Analysis of conductive olfactory dysfunction using computational fluid dynamics

Conductive olfactory dysfunction (COD) is caused by an obstruction in the nasal cavity and is characterized by changeable olfaction. COD can occur even when the olfactory cleft is anatomically normal, and therefore, the cause in these cases remains unclear. Herein, we used computational fluid dynamics to examine olfactory cleft airflow with a retrospective cohort study utilizing the cone beam computed tomography scan data of COD patients. By measuring nasal–nasopharynx pressure at maximum flow, we established a cut-off value at which nasal breathing can be differentiated from combined mouth breathing in COD patients. We found that increased nasal resistance led to mouth breathing and that the velocity and flow rate in the olfactory cleft at maximum flow were significantly reduced in COD patients with nasal breathing only compared to healthy olfactory subjects. In addition, we performed a detailed analysis of common morphological abnormalities associated with concha bullosa. Our study provides novel insights into the causes of COD, and therefore, it has important implications for surgical planning of COD, sleep apnea research, assessment of adenoid hyperplasia in children, and sports respiratory physiology.

Skull base low-grade non-intestinal adenocarcinoma in a paediatric patient

Background: Non-intestinal adenocarcinomas of the sinonasal tract are uncommon neoplasms in adults, and particularly rare in the paediatric population. Case presentation: A 10-year-old male presented to the Paediatric Otolaryngology clinic with symptoms of recurrent epistaxis, persistent clear nasal discharge, and a left-sided polypoidal swelling causing nasal obstruction. An endoscopic biopsy of the polyp under general anaesthesia found a mass arising from the anterior olfactory cleft, and the histology report described the mass as a low-grade non-intestinal adenocarcinoma. CT and MRI of the sinuses post-biopsy demonstrated no bony structure infiltration. The patient underwent a further endoscopic operation for definitive excision of the nasal mass, and the histology findings confirmed a complete resection of the tumour. Conclusion: This case demonstrates the first case of a primary low-grade non-intestinal adenocarcinoma originating from the olfactory cleft.

Integrative genomics analysis of nasal intestinal-type adenocarcinomas demonstrates the major role of CACNA1C and paves the way for a simple diagnostic tool in male woodworkers

Background Nasal intestinal-type adenocarcinomas (ITAC) are strongly related to chronic wood dust exposure: The intestinal phenotype relies on CDX2 overexpression but underlying molecular mechanisms remain unknown. Our objectives were to investigate transcriptomic and methylation differences between healthy non-exposed and tumor olfactory cleft mucosae and to compare transcriptomic profiles between non-exposed, wood dust-exposed and ITAC mucosa cells. Methods We conducted a prospective monocentric study (NCT0281823) including 16 woodworkers with ITAC, 16 healthy exposed woodworkers and 13 healthy, non-exposed, controls. We compared tumor samples with healthy non-exposed samples, both in transcriptome and in methylome analyses. We also investigated wood dust-induced transcriptome modifications of exposed (without tumor) male woodworkers’ samples and of contralateral sides of woodworkers with tumors. We conducted in parallel transcriptome and methylome analysis, and then, the transcriptome analysis was focused on the genes highlighted in methylome analysis. We replicated our results on dataset GSE17433. Results Several clusters of genes enabled the distinction between healthy and ITAC samples. Transcriptomic and IHC analysis confirmed a constant overexpression of CDX2 in ITAC samples, without any specific DNA methylation profile regarding the CDX2 locus. ITAC woodworkers also exhibited a specific transcriptomic profile in their contralateral (non-tumor) olfactory cleft, different from that of other exposed woodworkers, suggesting that they had a different exposure or a different susceptibility. Two top-loci (CACNA1C/CACNA1C-AS1 and SLC26A10) were identified with a hemimethylated profile, but only CACNA1C appeared to be overexpressed both in transcriptomic analysis and in immunohistochemistry. Conclusions Several clusters of genes enable the distinction between healthy mucosa and ITAC samples even in contralateral nasal fossa thus paving the way for a simple diagnostic tool for ITAC in male woodworkers. CACNA1C might be considered as a master gene of ITAC and should be further investigated. Trial registration: NIH ClinicalTrials, NCT0281823, registered May 23d 2016, https://www.clinicaltrials.gov/NCT0281823.

Comparison of Olfactory Cleft Width and Volumes in Patients with COVID-19 Anosmia and COVID-19 Cases Without Anosmia

<b><i>Introduction:</i></b> The aim of this study was to assess the relationship between olfactory cleft width/volume and COVID-19-related anosmia. <b><i>Methods:</i></b> This study consisted of PCR-proven COVID-19 patients. Cases with COVID-19-related anosmia constituted Group 1 and cases without any olfactory dysfunction (OD) throughout COVID-19 infection or after recovery constituted Group 2. A total of 50 patients were included in the study, comprising 24 cases in Group 1 and 26 cases in Group 2. Group 1 patients underwent a 4-item-odor identification test during active symptoms and a Sniffin’ Sticks test after reconversion of PCR results to negative. All patients in Group 2 also underwent the Sniffin’ Stick test to document normosmia. All cases had paranasal sinus CT performed. Olfactory cleft widths and olfactory volumes were measured. The differences in width and volume between groups and the correlation with odor test scores (threshold-discrimination-identification [TDI]) were calculated. In addition, regression analyzes analysis was performed for cleft widths, volumes, and TDI scores according to age. <b><i>Results:</i></b> Olfactory cleft widths and olfactory volumes were significantly higher in Group 1 than those in Group 2 (<i>p</i> = 0.001; <i>p</i> &#x3c; 0.01). There was a significant negative correlation between total TDI scores and olfactory cleft widths and total olfactory volumes (<i>r</i> = −0.665; <i>r</i> = −0.731, respectively). Patients younger than 40 years of age had significantly higher right olfactory cleft width, left olfactory cleft width, and olfactory cleft volume than those in patients older than 40 years of age (<i>p</i> = 0.004, <i>p</i> = 0.005, <i>p</i> = 0.003; <i>p</i> &#x3c; 0,01, respectively). However, patients younger than 40 years of age had a significantly lower total TDI score and in all other values individually (t-d-i) than those in patients older than 40 years of age (<i>p</i> = 0.004; <i>p</i> &#x3c; 0.01). <b><i>Conclusion:</i></b> Patients with COVID-19-related OD had larger olfactory cleft width and volumes than those without OD in this study. Total TDI score was found to be inversely correlated with cleft width and volume.

Steroids and Olfactory Training for Postviral Olfactory Dysfunction: A Systematic Review

Background: Postviral olfactory dysfunction (PVOD) is a clinical challenge due to limited therapeutic options and poor prognosis. Both steroids and olfactory training have been proved to be effective for olfactory dysfunction with varied etiologies. We sought to perform a systematic review to summarize the evidence of steroids or olfactory training for patients with PVOD.Methods: A systematic literature review using PubMed, Embase, Cochrane Library, and Web of Science was conducted to identify studies assessing olfactory change in patients with PVOD receiving steroid or olfactory training.Results: Of the initial 273 abstracts reviewed, 20 articles with data from 2,415 patients with PVOD were included. Treatments including topical steroids, systemic steroids, classical olfactory training (COT), modified olfactory training (MOT), and olfactory training with steroid were analyzed. Both psychophysical olfactory testing and subjective symptom scores were utilized to assess the olfactory function. The routine use of nasal steroid spray alone during the management of PVOD seems to have no positive effect on olfactory dysfunction. Direct injection of steroid or nasal steroid spray into the olfactory cleft significantly improved the olfactory function in patients with PVOD. Olfactory improvement is greater than that of the natural course of the disease with short-term COT. Patients with PVOD would benefit more from long-term COT (&gt;12 weeks). Treatment duration, various odorants, olfactory training devices, changing the types of odors periodically, different molecular odorants, and different concentrations of odorants tended to increase the efficiency of MOT. Clinically significant improvement after olfactory training was defined as an increase of threshold, discrimination, and identification (TDI) score ≥6. From week 24 to week 36, both COT and MOT groups reached the maximum therapeutic effect regarding the number of participants achieving clinically significant improvement. A combination of local or oral steroids with olfactory training is more efficient than COT only.Conclusion: Olfactory function in patients with PVOD was effectively improved through direct steroid administration in the olfactory cleft, COT, or modification of COT. The addition of topical steroids to COT therapy showed a tendency for greater olfactory improvement in patients with PVOD.

Olfactory Cleft Opacification in COVID-19 Related Smell Loss: CT Findings and Correlation With Objective Testing

Objectives: Besides the common symptoms of the coronavirus disease 2019 (COVID-19) including fever, shortness of breath, and cough, a “sudden loss of smell” has recently been added as a diagnostic symptom. The relationship between paranasal sinus computed tomography (PNS CT) and sudden loss of smell in COVID-19 was examined. Materials and Methods: Two groups were selected for the study, the COVID-19 and the control groups. The control group consisted of 40 patients who applied to our clinic with headache and therefore underwent PNS CT. The other group consisted of 40 patients with COVID-19 who were diagnosed with sudden loss of smell with the Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test. Clinical and demographic characteristics, tomography results, and olfactory test scores of patients with COVID-19 loss of smell and control group patients were recorded. The relationship between CT changes in the olfactory cleft and the degree of loss of smell was evaluated. The “Opacification in the olfactory cleft” was accepted as a positive CT finding. Results: Comparison of patients with COVID-19 who had a loss of smell and the control group indicated that a significant difference was observed in terms of CT findings ( P = .022). When we evaluated the paranasal CTs obtained from our patients with loss of smell, the CT of 13 patients showed pathological findings ( P < .05). As the COVID-19 progressed (pneumonia and respiratory failure), the degree of loss of smell increased ( P < .05). A statistically significant relationship was found between the CCCRC score and the presence of PNS CT findings ( P = .0012). Conclusion: The PNS CT findings are significant in patients with COVID-19 with a loss of smell and were significantly associated with the degree of loss of smell. In patients with olfactory loss due to COVID-19, PNS CT can help in diagnosis. However, for this imaging to be diagnostic, a larger patient series is needed.