Paranasal Sinus Mucosa Research Articles

Variability of the Microbiota in Chronic Rhinosinusitis: A Scoping Review.

Chronic rhinosinusitis (CRS) is characterized by a persistent inflammation of the nasal and paranasal sinus mucosa that could be potentially linked to a dysregulation between the microbiota and the immune system. We aim to explore general, methodological, and microbiological aspects of microbiota research in CRS compared to disease-free individuals. Embase, Ovid MEDLINE, PubMed, Scopus, and Web of Science. All studies comparing the composition of the resident microbiota of the sinonasal cavities in 2 groups: CRS and normal participants. We conducted systematic study selection, data extraction, and analysis first using the title and abstract, and then the full texts based on predefined inclusion and exclusion criteria. Compiled and presented findings include sampling site and technique, and microbiological results such as the relative abundance and the variability of the composition of the microbiota in both groups. Twenty-seven studies, using genomic identification with 16s RNA were analyzed. Case definitions primarily followed EPOS or AAO-HNS guidelines, with endoscopic swabs (82%), and middle meatus sampling (74%) being prevalent techniques. Despite relative abundance variability, patterns emerged across studies, indicating an increase in Haemophilus (19%) and Pseudomonas (11%), and decrease in Propionibacterium (15%) and Anaerococcus (11%). Another pattern was observed, showing a decreased alpha diversity (6/19; 22%) in CRS compared to normal individuals. While variations exist among studies, analysis of CRS microbiota suggests an association with dysbiosis, potentially contributing to chronic inflammation. Future research must prioritize standardized criteria for diagnostics and patient selection, fostering a more comprehensive understanding of CRS microbiota.

Endoscopic Features of Chronic Rhinosinusitis in Patients with Gastroesophageal Reflux Disease.

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.

Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) is characterized by prolonged inflammation of the nasal and paranasal sinus mucosa lasting over 12 weeks. CRS is divided into two main types based on the presence of nasal polyps: CRS without nasal polyps and CRS with nasal polyps. The condition is further classified into endotypes based on type 1, type 2, and type 3 inflammatory signatures, with differences in terms of disease severity, prognosis, and treatment response. Recent studies have emphasized the importance of the epithelial-mesenchymal transition (EMT) in CRS progression. In CRS, the EMT can be triggered by infections, allergens, hypoxia, and environmental pollutants. Specifically, EMT induction proceeds through the following mechanisms: viral and bacterial infections disrupt the epithelial barrier, house dust mites and other allergens activate the TGF-β and EGFR signaling pathways, hypoxia increases HIF-1α and other mesenchymal markers, and diesel exhaust particles and particulate matter cause oxidative stress. Maintaining the integrity of the epithelial barrier is essential for nasal mucosa homeostasis. In CRS, barrier damage activates repair processes that trigger the EMT, resulting in barrier dysfunction and tissue remodeling. Epithelial barrier dysfunction allows antigens and pathogens to penetrate, perpetuating inflammation and promoting the EMT. This disruption is a hallmark of CRS, emphasizing the importance of barrier integrity in the development of the disease. Key signaling pathways regulating the EMT in CRS include TGF-β, Wnt, HMGB1, AGE/ERK, TNF-α, and various miRNAs. These signaling pathways connect to various downstream pathways, such as the Smad2/3, GSK-3β/β-catenin, RAGE, and NF-κB pathways. This review focuses on the complex mechanisms of the EMT in CRS, emphasizing the role of epithelial barrier dysfunction and subsequent EMT processes in driving the disease’s development and progression. A deeper understanding of these EMT-driven mechanisms will help identify the potential therapeutic targets aimed at restoring epithelial integrity and reversing the EMT.

Murine model of eosinophilic chronic rhinosinusitis with nasal polyposis inducing neuroinflammation and olfactory dysfunction

BackgroundChronic rhinosinusitis (CRS) is a common inflammatory condition affecting the nasal and paranasal sinus mucosa, often accompanied by olfactory dysfunction. Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a subtype of CRS characterized by eosinophilic infiltration. Animal models for ECRSwNP with olfactory dysfunction are necessary for exploring potential therapeutic strategies. ObjectiveThe aim of this study was to establish a mouse model of ECRSwNP combined with olfactory dysfunction in a shorter timeframe using intranasal ovalbumin (OVA) and Aspergillus protease (AP) administration. The efficacy of the model was validated by evaluating sinonasal inflammation, cytokine levels, olfactory function, and neuroinflammation in the olfactory bulb. MethodsMale BALB/c mice were intranasally administered OVA and AP for 6 and 12 weeks to induce ECRSwNP. The resultant ECRSwNP mouse model underwent histological assessment, cytokine analysis of nasal lavage fluid, olfactory behavioral tests, and gene expression profiling to identify neuroinflammatory markers within the olfactory bulb. ResultsThe developed mouse model exhibited substantial eosinophil infiltration, increased levels of inflammatory cytokines in nasal lavage fluid, and confirmed olfactory dysfunction through behavioral assays. Furthermore, olfactory bulb inflammation and reduced mature olfactory sensory neurons were observed in the model. ConclusionThis study successfully established a validated mouse model of ECRSwNP with olfactory dysfunction within a remarkably short span of 6 weeks, providing a valuable tool for investigating the pathogenesis and potential therapies for this condition. The model offers an efficient approach for future research in CRSwNP and olfactory dysfunction.

Deep immune profiling of chronic rhinosinusitis in allergic and non-allergic cohorts using mass cytometry

Chronic rhinosinusitis (CRS) is a persistent nasal and paranasal sinus mucosa inflammation comprising two phenotypes, namely CRS with nasal polyps (CRSwNP) and without (CRSsNP). CRSwNP can be associated with asthma and hypersensitivity to non-steroidal anti-inflammatory drug (NSAID) in a syndrome known as NSAID-exacerbated respiratory disease (N-ERD). Furthermore, CRS frequently intertwines with respiratory allergies. This study investigated levels of 33 different nasal and serum cytokines and phenotypic characteristics of peripheral blood mononuclear cells (PBMCs) within cohorts of CRS patients (n = 24), additionally examining the influence of comorbid respiratory allergies by mass cytometry. N-ERD patients showed heightened type 2 nasal cytokine levels. Mass cytometry revealed increased activated naive B cell levels in CRSwNP and N-ERD, while resting naive B cells were higher in CRSsNP. Th2a cell levels were significantly elevated in allergic subjects, but not in CRS groups. In conclusion, there are distinct immunological features in PBMCs of CRS phenotypes and allergy.

Remodeling of Paranasal Sinuses Mucosa Functions in Response to Biofilm-Induced Inflammation.

Rhinosinusitis (RS) is an acute (ARS) or chronic (CRS) inflammatory disease of the nasal and paranasal sinus mucosa. CRS is a heterogeneous condition characterized by distinct inflammatory patterns (endotypes) and phenotypes associated with the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. Mucosal barrier and mucociliary clearance dysfunction, inflammatory cell infiltration, mucus hypersecretion, and tissue remodeling are the hallmarks of CRS. However, the underlying factors, their priority, and the mechanisms of inflammatory responses remain unclear. Several hypotheses have been proposed that link CRS etiology and pathogenesis with host (eg, "immune barrier") and exogenous factors (eg, bacterial/fungal pathogens, dysbiotic microbiota/biofilms, or staphylococcal superantigens). The abnormal interplay between these factors is likely central to the pathophysiology of CRS by triggering compensatory immune responses. Here, we discuss the role of the sinonasal microbiota in CRS and its biofilms in the context of mucosal zinc (Zn) deficiency, serving as a possible unifying link between five host and "bacterial" hypotheses of CRS that lead to sinus mucosa remodeling. To date, no clear correlation between sinonasal microbiota and CRS has been established. However, the predominance of Corynebacteria and Staphylococci and their interspecies relationships likely play a vital role in the formation of the CRS-associated microbiota. Zn-mediated "nutritional immunity", exerted via calprotectin, alongside the dysregulation of Zn-dependent cellular processes, could be a crucial microbiota-shaping factor in CRS. Similar to cystic fibrosis (CF), the role of SPLUNC1-mediated regulation of mucus volume and pH in CRS has been considered. We complement the biofilms' "mechanistic" and "mucin" hypotheses behind CRS pathogenesis with the "structural" one - associated with bacterial "corncob" structures. Finally, microbiota restoration approaches for CRS prevention and treatment are reviewed, including pre- and probiotics, as well as Nasal Microbiota Transplantation (NMT).

The role of Th17 lymphocytes in the pathogenesis of chronic rhinosinusitis

Abstract Chronic rhinosinusitis (CRS) encompasses inflammatory conditions affecting the nasal and paranasal sinus mucosa. Two major subtypes are distinguished by the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. This review examines the role of T helper 17 (Th17) cells and interleukin-17 (IL-17) cytokines in CRS immunopathology. Th17 lymphocytes produce inflammatory mediators, including IL-17A and IL-17F, which can disrupt sinonasal epithelial barrier function. Multiple studies correlate IL-17 levels and Th17 signaling with mucosal inflammation in CRS patients. However, significant endotypic and phenotypic variability modifies IL-17 involvement. CRSwNP often presents hallmark Th2-linked eosinophilic inflammation, while CRSsNP and subsets of Asian CRSwNP display Th17-associated neutrophilia. Overall, the literature implicates Th17 and IL-17 activity in CRS, but the heterogeneity of immunological subtypes mediates variable cytokine profiles. Further research into precise immunopathogenic mechanisms is needed to elucidate the contribution of Th17/IL-17 to disease and personalized therapeutic development.

RED-GREEN-BLUE COLOR ANALYSIS OF NASAL MUCOSA OF MIDDLE MEATUS IN THE DIAGNOSIS OF CHRONIC RHINOSINUSITIS WITHOUT POLYPOSIS (CRSSNP)

INTRODUCTION: Chronic Rhinosinusitis (CRS) can be defined broadly as a chronic inflammatory condition of the nose and paranasal sinus mucosa. There is need of a simple; easy to perform objective test that can make diagnosis of CRSsNP even in OPD settings. This prompted us to investigate use of smart phones as an objective method in cases of CRSsNP. OBJECTIVE- This study was done to analyse the color changes of middle meatus area by doing RGB analysis with Smartphone for objective diagnosis of CRSsNP. It was also seen whether severity of CRSsNP could be measured objectively by comparing RGB analysis to SNOT-22 score METHODS- Prospective, Observational, Analytical and hospital-based study of 75 patients presenting with symptoms of CRSsNP in the OPD setting RESULT- A total of 75 and 50 patients were included in case and control groups respectively. On further analysis, there was statistically significant difference in the color changes in the form of RGB values in CRSsNP and control group only at uncinate process (middle part) with R value (p=0.007), R value at middle turbinate (anterior end) (p <0.001) and B value at middle turbinate (anterior end) (p <0.001). CONCLUSION- This study concluded that R values at middle part of uncinate process and anterior end of middle turbinate along with B value at anterior end of middle turbinate may provide the diagnosis of CRSsNP objectively using the smart phone. KEYWORDS- Chronic rhinosinusitis, chronic rhinosinusitis without nasal polyposis, sinonasal outcome test, red-green-blue.

Eosinophilic Chronic Rhinosinusitis and Pathogenic Role of Protease.

Chronic rhinosinusitis (CRS) is an inflammation of the nasal and paranasal sinus mucosa, and eosinophilic CRS (eCRS) is a subtype characterized by significant eosinophil infiltration and immune response by T-helper-2 cells. The pathogenesis of eCRS is heterogeneous and involves various environmental and host factors. Proteases from external sources, such as mites, fungi, and bacteria, have been implicated in inducing type 2 inflammatory reactions. The balance between these proteases and endogenous protease inhibitors (EPIs) is considered important, and their imbalance can potentially lead to type 2 inflammatory reactions, such as eCRS. In this review, we discuss various mechanisms by which exogenous proteases influence eCRS and highlight the emerging role of endogenous protease inhibitors in eCRS pathogenesis.

Mucocutaneous lesions associated with lymphoproliferative disorder: a case report

Introduction: Leukemia is a type of blood cancer characterized by the accumulation of mature or immature cells in the bone marrow (BM), peripheral blood, lymph nodes, and lymphoid tissues. These cells can cause extranodal infiltration in tissues such as skin (leukemia cutis [LC]) and mucous membranes, being these locations rare. Case presentation: The patient was referred to a university hospital, where BM and computed tomography tests were performed, showing peripheral lymphatic involvement and maxillary paranasal sinus (PNS) opacity. Subsequently, functional endoscopic sinus surgery (FESS) of the PNS was performed and biopsies were taken from the skin lesion and PNS mucosa. Based on the results of the BM tests, the patient was diagnosed with B-cell acute lymphoblastic leukemia, so chemotherapy (CT) was initiated. The biopsy report described infiltration of leukemoid neoplastic cells in both locations (skin lesion and PNS mucosa), confirmed by immunohistochemistry. During CT, the patient developed bone marrow aplasia, tumor lysis syndrome and septic and hypovolemic shock, which eventually led to his death. Conclusion: LC is a rare condition associated with poor prognosis, so once detected it is necessary to initiate systemic treatment and look for possible extramedullary metastases. PNS opacity in patients with oncologic immunosuppression is usually considered as nasosinusal infection; however, it may also be secondary to an unusual infiltrative involvement of leukemia.

Double Blinded Randomized Controlled Trial Comparing Budesonide and Saline Nasal Rinses in the Post-operative Management of Chronic Rhinosinusitis.

Post-operative management of chronic rhinosinusitis is very crucial for outcomes following surgery, Normal saline nasal irrigation and steroid spray form the standard treatment of care in this period. However nasal irrigation may not be adequate and spray is usually started after 2weeks of surgery which in any case does not deliver optimum dosage of drug to the paranasal sinus mucosa. Budesonide nasal irrigation in a high-volume low-pressure system could be the solution for a better outcome. A double blinded randomized control trial with 88 patients in 2 groups of 44 each received normal saline or Budesonide nasal irrigation (0.5mg in 200ml) twice daily. Patients were followed up at 2weeks post-operatively and 3months, a SNOT 22 and Lund Kennedy Endoscopic scores were assessed for subjective and objective assessment. Subset analysis of only CRS patients (55) were done, and results presented. Patient reported subjective score at 3months post operatively, SNOT22 was significantly (p < 0.0001) improved with the use of Budesonide irrigation (26.69 ± 2.92) as compared to Normal saline (30.54 ± 2.81) and objective assessment score, LKES was significantly (p = 0.0031) better in Budesonide group (4.06 + 0.74) in comparison to Normal saline in the saline (4.50 + 0.67) respectively. The mean scores 3months post op visit was significantly lower for both subjective SNOT (p < 0.001) and objective score LKES (p < 0.0001) in Budesonide groups. Budesonide nasal irrigation with positive pressure high volume device has better patient benefits and wound healing when compared to normal saline irrigation in the post-operative management of chronic rhinosinusitis.

Association Between Particulate Matter Exposure and Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) is a relatively common inflammatory disease of the nasal and paranasal sinus mucosa. Several epidemiological studies have established an association between particulate matter (PM) and CRS. Based on those data, PM has emerged as an important environmental factor in the development of CRS. Recent research has investigated the mechanisms and treatment options for CRS caused by PM through cellular experimentation. Therefore, the authors would like to explain the definition of PM, present research investigating the relationship between PM and CRS, and summarize the involved mechanisms reported to date.

A study on olfactory improvement assessed with butanol threshold test in chronic rhinosinusitis patients after fess at a tertiary care centre in Malabar region

Background: Chronic Rhinsinusitis is a hetreogenous disorder with a broad range of etiologic factors involving mucosa of nasal cavity and paranasal sinuses. Olfactory dysfunction has been reported in approximately 60-80% of patients who suffer from CRS. Methods: Hospital based prospective observational study in the department of ENT, KMCT medical college, Mukkam done in Patients diagnosed with CRS who require FESS having anosmia or hyposmia as an additional symptom. Calculated sample size was 87. Butanol threshold test was done in patients before undergoing FESS and at 1st week,6th week and 24 weeks following FESS and improvement noted. Independent sample t test and ANOVA were used to test statistical significance Results: Out of 87 subjects, 36% belonged to age group of 36-45 years 15-25 years was the least involved group and majority of patients had nasal obstruction (83.9%) or nasal discharge (81.6%). 69% of patients experienced facial pain and 79.3% had post nasal discharge. Pre operative BTT showed a mean value of 4.89.BTT at 1st week post op showed a mean value of 3.63. At 6 weeks post op BTT value showed significant difference from pre op value with a mean of 2.05 and at 24 weeks post op the mean BTT was 1.70 Conclusions: Summarising the results from our study we affirm that FESS improves olfactory function substantially in CRS patients especially in patients with polyps.

Assessment of chronic rhinosinusitis severity indicators: radiological and clinical perspective

Introduction: Chronic rhinosinusitis (CRS) is inflammation of the nasal cavity and paranasal sinus mucosa. The aim of this study was to examine which of the available radiological and clinical parameters is the best indicator of the CRS severity. Methodology: In order to classify CRS, we used both a subjective assessment tool such as SNOT-22 questionnaire, as well as an objective tool such as clinical examination. We introduced three forms of CRS (mild, moderate and severe). Within these groups, we evaluated the computerized tomography (CT) parameters used as an indicator of bone remodeling, the Lund-Mackay score (LMS), CT properties of the soft tissue content in the maxillary sinuses, presence of nasal polypus (NP), presence of fungal infection and parameters indicating allergic status. Results: Frequencies of NP, positive eosinophil count, presence of fungi, areas of high attenuation, and duration of CRS and LMS significantly increased with the increased severity of CRS. Anterior wall thickness and density increased in the severe forms of CRS in the group assessed by SNOT-22. Positive correlation was detected between LMS and maximal density of sinus content and between duration of CRS and anterior wall thickness. Conclusions: Morphological changes of sinus wall detected in CT could be a useful indicator of CRS severity. Changes in bone morphology are more likely to occur in patients with longer-lasting CRS. The presence of fungi, allergic inflammation of any origin and nasal polypus potentiates more severe forms of CRS both clinically and subjectively.

Prioritization of nasal polyp-associated genes by integrating GWAS and eQTL summary data.

Background: Nasal polyps (NP) are benign inflammatory growths of nasal and paranasal sinus mucosa that can substantially impair patients' quality of life by various symptoms such as nasal obstruction, insomnia, and anosmia. NP often relapse even after surgical treatment, and the curative therapy would be challenging without understanding the underlying mechanisms. Genome wide association studies (GWASs) on NP have been conducted; however, few genes that are causally associated with NP have been identified. Methods: We aimed to prioritize NP associated genes for functional follow-up studies using the summary data-based Mendelian Randomization (SMR) and Bayesian colocalization (COLOC) methods to integrate the summary-level data of the GWAS on NP and the expression quantitative trait locus (eQTL) study in blood. We utilized the GWAS data including 5,554 NP cases and 258,553 controls with 34 genome-wide significant loci from the FinnGen consortium (data freeze 8) and the eQTL data from 31,684 participants of predominantly European ancestry from the eQTLGen consortium. Results: The SMR analysis identified several genes including TNFRSF18, CTSK, and IRF1 that were associated with NP due to not linkage but pleiotropy or causality. The COLOC analysis strongly suggested that these genes and the trait of NP were affected by shared causal variants, and thus were colocalized. An enrichment analysis by Metascape suggested that these genes might be involved in the biological process of cellular response to cytokine stimulus. Conclusion: We could prioritize several NP associated genes including TNFRSF18, CTSK, and IRF1 for follow-up functional studies in future to elucidate the underlying disease mechanisms.

EFFECT OF INFLAMMATORY FACTORS IN THE PATHOGENESIS OF CHRONIC RHINOSINUSITIS

Abstract: Both immune mechanisms, involved in inflammatory processes induced by viral and bacterial pathogens or allergy-inducing agents, and non-immune mechanisms play a direct role in the pathogenesis of chronic rhinosinusitis (CRS). Contrary to popular belief, bacterial infection plays a much smaller role. As a rule, this is a secondary process – following the development of inflammatory processes in the mucosa of the paranasal sinuses, its defense mechanisms are disrupted, which promotes the development of infection. Bacterial infection of the paranasal sinuses is associated with the formation of a biofilm responsible for the persistence of rhinosinusitis, or bacterial endotoxins acting as superantigens cause the persistence of the inflammatory process. The main role in the inflammatory process is played by CD4+ and CD8+ T lymphocytes, as the centers regulating cytotoxic and humoral immune responses. They act in various ways, mainly cytotoxic, and as such can interact with virtually all nucleated host cells showing expression of antigens of endogenous origin and through cytokines, mainly pro-inflammatory cytokines, and they increase migration of inflammatory cells into the mucosa of the nasal cavity and paranasal sinuses. The paper discusses in detail the interaction of immunocompetent cells and their impact on chronic inflammatory processes in the mucosa of paranasal sinuses. Atopy is another factor contributing to the CRS, increasing the action of pro-inflammatory cytokines and promoting processes that lead to obstruction of the ostiomeatal complex. The complexity of the clinical picture of the CRS in relation to ongoing research on pathogenesis indicates that it is still not possible to strictly define the phenotypes of the disease.

Current possibilities of using silver proteinate in the treatment of inflammatory diseases of the nose and paranasal sinuses

The article evaluates the possibility of using silver proteinate to treat acute inflammatory diseases of the nasal cavity and paranasal sinus mucosa, as well as their complications. Acute rhinitis and rhinosinusitis are among the most common upper respiratory diseases. Viral pathogens are the main agents that trigger the pathological process. At the same time, the bacterial superinfection in some cases may develop due to viral infection, which promotes further development of lingering clinical symptoms up to a complicated course of the disease. The course of rhinosinusitis with underlying COVID-19 infection can be complicated by fungal superinfection and postnasal drip. For these reasons, topical drugs that could be used in the early stages of these conditions should have a number of properties, such as activity against most respiratory viruses and aetiologically significant bacterial pathogens; lack of opportunity to evolute and implement rapid resistance mechanisms in microorganisms; additive effects with other antibacterial drugs; acceleration of regeneration of the nasal cavity and paranasal sinus mucosa with underlying infectious alteration; vasoconstrictive and anti-inflammatory action, without causing an addictive effect, which enables repeated use of the drug in chronic diseases, as well as the absence of local and systemic toxic effects. Sialor (silver proteinate) has all the specified characteristics that were proved in various studies, and consistently demonstrated high clinical efficacy for many years.

TIM-4 in macrophages contributes to nasal polyp formation through the TGF-β1-mediated epithelial to mesenchymal transition in nasal epithelial cells.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is caused by prolonged inflammation of the paranasal sinus mucosa. The epithelial to mesenchymal transition (EMT) is involved in the occurrence and development of CRSwNP. The T-cell immunoglobulin domain and the mucin domain 4 (TIM-4) is closely related to chronic inflammation, but its mechanism in CRSwNP is poorly understood. In our study, we found that TIM-4 was increased in the sinonasal mucosa of CRSwNP patients and, especially, in macrophages. TIM-4 was positively correlated with α-SMA but negatively correlated with E-cadherin in CRS. Moreover, we confirmed that TIM-4 was positively correlated with the clinical parameters of the Lund-Mackay and Lund-Kennedy scores. In the NP mouse model, administration of TIM-4 neutralizing antibody significantly reduced the polypoid lesions and inhibited the EMT process. TIM-4 activation by stimulating with tissue extracts of CRSwNP led to a significant increase of TGF-β1 expression in macrophages in vitro. Furthermore, coculture of macrophages and human nasal epithelial cells (hNECs) results suggested that the overexpression of TIM-4 in macrophages made a contribution to the EMT process in hNECs. Mechanistically, TIM-4 upregulated TGF-β1 expression in macrophages via the ROS/p38 MAPK/Egr-1 pathway. In conclusion, TIM-4 contributes to the EMT process and aggravates the development of CRSwNP by facilitating the production of TGF-β1 in macrophages. Inhibition of TIM-4 expression suppresses nasal polyp formation, which might provide a new therapeutic approach for CRSwNP.

Different Roles of Dendritic Cells for Chronic Rhinosinusitis Treatment According to Phenotype.

Dendritic cells (DCs) are antigen-presenting cells derived from the bone marrow that play an important role in the association between the innate and adaptive immune responses. The onset and development of chronic rhinosinusitis (CRS) involve a serious imbalance in immune regulation and mechanical dysfunction caused by an abnormal remodeling process. Recent studies have shown that an increase in DCs in CRS and their function of shaping the nasal mucosal immune response may play an important role in the pathogenesis of CRS. In this review, we discuss DC subsets in mice and humans, as well as the function of DCs in the nasal sinus mucosa. In addition, the mechanism by which DCs can be used as targets for therapeutic intervention for CRS and potential future research directions are also discussed.

An Analytical Study of the Relation between Smoking and Allergy in Sinonasal Polyposis

Introduction: Nasal polyposis (NP) is a disease in which abnormal hyperplastic inflammatory lesions originate from the sinus and paranasal sinus mucosa. Objectives of the study: The main objective of the study is to find the relation between smoking and allergy in sinonasal polyposis. Material and methods: This cross-sectional study was conducted in Sharif medical and dental college, Lahore during 2020 to 2021. The data was collected from both genders. The sample size for this study was 50 (smokers and nonsmokers), ad those patients which was suffering from nose allergy was selected for this study. Result: The data was collected from 50 patients, out of which 22 were smokers and 28 were nin-smokers. The mean age for smokers was 46.4 ± 5.3 years and 42.5 ± 5.4 for non-smokers. There were 14 (69.1%) male and 8 (30.9%) females in smokers group and 16 (57%) males and 12 (42.85%) females in non-smokers group. The mean duration of sinonasal polyposis for smokers group was 2.3 ± 2.8 years and for non-smokers was 2.5 ± 1.3 years. Conclusion: It is concluded that tobacco smoke may significantly affect in patients with sinonasal polyposis. Consequently, careful evaluation and management of smokers should be performed.