Alpha-lipoic acid does not improve olfactory training results in olfactory loss due to COVID-19: a double-blind randomized trial

Abstract Objectives Olfactory loss is a recognized long-term dysfunction after Coronavirus Disease 2019 (COVID-19) infection. This investigation aimed to assess the effect of alpha-lipoic acid as an adjuvant treatment of olfactory training on the improvement of smell loss in post-COVID-19 patients. Methods This randomized controlled trial included 128 adult outpatients who had persistent smell loss for more than 3-months after COVID-19 infection. The participants were randomly allocated into two groups: the intervention treatment group, which received alpha-lipoic acid associated to olfactory training, and comparison treatment group, which received placebo pills associated to olfactory training. The participants were followed-up for 12-weeks. Olfactory dysfunction was assessed in terms of Visual Analog Scale (VAS), and the Connecticut Chemosensory Clinical Research Center (CCCRC) test for the Brazilian population. Results A total of 100 participants completed the follow-up period and were analyzed in this study. Both groups have improved CCCRC score (p= 0.000), olfactory threshold (p= 0.000), identification score (p= 0.000) and VAS score (p= 0.000) after 12-weeks follow-up. No significant differences were determined between the intervention and comparison treatment groups in CCCRC score (p= 0.63), olfactory threshold (p= 0.50), identification score (p= 0.96) and VAS score (p= 0.97). In all these criteria, comparison treatment group went slightly worse. At the endpoint of the study, the frequency of anosmia reduced to 2% in the intervention treatment group and to 7.8% in the comparison treatment group. Also, 16.8% of the intervention group' subjects, and 15.7% of comparison treatment group's patients reached normosmia. Conclusions Overall, there was a strongly significant difference in olfactory function between baseline and endpoint for both groups. However, based on the lack of significant difference between the intervention treatment and the comparison treatment groups in terms of olfactory changes, our study appoints that the alpha-lipoic acid is not better than olfactory training alone to treat olfactory loss after COVID-19. Level of evidence Level 2.

Improvement of hedonic perception of odors as a marker of treatment response to escitalopram: olfactory changes through an open-label antidepressant trial

Objectives: To assess olfactory functions (threshold, identification, and hedonic valence) of depressed subjects before and after an 8-week trial of escitalopram and compare the results of responders and nonresponders. Methods: Fifty-two depressed subjects were recruited. Participants received escitalopram and were evaluated at two visits: baseline (V0) and week 8 (V8). They were categorized as responders (Montgomery-Åsberg Depression Rating Scale [MADRS] score reduction of > 50%) or nonresponders to treatment. Participants were evaluated with the Mini International Neuropsychiatric Interview (MINI) at V0 and, at V0 and V8, completed psychometric and olfactory assessments, including MADRS and the State-Trait Anxiety Inventory (STAI), as well as the Sniffin' Sticks® test (threshold and identification tasks). The hedonic valence of smell was assessed on a 10-cm linear scale after presenting two pleasant and two unpleasant odors. Forty-three participants completed the study (24 responders and 19 nonresponders). The Mann-Whitney, chi-square, and Fisher's exact tests were used to compare olfactory, clinical, and demographic variables between groups and within the same group at V0 and V8. The Spearman coefficient was used to calculate the correlation between clinical characteristics and olfactory variables. Results: The hedonic score of pleasant odors increased significantly between V0 and V8 only for responders (V = 61.5, p = 0.018), with no significant change in nonresponders (V = 90.5, p = 0.879). Comparison of olfactory performances between groups at V0 and V8 separately did not show a significant difference between responders and nonresponders to escitalopram. Olfactory threshold and identification scores were not different between V0 and V8 for responders or nonresponders. Conclusion: Depressed subjects have olfactory anhedonia, which appears to regress following a positive antidepressant response. Hedonic valence may be an indicator of cognitive changes associated with depression; improvement of this valence may indicate a clinical response to antidepressants.

Olfactory neuroblastoma with rhabdomyoblasts: A rare case report and review of the literature

Herein we present a case of a 62-year-old male patient who was admitted with the chief complaints of nasal obstruction. The histopathological and immunohistochemical evaluation led to a diagnosis of olfactory neuroblastoma with rhabdomyoblasts. A review of the literature revealed that this is only the fourth case of olfactory neuroblastoma with rhabdomyoblasts. Thus, investigation of more cases and longer follow-up is necessary to understand the disease and identify the best treatment to improve prognosis.

Distúrbios do olfato, uma revisão narrativa do diagnóstico ao tratamento / Olfactory dysfunction: a narrative review from diagnosis to treatment

Os distúrbios do olfato (DO) impactam de forma significativa na qualidade de vida dos indivíduos, e o conhecimento teórico a respeito do assunto deve ser de domínio dos alergologistas e imunologistas clínicos, possibilitando, assim, o seu diagnóstico e implementação de intervenções. Suas causas podem ser variadas, entre elas estão: rinite alérgica, rinossinusite crônica com ou sem pólipos, infecções de vias aéreas superiores, exposição a substâncias químicas, doenças neurológicas, drogas, traumas e o próprio envelhecimento. O olfato pode ser avaliado e mensurado através de testes com metodologias diferentes, cujo objetivo é avaliar parâmetros como a identificação de odores, limiar e discriminação olfativa. Esses testes são de fundamental importância para caracterizar objetivamente a queixa do paciente, como também avaliar o olfato antes e após determinada aplicação terapêutica. O tratamento das desordens olfativas é baseado em sua etiologia, portanto determinar a sua causa é indispensável para uma melhor eficácia no manejo. Entre as principais opções estão os corticoides tópicos, com impacto significativo nos pacientes com doença sinusal associada, treinamento olfatório e outras intervenções como ômega 3, vitamina A intranasal, e terapias que ainda requerem mais estudos.

Olfactory dysfunction significantly impacts quality of life, and allergists and clinical immunologists must be informed about it for diagnostic and interventional purposes. The causes are varied: allergic rhinitis, chronic rhinosinusitis with or without polyps, upper airway infections, exposure to chemicals, neurological diseases, drugs, trauma, and aging itself. Olfactory function can be evaluated and measured by several tests that use different methodologies to evaluate and identify odors, olfactory threshold, and olfactory discrimination. These tests are fundamental for objectively characterizing patient complaints and evaluating olfactory function before and after therapeutic interventions. Olfactory disorders are treated according to their etiology, so determining their cause is a major factor in treatment efficacy. The main options include topical corticosteroids, which have a significant impact on patients with sinus disease, olfactory training, other therapies (such as omega 3 and intranasal vitamin A), in addition to therapies that require further research.

OLFATO: forma más antigua de comunicación y sentido preciso que el otorrinolaringólogo debe conocer a profundidad / SMELL: oldest form of communication and precise sense that the otolaryngologist must know in depth

Introducción: el papel clave del olfato, antiguo sistema sensorial, es proporcionar información sobre las sustancias químicas en el medio ambiente. El olfato desempeña un papel en la detección de compuestos peligrosos, el mantenimiento de la nutrición, el comportamiento interpersonal, la salud neurológica y la sensación de placer, entre otras funciones. En consecuencia, la disfunción olfativa puede conducir a un riesgo de lesiones, desnutrición, aislamiento social y una mala calidad de vida. Materiales y métodos: se realizó una exploración bibliográfica y se identificaron artículos de acuerdo con los criterios de inclusión y exclusión definidos y se tomaron aquellos con calidad en la evidencia. Discusión: el sistema olfativo humano tiene diferencias anatómicas, fisiológicas y genéticas considerables con respecto al de otros mamíferos. Conclusiones: las destrezas olfativas varían con factores como la edad, el sexo, la etapa de desarrollo, ciertas enfermedades otorrinolaringológicas y enfermedades generales.

Introduction: The key role of the ancient olfactory sensory system is to provide information about chemicals in the environment. Smell plays a role in the detection of dangerous compounds, the maintenance of nutrition, interpersonal behavior, neurological health, and the sensation of pleasure, among other functions. Consequently, olfactory dysfunction can lead to a risk of injury, malnutrition, social isolation, and a poor quality of life. Materials and methods: A bibliographical exploration was carried out and articles were identified according to the inclusion and exclusion criteria defined and those with quality evidence were taken. Discussion: The human olfactory system has considerable anatomical, physiological, and genetic differences from that of other mammals. Conclusions: Olfactory skills vary with factors such as age, sex, stage of development, certain ear, nose and throat diseases and general diseases.

Diesel exhaust inhalation exposure induced toxicity on olfactory bulb in mice through inflammatory response mediated by activating glial cells / 环境与职业医学

Background Air pollution is related to the occurrence and development of mental diseases. Olfactory bulb damage might be the potential prodromal symptom and sign of these diseases. The toxicity of diesel exhaust (DE), one of the main sources of air pollution, on olfactory bulb and the underlying mechanisms remain to be elucidated. Objective To explore the toxicity of DE on mouse olfactory bulb and underlying mechanisms. Methods A total of 40 C57BL/6 mice were randomly divided into four groups for exposure to DE by systemic inhalation: control group (filtered air), low exposure group (750 μg·m−3 DE), medium exposure group (1500 μg·m−3 DE), and high exposure group (3000 μg·m−3 DE). The mouse inhalation exposure to DE was performed 1 h per day for 28 d. HE staining was performed to observe pathological changes in mouse olfactory bulb tissue. TUNEL assay was used to observe apop-tosis in olfactory bulb. Kyoto Encyclopedia of Genes and Genomes (KEGG) was exhibited to explore potential mechanisms of olfactory bulb damage associated with DE. Quantitative real-time PCR (qPCR) was used to determine mRNA expression levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Immunofluorescence staining was conducted to observed the microglia and astrocyte activation in olfactory bulb. Results The HE staining results showed that the number of periglomerular cells in the glomerular layer of olfactory bulb decreased in a dose-dependent manner, and the cells in the granule cell layer of olfactory bulb became disordered after DE exposure. The TUNEL staining showed that TUNEL positive cells in olfactory bulb tissue and neuronal apoptosis increased in the exposed groups compared with the control group (P＜0.05). The KEGG pathway analysis showed that DE associated with significant enrichment of TNF signaling pathway in olfactory bulb tissue. The qPCR results showed that the TNF-α relative expression level significantly increased by 67% and the IL-6 relative expression level by 340% in the DE high exposure dose group compared with the control group (P＜0.05). According to the immunofluorescence staining results, the numbers of activated microglia and astrocytes in olfactory bulb tissue significantly increased in the DE high exposure group, the relative fluorescence intensity of ionized calcium binding adaptor molecule 1 (IBA-1) increased by 120%, the granule cell layer relative fluorescence intensity of glial fibrillary acidic protein (GFAP) increased by 400%, and the glomerular layer relative fluorescence intensity of GFAP increased by 240% than those in the control group (P＜0.05). Conclusion Inhalation exposure to DE can lead to glial cell activation including microglia and astrocytes in olfactory bulb tissue by activating inflammatory pathways and releasing inflammatory factors TNF-α and IL-6, leading to neuronal apoptosis in olfactory bulb tissue.

Development of an olfactory epithelial organoid culture system based on small molecule screening / 生物工程学报

Olfactory epithelium, which detects and transmits odor signals, is critical for the function of olfactory system. Olfactory epithelium is able to recover spontaneously after injury under normal circumstances, but this ability is dampened in certain diseases or senility, which causes olfactory dysfunction. The olfactory epithelium consists of basal cells, sustentacular cells and olfactory sensory neurons. In order to develop an olfactory epithelial organoid containing multiple olfactory cell types in vitro, we used three-dimensional culture model and small molecules screening. This organoid system consists of horizontal basal-like cells, globose basal-like cells, sustentacular-like cells and olfactory sensory neurons-like cells. Through statistical analysis of clone diameter, immunofluorescence staining and qPCR detection of the expression level of related marker genes. We identified a series of growth factors and small molecule compounds that affected the proliferation, composition and gene expression of the organoids. CHIR-99021, an activator of Wnt signaling pathway, increased the colony formation and proliferation rate of olfactory epithelial organoids and the expression level of marker genes of olfactory sensory neurons-like cells. In addition, each factor in the culture system increased the proportion of c-Kit-positive globose basal-like cell colonies in organoids. Moreover, EGF and vitamin C were both beneficial to the expression of horizontal basal-like cell marker genes in organoids. The established olfactory epithelial organoid system mimicked the process of olfactory epithelial stem cells differentiating into various olfactory epithelial cell types, thus providing a research model for studying olfactory epithelial tissue regeneration, the pathological mechanism of olfactory dysfunction and drug screening for olfactory dysfunction treatment.

A prospective study of the effect of functional endoscopic sinus surgery on the recovery of olfactory function in patients with chronic rhinosinusitis with nasal polyposis / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the efficacy of functional endoscopic sinus surgery（FESS） in the treatment of olfactory dysfunction in patients with chronic rhinosinusitis with nasal polyps （CRSwNP） , at the same time, it provides an evidence for the prognosis evaluation of olfaction and the clinical application of oERPs to evaluate the plasticity of olfaction cortex. Methods:From October 2021 to October 2022, 45 patients with CRSwNP who underwent FESS nine-step standardized treatment in our department were recruited as the research subjects, divided into 22 patients with eosinophilic CRSwNP（ECRS）and 23 patients with non-eosinophilic CRSwNP（nECRS）. VAS-olfactory dysfunction （VAS-OD） score, SNOT-22 olfactory score, Sniffin' Sticks test and oERPs collection and processing were performed before the operation. All items were evaluated again 3 months after the operation. Results:VAS-OD and SNOT-22 olfactory score were significantly lower in all CRSwNP patients after the operation than those before the operation[F（1, 43） =357.429, P<0.001; F（1, 43） =185.657, P<0.001], the scores of T, D, I and TDI scores in Sniffin' Sticks test were significantly higher than those before the operation[F（1, 43） =126.302, P<0.001; F（1, 43） =311.301, P<0.001; F（1, 43） =131.401, P<0.001; F（1, 43） =295.885, P<0.001]; The decrease of VAS-OD and SNOT-22 olfactory score in the ECRS group was smaller than that in the nECRS group[F（1, 43） =4.825, P=0.033; F（1, 43） =9.916, P=0.003], T, D and TDI scores were significantly lower in nECRS group than those in nECRS group[F（1, 43） =6.719, P=0.013; F（1, 43） =4.890, P=0.032; F（1, 43） =4.469, P=0.040]; There was a positive correlation between preoperative eosinophil-to-lymphocyte ratio（ELR） and SNOT-22 olfactory score and how much it changes（r=0.455, P=0.002; r=-0.414, P=0.005）, a negative correlation between T, TDI score and how much they change respectively（r=-0.431, P=0.003; r=-0.385, P=0.009; r=-0.383, P=0.010; r=-0.316, P=0.035）. The latency of P3 was significantly shorter after operation than that before operation in all CRSwNP patients[F（1, 14） =24.840, P<0.001], however, the amplitude has no significant surgical effect. Conclusion:FESS could significantly improve the olfactory function of CRSwNP patients, while changes in plasticity may occur in the olfactory cortex. In addition, the preoperative peripheral blood eosinophil granulocyte level can predict the postoperative olfactory improvement.

Olfactory stimulus as environmental enrichment for shelter dogs: a pilot study / Estímulo olfativo como enriquecimento ambiental para cães de abrigo: um estudo piloto

Environmental enrichment techniques include olfactory stimuli for improving animal welfare. This study aimed to analyze the reactions of 41 shelter dogs exposed to odorous stimuli, such as the method used in another study on wild canids. The focal animal method analyzed the dogs' reactions, with all behaviors recorded. Behavioral responses were classified as positive (P+), negative (N-), or other (Ot). Independent variables were all dogs and the size of the packs. The behavior between the basal (without stimulus), exposure, and after-stimulus withdrawal was analyzed. For all dogs, olfactory stimuli significantly increased P+ (P=0.001) and N- (P=0.004), contrasting with the decrement of Ot behaviors (P=0.001) from the basal to the exposure phase. After the withdrawal of the stimuli, P+, N-, and Ot behaviors returned to basal levels (P>0.05). There were no significant differences (P>0.05) in the conduct of small or large packs exposed to stimuli. Dogs are sensitive to olfactory stimuli, but arousal is generalized to P+ and N-. It is undesirable to an N- increase for improvement of animal welfare. Contrary to what was observed in a study with wild canids, the method failed in shelter dogs because N- was increased. The introduction of sudden novelty (olfactory stimulus) in an impoverished shelter environment may have caused excitement in the dogs. It is suggested that changes in the method, such as stimuli exposition to each dog in an isolated room, are necessary to increase sheltered dog well-being.(AU)

As técnicas de enriquecimento ambiental incluem estímulos olfativos para aumentar o bem-estar animal. O objetivo deste estudo foi analisar as reações de 41 cães de abrigo expostos a estímulos odoríferos, como o método utilizado em outro estudo com canídeos selvagens. As reações dos cães foram analisadas pelo método animal focal, com todos os comportamentos registrados. As respostas comportamentais foram classificadas como positivas (P+), negativas (N-) ou outras (Ot). As variáveis independentes foram todos os cães e o tamanho das matilhas. Foi analisado o comportamento entre o basal (sem estímulo), exposição e após a retirada do estímulo. Para todos os cães, os estímulos olfativos aumentaram significativamente P+ (P=0,001) e N- (P=0,004), contrastando com a diminuição dos comportamentos Ot (P=0,001) da fase basal para a de exposição. Após a retirada dos estímulos, os comportamentos P+, N- e Ot retornaram aos níveis basais (P>0,05). Não houve diferenças significativas (P>0,05) no comportamento de matilhas pequenas ou grandes expostas a estímulos. Os cães são sensíveis a estímulos olfativos, mas a excitação parece ser generalizada para ambos, P+ e N-. É indesejável um aumento de N- para melhoria do bem-estar animal. Ao contrário do que foi observado em um estudo com canídeos selvagens, o método falhou em abrigar cães porque o N- foi aumentado. A introdução de uma novidade repentina (estímulo olfativo) em um ambiente de abrigo empobrecido, pode ter causado excitação exagerada nos cães. Sugere-se alterações no método, como a exposição de estímulos a cada cão em uma sala isolada necessária para aumentar o bem-estar do cão abrigado.(AU)

Long-term Recovery Patterns of Olfactory Function after Trans-sphenoidal Approach with Nasoseptal Flap Elevation

Abstract Introduction Nasoseptal flap is widely used in reconstruction of the skull base to prevent cerebrospinal fluid leakage after surgery for skull base lesions. There has been a debate on whether more severe olfactory dysfunction occurs after nasoseptal flap elevation than the conventional trans-sphenoidal approach. Objective To compare the long-term recovery patterns associated with nasoseptal flap and the conventional trans-sphenoidal approach. Methods The subjects were divided into the conventional trans-sphenoidal approach group and the nasoseptal flap elevation group. We followed up self-reported olfactory score using the visual analogue scale and threshold discrimination identification (TDI) score of the Korean Version of the Sniffin Stick test II for 12 months, with olfactory training. Results The study included 31 patients who underwent the trans-sphenoidal approach. Compared with preoperative status, the mean visual analogue scale and TDI scores in the conventional trans-sphenoidal approach group recovered 2 months postoperatively, while in the nasoseptal flap elevation group the visual analogue scale and TDI scores recovered 6 months and 3 months after surgery, respectively. Twelve months after surgery, the visual analogue scale and TDI scores in the conventional trans-sphenoidal approach group were 9.3 ± 0.5 and 28.5 ± 4.3, while those from the nasoseptal flap elevation group were 8.9 ± 1.5 and 27.2 ± 4.7 (p = 0.326; 0.473). Only one of the patients in the nasoseptal flap elevation group had permanent olfactory dysfunction. Conclusion The olfactory function recovered more gradually in the nasoseptal flap elevation group than in the conventional trans-sphenoidal approach group, but there was no difference between the two groups after 6 months.

Effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging mice / 中国针灸

OBJECTIVE@#To observe the effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging (SAMP8) mice, and to explore the action pathway of moxa smoke.@*METHODS@#Forty-eight six-month-old male SAMP8 mice were randomly divided into a model group, an olfactory dysfunction group, a moxa smoke group and an olfactory dysfunction + moxa smoke group, with 12 mice in each group. Twelve age-matched male SAMR1 mice were used as the blank group. The olfactory dysfunction model was induced in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group by intraperitoneal injection of 3-methylindole (3-MI) with 300 mg/kg, and the moxa smoke group and the olfactory dysfunction + moxa smoke group were intervened with moxa smoke at a concentration of 10-15 mg/m3 for 30 min per day, with a total of 6 interventions per week. After 6 weeks, the emotion and cognitive function of mice was tested by open field test and Morris water maze test, and the neuronal morphology in the CAI area of the hippocampus was observed by HE staining. The contents of neurotransmitters (glutamic acid [Glu], gamma-aminobutyric acid [GABA], dopamine [DA], and 5-hydroxytryptamine [5-HT]) in hippocampal tissue of mice were detected by ELISA.@*RESULTS@#The mice in the blank group, the model group and the moxa smoke group could find the buried food pellets within 300 s, while the mice in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group took more than 300 s to find them. Compared with the blank group, the model group had increased vertical and horizontal movements (P<0.05) and reduced central area residence time (P<0.05) in the open field test, prolonged mean escape latency on days 1-4 (P<0.05), and decreased search time, swimming distance and swimming distance ratio in the target quadrant of the Morris water maze test, and decreased GABA, DA and 5-HT contents (P<0.05, P<0.01) and increased Glu content (P<0.05) in hippocampal tissue. Compared with the model group, the olfactory dysfunction group had increased vertical movements (P<0.05), reduced central area residence time (P<0.05), and increased DA content in hippocampal tissue (P<0.05); the olfactory dysfunction + moxa smoke group had shortened mean escape latency on days 3 and 4 of the Morris water maze test (P<0.05) and increased DA content in hippocampal tissue (P<0.05); the moxa smoke group had prolonged search time in the target quadrant (P<0.05) and increased swimming distance ratio, and increased DA and 5-HT contents in hippocampal tissue (P<0.05, P<0.01) and decreased Glu content in hippocampal tissue (P<0.05). Compared with the olfactory dysfunction group, the olfactory dysfunction + moxa smoke group showed a shortened mean escape latency on day 4 of the Morris water maze test (P<0.05). Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a decreased 5-HT content in the hippocampus (P<0.05). Compared with the blank group, the model group showed a reduced number of neurons in the CA1 area of the hippocampus with a disordered arrangement; the olfactory dysfunction group had similar neuronal morphology in the CA1 area of the hippocampus to the model group. Compared with the model group, the moxa smoke group had an increased number of neurons in the CA1 area of the hippocampus that were more densely packed. Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a reduced number of neurons in the CA1 area of the hippocampus, with the extent between that of the moxa smoke group and the olfactory dysfunction group.@*CONCLUSION@#The moxa smoke could regulate the contents of neurotransmitters Glu, DA and 5-HT in hippocampal tissue through olfactory pathway to improve the learning and memory ability of SAMP8 mice, and the olfactory is not the only effective pathway.

Effect of cadmium chloride toxicity on olfactory mucosa / Efecto de la toxicidad del cloruro de cadmio en la mucosa olfativa

SUMMARY: Cadmium is a highly toxic metal and affects the respiratory mucosa. The aim of the study is to show the inflammation and degenerative effect of cadmium on the olfactory mucosa. In this study, eight-week-old Wistar rats with an average weight of 170-190 g were divided into two groups (control and experiment) with 20 animals in each group and used in the experiments. The rats in the experimental group were given 2 mg/kg/day powdered cadmium chloride dissolved in water intraperitoneally every day for two weeks. At the end of the experiment, the nasal cavity was completely removed with anesthesia. Concha nasalis superior was separated, fixed with zinc-Formalin solution and decalcified with 5 % EDTA (Ethylene-diaminetetraacetic acid). After routine histopathological procedure, APAF-1 antibody was used for expression of Hematoxylin-Eosin (HE) and immunohistochemistry. Histopathological examination revealed interruptions in the basement membrane structure due to cadmium and degenerative changes in stem cells, degeneration in sensory cells and pycnosis in nuclei, dilatation in blood vessels and increased inflammation in connective tissue. APAF-1 expression was found to increase in epithelial cells and olfactory glands (Bowman gland) cells. It has been thought that cadmium toxicity increases cell degeneration and inflammation in the olfactory mucosa and may significantly affect cell death and olfactory metabolism by inducing the pro-apoptotic process.

El cadmio es un metal altamente tóxico que afecta la mucosa respiratoria. El objetivo fue mostrar el efecto inflamatorio y degenerativo del cadmio sobre la mucosa olfativa. En este estudio, ratas Wistar de ocho semanas de edad con un peso promedio de 170-190 g se dividieron en dos grupos (control y experimental) con 20 animales en cada grupo. Las ratas del grupo experimental recibieron 2 mg/kg/día de cloruro de cadmio en polvo disuelto en agua por vía intraperitoneal todos los días durante dos semanas. En los animales se exirpó la cavidad nasal bajo anestesia. Se separó la concha nasal superior, se fijó con solución de zinc-Formalina y se descalcificó con EDTA (ácido etilendiaminotetraacético) al 5 %. Después del procedimiento histopatológico de rutina, Hematoxilina- Eosina (HE) e inmunohistoquímica, se utilizó el anticuerpo APAF-1. El examen histopatológico reveló interrupciones en la estructura de la membrana basal debido al cadmio y cambios degenerativos en las células madre, degeneración en las células sensoriales y picnosis en los núcleos, dilatación de los vasos sanguíneos y aumento de la inflamación en el tejido conjuntivo. Se encontró que la expresión de APAF-1 aumenta en las células epiteliales y en las células de las glándulas olfatorias (glándulas de Bowman). Se ha pensado que la toxicidad del cadmio aumenta la degeneración celular y la inflamación en la mucosa olfativa y puede afectar significativamente la muerte celular y el metabolismo olfativo al inducir el proceso proapoptótico.

Age-dependent differences of the depth of olfactory fossa in children

Abstract Objective: With this radio-anatomical study, we aimed to describe the distribution of the depth of the olfactory fossa based on the Keros classification in the pediatric population in our region and to reduce complication rates by providing normative data. Methods: This was a retrospective study conducted with computed tomography imaging of the paranasal sinuses of 390 pediatric patients referred over a six-year period in Sakarya and Kocaeli University Faculty of Medicine. Patients were divided into 3 groups as 1-6, 6-12, and 12-18 years old. The depth of the olfactory fossa was measured and classified according to the Keros classification. The incidence of Keros asymmetries was also investigated. Results: The distribution of the depth of a total of 780 olfactory fossa according to the Keros classification was 24.7% Keros I, 65.9% Keros II, and 9.4% Keros III. When the groups were evaluated with each other and within each group, it was seen that the prevalence of Keros I type was significantly higher in the first group (p < 0.05), and the prevalence of Keros type II was significantly higher in the second and third groups (p < 0.05). Apart from this, the number of Keros type III increased in the third group compared to the first two groups and showed a statistically significant difference (p < 0.05). Among all patients, asymmetry of the olfactory fossa was detected in 29 patients (7.4%). Although the number of olfactory fossa asymmetry was low in group I, it was not significantly different between the groups (p > 0.05). Conclusion: In our study, high Keros I rate and low Keros III rate in children aged -6 were remarkable. Especially for children under the age of six, questions arise about the validity of the Keros classification. More detailed studies in larger populations, in different ethnicities, and with various age groups are needed. Level of evidence: Level 3.

Changes in olfaction and taste in patients hospitalized for COVID-19 and their relationship to patient evolution during hospitalization

Abstract Objectives: During the COVID-19 pandemic, several cases of changes in olfaction and taste associated with the infection have been reported. Therefore, otolaryngologists are frequently the first medical professionals sought by patients. The aim of this study was to evaluate the frequency of olfaction and taste disorders in patients hospitalized with COVID-19, and their association with other clinical manifestations and patient evolution during hospitalization. Methods: 248 patients, admitted to three public hospitals in Belo Horizonte, Minas Gerais, Brazil, were prospectively included: Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG), Hospital Júlia Kubitschek (HJK) and Hospital Eduardo de Menezes (HEM), who, upon admission to hospital, presented with Severe Acute Respiratory Syndrome due to COVID-19. Clinical and laboratory variables and outcomes during hospitalization were prospectively collected from the electronic medical records. The collection of sociodemographic and symptomatology data during the acute phase was carried out prospectively in electronic medical records and confirmed with the patients at a subsequent outpatient visit. Results: The most frequently reported symptoms were dyspnea (77.4%), cough (69.8%) and fever (55.2%). During the acute phase of the disease, 95 (38.3%) and 87 (35.1%) patients reported taste and olfaction disorders, respectively. There was a lower prevalence of dysosmia among patients with previous comorbidities (p < 0.05). Both symptoms were associated with less need for intensive care admission (p = 0.001 for dysgeusia and p = 0.021 for dysosmia) and a negative correlation with length of hospital stay (dysosmia: r= −0.175, p < 0.05; dysgeusia: r = −0.29, p < 0.001) and length of stay in the ICU (dysosmia: r = −0.136, p < 0.05; dysgeusia: r = −0.215, p < 0.05). The absence of taste disorders was also associated with a greater need for mechanical ventilation (p < 0.001). Conclusion: Changes in taste and olfaction were reported by a large number of patients in the acute phase of COVID-19. In this study, both were markers of better clinical patient evolution. Level of evidence: 1B.

Olfactory neuroepithelium in the middle turbinate: is there any impact on olfaction function after lateral marsupialization for concha bullosa surgery?

Abstract Introduction: The effect of the quantity of olfactory neuroepithelium in the middle turbinate on the postoperative olfactory function for middle turbinate concha bullosa patients has not yet been evaluated. Objective: The primary aim of this study was to investigate the olfactory structures in the middle turbinate by immunohistochemical analysis of the olfactory marker protein and to correlate the immunostaining results with the olfaction test results for patients with middle turbinate concha bullosa. Methods: Surgical materials of 18 middle turbinate concha bullosa patients who had undergone lateral marsupialization surgery were immunostained with olfactory marker protein antibodies. Smell diskettes olfaction test was applied to all of the study group patients both preoperatively and three months postoperatively. A visual analog scale was used to quantify the sense of nasal obstruction. Results: It was observed that the postoperative smell scores and the nasal obstruction visual analog scale values were significantly improved as compared to the preoperative values (p<0.05). In addition, there was a significant correlation between the smell score gain and the visual analog scale gain values (r = 0.682). Results also indicated no significant correlation between the olfactory marker protein staining scores and the smell scores (p > 0.05). Conclusion: This first paper demonstrated that the quantity of the olfactory mucosa in the middle turbinate was not a determining factor for the postoperative smell function degree for middle turbinate concha bullosa patients. The underlying cause of the olfactory deficit for middle turbinate concha bullosa patients seems to be obstruction related rather than the middle turbinate's olfactory mucosa containing status.

Prevalence of respiratory epithelial adenomatoid hamartomas (REAH) associated with nasal polyposis: an epidemiological study - how to diagnose

Abstract Objectives: To highlight the prevalence of respiratory epithelial adenomatoid hamartomas in the olfactory cleft of patients with nasal polyposis. To demonstrate characteristics indicative of hamartoma on the CT scans of paranasal sinuses during surgery and in histopathological exams. Methods: Cross-sectional study carried out in Hospital das Clínicas da UFMG and Núcleo de Otorrino BH. We performed 114 nasal endoscopic surgeries for polyposis, between February 2015 and November 2019. We assessed the olfactory cleft width in all preoperative CT scans. Upon seeing an indication of hamartoma on the CT scan, we took a tissue sample from the olfactory cleft during the surgery and sent for histopathological exam. We referred the samples to a pathologist experienced in the anatomopathological diagnosis of respiratory epithelial adenomatoid hamartomas. Results: Of the 114 patients with polyposis, 54 (47.4%) had olfactory cleft enlargement and, 100% of them had tissue with a dense and hardened polypoid aspect, with a slight cerebri-form appearance in this region during the surgery. Histology confirmed a respiratory epithelial adenomatoid hamartoma. Conclusion: This observation suggests that the presence of hamartomas in polyposis is common, but underdiagnosed. Level of evidence: Step 3 (Level 3).

Postinfectious Olfactory Complaints: A Follow-up Study

Abstract Introduction Acute upper respiratory infection (AURI) is the most common cause of postinfectious olfactory dysfunction (PIOD). Objective We investigated the prevalence of PIOD in a large group of patients reporting persistent smell impairment perception after the AURI resolution. Methods Olfactometry was performed within 1 month after the common cold resolution and after 1 year in 467 (299 males, mean age 41.7 years) outpatients. The Sniffin' Sticks olfactory test (Burghart instruments, Wedel, Germany) was used. Results Anosmia was documented in 28 (6%) patients, hyposmia in 33 (7%), and cacosmia in 55 (11.7%). After 1 year, PIOD improved in 82 (79.6%) patients re-tested. Conclusion The current study demonstrated that persistent olfactory dysfunction is a relevant symptom in patients with AURI, even though many patients had normal olfactometry. Thus, smell impairment deserves careful attention and requires objective documentation.

Relation between Vitamin B12 Levels and Smell Affection in COVID-19 Patients

Abstract Introduction Olfactory and gustative alterations are frequent in the initial stages of the COVID-19 infection. Vitamin B12 deficiency has been linked to olfactory dysfunction. Objective The present study aimed to assess the relationship between vitamin B12 levels and smell affection in COVID-19 patients. Methods The present study included 201 laboratory-confirmed COVID-19 patients. Smell affection was assessed using self-rated olfactory function. Serum vitamin B12 levels were assessed using commercial enzyme-linked immunosorbent assay (ELISA) kits. Results According to the smell function assessment, the patients were classified into three categories: normal osmesis (n = 77), hyposmia (n = 49), and anosmia (n = 75) (►Fig. 1). Four weeks later, 195 patients (97.0%) had their normal smell function restored. The remainder 6 patients included 4 anosmic and 2 hyposmic patients. Patients with hyposmia or anosmia had significantly lower vitamin B12 levels when compared with patients with normal osmesis (median [IQR]: 363.0 [198.0-539.0] versus 337.0 [175.0-467.0] and 491.0 [364.5-584.5] pg/ml, respectively, p < 0.001). Conclusion Vitamin B12 appears to have some contribution to smell affection in patients with COVID-19 infection.

Correlation and agreement of olfactory perception assessed by the Connecticut Chemosensory Clinical Research Center olfactory test and the Brief-Smell Identification Test / Correlação e concordância da percepção olfativa avaliada pelos testes olfativos chemosensory clinical research center e brief-smell identification test,

Abstract Introduction: Assessing olfactory perception in olfactory disorders is of utmost importance in therapy management. However, the University of Pennsylvania Smell Identification Test and the Sniffin' Sticks are the only tests validated in Brazil. Objectives: To evaluate the correlation and agreement between the Chemosensory Clinical Research Center olfactory test and the Brief-Smell Identification Test - University of Pennsylvania Smell Identification Test - in healthy participants and in participants with olfactory disorders based on the results and technical aspects of both tests. Methods: Fifty participants without olfactory complaints and 50 participants with olfactory disorders who underwent the Chemosensory Clinical Research Center olfactory test and the Brief-Smell Identification Test were included. The following tests were used for statistical analysis: Mann-Whitney U test, Spearman's correlation, intraclass correlation coefficient and Bland-Altman plot. An alpha error (significance level) of 0.05 was considered in the statistical analysis. Results: Both tests were effective in distinguishing the groups without the presence of overlapping values for the measured markers. Additionally, there was a strong correlation between Spearman's correlation and intraclass correlation coefficient between the tests and for both nostrils. However, the correlations were lower when the groups were individually evaluated. The Bland-Altman plot showed no bias when all participants were simultaneously evaluated. Conclusions: The tests to assess olfactory perception presented a high level of agreement. In our sample, we could infer that the Connecticut Chemosensory Clinical Research Center olfactory test is similar to the Brief-Smell Identification Test and can be used in the routine diagnosis of patients with complaints of olfactory disorders, considering the advantage of its low cost.

Resumo Introdução: Avaliar a percepção olfativa em distúrbios olfativos é de extrema importância para a correta conduta terapêutica. No entanto, apenas o teste University of Pennsylvania smell identification test e o teste sniffin'sticks são validados no Brasil. Objetivos: Avaliar a correlação e concordância entre os testes Connecticut chemosensory clinical research center e do brief-smell identification test e University of Pennsylvania smell identification test em participantes saudáveis e em participantes com distúrbios olfativos de acordo com os resultados e aspectos técnicos dos dois testes. Método: Cinquenta participantes sem queixas olfativas e 50 participantes com distúrbios olfativos submetidos ao teste Connecticut chemosensory clinical research center e ao brief-smell identification test foram incluídos. Os seguintes testes foram usados para análise estatística: teste U de Mann-Whitney, correlação de Spearman, coeficiente de correlação intraclasse e plotagem de Bland-Altman. Um erro alfa (nível de significância) de 0,05 foi considerado nas análises estatísticas feitas no estudo. Resultados: Ambos os testes foram eficazes para diferenciar os grupos sem a presença de valores sobrepostos para os marcadores medidos. Além disso, houve uma forte correlação entre a correlação de Spearman e o coeficiente de correlação intraclasse entre os testes e para as duas narinas. Entretanto, as correlações foram menores quando os grupos foram avaliados individualmente. O gráfico de Bland-Altman não mostrou viés quando todos os participantes foram avaliados simultaneamente. Conclusões: Os testes para avaliar a percepção olfativa apresentaram um elevado nível de concordância. Em nossa amostra, podemos inferir que o Connecticut chemosensory clinical research center é equivalente ao brief-smell identification test e pode ser usado no diagnóstico de rotina de pacientes com queixas de distúrbios olfativos, considerando a vantagem de seu baixo custo.

Effect of intranasal administration of NeuroEPO in the histological structure of the olfactory mucosa of Wistar rats / Efecto de la administración intranasal de NeuroEPO en la estructura histológica de la mucosa olfatoria de ratas Wistar

Introduction: Strokes and neurodegenerative diseases are major global health problems, not only because they cause high mortality and disability, but due to the lack of effective therapies. NeuroEPO, a variant of recombinant human erythropoietin (rHu-EPO) with a low sialic acid content, has shown encouraging results as a potential neuroprotective agent when administered intranasally. Objective: To determine the effect of intranasal administration of NeuroEPO on the histological structure of the olfactory mucosa of Wistar rats. Materials and Methods: An experimental, prospective, and longitudinal study was conducted on Wistar rats. Ten healthy animals were randomly distributed into two groups of five each. The control group received a vehicle (0.3 μl/g/day) and the treated group received NeuroEPO (300 μg/kg/day). Both treatments were administered intranasally for 28 days. The histological characteristics of the olfactory mucosa were evaluated. The medians between the study groups were compared using the Mann-Whitney U test. Results: There were no alterations in the histological characteristics of the olfactory epithelium. However, slight hypertrophy and hyperplasia of the Bowman's glands were observed at the level of the lamina propria in the group treated with NeuroEPO. Conclusions: The administration of the nasal formulation of NeuroEPO did not induce histological alterations of the olfactory mucosa of Wistar rats under the experimental conditions of this research.

Introducción: Los accidentes cerebrovasculares y las enfermedades neurodegenerativas constituyen un importante problema de salud mundial. No solo porque causan una alta mortalidad y discapacidad, sino por la falta de terapias eficaces para tratarlos. La NeuroEPO, una variante de la eritropoyetina humana recombinante (rHu-EPO) con bajo contenido en ácido siálico, ha mostrado resultados alentadores como potencial agente neuroprotector al ser administrada por vía intranasal. Objetivo: Determinar el efecto de la administración intranasal de NeuroEPO en la estructura histológica de la mucosa olfatoria de ratas Wistar. Materiales y Métodos: Se realizó un estudio experimental, prospectivo y de corte longitudinal en ratas Wistar. Se utilizaron diez animales sanos distribuidos aleatoriamente en dos grupos de cinco cada uno. El grupo control recibió vehículo (0,3 μl/g/día) y el grupo tratado recibió NeuroEPO (300 μg/kg/día). Ambos tratamientos fueron administrados por vía intranasal durante 28 días. Fueron evaluadas las características histológicas de la mucosa olfatoria. Las medianas de los grupos del estudio fueron comparadas mediante la prueba U de Mann-Whitney. Resultados: No se evidenciaron alteraciones en las características histológicas del epitelio olfatorio. Sin embargo, a nivel de la lámina propia en el grupo tratado con NeuroEPO, se observó una ligera hipertrofia e hiperplasia de las glándulas de Bowman. Conclusiones: La administración de la formulación nasal de NeuroEPO no indujo alteraciones histopatológicas de la mucosa olfatoria de ratas Wistar en las condiciones experimentales de esta investigación.