Eosinophilic Polyps Research Articles

SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage

BackgroundPrevious study implied that local M2 polarization of macrophage promoted mucosal edema and exacerbates Th2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. ObjectiveWe thought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. MethodsRT-qPCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5 knockout mice were used to establish nasal polyp model with Th2 inflammation and investigate the effects of SIRT5 in macrophages on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. ResultsClinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophages markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5 deficiency mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages through promoting glutaminolysis. ConclusionsSIRT5 plays a crucial role in promoting the development of CRSwNP by supporting the alternative polarization of macrophage and thus provides a potential target for CRSwNP interventions.

Analysis of Clinical Characteristics and Post-Treatment Prognosis of Eosinophilic and Neutrophilic Chronic Rhinosinusitis With Nasal Polyps in Korean Patients

Background and Objectives The aim of this study was to examine the clinical characteristics and prognosis of chronic rhinosinusitis with nasal polyps (CRSwNP) following endoscopic sinus surgery (ESS), focusing on distinct histological endotypes characterized by eosinophil and neutrophil infiltration.Subjects and Method A total of 207 patients diagnosed with CRSwNP who underwent ESS between August 2014 and September 2018 were included in the study. Patients were categorized into different groups based on eosinophil and neutrophil counts in the tissues. The demographic data, Lund-Mackay score, Lund-Kennedy (L-K) endoscopic score, Sino-Nasal Outcome Test-22 and Kaplan-Meier estimation were analyzed according to different histologic endotypes.Results The histologic types were divided into four groups: the eosinophilic polyp (EP)+ neutrophlic polyp (NP) group, the EP group, the NP group, and the nonEP+nonNP group. Among the groups, the highest level of inflammation (L-K score, <i>p</i><0.05) was observed in the EP+NP group, and the worst prognosis was observed in the EP+NP group according to the results of the Kaplan-Meier analysis (<i>p</i><0.001).Conclusion Compared to non-neutrophil-infiltration polyps, neutrophil infiltration was associated with worse outcome when it was accompanied with eosinophilic infiltration. This discovery underlines how crucial it is to take neutrophils in nasal polyps into account in order to better understand their clinical behavior and maybe design customized treatments for better patient outcomes.

Nasal polyps and its histopathological classification: A retrospective study

Background: The diagnosis of nasal polyp is made according to clinical and radiological criteria, while histopathologic examination is important for an accurate diagnosis. Histological classification of nasal polyps and its clinical implications are very rarely reported in the literature. Aims and Objectives: The aim of this study was to study clinical presentation and site of occurrence of nasal polyps and histologically classify nasal polyps in relation to studies published in the literature. We classified the histological changes as described by Davidson and Hellquist. Materials and Methods: Based on the inclusion and exclusion criteria, the 315 subjects were included in our study, which include eosinophilic polyp, fibro-inflammatory polyp, polyp with sero-mucinous gland hyperplasia, and polyp with stromal atypia. Results: Sinonasal polyps can be classified in the following way histologically: edematous or eosinophilic polyp 189 cases (60%); fibro-inflammatory polyp: 66 cases (21%); polyp with seromucinous gland hyperplasia: 35 cases (11%), polyp with stroma atypia: no case (0%), and fibrotic 25 cases (8%). Conclusion: We concluded that the nasal polyps mainly present as an edematous or eosinophilic pattern on histopathological examination. Studies on the histopathology of nasal polyps would help us to understand this disease more appropriately for treatment plan. Further differentiation of nasal polyps may help to develop new therapeutic strategies that are tailored according to the respective group.

BMP-2 and IL-1β as Markers of Nasal Mucosa Inflammation in Rhinosinusitis with Nasal Polyps.

Rhinosinusitis with nasal polyps is characterized by chronic inflammation and hyperplasia of the nasal mucosa. The key mechanism for polyp formation is the expression of molecules that regulate proliferation and inflammation. We studied immunolocalization of bone morphogenetic protein-2 (BMP-2) and IL-1β in the nasal mucosa in patients aged 35-70 years (n=70, mean age 57.4±1.52 years). The typology of polyps was determined depending on the distribution of inflammatory cells, subepithelial edema, the presence of fibrosis and cysts. The immunolocalization of BMP-2 and IL-1β had the same pattern in edematous, fibrous, and eosinophilic (allergic) polyps. Goblet and connective tissue cells, microvessels and terminal sections of the glands were positively stained. BMP-2+ and IL-1β+ cells predominated in polyps of the eosinophilic type. BMP-2/IL-1β can be considered as a specific marker of inflammatory remodeling of the nasal mucosa in refractory rhinosinusitis with nasal polyps.

Central Compartment Atopic Disease and Its Surgical Outcomes: Olfactory Changes and Technical Notes.

Central compartment atopic disease (CCAD) is a recent, novel phenotype of chronic rhinosinusitis. Only a few studies have assessed olfactory function in patients with CCAD. We aimed to investigate olfactory function changes after functional endoscopic sinus surgery (FESS) in patients with CCAD and proposed some surgical techniques to enhance the postoperative olfactory outcomes in such patients. A retrospective cohort study. We collected data from 23 patients (8 men and 15 women) with CCAD who underwent FESS performed by a surgeon in Taiwan, between June 2018 and December 2021. The demographic data, olfactory function, and serum and tissue eosinophil percentages of the included patients were analyzed. The Top International Biotech Smell Identification Test (TIBSIT; Top International Biotech, Taipei, Taiwan) was used to assess olfactory function. Of the 23 patients, most (95%) showed a positive reaction to aeroallergens, and 2 patients (8.7%) had asthma. Ten patients (43.5%) had peripheral eosinophilia, and 9 (39%) had eosinophilic nasal polyps. Moreover, the patients presented with variable olfactory dysfunction; the mean preoperative TIBSIT (pr-TIBSIT) score was 12.8 ± 2.3 (range: 0-43), whereas the mean postoperative TIBSIT (po-TIBSIT) score was 29.2 ± 1.9 (range: 16-44). The po-TIBSIT score was significantly better than the pre-TIBSIT score (paired t test, P < .0001). The improvement in olfactory function was not significantly correlated with the patients' age, serum eosinophil percentages, and nasal polyp eosinophil counts. Our findings indicate that CCAD is significantly associated with olfactory dysfunction and that FESS can effectively improve olfactory function. To optimize postoperative olfactory outcomes, precise removal of polyps from the olfactory cleft without damaging the neuroepithelium is recommended. Our study provides valuable insights into the management of CCAD patients undergoing FESS and can guide surgical decision-making to achieve optimal olfactory function outcomes.

Chronic rhinosinusitis patient with nasal polyps at Dr. Soetomo General Academic Hospital Center

Background: Nasal polyps are benign chronic inflammatory masses with epithelial tissues of the nasal mucosa and paranasal sinuses. The clinical diagnosis is made based on sinonasal symptoms for more than three months and the presence of polyps in the nasal cavity. The classification of nasal polyps based on the histopathological structure is divided into three types, i.e., oedematous, eosinophilic polyps, inflammatory polyps, and chronic seromucous inflammatory polyps. This study aims to describe the profile of patients with nasal polyps at Dr. Soetomo Public Hospital Surabaya. Methods: This study applied a descriptive method with a retrospective approach by obtaining data from the medical records of the outpatient unit in the Ear, Nose, Throat, and Head-Neck (ENT-HN) Department of Dr. Soetomo Public Hospital Surabaya for the period January 2017-December 2018 based on age, gender, clinical symptoms, symptoms duration, polyp types, location of nasal polyp, and comorbidities. Results: The number of patients with nasal polyps was slightly more in women, as many as 13 patients or 52%, mostly aged 51-60 years old, amounting to 11 patients or 44%. The most common clinical symptom experienced by patients was nasal obstruction, as many as 24 patients or 96%. Patients who experienced symptom duration for one to three years before treatment amounted to 13 patients or 52%. Patients with histopathology of inflammatory nasal polyps were 19 patients or 76%, while patients of nasal eosinophil polyps were six patients or 24%. Additionally, patients with comorbidity in nasal polyps of allergic rhinitis medical history were 11 patients or 44%. Also, bilateral nasal polyps were mostly experienced by patients, reaching 14 patients or 56%. Conclusion: This study reveals nasal polyps in women aged 51-60 years with clinical symptoms of nasal obstruction with the results of a histopathological examination of the inflammation type at bilateral polyps.

Type 2 and Type 17 Invariant Natural Killer T Cells Contribute to Local Eosinophilic and Neutrophilic Inflammation and Their Function Is Regulated by Mucosal Microenvironment in Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by heterogeneous inflammatory endotypes of unknown etiology. Invariant natural killer T (iNKT) cells are multifunctional innate T cells that exhibit Th1-, Th2-, and Th17-like characteristics. We investigated functional relationships between iNKT cells and inflammatory subtypes of CRSwNP. Eighty patients with CRSwNP and thirty-two control subjects were recruited in this study. Flow cytometry was used to analyze the frequencies and functions of iNKT cells and their subsets in peripheral blood mononuclear cells (PBMCs) and tissues. Polyp tissue homogenates were used to study the multifunctionality of iNKT cells. iNKT cells were significantly increased in polyps (0.41%) than in control mucosa (0.12%). iNKT cells were determined in the paucigranunlocytic (n=20), eosinophilic (n=22), neutrophilic (n=23), and mixed granulocytic (n=13) phenotypes of CRSwNP. The percentages of iNKT cells and HLA-DR+PD-1+ subsets were lower in eosinophilic or mixed granulocytic polyps than those of other phenotypes. iNKT cells and subsets were enriched in polyp tissues than in matched PBMCs. The evaluation of surface markers, transcription factors, and signature cytokines indicated that the frequencies of iNKT2 and iNKT17 subsets were significantly increased in eosinophilic and neutrophilic polyps, respectively, than in the paucigranulocytic group. Moreover, the production of type 2 (partially dependent on IL-7) and type 17 (partially dependent on IL-23) iNKT cells could be stimulated by eosinophilic and neutrophilic homogenates, respectively. Our study revealed that type 2 and type 17 iNKT cells were involved in eosinophilic and neutrophilic inflammation, respectively, in CRSwNP, while different inflammatory microenvironments could modulate the functions of iNKT cells, suggesting a role of iNKT cells in feedback mechanisms and local inflammation.

Expression and Role of Calcitonin Gene-Related Peptide in Patients With Chronic Rhinosinusitis With Nasal Polyposis

Background and Objectives A recent study revealed that calcitonin gene-related protein (CGRP) plays an important role in inflammatory airway diseases. However, the influence of CGRP on chronic rhinosinusitis (CRS) has not been studied. This study investigated the expression, activity, and potential pathogenic role of CGRP in patients with CRS with nasal polyposis (CRSwNP).Subjects and Method Patients with CRSwNP and control subjects were enrolled. The CRSwNP group was divided according to the presence of eosinophilic polyps and non-eosinophilic polyps. Nasal polyps (NPs) and uncinate tissues (UTs) from patients with CRSwNP and UTs from control subjects were obtained to investigate the expression of α-/β-CGRP and chromogranin A. In addition, the expression patterns of cytokines following exposure to exogenous CGRP were analyzed in dispersed nasal polyp cells (DNPCs) from patients with eosinophilic or non-eosinophilic CRSwNP. The effects of CGRP on lipopolysaccharide (LPS)-induced nuclear factor-kappa light chain enhancer of activated B cells (NF-κB) signaling change were evaluated in THP-1 cells.Results The expression of α-/β-CGRP and number of CGRP-producing cells were significantly higher in NPs from patients with CRSwNP than in UTs from controls. Exogenous CGRP decreased the expression of inflammatory cytokines and increased that of the anti-inflammatory cytokines in DNPCs from patients with eosinophilic nasal polyps (EPs) and also increased the expression of tissue remodeling-related and anti-inflammatory cytokines in DNPCs from patients with non-eosinophilic nasal polyps (N-EPs). CGRP inhibited the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB) phosphorylation and NF-κB translocation in LPS-stimulated M1 macrophages.Conclusion CGRP expression in NPs may play a significant role in nasal polypogenesis through inflammatory modulation, and it could be a future target to modulate certain aspects of CRSwNP.

Применение эозинофильно-нейтрофильного индекса ЭНИ и показателя степени интенсивности воспалительной инфильтрации для оценки воспалительного процесса при полипозном риносинусите

Introduction. Identification of the cellular composition of polyps in polypous rhinosinusitis (PRS) is important. In practice, to determine the quantitative indicators of the number and ratio of eosinophilic and neutrophilic leukocytes in polyp tissue, the eosinophil-neutrophil index (ENI) was introduced, which is equal to the ratio of the arithmetic mean number of eosinophils to the arithmetic mean number of neutrophils in 10 considered fields of view at a magnification of the microscope ×400, and the indicator degree of cellular inflammatory infiltration. Objective. To conduct a pathomorphological study of the tissue of resected nasal polyps with the determination of ENI parameters and the degree of cellular inflammatory infiltration in various PRS phenotypes and evaluate the possibility of using these indicators as predictors of PRS drug control. Materials and methods. We examined 292 people (126 men, 166 women), mean age 52.12±13.04 years, with bilateral PRS, which were divided into 4 phenotypic groups: I group: PRS without concomitant bronchial asthma (BA) and respiratory allergies; IIa group: PRS + allergic BA (aBA) and allergic rhinitis (AR); IIb group: PRS + AR without BA; III group: PRS + nonallergic BA (nBA). During pathological examination, polyps were divided into 3 histological types: «eosinophilic,» «neutrophilic,» and «mixed»; the ENI index was determined, 3 degrees of inflammatory infiltration were established: weak (I degree) when the arithmetic mean of eosinophils, lymphocytes, neutrophils, macrophages, histiocytes, and mast cells in 10 representative fields of view does not exceed 200 cells; moderate (II degree) when the arithmetic mean varies from 201 to 400 cells; and significant (III degree) where the arithmetic mean is &gt; 400 cells. In the PRS+BA groups, the state of BA control was determined using the ACQ-7 (Asthma Control Questionnaire). An analysis of the dynamics of ENI indicators and the degree of inflammatory infiltration was carried out depending on the effectiveness of conservative therapy with topical glucocorticoids (GCs) during the observation period of 1 year. The patients were divided into 3 groups: group 1, patients with positive dynamics, with a decrease in the degree of nasal polyps; group 2, the severity of polyps remained at the same level; group 3, the prevalence of polyps was higher than a year ago. Results. In all phenotypes of PRS, the eosinophilic type of inflammation prevails. The minimum indicators of ENI (11 [6;16]) and the degree of inflammatory infiltration (1 [1; 1]) were in the PRS +AR group, the highest intensity of inflammation was found in the PRS+nBA group (2.03 [2; 2]). According to the cellular composition of polyps in group 1, eosinophilic polyps were 87%; neutrophilic, 8%; mixed type, 5%; in group 2a, 97% of eosinophilic and 3% of mixed type in the absence of neutrophilic polyps, in group 2b ORS + AR, eosinophilic polyps were detected in 100%; in group 3, eosinophilic 88%, neutrophilic 6%, and mixed polyps 6% were diagnosed. Changes in ENI parameters and the intensity of inflammatory infiltration depending on the effectiveness of conservative therapy were revealed. In the group with positive dynamics, there was a decrease in these two indicators after 6 months of using intranasal GCs, in the absence of dynamics during therapy there were no changes in these indicators, and with low drug control, their increase was noted, which after the next 12 months was manifested by aggressive growth of polyps. At the same time, a correlation was found between the increase in the magnitude of indicators of local inflammation of the tissue of nasal polyps with a deterioration in the degree of control of BA of any etiology and the absence of significant correlations between blood eosinophilia and the level of eosinophilic infiltration of polypous tissue. Conclusions. 1. During the pathological examination of the surgical material, it is necessary to establish the histological type of nasal polyps (eosinophilic, neutrophilic, and mixed) to determine the further tactics of treating patients with PRS. 2. Pathological determination of the density of the inflammatory infiltrate in the tissue of resected nasal polyps with the calculation of ENI in clinical practice is necessary to control the dynamics of the course of inflammation, predict the possibility of relapse, and adjust the treatment of patients with PRS. 3. Correlation analysis in patients with PRS did not reveal a significant relationship between the severity of tissue eosinophilic infiltration of polyp tissue and the level of eosinophils in the peripheral blood, so the determination of peripheral blood eosinophilia is not enough to characterize local inflammation in PRS. 4. A decrease in ENI and the degree of density of the inflammatory infiltrate in nasal polyps in dynamics indicates the effectiveness of the ongoing conservative therapy. 5. An increase in the intensity of inflammatory infiltration in the tissues of polyps is accompanied by a deterioration in the medical control of asthma in phenotypes of PRS in combination with aBA and nBA.

Understanding Systemic and Local Inflammation Induced by Nasal Polyposis: Role of the Allergic Phenotype.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by persistent symptoms associated to the development of nasal polyps. To this day, the molecular mechanisms involved are still not well defined. However, it has been suggested that a sustained inflammation as allergy is involved in its onset. In this exploratory study, the aim was to investigate the effect of the allergic status in the development of CRSwNP. To achieve this, we recruited 22 patients with CRSwNP and classified them in non-allergic and allergic using ImmunoCAP ISAC molecular diagnosis. Plasma samples were analyzed using liquid chromatography coupled to mass spectrometry (LC-MS). Subsequently, significant metabolites from plasma that were commercially available were then analyzed by targeted analysis in some nasal polyps. Additionally, nasal polyp and nasal mucosa samples were examined for eosinophils, neutrophils, CD3+ and CD11c+ cells, as well as collagen deposition and goblet cell hyperplasia. We found that 9 out of the 22 patients were sensitized to some aeroallergens (named as allergic CRSwNP). The other 13 patients had no sensitizations (non-allergic CRSwNP). Regarding metabolomics, bilirubin, cortisol, lysophosphatidylcholines (LPCs) 16:0, 18:0 and 20:4 and lysophosphatidylinositol (LPI) 20:4, which are usually related to a sustained allergic inflammation, were unexpectedly increased in plasma of non-allergic CRSwNP compared to allergic CRSwNP. LPC 16:0, LPC 18:0 and LPI 20:4 followed the same trend in nasal polyp as they did in plasma. Comparison of nasal polyps with nasal mucosa showed a significant increase in eosinophils (p < 0.001) and neutrophils (p < 0.01) in allergic CRSwNP. There were more eosinophils in polyps of non-allergic CRSwNP than in their nasal mucosa (p < 0.01). Polyps from non-allergic CRSwNP had less eosinophils than the polyps of allergic CRSwNP (p < 0.05) and reduced amounts of collagen compared to their nasal mucosa (p < 0.001). Our data suggests that there is a systemic inflammatory response associated to CRSwNP in the absence of allergy, which could be accountable for the nasal polyp development. Allergic CRSwNP presented a higher number of eosinophils in nasal polyps, suggesting that eosinophilia might be connected to the development of nasal polyps in this phenotype.

Aspirin Exacerbated Respiratory Disease and Nasal Polyp Phenotyping.

Aspirin exacerbated respiratory disease (AERD) is known by the triad of chronic rhinosinusitis with nasal polyposis (CRSwNP), aspirin hypersensitivity, and asthma, but its etiology and physiopathogenesis are still unclear. This cross-sectional study was designed to investigate allergy and inflammatory cells (neutrophils vs. eosinophils) dominancy in nasal polyp tissue of patients with AERD compared to non-AERD patients. CRSwNP patients scheduled for endoscopic sinus surgery were recruited in this study. Nasal polyp tissue was analyzed for infiltrating cells, and Eosinophil dominant and neutrophil dominant polyps were determined. AERD was confirmed by oral aspirin challenge (OAC). Demographics data; history of asthma, exacerbation by using NSAIDs, routine use of aspirin, type of surgery (primary or revision), and results of skin prick test and spirometry were recorded. Pathology results and contributing factors compared between AERD and non-AERD patients. Sixty-five patients (39 women, 26 men) were enrolled in the study (mean age 38.83 ± 12.43 years). Thirty (46%) patients had positive OAC tests. Totally 41 patients (63.1%) had eosinophilic polyps. 80% of patients with eosinophilic polyp had positive OAC and were AERD (P < 0.05). There was no significant difference in demographics, revision surgery, and concomitant asthma between AERD and non-AERD groups (P > 0.05). The positive skin prick test was higher in AERD and also in eosinophilic polyp patients, but it was not statistically significant (P = 0.086 and P = 0.177). Eosinophilic polyps are more common in AERD. A positive skin prick test is associated with AERD and eosinophilic polyp.

Impact of reslizumab on the course of chronic rhinosinusitis in patients with eosinophilic asthma

To evaluate the therapeutic potential of reslizumab-humanized anti-IL-5 monoclonal antibody for the treatment of CRS with polyps in patients with severe asthma. We investigated the cases of 9 patients with severe asthma treated with intravenous reslizumab at a dose of 3 mg per 1 kg of weight with regularity once in 4 weeks. The presence of CRS with polyps was revealed in 7 of 9 patients, SCT scanning of the paranasal sinuses indicated changes in all the patients, 2 patients had symptoms of chronic non-allergic rhinitis (NARES).The treatment effectiveness control was carried out after 6 months from the beginning of the treatment by the dynamics of nasal symptoms (SNOT-22), endoscopic image of the nose, total polyp score (TPS), changes in the SCT of the paranasal sinuses on the Lund-Mackay scale, rhinocytogram, the content of eosinophilic cationic protein in the blood, the level of systemic eosinophilia. The effectiveness of asthma control was assessed by the reduction of the frequency of asthma exacerbations, the need for systemic corticosteroids, spirometry data and Asthma Control Test (ACT) results. Along with a marked improvement in asthma control, 8 out of 9 patients displayed clinical, endoscopic, radiological signs of weakening of nasal symptoms. More significant improvement in asthma control was achieved in patients having CRS with polyps. In the group of patients having CRS with polyps, it was possible to detect anamnestic presence of NARES symptoms in the early stages of the disease. This indicates that NARES can be a precursor to the development of eosinophilic, non-IgE-induced asthma and nasal polyps. Treatment with reslizumab in patients with eosinophilic asthma and concomitant CRS with polyps and chronic non-allergic rhinitis (NARES) leads not only to improved control of asthma symptoms, but also to a significant regression of nasal symptoms.

Defective STING expression potentiates IL-13 signaling in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps

Stimulator of interferon genes (STING) activation favors effective innate immune responses against viral infections. Its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown. Our aim was to explore the expression, regulation, and function of STING in CRSwNP. STING expression in sinonasal mucosal samples was analyzed by means of quantitative RT-PCR, immunohistochemistry, flow cytometry, and Western blotting. Regulation and function of STING expression were explored by using cultured primary human nasal epithelial cells (HNECs) and cells of the line BEAS-2B invitro. STING expression was reduced in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues. STING was predominantly expressed by epithelial cells in nasal tissue and was downregulated by IL-4 and IL-13 in a signal transducer and activator of transcription 6 (STAT6)-dependent manner. HNECs derived from eosinophilic polyps displayed compromised STING-dependent type I interferon production but heightened IL-13-induced STAT6 activation and CCL26 production as compared with HNECs from noneosinophilic polyps and control tissues, which were rescued by exogenous STING overexpression. Knocking down or overexpressing STING decreased or enhanced expression of suppressor of cytokine signaling 1 (SOCS1) in BEAS-2B cells, respectively, independent of the canonic STING pathway elements TBK1 and IRF3. Knocking down SOCS1 abolished the inhibitory effect of STING on IL-13 signaling in BEAS-2B cells. STING expression was positively correlated with SOCS1 expression but negatively correlated with CCL26 expression in nasal epithelial cells from patients with CRSwNP. Reduced STING expression caused by the type 2 milieu not only impairs STING-dependent type I interferon production but also amplifies IL-13 signaling by decreasing SOCS1 expression in nasal epithelial cells in eosinophilic CRSwNP.

Microfilaria-dependent thoracic pathology associated with eosinophilic and fibrotic polyps in filaria-infected rodents

BackgroundPulmonary manifestations are regularly reported in both human and animal filariasis. In human filariasis, the main known lung manifestations are the tropical pulmonary eosinophilia syndrome. Its duration and severity are correlated with the presence of microfilariae. Litomosoides sigmodontis is a filarial parasite residing in the pleural cavity of rodents. This model is widely used to understand the immune mechanisms that are established during infection and for the screening of therapeutic molecules. Some pulmonary manifestations during the patent phase of infection with L. sigmodontis have been described in different rodent hosts more or less permissive to infection.MethodsHere, the permissive Mongolian gerbil (Meriones unguiculatus) was infected with L. sigmodontis. Prevalence and density of microfilariae and adult parasites were evaluated. Lungs were analyzed for pathological signatures using immunohistochemistry and 3D imaging techniques (two-photon and light sheet microscopy).ResultsMicrofilaremia in gerbils was correlated with parasite load, as amicrofilaremic individuals had fewer parasites in their pleural cavities. Fibrotic polypoid structures were observed on both pleurae of infected gerbils. Polyps were of variable size and developed from the visceral mesothelium over the entire pleura. The larger polyps were vascularized and strongly infiltrated by immune cells such as eosinophils, macrophages or lymphocytes. The formation of these structures was induced by the presence of adult filariae since small and rare polyps were observed before patency, but they were exacerbated by the presence of gravid females and microfilariae.ConclusionsAltogether, these data emphasize the role of host-specific factors in the pathogenesis of filarial infections.

Frequency of inflammatory cell types in polyps of patients with diffuse sinonasal polyposis and association with effective factors in recurrence

Background: Sinonasal polyposis (SNP) is a chronic disease of nasal and paranasal sinus mucosa. Nasal polyps can be divided into two groups based on inflammatory cells’ types, namely eosinophilic and neutrophilic polyps. Eosinophilic chronic rhinosinusitis responds to corticosteroids; however, this response is less in the neutrophilic type. Objectives: The present study aimed to determine the frequency of inflammatory cell types in the polyp tissue of patients with diffuse SNP and its association with effective factors in recurrence. Materials and Methods: This cross-sectional study was carried out on 130 patients with diffuse SNP referring to the Ear, Nose, and Throat (ENT) clinics of Tabriz University of Medical Sciences, Tabriz, Iran, using random sampling. The severity of the disease was assessed by the Sinonasal Outcome Test 20 (SNOT-20) questionnaire filled out by an ENT surgeon. Computed tomography scans were graded by the Lund-Mackay score. The variety of the cells were determined following hematoxylin-eosin staining and pathologist LM examination; then, the obtained data were statistically evaluated and their associations with the previously known factors of recurrence in other studies were reported. Results: The most frequent cells were eosinophils, and mast cells showed the lowest frequency of inflammatory cells in the polyps of patients with diffuse SNP. Eosinophilic polyps were more common in female patients. There was no significant difference between inflammatory cells associated with age, history of surgery, and SNOT-20 score. A significant relationship was only observed between the Lund-Mackay scores of neutrophil and mast cell polyps. Conclusions: The investigation of the dominant inflammatory cell in the histopathology sample of the sinonasal polyps can help in tracking and rationalizing patient management and expectations.

Decreased nasal polyp eosinophils but increased mast cells in a patient with aspirin-exacerbated respiratory disease treated with reslizumab

Decreased nasal polyp eosinophils but increased mast cells in a patient with aspirin-exacerbated respiratory disease treated with reslizumab

Can the systemic immune inflammation index preoperatively predict nasal polyp subtypes?

Chronic rhinosinusitis with nasal polyps can be classified as eosinophilic or neutrophilic based on the major inflammatory cell type in the tissue. There is a need for predictive parameters to enable rhinologists to identify the type of nasal polyp in a patient without surgery. The aim of the present study was to test the predictive value of the markers of inflammation to estimate eosinophilic nasal polyps. The study analyzed 299 patients who underwent sinus surgery for nasal polyps from 2012 to 2019. Patients were divided into two groups according to pathology results (eosinophilic polyps = group 1, neutrophilic polyps = group 2). The values of preoperative complete blood count, systemic immune inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were compared. In our series, results of ROC analyses for both mean eosinophil count and systemic immune inflammation index were statistically significant. For the eosinophil count (AUC = 0.681, p < 0.001) and systemic immune inflammation index (AUC = 0.621, p = 0.001). Patients with an eosinophil cut-off value of 0.25 cells × 109/L had ORs of 49.27 (95% CI 11.68-207.81) and sensitivity: 0.69, specificity: 0.64. Patients with a systemic immune inflammation index cut-off value of 332.39 had ORs of 1.003 (95% CI 1.002-1.004) and sensitivity: 0.84, specificity: 0.39. The systemic immune inflammation index and absolute blood eosinophil count could be used to predict nasal polyp subtypes before surgery. We believe that systemic immune inflammation index should also be studied to estimate postoperative recurrence.

Reduced A20 expression in nasal epithelial cells correlates with disease severity in patients with chronic rhinosinusitis with nasal polyps

Abstract Objective Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disorder characterized by heightened and sustained inflammation. A20 is a novel multifunctional protein with immunomodulatory effects. We sought to investigate the expression of A20 in sinonasal mucosa, and its association with local inflammation and disease severity in patients with CRSwNP. Methods The expression of A20 in sinonasal samples was assessed by quantitative RT-PCR, IHC, and Western blot. The numbers of local inflammatory cells were counted. CT scan findings and symptom severity were scored. Primary nasal epithelial cells were cultured to explore the regulation of A20 expression. Results Compared with control tissues and non-eosinophilic polyps, the mRNA and protein expression of A20 was significantly down-regulated in eosinophilic polyps. A20 was mainly expressed by epithelial cells. The expression of A20 in nasal epithelial cells was significantly reduced in eosinophilic polyps in comparison with those in non-eosinophilic polyps and control tissues. There was a further decrease in A20 expression in nasal epithelial cells in patients with eosinophilic polyps with asthma compared to those without asthma. A20 mRNA was induced by TNF-α, LPS, dsRNA, and dexamethasone, whereas was inhibited by IL-4 and IL-13 in human primary nasal epithelial cells. A20 mRNA levels in nasal epithelial cells negatively correlated with IL-4 and IL-13 levels and eosinophil numbers in sinonasal mucosa. Importantly, mRNA levels of A20 in nasal epithelial cells negatively correlated with disease duration and so on. Conclusions The decreased expression of A20 might contribute to eosinophilic inflammation and disease progression in patients with CRSwNP.

Prevalence of Allergic Fungal Rhinosinusitis Among Patients with Nasal Polyps

Objective: The objective of the study was to determine the frequency of allergic fungal rhinosinusitis among patients with nasal polyps.Methods: This study was performed at Department of ENT and Head Surgery, Jinnah Post Graduate Medical Center, Karachi during July 2018 to January 2019. Patients with nasal polyp fulfilling the inclusion criteria were enrolled. Sino-nasal contents were removed during operation and divided into two parts. Sample one was preserved in formalin solution and sent for histopathology to verify eosinophilic mucin and polyps. Another sample was preserved in 10% of potassium hydroxide solution to observe fungal hyphae by culture and fungal staining SPSS v-23.0 was used for the analysis.Results: Total of one hundred and fifty patients was included in the present study. There were sixtyone females (40.7%) and eighty-nine (59.3%) males. The mean age of patients was 30.5 ± 11.4 years. Out of 150 patients with nasal polyps, 33(22.0%) had allergic fungal rhino sinusitis (AFRS). In this study, it was found that, AFRS was associated with gender and smoking (p=0.036).Conclusion: AFRS is perceived generally among patients with nasal polyps. In this way, each patient with nasal polyp ought to be assessed for the existence of AFRS

Common fibrin deposition and tissue plasminogen activator downregulation in nasal polyps with distinct inflammatory endotypes

Common fibrin deposition and tissue plasminogen activator downregulation in nasal polyps with distinct inflammatory endotypes