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Although biofilms have been implicated in the pathogenesis of chronic rhinosinusitis (CRS), there is little evidence that their presence or absence has any effect on the outcomes of endoscopic sinus surgery (ESS). The aim of this study was to investigate the effect of biofilms on postsurgical outcomes after ESS. A prospective, blinded study of 51 consecutive patients undergoing ESS for CRS was conducted. Preoperatively, patients assessed their symptoms using internationally accepted standardized symptom scoring systems and quality-of-life (QOL) measures, i.e., the 10-point Visual Analog Scale (VAS), Sino-Nasal-Outcome-Test 20, and global severity of CRS. Their sinonasal mucosa was graded using the Lund-Kennedy scale and the extent of radiological disease on computed tomography scans was scored using the Lund-McKay scale. Random sinonasal tissue samples were assessed for biofilm presence using confocal laser microscopy. At each postoperative visit, patients reassessed their sinus symptoms and completed QOL measures. Postsurgical state of their sinonasal mucosa was graded endoscopically. Bacterial biofilms were found in 36 of 51 (71%) CRS patients. Patients with biofilms presented with significantly worse preoperative radiology and nasendoscopy scores (p = 0.003 and 0.01, respectively). After a median follow-up period of 16 months postsurgery, biofilm-positive patients had statistically worse sinus symptoms (VAS, p = 0.002) and worse nasendoscopy scores (p = 0.026). They also required extra postoperative visits and multiple antibiotic treatments deviating from the standard postoperative care required by biofilm-negative patients. This study has shown that patients with biofilms have more severe disease preoperatively and persistence of postoperative symptoms, ongoing mucosal inflammation, and infections. This study strengthens the evidence for the role that biofilms may play in recalcitrant CRS.

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory airway disease involving non-eosinophilic and eosinophilic phenotypes, which translate to various endotypes. Activated eosinophils and neutrophils are known to generate extracellular traps consisting of DNA and cytotoxic granule proteins. We sought to investigate the presence of eosinophil and neutrophil extracellular traps (EETs and NETs, respectively) in human CRS tissues and to clarify the associations with their clinical features. Nasal polyp (NP) or ethmoid tissue slides of 43 subjects from endoscopic sinus surgery for CRS were analysed. Quantitative analysis of EETs and NETs was performed by confocal microscopy using immunofluorescent staining. For correlation study, the presence of NPs, number of infiltrating tissue eosinophils, preoperative Lund–Mackay scores, and other comorbidities were analysed. EET formation was observed to varying degrees in all CRS groups and was correlated with the number of tissue eosinophils (r  =  0.83, p  < 0.001) regardless of the presence of NPs. Patients with more EETs demonstrated higher Lund–Mackay scores (r  =  0.51, p  = 0.009), blood eosinophilia (r  =  0.80, p  < 0.001), and decreased olfactory function (r  = −0.65, p  < 0.001). No correlation between the extent of EET formation and the presence of atopy or asthma was apparent. However, none of the CRS groups containing neutrophils formed NETs in this study. Eosinophilic CRS indicates the presence of EETs. Formation of EETs could have a role in clinical decision-making and prediction of treatment outcome of CRS, regardless of NP status.

The ongoing coronavirus disease 2019 (COVID-19) pandemic is associated with substantial morbidity and mortality. Although much has been learned in the first few months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation, and many patients with anosmia show no or only minor respiratory symptoms 1 . Studies in animals infected experimentally with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, provide opportunities to study aspects of the disease that are not easily investigated in human patients. Although the severity of COVID-19 ranges from asymptomatic to lethal 2 , most experimental infections provide insights into mild disease 3 . Here, using K18-hACE2 transgenic mice that were originally developed for SARS studies 4 , we show that infection with SARS-CoV-2 causes severe disease in the lung and, in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Furthermore, we show that infusion of convalescent plasma from a recovered patient with COVID-19 protected against lethal disease. Mice developed anosmia at early time points after infection. Notably, although pre-treatment with convalescent plasma prevented most signs of clinical disease, it did not prevent anosmia. Thus, K18-hACE2 mice provide a useful model for studying the pathological basis of both mild and lethal COVID-19 and for assessing therapeutic interventions. Transgenic K18-hACE2 mice are a useful model of COVID-19 including anosmia; infection of these mice resulted in severe pneumonia and, in some cases, infection in the brain, which was prevented by convalescent plasma.

Particulate matter (PM) is a major environmental pollutant implicated in various respiratory diseases. However, its impact on the upper respiratory tract, particularly the nasal and paranasal sinus mucosa, remains poorly understood. This study aimed to investigate the acute inflammatory effects of PM exposure on the sinonasal mucosa and evaluate the natural recovery process in a controlled rat model. Ten-week-old male Sprague Dawley rats were exposed to incense-derived PM in a custom-designed exposure chamber for 2 h daily for seven consecutive days. Rats were sacrificed at 3, 7, and 14 days post-exposure. Histopathologic changes were assessed using hematoxylin and eosin and Alcian blue staining, and mucosal gene expression of inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-5 and MUC5AC was quantified using real-time reverse transcription polymerase chain reaction. PM exposure induced significant histological alterations, including epithelial thickening, inflammatory cell infiltration, and goblet cell hyperplasia, which peaked at 7 days post-exposure. Expression levels of TNF-α and IFN-γ were significantly elevated at 7 days compared to controls. The sinonasal mucosa in the 14-day post-exposure groups exhibited a remarkable decrease in goblet cell numbers, and IL-1β and TNF-α expression. Short-term exposure to high concentrations of PM resulted in acute inflammatory changes in the sinonasal mucosa of rats, including epithelial thickening and goblet cell hyperplasia. These changes were partially resolved after exposure ended, indicating that PM-induced sinonasal inflammation may be at least partially reversible.

Innate and adaptive defense mechanisms protect the respiratory system from attack by microbes. Here, we present evidence that the bitter taste receptor T2R38 regulates the mucosal innate defense of the human upper airway. Utilizing immunofluorescent and live cell imaging techniques in polarized primary human sinonasal cells, we demonstrate that T2R38 is expressed in human upper respiratory epithelium and is activated in response to acyl-homoserine lactone quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Receptor activation regulates calcium-dependent NO production, resulting in stimulation of mucociliary clearance and direct antibacterial effects. Moreover, common polymorphisms of the TAS2R38 gene were linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria. Lastly, TAS2R38 genotype correlated with human sinonasal gram-negative bacterial infection. These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation contributes to individual differences in susceptibility to respiratory infection.

Background Optimising intranasal distribution and retention of topical therapy is essential for effectively managing patients with chronic rhinosinusitis, including those that have had functional endoscopic sinus surgery (FESS). This study presents a new technique for quantifying in vitro experiments of fluticasone propionate deposition within the sinuses of a 3D-printed model from a post-FESS patient. Methods Circular filter papers were placed on the sinus surfaces of the model. Deposition of fluticasone on the filter paper was quantified using high-performance liquid chromatography (HPLC) assay-based techniques. The deposition patterns of two nasal drug delivery devices, an aqueous nasal spray ( Flixonase ) and metered dose inhaler ( Flixotide ), were compared. The effects of airflow (0 L/min vs. 12 L/min) and administration angle (30° vs. and 45°) were evaluated. Results Inhaled airflow made little difference to sinus deposition for either device. A 45° administration angle improved frontal sinus deposition with the nasal spray and both ethmoidal and sphenoidal deposition with the inhaler. The inhaler provided significantly better deposition within the ethmoid sinuses (8.5x) and within the maxillary sinuses (3.9x) compared with the nasal spray under the same conditions. Conclusion In the post-FESS model analysed, the inhaler produced better sinus deposition overall compared with the nasal spray. The techniques described can be used and adapted for in vitro performance testing of different drug formulations and intranasal devices under different experimental conditions. They can also help validate computational fluid dynamics modelling and in vivo studies.

DEK::AFF2 carcinoma of the sinonasal tract is an emerging entity. The tumor is typically characterized by papillary proliferation of non-keratinizing squamous epithelial cells with monotonous cytologic features, which may mimic other sinonasal tumors. The confirmation of this gene fusion has thus far relied solely on next-generation sequencing, fluorescence in situ hybridization (FISH), or reverse transcription polymerase chain reaction (RT-PCR). This current study aimed to validate an immunohistochemical assay for AFF2 C-terminus as an ancillary marker. We first analyzed publicly available RNA sequencing data of sinonasal tumors from the national center for biotechnology information (NCBI) sequence read archive and identified 3 DEK::AFF2 carcinomas out of 28 sinonasal tumors. The gene expression of AFF2 was significantly higher in the fusion-positive cases compared to the wild-type tumors (p < 0.001), while DEK was not. We then optimized an immunohistochemical assay with an anti-AFF2 C-terminus antibody for ancillary diagnosis. Seventeen DEK::AFF2 carcinomas, including 11 cases with predominantly low-grade morphology and one showing glandular differentiation, as well as 78 DEK FISH-negative sinonasal tumors were evaluated by AFF2 immunohistochemistry (IHC). Sixteen of the 17 DEK::AFF2 carcinomas showed nuclear AFF2 expression in ≥30% of tumor cells, including one decalcified case that failed FISH and RT-PCR confirmation. The one case that was negative for AFF2 IHC in the tumor cells also lacked expression in the internal positive control. It was thus considered a failure of the IHC rather than a truly negative case and was excluded from the statistical analysis. All DEK FISH-negative sinonasal tumors were negative for nuclear AFF2 expression. The nuclear expression of AFF2 IHC showed 100% sensitivity and specificity for DEK::AFF2 carcinoma. Accordingly, AFF2 IHC is a highly sensitive and specific ancillary marker that distinguishes DEK-AFF2 carcinoma from the other sinonasal tumors with overlapping morphological features and may be an especially useful alternative for decalcified specimens.

Postoperative bleeding and adhesion formation are the two most common complications after endoscopic sinus surgery (ESS). Continued bleeding risks airway compromise from the inhalation of blood clots and from the aspiration of blood-stained vomitus. Additionally, adhesion formation is the most common reason for patients requiring revision surgery. This study aimed to determine the efficacy of a novel chitosan/dextran (CD) gel on hemostasis and wound healing after ESS. A randomized controlled trial was performed involving 40 patients undergoing ESS for chronic rhinosinusitis. Immediately after surgery a baseline Boezaart Surgical Field Grading Scale was taken. Computer randomization was performed with one side receiving CD gel and the other side receiving no treatment (control). Boezaart bleeding scores were then calculated for each side every 2 minutes. Patient's endoscopic features of wound healing were assessed at 2, 6, and 12 weeks after surgery. CD gel achieved rapid hemostasis with the mean time to hemostasis at 2 minutes (95% CI, 2-4 minutes) compared with 10 minutes (95% CI, > or =6 minutes) for the control (p < 0.001). There were significantly less adhesions at all time points with CD gel versus control: 2 versus 18 at 2 weeks (p < 0.001), 3 versus 16 at 6 weeks (p < 0.001), and 2 versus 12 at 3 months (p < 0.001). There was no significant difference between CD gel and control with respect to crusting, mucosal edema, infection, or granulation tissue formation. CD gel is rapidly hemostatic immediately after ESS and prevents adhesion formation, addressing two of the most common complications of sinus surgery.

This study aimed to develop and evaluate a deep learning algorithm for detecting and classifying intrasinus calcifications on paranasal sinus (PNS) computed tomography (CT) for the diagnosis of fungal sinusitis and differentiation of fungal and non-fungal sinusitis. A dataset of 277 PNS CT cases from Korea University Guro Hospital, supplemented by temporal and geographic external test sets, was utilized. A 3D U-Net model was employed to segment maxillary sinus regions. YOLO v5 identified calcifications, followed by classification into three patterns: normal sinus or chronic sinusitis without calcifications, dense peripheral dystrophic calcification, and central punctate fungal calcification. A separate convolutional neural network (CNN) refined the classification to ensure accurate categorization of calcification patterns. The 3D U-Net model achieved a Dice Similarity Coefficient of 0.9674, indicating accurate segmentation. YOLO v5 demonstrated precision of 79.50% and recall of 92.14% in detecting calcifications. The CNN classification model attained F1 scores of 94.73%, 90.60%, and 94.01%, and overall accuracies of 97.48%, 86.87%, and 94.01% for internal, temporal, and geographic test sets, respectively. This study demonstrated the capability of deep learning algorithms to accurately detect and classify fungal sinusitis-related calcifications on PNS CT scans. The developed framework achieved high accuracy in segmentation of sinus area and detection/classification of intrasinus calcifications. The framework also demonstrated its potential for broader application to radiographic imaging.

Purpose Budesonide improves the prognosis of chronic rhinosinusitis (CRS). However, few reports have examined whether its use for nasal irrigation, compared to normal saline, improves the prognosis of patients after endoscopic sinus surgery (ESS). We compared the effects of nasal irrigation with budesonide and normal saline in CRS patients after ESS. Methods Sixty CRS patients who had undergone ESS were randomly divided into an experimental group (30 patients), which used budesonide nasal irrigation, and a control group (30 patients), which used normal saline nasal irrigation. All patients received regular follow-up evaluations and were assessed via questionnaires, including the Lund–Kennedy endoscopic score (LKES), the symptom visual analog scale (VAS), the 22-item Sino-Nasal Outcome Test (SNOT-22), the Short-Form 36-Item Questionnaire (SF-36), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS) and a side effects scale. Results Scores of polyposis, mucosal edema, secretions and total score of LKES; VAS scores of nasal blockage, hyposmia and rhinorrhea; and SNOT-22 results in both groups were significantly improved 3 months after ESS. Scores of polyposis, mucosal edema, secretions and scarring and total score of LKES in experimental group were significantly better than in control group 3 months after ESS. No significant differences were observed in SF-36, SAS or SDS before or 3 months after ESS within or between the two groups. The side effects of the two groups were not significantly different. Conclusions Nasal irrigation improved the prognosis of CRS patients after ESS. Budesonide nasal irrigation had a better effect than normal saline nasal irrigation.