UNASSIGNED: Yujiang Paidu Decoction (YJPD) has demonstrated clinical efficacy in the treatment of chronic rhinosinusitis. However, the effects and mechanisms of the YJPD on chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear.
UNASSIGNED: This study aimed to elucidate the potential mechanism of action of YJPD in the treatment of CRSwNP based on network pharmacology, transcriptomics and experiments.
UNASSIGNED: A CRSwNP mouse model was established using ovalbumin (OVA) and staphylococcus aureus enterotoxin B (SEB) for 12 weeks and the human nasal epithelial cell (HNEpC) model was induced with IL-13 in vitro. Behavioral tests, scanning electron microscopy (SEM), micro-CT and pathological change of nasal tissues were observed to investigate the therapeutic effects of YJPD. Network pharmacology and transcriptomics were launched to explore the pharmacological mechanisms of YJPD in CRSwNP treatment. Finally, an ELISA, immunofluorescence, RT-qPCR, Western blotting and Tunel were performed for validation.
UNASSIGNED: Different doses of YJPD intervention effectively alleviated rubbing and sneezing symptoms in CRSwNP mice. Additionally, YJPD significantly reduced abnormal serological markers, structural damage of the nasal mucosa, inflammatory cell infiltration, goblet cell increases, and inhibited OVA-specific IgE levels and the secretion of Th2 cytokines such as IL-4, IL-5, and IL-13. Moreover, transcriptomics and network pharmacology analyses indicated that YJPD may exert anti-inflammatory and anti-apoptotic effects by inhibiting the MAPK/AP-1 signaling pathway. The experimental findings supported this conclusion, which was further corroborated by similar results observed in IL13-induced HNEpCs in vitro.
UNASSIGNED: YJPD could alleviate inflammatory status and epithelial apoptosis by inhibiting aberrant activation of MAPK/AP-1 signaling pathway. This finding provides a strong basis for using YJPD as a potential treatment in CRSwNP.

Rhinosinusitis is a common inflammatory disease of the sinonasal mucosa and paranasal sinuses. The pathogenesis of rhinosinusitis involves a variety of factors, including genetics, nasal microbiota status, infection, and environmental influences. Pathogenic microorganisms, including viruses, bacteria, and fungi, have been proven to target the cilia and/or epithelial cells of ciliated airways, which results in the impairment of mucociliary clearance, leading to epithelial cell apoptosis and the loss of epithelial barrier integrity and immune dysregulation, thereby facilitating infection. However, the mechanisms employed by pathogenic microorganisms in rhinosinusitis remain unclear. Therefore, this review describes the types of common pathogenic microorganisms that cause rhinosinusitis, including human rhinovirus, respiratory syncytial virus, Staphylococcus aureus, Pseudomonas aeruginosa, Aspergillus species, etc. The damage of mucosal cilium clearance and epithelial barrier caused by surface proteins or secreted virulence factors are summarized in detail. In addition, the specific inflammatory response, mainly Type 1 immune responses (Th1) and Type 2 immune responses (Th2), induced by the entry of pathogens into the body is discussed. The conventional treatment of infectious sinusitis and emerging treatment methods including nanotechnology are also discussed in order to improve the current understanding of the types of microorganisms that cause rhinosinusitis and to help effectively select surgical and/or therapeutic interventions for precise and personalized treatment.

Chronic rhinosinusitis (CRS) is a complex inflammatory condition affecting the nasal and paranasal sinus mucosa. Gastroesophageal reflux disease (GERD) has been implicated as a potential exacerbating factor in CRS, but the specific endoscopic features of nasopharyngeal pathology in this context remain poorly understood. Background and Objectives: Chronic rhinosinusitis is a multifactorial disease with various underlying etiologies, including inflammation, anatomical factors, and environmental triggers. While gastroesophageal reflux disease has been suggested as a potential contributor to chronic rhinosinusitis, the specific endoscopic features indicative of nasopharyngeal pathology in CRS patients with GERD symptoms have not been clearly elucidated. Our aim is to identify specific endoscopic features of nasopharyngeal pathology in patients with CRS associated with GERD symptoms and to propose a method for assessing the influence of gastroesophageal reflux disease on the mucosal layer of the nose and nasopharynx. Materials and Methods: We conducted a cross-sectional observational study involving 521 adult patients presenting with symptoms suggestive of CRS. From this cohort, 95 patients with the highest scores on the Reflux Symptom Index (RSI) and Reflux Symptom Score-12 (RSS-12) questionnaires were selected as the main group. Endoscopic examinations were performed to assess the nasal and nasopharyngeal mucosa. Results: Our study revealed significant alterations in the nasopharyngeal mucosa of patients with CRS associated with GERD symptoms. Increased vascularity of the nasopharyngeal mucosa was observed in 91 patients (95.7%), while hypertrophy was noted in 83 patients (87.4%). Mucus was present in the nasopharynx of 77 patients (81.1%), exhibiting varying characteristics of color and consistency. Asymmetric hypertrophy of the oropharyngeal mucosa was noted in 62 patients (65.3%). Conclusions: We propose a method for assessing the influence of gastroesophageal reflux disease on the mucosal layer of the nose and nasopharynx, which may aid in diagnostic and management decisions. Further research is warranted to explore the potential impact of GERD symptoms on the course and severity of CRS exacerbations.

Neutrophil infiltration plays a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, pertinent mechanisms remain poorly elucidated. Here, we obtained the data from gene expression omnibus (GEO) and gene set enrichment analysis (GSEA) to identify and validate neutrophil-associated hub genes in CRSwNP. We found that four neutrophil-associated hub genes, namely ICAM1, IL-1β, TYROBP, and BCL2A1, were markedly upregulated and positively correlated with neutrophil infiltration levels in patients with CRSwNP. Subsequently, this was confirmed by real-time quantitative PCR. In conclusion, we identified the role of neutrophil infiltration in the pathophysiology of CRSwNP, which may be the potential targets for the diagnosis and treatment of CRSwNP.

To evaluate whether radiomics models based on unenhanced paranasal sinuses CT images could be a useful tool for differentiating inverted papilloma (IP) from chronic rhinosinusitis with polyps (CRSwNP). This retrospective study recruited 240 patients with CRSwNP and 106 patients with IP from three centers. 253 patients from Qilu Hospital were randomly divided into the training set (n = 151) and the internal validation set (n = 102) with a ratio of 6:4. 93 patients from the other two centers were used as the external validation set. The patients with the unilateral disease (n = 115) from Qilu Hospital were selected to further develop a subgroup analysis. Lesion segmentation was manually delineated in CT images. Least absolute shrinkage and selection operator algorithm was performed for feature reduction and selection. Decision tree, support vector machine, random forest, and adaptive boosting regressor were employed to establish the differential diagnosis models. 43 radiomic features were selected for modeling. Among the models, RF achieved the best results, with an AUC of 0.998, 0.943, and 0.934 in the training set, the internal validation set, and the external validation set, respectively. In the subgroup analysis, RF achieved an AUC of 0.999 in the training set and 0.963 in the internal validation set. The proposed radiomics models offered a non-invasion and accurate differential approach between IP and CRSwNP and has some significance in guiding clinicians determining the best treatment plans, as well as predicting the prognosis.

UNASSIGNED: Rhinosinusitis disability index (RSDI) questionnaire is used to assess the severity of chronic rhinosinusitis (CRS) from the patient\'s perspective. The severity of CRS can be measured objectively with the endoscope and computed tomogram (CT) using the Lund-Kennedy endoscopic score and Mackay-Lund scores respectively. The objective of the study is to evaluate whether baseline RSDI and Lund-Kennedy (LK) endoscopy scoring can help predict the Mackay-Lund CT (MKLCT) scores after medical treatment in patients with CRS.
UNASSIGNED: This is a prospective, observational study, carried out from 1st October 2017 to 30th September 2019 in the ENT out- patient department at a tertiary hospital in Northern India. 90 patients diagnosed with CRS were enrolled consecutively in the study. RSDI questionnaire was filled out for all the participants. They all underwent a diagnostic endoscopy and CRS was graded according to the Lund-Kennedy endoscopic scores. All participants were given medical treatment. Patients underwent CT of the paranasal sinuses after medical treatment and the MLKCT scores were calculated. The baseline RSDI and Lund-Kennedy scores were correlated with the MKLCT scores using Spearman\'s Rank correlation tests. The diagnostic ability of the RSDI and LK endoscopy scores to predict the least MKLCT scores was compared using the receiver operator characteristics curves (ROC).
UNASSIGNED: A statistically significant correlation was seen with LK endoscopy scores and MKLCT scores (r = 0.396, p < 0.001) Among the individual parameters of the LK endoscopy scores only the polyp score had a statistically significant correlation with MKLCT scores (r = 0.593, p < 0.001). A weak negative correlation (r = - 0.058, p = 0.586) was seen between the RSDI scores and MKLCT scores. AUC in ROC curves for a LK endoscopy scores and RSDI scores were 0.690 and 0.462 respectively. Cut-off for predicting a MKLCT score of one or more for RSDI score was 25, with a sensitivity of 61% and specificity of 38.5%. Similarly, the cut-off for LK endoscopic score was 4.5, with a sensitivity of 68.8% and specificity of 61.5%.
UNASSIGNED: Statistically significant (p < 0.001) association was found between baseline Lund-Kennedy endoscopic scores and Mackay-Lund CT scores post medical treatment. No significant association was found between RSDI scores and Mackay-Lund CT scores. ROC analysis indicated that Lund- Kennedy endoscopy score is a more accurate tool than RSDI score to predict a Mackay-Lund CT scores after medical treatment.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12070-024-04708-6.

BACKGROUND: International frontal sinus anatomy classification (IFAC) was introduced in 2016 to standardize the nomenclature of the cells in the frontal recess region, facilitate better communication between surgeons and precision in surgical planning, and improve surgical teaching. This study aims to estimate the radiological prevalence of the different frontal recess cells according to the IFAC and to evaluate the relationship of these cells with the frontal sinus opacification in patients with chronic rhinosinusitis.
METHODS: In this study, 90 participants diagnosed with chronic rhinosinusitis (CRS) who underwent computed tomogram (CT) of the para nasal sinuses were enrolled consecutively. The CT images were were studied in detail using RadiAnt DICOM viewer. The frontal recess cells were grouped as per the IFAC guidelines and their respective prevalence was calculated. The frontal recess cells were grouped as per the Opacification or mucosal thickening within these cells and the frontal sinuses were noted. A multivariate logistic regression analysis was done to evaluate the association between frontal sinus opacification and presence of various IFAC cells.
RESULTS: A total of 640 IFAC cells were documented in 180 sides, of which 326 were anterior cells, 263 were posterior cells and 51 were medial cells. The most prevalent cell was the agger nasi cells(ANC), present in 91.7% of 180 sides, the supra agger nasi cells(SANC), Supra agger nasi frontal cells(SAFC), supra bulla cells(SBC), supra bulla frontal cells(SBFC), supra orbital ethmoidal cells(SOEC) and frontal septal cells(FSC) were present in 47.8%,37.8%, 65.6%,28.9%, 51.1% and 28.3% respectively. There was no significant association of presence of IFAC cells and frontal sinus opacification except for SBFC(p = 0.038). A significantly higher number of diseased frontal recess cells were seen with involved frontal sinuses when compared with non-involved frontal sinuses across all types of IFAC cells.
CONCLUSIONS: The ANC were the most prevalent among all the IFAC cells and the FSC were the least prevalent. There was no significant association with the presence of different types of IFAC cells and frontal sinus opacification except for SBFC. However, there was a significantly higher number of diseased IFAC cells associated with frontal sinus opacification than in those without frontal sinus opacification.

In recent years, there has been growing interest in understanding the potential role of microbiota dysbiosis or alterations in the composition and function of human microbiota in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). This systematic review evaluated the literature on CRSwNP and host microbiota for the last ten years, including mainly nasal bacteria, viruses, and fungi, following the PRISMA guidelines and using the major scientific publication databases. Seventy original papers, mainly from Asia and Europe, met the inclusion criteria, providing a comprehensive overview of the microbiota composition in CRSwNP patients and its implications for inflammatory processes in nasal polyps. This review also explores the potential impact of microbiota-modulating therapies for the CRSwNP treatment. Despite variability in study populations and methodologies, findings suggest that fluctuations in specific taxa abundance and reduced bacterial diversity can be accepted as critical factors influencing the onset or severity of CRSwNP. These microbiota alterations appear to be implicated in triggering cell-mediated immune responses, cytokine cascade changes, and defects in the epithelial barrier. Although further human studies are required, microbiota-modulating strategies could become integral to future combined CRSwNP treatments, complementing current therapies that mainly target inflammatory mediators and potentially improving patient outcomes.

Observational studies have linked autoimmune diseases (ADs) with rhinosinusitis (RS) manifestations. To establish a causal relationship between ADs and RS, and to explore the potential mediating role of inflammatory mediators between ADs and RS, we utilized Mendelian randomization (MR) analysis. Using a two-sample MR methodology, we examined the causality between multiple sclerosis (MS), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis (PsO), type 1 diabetes (T1D), Sjogren\'s syndrome (SS), celiac disease (CeD), Crohn\'s disease (CD), hypothyroidism (HT), Graves\' disease (GD), and Hashimoto\'s thyroiditis and their association with chronic and acute rhinosinusitis (CRS and ARS, respectively).To achieve this, we employed three distinct MR techniques: inverse variance weighting (IVW), MR-Egger, and the weighted median method. Our analysis also included a variety of sensitivity assessments, such as Cochran\'s Q test, leave-one-out analysis, MR-Egger intercept, and MR-PRESSO, to ensure the robustness of our findings. Additionally, the study explored the role of inflammation proteins as a mediator in these relationships through a comprehensive two-step MR analysis. Among the ADs, MS, RA, T1D, CeD, and HT were determined as risk factors for CRS. Only CeD exhibited a causal relationship with ARS. Subsequent analyses identified interleukin-10 (IL-10) as a potential mediator for the association of MS, RA and HT with CRS, respectively., while C-X-C motif chemokine 10 levels (CXCL10) and T-cell surface glycoprotein CD6 isoform levels (CD6) were found to influence HT\'s effect on CRS. Our findings demonstrate a causative link between specific autoimmune diseases and rhinosinusitis, highlighting IL-10, CXCL10, and CD6 as potential mediators in this association.

Background: The objective of this study was to evaluate, the clinical benefit of benralizumab in patients with uncontrolled severe asthma associated with chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods: The study included patients with uncontrolled severe asthma associated with CRSwNP who started therapy with benralizumab. Pulmonary function, eosinophilia, IgE, comorbidity, changes in the Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), Visual Analogue Scale (VAS), Quality of Life (AQLQ), VAS (obstruction, drip, anosmia, facial pressure), SNOT-22, decrease or withdrawal of steroids and other medication, hospital admissions and emergency visits were analysed. The FEOS scale and EXACTO were employed in the assessment of response. Results: We analyzed 58 patients who completed minimal treatment at 12 months. After treatment with benralizumab, exacerbations were reduced by 82% (p < 0.001), steroid cycles by 84% (p < 0.001), emergencies visit by 83% p < 0.001) and admissions by 76% (p < 0.001), improving all the scales for asthma control, (p < 0.001). In terms of lung function, differences were observed in FVC% (p < 0.001), FEV1% (p < 0.001), and FEV1/FVC% (69.5 ± 10 vs. 74 ± 10, p < 0.001). In relation to CRSwNP, differences were observed in SNOT-22 (54.66 ± 17 vs. 20.24 ± 9, p < 0.001), VAS obstruction (7.91 ± 1 vs. 1.36 ± 1, p < 0. 001), VAS drip (7.76 ± 1 vs. 1.38 ± 1, p < 0.001), VAS anosmia (7.66 ± 1 vs. 1.38 ± 1, p < 0.001) and VAS facial pressure (7.91 ± 1 vs. 1.22 ± 1, p < 0.001). The mean FEOS score after treatment was 73 ± 14. A complete response/super response was achieved in 33 patients (57%), good response in 16 (28%) and partial response in 9 (15%). Conclusions: The administration of benralizumab to patients with uncontrolled severe asthma associated with CRSwNP has been demonstrated to improve nasal symptoms, asthma control and lung function. This resulted in a reduction in the need for oral steroids, maintenance and rescue medication, emergency room visits, and hospital admissions, with 57% of patients achieving the clinical remission criteria.