Although elastography can assist in the differential diagnosis of thyroid nodules, its diagnostic performance is not ideal at present. Further improvements in the technique and the diagnostic criteria are necessary for this examination to provide a useful contribution to diagnosis.

BackgroundChronic rhinosinusitis with nasal polyps is characterized by local inflammation and is categorized into two subtypes in Japan: eosinophilic chronic rhinosinusitis, and non-eosinophilic chronic rhinosinusitis. The objective of this study was to investigate the expression of key transcription factors for Treg and Th1/Th2/Th17 cells, in relation to the mRNA expression of representative cytokines in these two subtypes of chronic rhinosinusitis with nasal polyps.MethodsThe expression of forkhead box P3 (FOXP3), T-box transcription factor (T-bet), GATA3, retinoid acid-related orphan receptor C (RORc), the suppressive cytokines TGF-β1 and IL-10, and Th1/Th2/Th17 cytokines (IFN-γ, IL-4, IL-5, IL-13, IL-17) were analyzed by means of RT-PCR in eosinophilic polyps. Eosinophilic polyps were defined as having an eosinophil count of more than 50 per microscopic field (×400 magnification) using five fields located in the subepithelial area of the polyps, while the non-eosinophilic polyps and controls did not fulfill this criteria. The numbers of T cells, CD4+ T cells, CD8+ T cells and Treg were histologically counted using sections that were immunostained for CD3, CD4, CD8, and FOXP3, respectively.ResultsIn eosinophilic polyps, we observed significantly fewer CD4+ T cells and CD8+ T cells, and lower GATA3, RORc and IL-10 mRNA expression, but a significantly higher IL-5, and IL-13 mRNA expression compared with controls, whereas FOXP3 and T-bet mRNA expression were not significantly different compared with controls. In non-eosinophilic polyps, FOXP3, IL-10, IL-17A, TGFβ1 and IFNγ mRNA expression was significantly higher compared with controls, whereas IL-4, 5 and 13 expression was not significantly different from controls.ConclusionWe showed a reduction of GATA3 and RORc mRNA, low Treg-related cytokines and elevated Th2 cytokine levels in eosinophilic chronic rhinosinusitis, whereas we demonstrated the upregulation of Treg cells and increases of Th1 and Th17 cytokines in non-eosinophilic chronic rhinosinusitis in the Japanese population. The different mRNA expression profiles of Treg and Th1/Th2/Th17 signature transcription factors and cytokines between eosinophilic chronic rhinosinusitis and non-eosinophilic chronic rhinosinusitis suggests heterogeneity in the pathogenesis of chronic rhinosinusitis with nasal polyps.

BackgroundAnosmia is a frequent symptom in coronavirus disease 2019 (COVID-19) patients that generally resolves within weeks. In contrast, the anosmia caused by other upper respiratory infections affects a small proportion of patients and may take months to resolve or never resolve. The mechanisms behind COVID-19-induced olfactory dysfunction remain unknown. Here, we address the unique pathophysiology of COVID-19-associated olfactory dysfunction.MethodsThe expression of ACE2 (virus binding receptor) and TMPRSS2 and Furin (host cell proteases facilitating virus entry) was examined in the nasal mucosa, composed of respiratory mucosa (RM), olfactory mucosa (OM), and olfactory bulb (OB) of mouse and human tissues using immunohistochemistry and gene analyses.ResultsCo-expression of ACE2, TMPRSS2, and Furin was observed in the RM and in the OM, especially in the supporting cells of the olfactory epithelium and the Bowman’s glands. Notably, the olfactory receptor neurons (ORNs) in the OM were positive for ACE2 but almost negative for TMPRSS2 and Furin. Cells in the OB expressed ACE2 strongly and Furin weakly, and did not express TMPRSS2. All three gene expressions were confirmed in the nasal mucosa and OB.ConclusionsACE2 was widely expressed in all tissues, whereas TMPRSS2 and Furin were expressed only in certain types of cells and were absent in the ORNs. These findings, together with clinical reports, suggest that COVID-19-related anosmia occurs mainly through sensorineural and central dysfunction and, to some extent, conductive olfactory dysfunction. The expression of ACE2, but not TMPRSS2 or Furin, in ORNs may explain the early recovery from anosmia.

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The posterior nasal nerve is the dominant source of the parasympathetic, sympathetic, and sensory fibers that innervate the nasal respiratory mucosa. Therefore, a posterior nasal neurectomy (PNN) is thought to induce denervation of the nasal mucosa and relieve the nasal symptoms of allergic rhinitis. However, the underlying mechanisms and therapeutic action of PNN remain unknown. To investigate the impact of PNN-induced denervation of the nasal mucosa on allergic rhinitis, we developed a rat model of PNN and examined the effects of PNN on allergic rhinitis in ovalbumin-sensitized rats. This rat model of PNN was characterized by the depletion of nerve fibers, choline acetyltransferase, and neuropeptides (eg, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and neuropeptide Y) in the nasal respiratory mucosa. These animals exhibited nasal gland and goblet cell hypertrophy in the septal mucosa and atrophy of the submucosal gland in the lateral nasal wall, as well as reduced nasal secretion due to deficient acetylcholine synthesis. In an ovalbumin-sensitized model of allergic rhinitis, PNN also induced the depletion of nerve fibers, choline acetyltransferase, and neuropeptides in the nasal mucosa and suppressed nasal secretion. However, PNN did not affect mucosal thickening, eosinophil and mast cell infiltration, interleukin-4 and interferon-γ mRNA expression, and allergic symptoms (ie, sneezing and nasal scratching). These results suggest that the peripheral nerves and corresponding neuropeptides regulate nasal secretion, but not hypersensitivity, in allergic rhinitis, and that allergic rhinitis-related mucosal reactions occur in a highly denervated mucosa after PNN. Posterior nasal neurectomy may be a therapeutic option for the treatment of hyperrhinorrhea, but not allergic rhinitis hypersensitivity. Allergic rhinitis is among the most common diseases; affecting 10-30% of people in industrialized countries. [1][2][3] This condition presents with symptoms that reduce the quality of life such as rhinorrhea, sneezing, nasal obstruction, and nasal itching. 4 Medical allergic rhinitis treatment is approached in a stepwise manner and includes agents such as antihistamines and nasal topical steroids. 1,2,5 However, for patients with allergic rhinitis refractory to medication therapy; surgical interventions such as endoscopic posterior nasal neurectomy (PNN) have been attempted.Endoscopic PNN, which involves the intranasal severing of the posterior nasal nerve, is a common surgical treatment for allergic rhinitis in Asia. 2,6,7 The posterior nasal nerve, which is a peripheral branch of the vidian nerve, innervates the nasal cavity via the pterygopalatine ganglion, which comprises parasympathetic and sympathetic vidian nerve fibers and sensory nerve fibers from the trigeminal nerve. Therefore, PNN is expected to suppress nasal hypersecretion by blocking autonomic vidian nerve fibers, similar to vidian neurectomy (VN), as well as hypersensitivity by simultaneously blocking sensory nerve fibers. 6...

The impact of SARS-CoV-2 on the olfactory pathway was studied over several time points using Syrian golden hamsters. We found an incomplete recovery of the olfactory sensory neurons, prolonged activation of glial cells in the olfactory bulb, and a decrease in the density of dendritic spines within the hippocampus. These data may be useful for elucidating the mechanism underlying long-lasting olfactory dysfunction and cognitive impairment as a post-acute COVID-19 syndrome.

A near loss of smell may result from conductive and/or neural olfactory disorders. However, an olfactory test to selectively detect neural disorders has not been established. We investigated whether onset latency of sensory response to intravenous odor injection can detect neural disorders in humans and mice. We showed that longer preoperative onset latency of odor recognition to intravenous odor in patients with chronic rhinosinusitis predicted worse recovery of olfactory symptoms following sinus surgery. The onset latency of the olfactory sensory neuron (OSN) response to intravenous odor using synaptopHluorin signals from OSN axon terminals was delayed in mice with reduced numbers of OSNs (neural disorder) but not with increased mucus or blocked orthonasal pathways (conductive disorders). Moreover, the increase in onset latency correlated with the decrease in mature OSN numbers. Longer onset latency to intravenous odor injection is a useful biomarker for presence and severity of olfactory disorders with neural etiology.

Background Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease, characterized by eosinophilic infiltration, T‐helper type 2 (Th2‐type) response, and olfactory dysfunction. A master regulator of Th2‐type inflammation, thymic stromal lymphopoietin (TSLP), is important for basophil activation. TSLP‐elicited basophils are a key factor in the pathogenesis of ECRS. Methods In order to elucidate the mechanisms of ECRS in humans, we aimed to establish a murine model of ECRS based on TSLP production in response to the topical application of MC903 (a vitamin D3 analog) and the subsequent TSLP‐induced basophil activation. Histological analyses were performed to assess immune cell infiltration into the nasal mucosa and to explore the impact of eosinophilic inflammation on the olfactory epithelium. The status of Th2‐type inflammation was evaluated by quantitative real‐time PCR and enzyme‐linked immunosorbent assay (ELISA). Results Eosinophils, basophils, and M2 macrophages increased significantly in the nasal mucosa of the mice treated with MC903 and ovalbumin (OVA), compared to those treated with OVA alone or the controls. Quantitative real‐time PCR and ELISA revealed elevated expression of interleukin (IL)‐4, IL‐5, IL‐13, TSLP, the chemokine CCL11, and CCL24 in the nasal mucosa of the ECRS mice. In parallel, thinned olfactory epithelium and decreased mature olfactory sensory neurons were observed in the ECRS mice. Conclusions Our model of ECRS displayed Th2‐type inflammation in the sinonasal region, including both eosinophil infiltration and basophil infiltration. Additionally, olfactory epithelium turned out to be affected by eosinophilic inflammation. These features are consistent with the characteristics of the human ECRS.