfatório Connecticut Chemosensory Clinical Research Center modificado (mCCCRC) e compará-la à do teste Sniffin' Sticks-12 (SS-12, Burghart Messtechnik GmbH, Wedel, Alemanha). Métodos Estudo transversal de caso-controle em que os pacientes foram divididos no grupo DP (GDP) e no grupo controle (GC). O custo e as dificuldades no manuseio das substâncias necessárias para a produção dos kits do teste mCCCRC foram avaliados. Características sociodemográficas, tabagismo, histórico de infecção por doença do coronavírus 2019 (coronavírus disease 2019, COVID-19, em inglês), autopercepção do olfato e cognição pelo Montreal Cognitive Assessment (MoCA) também foram avaliados. O GDP foi avaliado pela parte III da Unified Parkinson's Disease Rating Scale (UPDRS-III) e pela escala de Hoehn and Yahr (H&Y). As correlações utilizaram o teste do coeficiente de correlação de postos de Spearman (ρ, ou rho). Resultados O mCCCRC foi facilmente poroduzido e manipulado com custo dez vezes inferior ao do SS-12. Os grupos (GDP: n= 34; GC: n= 38) eram similares em termos de idade, sexo, escolaridade, tabagismo e histórico de COVID-19. Os resultados obtidos em ambos os testes mostraram excelente correlação (rho = 0.65; p< 0.0001). O GC teve um desempenho cognitivo melhor e pontuou melhor nos dois testes (p< 0.0001). Houve uma tendência a uma correlação negativa com a idade, mas boa correlação com a pontuação no MoCA (p= 0.0029). Os resultados olfativos do GDP não mostraram correlação com desempenho motor ou duração da doença. A autopercepção de hiposmia foi baixa em ambos os grupos. Conclusão O mCCCRC é um teste de fácil aplicação, baixo custo, e apresentou um desempenho semelhante ao do SS-12 na avaliação olfativa de pacientes com DP e controles saudáveis.

Long-COVID olfactory dysfunction: allele E4 of apolipoprotein E as a possible protective factor / Disfunção olfativa na COVID longa: o alelo E4 da apolipoproteína E como um possível fator protetor

Abstract Background Olfactory dysfunction (OD) represents a frequent manifestation of the coronavirus disease 2019 (COVID-19). Apolipoprotein E (APOE) is a protein that interacts with the angiotensin-converting enzyme receptor, essential for viral entry into the cell. Previous publications have suggested a possible role of APOE in COVID-19 severity. As far as we know, no publications found significant associations between this disease's severity, OD, and APOE polymorphisms (E2, E3, and E4). Objective To analyze the epidemiology of OD and its relationship with APOE polymorphisms in a cohort of Long-COVID patients. Methods We conducted a prospective cohort study with patients followed in a post-COVID neurological outpatient clinic, with OD being defined as a subjective reduction of olfactory function after infection, and persistent OD being defined when the complaint lasted more than 3 months after the COVID-19 infection resolution. This cross-sectional study is part of a large research with previously reported data focusing on the cognitive performance of our sample. Results The final sample comprised 221 patients, among whom 186 collected blood samples for APOE genotyping. The persistent OD group was younger and had a lower hospitalization rate during the acute phase of the disease (p < 0.001). Furthermore, the APOE variant E4 allele frequency was lower in this group (p = 0.035). This study evaluated OD in an outpatient population with COVID-19. In the current literature on this disease, anosmia is associated with better clinical outcomes and the E4 allele is associated with worse outcomes. Conclusion Our study provides new information to these correlations, suggesting APOE E4 as a protective factor for OD.

Resumo Antecedentes A disfunção olfatória (DO) é uma manifestação frequente da doença do coronavírus 2019 (COVID-19). A apolipoproteína E (APOE) é uma proteína que interage com o receptor da enzima conversora de angiotensina, essencial para a entrada viral na célula. Publicações anteriores sugeriram um possível papel da APOE na gravidade da COVID-19. Até onde sabemos, nenhuma publicação encontrou associações significativas entre a gravidade dessa doença, DO e polimorfismos da APOE (E2, E3 e E4). Objetivo Analisar a epidemiologia da DO e sua relação com os polimorfismos do gene APOE em uma coorte de pacientes com COVID longa. Métodos Um estudo de coorte prospectiva com pacientes acompanhados em ambulatório neurológico pós-COVID, com DO sendo definida como uma redução subjetiva da função olfativa após a infecção e a DO persistente sendo definida quando a queixa durou mais de 3 meses após a resolução da infecção por COVID-19. Este estudo transversal é parte de uma pesquisa maior com dados anteriormente relatados, focando na performance cognitiva dos pacientes. Resultados Foram selecionados 221 pacientes para esse estudo, dos quais 186 haviam coletado amostras de sangue para genotipagem APOE. O grupo DO persistente foi mais jovem e apresentou menor taxa de internação na fase aguda da doença (p < 0,001). Além disso, a frequência do alelo E4 da APOE foi menor nesse grupo (p = 0,035). Este estudo avaliou a DO em uma população com COVID longa. Na literatura atual sobre essa doença, a anosmia está associada a melhores desfechos clínicos e o alelo E4 está associado a piores desfechos. Conclusão Nosso estudo acrescenta novas informações a essas correlações, sugerindo a APOE E4 como um fator de proteção para DO.

Validation of the questionnaire of olfactory disorders (QOD) for the Brazilian population

Abstract Background The incidence of olfactory disorders has increased in recent years, mainly related to COVID-19 infection. In Brazil, over 37 million cases of COVID-19 have been reported, and approximately 10 % of those cases continue to experience olfactory disorders for more than one month. Despite the significant negative impact on well-being, there is currently no validated instrument to assess how olfactory disorders impact the quality of life in Brazil. Objectives: This study aimed to validate the Questionnaire of Olfactory Disorders (QOD) for Brazilian Portuguese. Methods: The authors first performed translation, back-translation, expert review, pre-testing, psychometric evaluation and cultural adaptation of the English version of the questionnaire. To assure linguistic and conceptual equivalence of the translated questionnaire, 126 participants from two Brazilian states and varying degrees of olfactory loss answered the QOD and the World Health Organization Quality of Life bref (WHOQOL-bref) questionnaires. The University of Pennsylvania Smell Identification Test (UPSIT®) was used to quantify the olfactory loss. Furthermore, to evaluate the reliability of the Portuguese version a test-retest was performed on a subgroup of patients. The authors observed a high Cronbach's alpha (α = 0.86) for internal consistency of the quality of Life (QOD-QOL) statements. Findings: As expected, there was a negative correlation between QOD-QOL and UPSIT® (Spearman's ρ = -0.275, p = 0.002), since QOL score increases and UPSIT® score decreases with worsening of olfactory function. Correlations were moderate between QOD-QOL and WHOQOL-bref mean (Spearman's ρ = -0.374, p < 0.001) and weak to moderate between the QOD-QOL and Visual Analog Scale of the QOD regarding professional life, leisure, and private life (Spearman's ρ = -0.316, p = 0.000; Spearman's ρ = -0.293, p = 0.001; Spearman's ρ = -0.261, p = 0.004; respectively). Conclusion: In conclusion, the authors have demonstrated a high internal consistency and validity of the Brazilian Portuguese version of the QOD for evaluating the quality of life in individuals with olfactory disorders.

Persistent olfactory dysfunction associated with poor sleep quality and anxiety in patients with long COVID.

Introduction: Poor sleep quality have been widely reported in patients with long COVID. Determining the characteristics, type, severity, and relationship of long COVID with other neurological symptoms is essential for the prognosis and management of poor sleep quality. Methods: This cross-sectional study was conducted at a public university in the eastern Amazon region of Brazil between November 2020 and October 2022. The study involved 288 patients with long COVID with self-report neurological symptoms. One hundred thirty-one patients were evaluated by using standardised protocols: Pittsburgh sleep quality index (PSQI), Beck Anxiety Inventory, Chemosensory Clinical Research Center (CCRC), and Montreal Cognitive Assessment (MoCA). This study aimed to describe the sociodemographic and clinical characteristics of patients with long COVID with poor sleep quality and their relationship with other neurological symptoms (anxiety, cognitive impairment, and olfactory disorder). Results: Patients with poor sleep quality were mainly women (76.3%), 44.04 ± 12.73 years old, with >12 years of education (93.1%), and had monthly incomes of up to US $240.00 (54.2%). Anxiety and olfactory disorder were more common in patients with poor sleep quality. Discussion: Multivariate analysis shows that the prevalence of poor sleep quality was higher in patients with anxiety, and olfactory disorder is associated with poor sleep quality. In this cohort of patients with long COVID, the prevalence of poor sleep quality was highest in the group tested by PSQI and were associated with other neurological symptoms, such as anxiety and olfactory dysfunction. A previous study indicates a significant association between poor sleep quality and psychological disorders over time. Recent studies involving neuroimaging found functional and structural changes in Long COVID patients with persistent olfactory disfunction. Poor sleep quality are integral part of complex changes related to Long COVID and should be part of patient's clinical management.

High prevalence of olfactory dysfunction detected in treatment-naive patients with head and neck cancer.

BACKGROUND: Previous studies demonstrated the difficulty of patients with Head and Neck Cancer (HNC) in sensing food taste, a function in which olfaction has a significant role. However, neither study employed psychophysical tests or control groups to establish the veracity of such complaints. AIMS/OBJECTIVES: In this study, we quantitatively tested the olfactory function of HNC individuals and compared their function to that of healthy controls. METHODS: Thirty-one HNC naïve treatment patients and thirty-one controls, matched for sex, age, schooling, and smoking, were tested with the University of Pennsylvania Smell Identification Test (UPSIT). RESULTS: The olfactory function was significantly worse among the patients diagnosed with head and neck cancer [UPSIT cancer = 22.9(CI 95%: 20.5-25.4) vs. UPSIT controls = 29.1(CI 95%: 26.9-31.3); p < .001]. Most patients with HNC had olfactory disorders (n = 29, 93.5%). The risk of olfactory loss was higher in the cancer group [OR: 10.5(CI 95%: 2.1-51.9; p = .001)]. CONCLUSION AND SIGNIFICANCE: Olfactory disorders can be detected in more than 90% of patients with head and neck cancer when evaluated using a well-validated olfactory test. Smell disorders may be a potential marker for early diagnosis of HNC.

Olfaction in nasal polyp patients after Reboot surgery: an endotype-based prospective study.

PURPOSE: To report biomarkers present in the olfactory mucosa in chronic rhinosinusitis with nasal polyps (CRSwNP) in comparison with nasal polyps and to nasal mucosal tissues from control patients. To evaluate the kinetics of smell over 6 months in patients who underwent Reboot surgery. METHODS: Cohort study from May 2021 to May 2022. We collected samples of olfactory mucosa and nasal polyps from 16 CRSwNP patients and inferior turbinate samples from 20 control subjects. The study was not randomized for surgical and/or medical treatment. Samples were analyzed by Luminex and Unicap 100 to measure biomarkers of inflammation (IL1-ß, IL4, IL5, IL6, IL17, CCL3, CCL4, G-CSF, SE-IgE, total IgE and ECP). 12 of the CRSwNP patients underwent Extended Sniffin'tests at timepoints 1-4 days pre-surgery, and 1, 3 and 6 months after Reboot surgery. RESULTS: Type-2 markers were significantly elevated in OM and polyp tissue in CRSwNP (n = 16) vs. controls (n = 20), P < 0.05. TDI scores improved already 1 month (P < 0.05) after surgery and remained stable for 6 months. Type-2 inflammation in nasal polyps was associated with decreased sense of smell and taste before surgery, but improved after surgery (P = 0.048). Type-3 inflammation was present in the olfactory mucosa and was associated with a better sense of smell before surgery, but a smaller improvement of smell afterward. CONCLUSIONS: Type-2 inflammation is present in the olfactory mucosa in CRSwNP patients and is associated with smell loss. Reboot surgery, aiming to completely remove inflamed sinus mucosa, significantly improves the smell in this group of patients.

Chemosensory Dysfunction 3-Months After COVID-19, Medications and Factors Associated with Complete Recovery.

OBJECTIVES: To examine the longitudinal prevalence and recovery of olfactory, gustatory, and oral chemesthetic deficits in a sizable cohort of SARS-CoV-2 infected persons using quantitative testing. To determine whether demographic and clinical factors, mainly the medications used after the COVID-19 diagnosis, influence the test measures. METHODS: Prospective cohort in a hospital with primary, secondary, tertiary, and quaternary care. Patients with confirmed COVID-19 were tested during the acute infection phase (within 15 days of initial symptom, n = 187) and one (n = 113) and 3 months later (n = 73). The University of Pennsylvania Smell Identification Test, the Global Gustatory Test, and a novel test for chemesthesis were administered at all visits. RESULTS: During the acute phase, 93% were anosmic or microsmic and 29.4% were hypogeusic. No one was ageusic. A deficit in oral chemesthesis was present in 13.4%. By 3 months, taste and chemesthesis had largely recovered, however, some degree of olfactory dysfunction remained in 54.8%. Remarkably, patients who had been treated with anticoagulants tended to have more olfactory improvement. Recovery was greater in men than in women, but was unrelated to disease severity, smoking behavior, or the use of various medications prior to, or during, COVID-19 infection. CONCLUSIONS: When using quantitative testing, olfactory disturbances were found in nearly all SARS-CoV-2 infected patients during the acute infection phase. Taste or chemesthetic deficits were low. Olfactory impairment persisted to some degree in over half of the patients at the 3-month follow-up evaluation, being more common in women and less common in those who had been treated earlier with anticoagulants. LEVEL OF EVIDENCE: 3.

Self-awareness of olfactory dysfunction in elderly individuals without neurodegenerative diseases.

PURPOSE: The decrease in smell in the elderly population is frequent and considered a natural process. However, sometimes it can be associated with the decline of cognitive functions, and it is considered a warning for the early stage of neurodegenerative diseases and social impairment. OBJECTIVE: To assess the prevalence of olfactory dysfunction in previous healthy elderly that attended a tertiary hospital in Brazil as escorts and the clinical alterations associated in this population. METHODS: Subjects 60 years or over attending the University Hospital of Campinas were evaluated. Each participant answered a questionnaire, followed by an otorhinolaryngological exam with flexible nasal endoscopy and the Connecticut smell test produced by the Connecticut Chemosensory Clinical Research Center (CCCRC). Elderly people with nasosinusal diseases or with a history of nasal surgery were excluded. RESULTS: Of the total of 103 participants, 16 (15.5%) reported olfactory complaints and 68 (66%) presented impairment in the olfactory test. It was observed that older individuals showed more changes in olfactory function (p = 0.001). Gender, education, lifestyle, comorbidities, medications in use and exposure to pollutants did not influence the impairment olfactory function of this population. CONCLUSIONS: There is a significant prevalence of olfactory dysfunction in the elderly population evaluated. Most of these elderlies also present an inability to identify odours, not having awareness of this olfactory impairment.

Terapia de rehabilitación olfatoria en pacientes con síndrome pos-COVID-19 / Olfactory rehabilitation therapy in patients with post-COVID-19 syndrome

El olfato desempeña una función importante en el desarrollo diario de la vida de las personas. Sus alteraciones pueden ser cualitativas (disosmias, parosmias o fantosmias) y cuantitativas (hiposmia o anosmia). Estas alteraciones pueden deberse por enfermedades rinosinusales, neurodegenerativas o infecciones respiratorias como el resfriado común, la gripe y también el SARS-CoV-2, el agente causal del COVID-19. En relación a esta etiología, su fisiopatología no es del todo clara y la anosmia es poco distinguible clínicamente del resto de las infecciones virales, con una duración variable desde ocho días hasta más de cuatro semanas, en cuyo caso se denomina síndrome pos-COVID-19 o COVID prolongado. Este cuadro se caracteriza por la presencia de síntomas que se desarrollan durante la enfermedad aguda por COVID-19,y que persisten durante más de cuatro semanas, sin explicación por un diagnóstico alternativo. El autor de este artículo realiza una revisión de la literatura médica a partir de un caso clínico con el fin de identificar y resumir la evidencia disponible sobre la terapia de rehabilitación olfatoria. (AU)

Sense of smell plays an important role in the daily development of people's lives. Its alterations can be both qualitative (dysosmias, parosmias, or phantosmias) and quantitative (hyposmia or anosmia). These alterations may be due to rhinosi-nusal diseases, neurodegenerative diseases, and respiratory infections such as common cold, influenza, and SARS-CoV-2,causative agent of COVID-19. In relation to this etiology, its pathophysiology is not entirely clear, and anosmia is clinically indistinguishable from the rest of the viral infections, with a variable duration ranging from eight days to more than four weeks, in which case it would be called post COVID- 19 syndrome or prolonged COVID. This condition is characterized by the presence of symptoms that develop during acute COVID-19 illness and persist for more than four weeks without an explanation by an alternative diagnosis.The author of this article carries out a review of the medical literature based on a clinical case in order to identify and summarize the available evidence on olfactory rehabilitation therapy. (AU)

Adaptation of the Pediatric Smell WheelTM to evaluate olfactory function in Brazilian children

Abstract Objective: Olfaction influences nutrition, safety, and the cognitive development of children. Presently there are few olfactory tests for children, and normative reference values are generally lacking. In this study, we validate the Pediatric Smell WheelTM (PSW) to evaluate olfactory function in Brazilian children. Methods: We modified and validated the PSW, a test developed in the United States, for administration in Brazil, and established normative data for Brazilian children. The validation process consisted of five phases. First, we identified odorants familiar to Brazilian children. Second, we established the test-retest reliability of the Brazilian PSW test that employed these odorants. Third, we compared the test scores of healthy children to those microsmic from adenoid hypertrophy. Fourth, we examined the test's ability to detect improvement in olfactory function before and after adenoidectomy. Finally, we determined a normative 10th percentile cut point for defining microsmia in a sample of 169 healthy Brazilian children between 5 and 12 years of age. Results: Eleven odors were identified for inclusion in the test. The test-retest reliability was modest (r = 0.54, p < 0.001), although likely attenuated based on the inclusion of only data from children with normal function. The test clearly differentiated the olfactory function of children with adenoid hypertrophy from that of healthy children and demonstrated the return of function after adenoidectomy. An overall score <7 was found useful in defining hyposmia, although additional age-related cut-points were also defined. Conclusion: A Brazilian version of the PSW was developed and validated and found to be efficacious in detecting smell dysfunction in children ranging in age from 5 to 12 years. Level of evidence: 1b (Diagnosis).

Danish Validation of a Retronasal Olfactory Powder Test and Development of a Novel Quick Retronasal Olfactory Test

Abstract Introduction Quality of life is closely linked to retronasal olfactory function. Familiarity with odors vary, so tests need validation. Testing can be time-consuming, so a quick test and a thorough test are needed for clinical and research settings. Objectives The objectives of this study were to validate the original retronasal powder olfactory test in a Danish population and to develop a novel quick retronasal test for easy application. Methods Ninety-seven participants were included in the study, 59 healthy controls and 38 patients with olfactory impairment. The retronasal test was modified by substituting unfamiliar odors and descriptors and validated with a criterion of correct identification rate of 50% in the original test and 90% in the quick test. Items with over 90% correct identification rate in the modified original test were included in the quick test, resulting in a 10-item test. Results The modified retronasal olfactory test achieved good test characteristics, with a 10th percentile cut-off value of 13: sensitivity was 88.9%, specificity 83.0%, positive predictive value 78%, negative predictive value 91.7%, and the receiver operating characteristics area under the curve (ROC-AUC) was 0.86. The quick test achieved acceptable test characteristics, with a 10th percentile cut-off value of 8.2: sensitivity was 72.2%, specificity 90.6%, positive predictive value 83.9%, negative predictive value was 82.8%, and ROC-AUC 0.81. Conclusion Validation of both tests demonstrated satisfactory accuracy. We recommend the quick test for screening purposes, and the modified original version for a thorough evaluation. The tests are easily implemented as they are easy to understand and very affordable.

Danish Validation of a Retronasal Olfactory Powder Test and Development of a Novel Quick Retronasal Olfactory Test.

Introduction Quality of life is closely linked to retronasal olfactory function. Familiarity with odors vary, so tests need validation. Testing can be time-consuming, so a quick test and a thorough test are needed for clinical and research settings. Objectives The objectives of this study were to validate the original retronasal powder olfactory test in a Danish population and to develop a novel quick retronasal test for easy application. Methods Ninety-seven participants were included in the study, 59 healthy controls and 38 patients with olfactory impairment. The retronasal test was modified by substituting unfamiliar odors and descriptors and validated with a criterion of correct identification rate of 50% in the original test and 90% in the quick test. Items with over 90% correct identification rate in the modified original test were included in the quick test, resulting in a 10-item test. Results The modified retronasal olfactory test achieved good test characteristics, with a 10th percentile cut-off value of 13: sensitivity was 88.9%, specificity 83.0%, positive predictive value 78%, negative predictive value 91.7%, and the receiver operating characteristics area under the curve (ROC-AUC) was 0.86. The quick test achieved acceptable test characteristics, with a 10th percentile cut-off value of 8.2: sensitivity was 72.2%, specificity 90.6%, positive predictive value 83.9%, negative predictive value was 82.8%, and ROC-AUC 0.81. Conclusion Validation of both tests demonstrated satisfactory accuracy. We recommend the quick test for screening purposes, and the modified original version for a thorough evaluation. The tests are easily implemented as they are easy to understand and very affordable.

Validation of the Connecticut olfactory test (CCCRC) adapted to Brazil / Validação do teste de olfato de Connecticut (CCCRC) adaptado para o Brasil

Abstract Introduction Olfactory changes are quite common in the population, causing a significant impact on the quality of life. Documentation of the olfactory function is essential for the diagnosis, treatment and follow-up of patients with inflammatory diseases of the upper airways, neurodegenerative diseases or viral infections. Among the different existing smell tests, the CCCRC is an inexpensive test, easy to apply, but it has not yet been evaluated on a large scale in the Brazilian population. Objective To validate the CCCRC smell test, after adaptation for the Brazilian population, evaluating the performance of healthy volunteers and the stability of the test in retests. Methods In this study, we carried out a cultural adaptation of the CCCRC test to Brazil. To validate and determine the normality scores, we applied the test to 334 healthy volunteers, aged >18 years of age. The retest was also carried out in up to four weeks on 34 additional volunteers to assess validity of the results. Results When evaluating the participants' performance, normosmia and mild hyposmia values were obtained in more than 95% of them. Women (58.4%) showed better accuracy than men (41.6%): p < 0.02, and individuals over 60 years of age showed worse performance (median: 6; 75th percentile: 6.5; 25th percentile). The test and retest of the 34 volunteers demonstrated that there was agreement (ICC, intraclass correlation coefficient) considered good in the left nostril (ICC = 0.65) and excellent in the right nostril (ICC = 0.77) in the combined score. Conclusion The CCCRC test adapted to Brazil showed normal values, similar to the originally-described test and validations in other countries, with a high reproducibility rate. Considering the highly favorable cost-benefit ratio, the adapted CCCRC is a very useful tool for measuring olfactory function in the Brazilian population.

Resumo Introdução Alterações olfativas são bastante comuns na população, causam significativo impacto na qualidade de vida. A documentação da função olfatória é fundamental para o diagnóstico, tratamento e seguimento de pacientes que cursam com doenças inflamatórias das vias aéreas superiores, neurodegenerativas ou infecções virais. Entre os diferentes testes de olfato existentes, o teste do Connecticut Chemosensory Clinical Research Center (CCCRC) é barato, de fácil aplicação, mas que ainda não foi avaliado em grande escala para a população brasileira. Objetivo Validar o teste de olfato CCCRC com adaptação para a população brasileira, avaliar o desempenho de voluntários saudáveis e a estabilidade do teste em retestes. Método Neste estudo fizemos adaptação cultural do teste CCCRC para o Brasil. Para validação e determinação dos escores de normalidade, aplicamos o teste em 334 voluntários saudáveis, com mais de 18 anos. O reteste foi ainda feito em até quatro semanas em 34 voluntários adicionais para avaliar concordância dos resultados. Resultados Avaliando o desempenho dos participantes, valores de normosmia e hiposmia leve foram obtidos em mais de 95% deles. Mulheres (58,4%) apresentaram melhor acurácia em relação aos homens (41,6%), p< 0,02; e indivíduos acima dos 60 anos apresentaram pior desempenho (mediana: 6; percentil 75: 6,5; percentil 25: 5). O teste e reteste dos 34 voluntários demonstrou que houve concordância (coeficiente de correlação intraclasse, CCI) considerada boa em narina esquerda (CCI = 0,65) e excelente em narina direita (CCI = 0,77) no escore combinado. Conclusão O teste CCCRC adaptado para o Brasil apresentou valores de normalidade semelhantes ao teste originalmente descrito e a validações em outros países, com alta taxa de reprodutibilidade. Considerando a relação custo-benefício altamente favorável, o CCCRC adaptado é uma ferramenta muito útil para mensuração da função olfatória na população brasileira.

Pathophysiological relationship between COVID-19 and olfactory dysfunction: A systematic review / Relação fisiopatológica entre Covid‐19 e disfunção olfativa: uma revisão sistemática

Abstract Introduction SARS-CoV-2 is the pathogen of COVID-19. The virus is composed of the spike, membrane and envelope. On physiological smell, odoriferous substances bind to proteins secreted by sustentacular cells in order to be processed by olfactory receptor neurons. Olfactory disorder is one of the main manifestations of COVID-19, however, research is still required to clarify the mechanism involved in SARS-CoV-2 induced anosmia. Objective This article aims to analyze current scientific evidence intended to elucidate the pathophysiological relationship between COVID-19 and the cause of olfactory disorders. Methods Pubmed, Embase, Scopus and ScienceDirect were used to compose this article. The research was conducted on November 24th, 2020. Original articles with experimental studies in human, animal and in vitro, short communications, viewpoint, published in the English language and between 2019 and 2020 were included, all related to the pathophysiological relationship between olfactory disorders and COVID-19 infection. Results Both human cell receptors ACE2 and TMPRSS2 are essential for the SARS-CoV-2 entrance. These receptors are mostly present in the olfactory epithelium cells, therefore, the main hypothesis is that anosmia is caused due to damage to non-neuronal cells which, thereafter, affects the normal olfactory metabolism. Furthermore, magnetic resonance imaging studies exhibit a relationship between a reduction on the neuronal epithelium and the olfactory bulb atrophy. Damage to non-neuronal cells explains the average recovery lasting a few weeks. This injury can be exacerbated by an aggressive immune response, which leads to damage to neuronal cells and stem cells inducing a persistent anosmia. Conductive anosmia is not sufficient to explain most cases of COVID-19 induced anosmia. Conclusion Olfactory disorders such as anosmia and hyposmia can be caused by COVID-19, the main mechanism is associated with olfactory epithelium damage, targeting predominantly non-neuronal cells. However, neuronal cells can also be affected, worsening the condition of olfactory loss.

Resumo Introdução SARS‐CoV‐2 é o patógeno da Covid‐19. O vírus é composto pela proteína spike (espigão), a membrana e o envelope. No olfato fisiológico, as substâncias odoríferas se ligam a proteínas secretadas pelas células sustentaculares para serem processadas pelos neurônios receptores olfativos. O distúrbio olfativo é uma das principais manifestações da Covid‐19; entretanto, pesquisas ainda são necessárias para esclarecer o mecanismo envolvido na anosmia induzida pela SARS‐CoV‐2. Objetivos Este artigo tem como objetivo analisar as evidências científicas atuais destinadas a elucidar a relação fisiopatológica entre a Covid‐19 e a causa dos distúrbios olfativos. Método As bases de dados Pubmed, Embase, Scopus e ScienceDirect foram usadas para compor este artigo. A pesquisa foi feita em 24 de novembro de 2020. Foram incluídos artigos originais com estudos experimentais em seres humanos, animais e estudos in vitro, comunicações breves, pontos de vista, publicados na língua inglesa e entre 2019 e 2020, todos relacionados à relação fisiopatológica entre distúrbios olfativos e infecção por Covid‐19. Resultados Ambos os receptores de células humanas ACE2 e TMPRSS2 são essenciais para a penetração do SARS‐CoV‐2. Esses receptores estão presentes principalmente nas células do epitélio olfativo; portanto, a principal hipótese é que a anosmia é causada por lesão de células não neuronais que, a partir daí, afeta o metabolismo olfativo normal. Além disso, estudos de ressonância magnética mostram uma relação entre a redução do epitélio neuronal e a atrofia do bulbo olfatório. Danos às células não neuronais explicam o tempo médio de recuperação, que demora algumas semanas. Essa lesão pode ser exacerbada por uma resposta imune agressiva, que leva a danos às células neuronais e células‐tronco, induz uma anosmia persistente. A anosmia condutiva não é suficiente para explicar a maioria dos casos de anosmia induzida por Covid‐19. Conclusão Distúrbios olfativos como anosmia e hiposmia podem ser causados pela Covid‐19 e o principal mecanismo está associado à lesão do epitélio olfativo, tem como alvo células predominantemente não neuronais. Porém, células neuronais também podem ser afetadas, o que piora o quadro de perda olfativa.

Association between chemosensory dysfunctions and inflammatory biomarkers in patients with SARS-CoV-2 infection: a systematic review and meta-analysis.

BACKGROUND: There is evidence that chemosensory dysfunctions, including smell and taste disorders, are common findings in patients with SARS-CoV-2 infection. However, the underlying biological mechanisms and the role of inflammatory markers are still poorly understood. AIM: To investigate the inflammatory biomarkers levels in patients with COVID-19 presenting chemosensory dysfunctions. METHODS: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A systematic literature search was performed from January 1, 2020, to May 12, 2022. Observational studies that provided data on hematological, biochemical, infection-related indices and cellular immunity, and coagulation function in patients with COVID-19 experiencing smell and/or taste disorders were considered eligible. Effect sizes were reported as standardized mean difference (SMD) with 95% confidence intervals (CI). A negative effect size indicated that the inflammatory biomarker levels were lower among patients with chemosensory dysfunctions. RESULTS: Eleven studies were included. Patients with chemosensory disturbances had lower levels of leukocytes (SMD - 0.18, 95% CI - 0.35 to - 0.01, p = 0.04), lactate dehydrogenase (SMD - 0.45, 95% CI - 0.82 to - 0.09, p = 0.01), IL-6 (SMD - 0.25, 95% CI - 0.44 to - 0.06, p < 0.01), and C-reactive protein (SMD - 0.33, 95% CI - 0.58 to - 0.08, p < 0.01) than patients without chemosensory disturbances. CONCLUSION: Patients with SARS-CoV-2 infection who have olfactory and gustatory disorders have a lower inflammatory response than patients who do not have chemosensory alterations. The presence of these symptoms may indicate a more favorable clinical course for COVID-19.

Phantosmia May Predict Long-Term Measurable Olfactory Dysfunction After COVID-19.

OBJECTIVES: Persistent olfactory dysfunction (OD) after 6 months caused by SARS-CoV-2 infection has been reported with a variable prevalence worldwide. This study aimed to determine the prevalence of long-term OD and identify predisposing factors. METHODS: A prospective cohort study was conducted on 100 adults with COVID-19. Olfactory function was assessed with the University of Pennsylvania Smell Identification Test and a symptom survey at the onset of disease and 30 days later. Patients with persistent quantitative OD at the second assessment were reevaluated after 1 year. Demographic variables, symptoms, and the degree of smell loss were analyzed. RESULTS: Participants included 100 patients. The mean age was 42.2 ± 15.6 years, 55 (55%) were female, and 56 (56%) were outpatients. Baseline smell loss was identified in 75/100 (75%) patients, decreasing to 39/95 (40%) after 1 month, and persisting in 29 patients after 1 year. Phantosmia at baseline was the only risk factor identified for persistent OD after 1 year (relative risk 2.51; 95% confidence interval 1.53-4.12; p < 0.001). Regardless of the outcome in smell function, a significant decline in olfaction was associated with the presence of phantosmia at 1 month (ß = -12.39; 95% CI -19.82 to -4.95; p < 0.01). CONCLUSIONS: SARS-CoV-2 (2019-2020 variants) produced a highly frequent OD that persisted in 29% of the patients after 1 year. The presence of phantosmia at baseline and 1 month was associated with a worse evolution, but phantosmia may interfere with the performance in an identification smell test. A longer follow-up is required in these patients. LEVEL OF EVIDENCE: 2 Laryngoscope, 132:2445-2452, 2022.

Avaliação da Disfunção Endotelial em Casos de COVID-19 com Dilatação Fluxo-Mediada / Evaluation of Endothelial Dysfunction in COVID-19 With Flow-Mediated Dilatation

Resumo Fundamento: Sabe-se que a inflamação desempenha um papel crucial em muitas doenças, incluindo a COVID-19. Objetivo: Utilizando a dilatação fluxo-mediada (DFM), objetivou-se avaliar os efeitos da inflamação na função endotelial de pacientes com COVID-19. Métodos: Este estudo foi realizado com um total de 161 indivíduos, dos quais 80 foram diagnosticados com COVID-19 nos últimos seis meses (48 mulheres e 32 homens com idade média de 32,10±5,87 anos) e 81 eram controles saudáveis (45 mulheres e 36 homens com idade média de 30,51±7,33 anos). Os achados do ecocardiograma transtorácico e da DFM foram analisados em todos os indivíduos. Resultados com p<0,05 foram considerados estatisticamente significantes. Resultados: O ecocardiograma e a DFM do grupo COVID-19 foram realizados 35 dias (intervalo: 25-178) após o diagnóstico. Não houve diferença estatisticamente significativa nos parâmetros ecocardiográficos. Em contraste, a DFM (%) foi significativamente maior no grupo controle (9,52±5,98 versus 12,01±6,18; p=0,01). Na análise multivariada com o modelo stepwise progressivo, a DFM foi significativamente diferente no grupo controle em relação ao grupo COVID-19 (1,086 (1,026-1,149), p=0,04). O teste de correlação de Spearman indicou que a DFM (r=0,27; p=0,006) apresentou correlação positiva fraca com a presença de COVID-19. Conclusão: Os achados deste estudo apontam para disfunção endotelial induzida por COVID-19, avaliada por DFM, na fase inicial de recuperação.

Abstract Background: Inflammation is known to play a crucial role in many diseases, including COVID-19. Objective: Using flow-mediated dilatation (FMD), we aimed to assess the effects of inflammation on endothelial function in COVID-19 patients. Methods: This study was conducted with a total of 161 subjects, of whom 80 were diagnosed with COVID-19 within the last six months (comprising 48 women and 32 men with a mean age of 32.10 ± 5.87 years) and 81 were healthy controls (comprising 45 women and 36 men with a mean age of 30.51 ± 7.33 years). We analyzed the findings of transthoracic echocardiography and FMD in all subjects. All results were considered statistically significant at the level of p < 0.05. Results: The echocardiography and FMD of the COVID-19 group were performed 35 days (range: 25-178) after diagnosis. There was no statistically significant difference in echocardiographic parameters. Differently, FMD (%) was significantly higher in the control group (9.52 ± 5.98 vs. 12.01 ± 6.18, p=0.01). In multivariate analysis with the forward stepwise model, FMD was significantly different in the control group compared to the COVID-19 group (1.086 (1.026 - 1.149), p=0.04). A Spearman's correlation test indicated that FMD (r=0.27, p=0.006) had a weak positive correlation with the presence of COVID-19. Conclusion: Our findings point to COVID-19-induced endothelial dysfunction, as assessed by FMD, in the early recovery phase.