Eosinophilic Chronic Rhinosinusitis Research Articles

A decreased prevalence of group 2 innate lymphoid cells in blood is associated with good postoperative outcomes in patients with chronic rhinosinusitis

ObjectiveDue to the high postoperative recurrence rate in eosinophilic chronic rhinosinusitis (eCRS) patients, there is a need for an index to predict the postoperative outcomes. Group 2 innate lymphoid cells (ILC2s) are important effector cells for type 2 immune responses in eosinophilic airway inflammation. The aim of this study was to investigate whether the prevalence of ILC2s in sinonasal tissues or in peripheral blood is associated with the postoperative outcome in CRS patients. MethodsTwelve patients with eCRS and ten patients with non-eCRS were recruited. We examined the ILC2 prevalence in sinonasal tissues and in peripheral blood before and after endoscopic sinus surgery (ESS). Pre- and postoperative blood eosinophil counts were also examined. Lund-Mackay computed tomography (LMK-CT) scores were used to evaluate the disease severities and the postoperative outcomes; cases with more than 50% improvement were categorized into the good outcome group, and cases with less than 50% improvement were categorized into the poor outcome group. ResultsThe ILC2 prevalence in sinonasal tissues was correlated with that in preoperative blood in eCRS and non-eCRS patients. The ILC2 prevalence in sinonasal tissues and in preoperative blood was not correlated with the pre- or postoperative LMK-CT scores. Postoperatively, the ILC2 prevalence in blood was decreased in eCRS and non-eCRS patients, and blood eosinophil count was also decreased in eCRS patients but not in non-eCRS patients. The ILC2 prevalence in postoperative blood was decreased in the good outcome group but not in the poor outcome group. Blood eosinophil counts were not decreased postoperatively in both good and poor outcome groups. ConclusionThe decreased ILC2 prevalence in postoperative blood may be a predictive biomarker for evaluating postoperative outcomes in eCRS and non-eCRS patients.

Expression and predictive value of type Ⅱ inflammatory cytokines in nasal secretion in eosinophilic chronic rhinosinusitis with nasal polyps

Objective:To analyze the expression of type Ⅱ inflammatory-related cytokines in nasal secretions of patients with eosinophilic chronic rhinosinusitis with nasal polyps（ECRSwNP）, and to preliminarily explore the role of type Ⅱ inflammatory cytokines in nasal secretions in predicting ECRSwNP. Methods:A prospective analysis was made of 91 patients with CRSwNP who underwent endoscopic sinus surgery in Peking University Third Hospital from November 2020 to June 2021. All the selected patients had their SNOT-22 score, Lund-Mackay score and blood eosinophilia collected before surgery. Percentage and absolute value; the nasal secretions of patients were collected before operation, and enzyme-linked immunosorbent assay was used to detect the typeⅡinflammatory cytokines（IL-4, IL-5, IL-13, IL-25, IL-33, Eotaxin-3, periostin）, intraoperative nasal polyp tissue was collected for eosinophil count. According to the proportion of eosinophils in the tissue≥10%, they were divided into ECRSwNP group and nECRSwNP group. The clinical baseline data and type Ⅱ inflammatory cytokines were compared between the two groups, and the related factors of ECRSwNP were evaluated by univariate logistic regression analysis. The receiver operating characteristic（ROC） curve was used to evaluate the predictive potential of each clinical index. Results:The SNOT-22 score, Lund-Mackay score, blood eosinophil percentage and absolute value in the ECRSwNP group were higher than those in the nECRSwNP group（P<0.05）. In the nECRSwNP group（P<0.01）. Logistic regression analysis found that IL-5, Eotaxin-3 and blood eosinophil percentage were risk factors for ECRSwNP（P<0.05）. ROC analysis found that IL-5, Eotaxin-3 and blood eosinophil percentage had predictive diagnostic value（P<0.01）, among which blood eosinophil percentage had the greatest predictive value（AUC=0.756）. The prediction model composed of Eotaxin-3, SNOT-22 score, sinus CT Lund-Mackay score, blood eosinophil percentage and blood eosinophil absolute value had better prediction effect on ECRSwNP（AUC=0.873）. Conclusion:Type Ⅱ inflammatory cytokines IL-5 and Eotaxin-3 in nasal secretions may be involved as biomarkers for early diagnosis of ECRSwNP.

Histone deacetylase activity is a novel target for epithelial barrier defects in patients with eosinophilic chronic rhinosinusitis with nasal polyps.

Studies have independently indicated that eosinophils and histone deacetylases (HDACs) may compromise the integrity of the epithelial barrier in nasal polyps; however, the underlying mechanisms are not clear. In this study, we aimed to investigate the role of eosinophilia and HDACs in regulation of tight junctions (TJs) and nasal epithelial barrier integrity in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Expression of mRNAs and proteins of TJs and HDACs of biopsy specimens and air-liquid interface (ALI) human nasal epithelial cell cultures (HNECs) from eosinophilic and noneosinophilic CRSwNP patients and healthy controls was assessed. The ALI HNECs were also assessed for changes in transepithelial electrical resistance (TER) and paracellular flux of fluorescein isothiocyanate (FITC)-labelled dextran. Meanwhile, the assessments for the effect of HDAC inhibitor in eosinophilic nasal polyps were also conducted. Decreased TER and increased paracellular flux of FITC-labelled dextran in the ALI cultures were found in both eosinophilic and noneosinophilic CRSwNP, along with irregular, patchy and reduced expression of claudin-1, 4, 7, occludin, zonula occludens (ZO)-1 and ZO-2 and increased expression of HDAC1, 9 and SIRT7 for both ALI culture cells and biopsy specimens, especially for the eosinophilic CRSwNP group. Treatment of eosinophilic CRSwNP ALI-HNECs with an HDAC inhibitor improved the TJs expression and epithelial barrier integrity. Our data suggest that eosinophilia and HDACs influence epithelial barrier function in CRSwNP patients by regulating TJ protein expression. Targeting HDACs with specific inhibitors may be a potential treatment option for patients with eosinophilic CRSwNP.

Cluster analysis of patients with chronic rhinosinusitis and asthma after endoscopic sinus surgery

BackgroundPatients with chronic rhinosinusitis with nasal polyps and asthma (CRSwAS) are highly heterogenous in severity and prognosis. The clinical phenotypes and inflammatory endotypes of CRSwAS and their association with outcomes of endoscopic sinus surgery (ESS) have not been fully studied yet. ObjectiveWe aimed to find out the clinical phenotypes of CRSwAS and explore their relationship with ESS outcomes using cluster analysis. MethodsWe recruited 103 consecutive adult patients with CRSwAS who had undergone ESS and been followed up for more than 1 year. For cluster analysis, we collected the data from 63 variables pertaining to demographic characteristics, preoperative disease status, surgical techniques, postoperative medical treatment, and outcomes. Eosinophilic CRS was defined as greater than or equal to 10 eosinophils/high-power field, and sinus computed tomography was evaluated by Lund-Mackay sinus computed tomography score (LM score). ResultsWe screened 92 eligible patients and 13 preoperative variables for balanced iterative reducing and clustering using hierarchies cluster analysis. Patients with CRSwAS were divided into 4 clusters with distinct ESS outcomes: (1) cluster 1, characterized by aspirin-exacerbated respiratory disease, eosinophilic CRS, high preoperative LM score, moderate-to-severe asthma, and uncontrolled CRS after ESS; (2) cluster 2, characterized as having female dominance (66.67%), non–aspirin-exacerbated respiratory disease, eosinophilic CRS, high preoperative LM score, moderate-to-severe asthma, and uncontrolled CRS after ESS; (3) cluster 3, characterized as having female dominance (95.83%), noneosinophilic CRS, low preoperative LM score, moderate asthma, and controlled CRS after ESS; and (4) cluster 4, characterized as men-only, smoker, noneosinophilic CRS, low preoperative LM score, mild asthma, and controlled CRS after ESS. ConclusionCRSwAS has distinct clusters, each corresponding to unique clinical and inflammatory characteristics and ESS outcomes.

Surgical Outcomes and Recurrence of Eosinophilic Chronic Rhinosinusitis

Surgical Outcomes and Recurrence of Eosinophilic Chronic Rhinosinusitis

Immunopathologic Role of Eosinophils in Eosinophilic Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a diverse chronic inflammatory disease of the sinonasal mucosa. CRS manifests itself in a variety of clinical and immunologic patterns. The histological hallmark of eosinophilic CRS (ECRS) is eosinophil infiltration. ECRS is associated with severe disease severity, increased comorbidity, and a higher recurrence rate, as well as thick mucus production. Eosinophils play an important role in these ECRS clinical characteristics. Eosinophils are multipotential effector cells that contribute to host defense against nonphagocytable pathogens, as well as allergic and nonallergic inflammatory diseases. Eosinophils interact with Staphylococcus aureus, Staphylococcal enterotoxin B, and fungi, all of which were found in the tissue of CRS patients. These interactions activate Th2 immune responses in the sinonasal mucosa and exacerbate local inflammation. Activated eosinophils were discovered not only in the tissue but also in the sinonasal cavity secretion. Eosinophil extracellular traps (EETs) are extracellular microbes trapping and killing structures found in the secretions of CRS patients with intact granule protein and filamentous chromatic structures. At the same time, EET has a negative effect by causing an epithelial barrier defect. Eosinophils also influence the local tissue microenvironment by exchanging signals with other immune cells and structural cells. As a result, eosinophils are multifaceted leukocytes that contribute to various physiologic and pathologic processes of the upper respiratory mucosal immune system. The goal of this review is to summarize recent research on the immunopathologic properties and immunologic role of eosinophils in CRS.

Predictive value of S100A4 in eosinophilic chronic rhinosinusitis with nasal polyps.

S100A4 is a pro-inflammatory mediator which has been implicated in airway inflammatory diseases. However, its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. The purpose of this study is to determine the expression of S100A4 and evaluate its potential value in distinguishing its endotypes. Sixty CRSwNP patients, 30 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 30 healthy controls (HC) were enrolled in this study, and serum and tissue samples were collected. Serum and tissue S100A4 levels were detected by enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, western blotting and immunofluorescence. Their clinical values in predicting postoperative recurrence of CRSwNP were evaluated by multivariate analysis and ROC curves. Serum levels of S100A4 were notably increased in the CRSwNP group than in the CRSsNP and HC groups (p < 0.05), and positively correlated with tissue and peripheral eosinophil count and percentage (p < 0.05). The serum S100A4 concentrations were significantly elevated in the Eos CRSwNP group in comparison with the non-Eos CRSwNP group (p < 0.05). Multivariate analysis and ROC curve presented that serum S100A4 levels were associated with CRSwNP endotypes. Additionally, tissue S100A4 mRNA and protein levels were significantly enhanced in the CRSwNP group than in the HC group and CRSsNP group, especially in the Eos CRSwNP group. Our results demonstrated that the S100A4 expression was increased in CRSwNP patients and associated with the endotypes. S100A4 could be a serologic biomarker for evaluating tissue eosinophilic inflammation and predicting endotypes in CRSwNP patients.

ANTROCHOANAL POLYP: AN UNCOMMON CAUSE OF CHRONIC NASAL CONGESTION IN PEDIATRIC PATIENTS

<h3>Introduction</h3> Chronic nasal congestion is a common pediatric problem, caused most frequently by viral infections and environmental allergies. We describe a rare case of pediatric antrochoanal polyp causing nasal obstruction. <h3>Case Description</h3> A 10-year-old female with chronic nasal congestion, allergic rhinitis, snoring, recurrent sinus infections, and hyposmia was found to have a left-sided nasal mass after several years of progressive symptoms, despite treatment with nasal corticosteroids and anti-histamines. CT scan showed opacification of the left maxillary and sphenoid sinuses, bilateral ostiomeatal obstruction, and a small, lobulated mass obstructing the left nasal cavity. She had no other recurrent infections or family history of cystic fibrosis; immunoglobulin levels and sweat testing were normal. After otolaryngological evaluation, the mass was resected and found to be an antrochoanal polyp filling the entire chonae and left maxillary sinus. After surgery, her sense of smell returned, nasal congestion resolved, and she had no further infectious sinusitis episodes or polyp recurrence after four years. <h3>Discussion</h3> Pediatric nasal polyps are rare but should be considered in cases of chronic nasal congestion/obstruction. While antrochoanal polyps (arising from the maxillary sinuses) are most common in children, nasal polyps may also originate in the ethmoid/sphenoid sinuses (choanal polyps). Polyps can develop from prolonged mucosal inflammation in the setting of both eosinophilic and non-eosinophilic chronic rhinosinusitis. Lastly, pediatric nasal polyps can be associated with systemic diseases (including cystic fibrosis, primary ciliary dyskinesia, and immunodeficiency) and should prompt additional testing including sweat test and serum immunoglobulin levels.

DYNAMICS OF CLINICAL SYMPTOMS UNDER THE INFLUENCE OF ENDOTYPE-ORIENTED PHARMACOTHERAPY OF CHRONIC RHINOSINUSITIS WITH NASAL POLYPOSIS

Chronic rhinosinusitis (CRS) is a clinical syndrome including several clinical phenotypes and endotypes with differences in pathophysiology. Chronic rhinosinusitis with nasal polyposis (NP) is the most severe CRS phenotype associated with treatment resistance and frequent recurrence after surgery. Among patients with CRS with NP, up to 96% have radiological changes that demonstrate damage to the paranasal sinuses and indicate a diffuse lesion. Pharmacotherapy based on endotyping using aminocapronic acid (ACA) competitively inhibits plasminogen and plasmin formation, inhibits C3a and C5a, which can affect the pathophysiological mechanisms of polypus growth, is promising.&#x0D; The aim of the study: to evaluate the clinical effectiveness of the additional appointment of ACA in comparison with patients receiving standard therapy of CRS with NP according to clinical recommendations.&#x0D; Material and methods. The study included 120 outpatients, divided into two groups: the main (n-60) and the control (n-60) ones. The main group (n-60) included 35 (58.3%) men and 25 (41.7%) women, the control group (n-60) included 32 (53.3%) men and 28 (46.7%) of women. The average age of the main group was 45.8 years; the control group was 47.0 years. Patients were prescribed basic treatment, but patients in the main group were additionally prescribed aminocapronic acid (ACA). The evaluation of the treatment effectiveness was based on the analysis of the dynamics of clinical symptoms: rhinorrhea, postnasal drip, nasal congestion, reduced sense of smell according to the SNOT 22 scale (from 0 to 5 points for each symptom) at V2 (5±1), V3 (10±1), V4 (20±1) and V5 (30±1) compared to V0, as well as the presence of indications for surgical treatment were determined at V3.&#x0D; Results. The use of aminocapronic acid in CRS with NP contributes to a reliable reduction in the severity of the main clinical symptoms (rhinorrhea, postnasal drip, nasal congestion, reduced sense of smell) at V2 and V3 in comparison with patients of the control group. This provided a statistically significant difference at 25% in the reduction of operated patients: 56.7% in the main group versus 81.7% in the control group (p&lt;0.05). Conservative treatment was continued for 43.3% of patients in the main group and for 18.3% of patients in the control group (p&lt;0.05). Such a difference in the dynamic of symptoms regression can be explained by the peculiarities of the biological action of ACA, which can influence the pathophysiological features that characterize the endotype of diffuse eosinophilic CRS with NP. After the removal of the operated patients, the groups did not differ significantly differ in the dynamics of the regression of rhinorrhea, postnasal drip, nasal congestion, decreased sense of smell at V4 and V5 (p&gt;0.05). Differences in the results of treatment are attributed to the clinical effects of ACA, since the group characteristics of the patients were commensurable.&#x0D; Conclusions:&#x0D; &#x0D; the use of ACA in addition to the basic therapy in patients suffering from CRS with NP contributes to a significant reduction in the severity of the main clinical symptoms in the first 10 days of treatment compared to patients in the control group;&#x0D; the positive dynamics of clinical symptoms correlates with a reliable, at 25%, reduction in the number of surgical interventions.&#x0D;

Differentiation of eosinophilic and non-eosinophilic chronic rhinosinusitis on preoperative computed tomography using deep learning.

This study aimed to develop deep learning (DL) models for differentiating between eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS (NECRS) on preoperative CT. Axial spiral CT images were pre-processed and used to build the dataset. Two semantic segmentation models based on U-net and Deeplabv3 were trained to segment the sinus area on CT images. All patient images were segmented using the better-performing segmentation model and used for training and testing of the transferred efficientnet_b0, resnet50, inception_resnet_v2, and Xception neural networks. Additionally, we evaluated the performances of the models trained using each image and each patient as a unit. A total of 878 chronic rhinosinusitis (CRS) patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University (Hubei, China) between October 2016 to June 2021 were included. The precision of each model was assessed based on the receiver operating characteristic curve. Further, we analyzed the confusion matrix and accuracy of each model. The Dice coefficients of U-net and Deeplabv3 were 0.953 and 0.961, respectively. The average area under the curve and mean accuracy values of the four networks were 0.848 and 0.762 for models trained using a single image as a unit, while the corresponding values for models trained using each patient as a unit were 0.893 and 0.853, respectively. Combining semantic segmentation with classification networks could effectively distinguish between patients with ECRS and those with NECRS based on preoperative sinus CT images. Furthermore, labeling each patient to build a dataset for classification may be more reliable than labeling each medical image.

The Percentage of PNAd-Expressing Vessels is Correlated with Disease Severity in Eosinophilic Chronic Rhinosinusitis.

Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory condition of the paranasal sinuses characterized by intractable nasal polyps with prominent eosinophil infiltration. These eosinophils are presumably recruited from peripheral blood via vessels expressing peripheral lymph node addressin (PNAd), a set of glycoproteins decorated with 6-sulfo sialyl Lewis x (sLex) glycans that serve as L-selectin ligands. Based on the severity classification algorithm proposed by the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) study group, ECRS is divided into mild, moderate and severe groups; however, as yet there are few reports comparing the clinicopathological differences among these groups. Our goal was to elucidate clinicopathological differences among the three different severities of ECRS with special reference to eosinophils and PNAd-expressing vessels. We performed quantitative immunohistochemical analysis of PNAd-expressing vessels using surgical specimens of nasal polyps from patients exhibiting varying severity of ECRS (n = 35) and from individuals with non-ECRS (n = 10). To this end, we immunostained tissue sections with anti-PNAd and anti-CD34 monoclonal antibodies, and then determined the number of vessels immunolabeled with each antibody. The number of eosinophils infiltrating nasal polyps was correlated with ECRS severity. We also found that the PNAd + /CD34 + vessel ratio, namely, the percentage of PNAd-expressing vessels among all vessels, was positively correlated not only with ECRS severity but also with the number of eosinophils infiltrating nasal polyps formed in ECRS. These results strongly suggest that PNAd-expressing vessels play at least a partial role in eosinophil recruitment to nasal polyps and consequent severity of ECRS.

Genetic variations in bitter and sweet taste receptors in Taiwanese patients with chronic rhinosinusitis.

Genetic variations of bitter and sweet taste receptors have been related to the pathophysiology of chronic rhinosinusitis (CRS). In this study, we attempted to explore the genetic variations of bitter and sweet taste receptors in Taiwanese CRS patients. Five hundred and sixty-six CRS patients and 5,660 control subjects were selected from participants in the Taiwan Precision Medicine Initiative. Amongst the 566 CRS patients, 186 were with nasal polyps (CRSwNP), while the other 380 were without (CRSsNP). Surgical specimens obtained from 292 CRS patients revealed that 177 were eosinophilic CRS, with the other 115 being non-eosinophilic CRS. There were 591,048 single nucleotide polymorphisms (SNPs) for analysis in all the eligible subjects, including 2 bitter taste receptor SNPs (rs713598, rs10246939) and 1 sweet taste receptor SNP (rs35874116). The minor allele frequencies (MAFs) of rs713598, rs10246939 and rs35874116 were 0.298, 0.297 and 0.078 for CRS patients and 0.306, 0.306 and 0.087 for the control subjects, were 0.301. 0.301 and 0.067 in CRSwNP patients, and 0.295, 0.295 and 0.084 in CRSsNP patients, and were 0.302, 0.302 and 0.085 in the eosinophilic CRS patients, and 0.283,0.287 and 0.087 in the non-eosinophilic CRS patients. The MAFs of rs713598, rs10246939 and rs35874116 were not significantly different between CRS patients and control subjects, between CRSwNP and CRSsNP patients, and between eosinophilic CRS and non-eosinophilic CRS patients. We did not find an association between three variants of the bitter taste receptor TAS2R38 and the sweet taste receptor TAS1R2 and Taiwanese CRS patients. This article is protected by copyright. All rights reserved.

Short-term postoperative efficacy of steroid-eluting stents for eosinophilic chronic rhinosinusitis with nasal polyps: A randomized clinical trial.

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a refractory clinical phenotype with a high symptom burden and relapse rate. Steroid-eluting stents are safe and effective for reducing polyp size, symptom burden, and the need for revision sinus surgery. In this study we aimed to evaluate the efficacy and safety of steroid-eluting stent implantation on the surgical outcomes of patients with ECRSwNP. This prospective, multicenter, randomized, intrapatient-controlled trial recruited patients 18 to 65 years of age with ECRSwNP who required surgery. Ninety-eight patients were enrolled and randomly implanted with absorbable steroid-eluting stents containing mometasone furoate in one sinus at the end of surgery. All patients received standard postoperative care and follow-up. The primary outcome was the Lund-Kennedy endoscopic score within 12weeks postsurgery. Secondary outcomes included nasal symptoms scores, nasal resistance, acoustic rhinometry, nasal nitric oxide levels, 3-dimensional volumetric computed tomography scores, and eosinophil counts in the ethmoid mucosa. Ninety-five patients completed the trial. At postoperative weeks 4, 8, and 12, the Lund-Kennedy scores were significantly lower on the treatment side than on the control side (all p<0.01). Compared with the treatment side, the control side exhibited higher tissue eosinophilia at week 4 and higher volumetric, nasal obstruction, and total nasal symptom scores at postoperative week 8 (p=0.011, p=0.011, p<0.01, and p=0.001, respectively). No adrenal cortical suppression or serious side effects were observed. Steroid-eluting stents reduce postoperative sinus mucosal edema, and eosinophilic inflammation, with persistent effects after stent disintegration, and are a good supplementary postsurgical treatment in patients with ECRSwNP.

Single-cell profiling identifies mechanisms of inflammatory heterogeneity in chronic rhinosinusitis.

The heterogeneous cellular microenvironment of human airway chronic inflammatory diseases, including chronic rhinosinusitis (CRS) and asthma, is still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on the nasal mucosa of healthy individuals and patients with three subtypes of CRS and identified disease-specific cell subsets and molecules that specifically contribute to the pathogenesis of CRS subtypes. As such, ALOX15+ macrophages contributed to the type 2 immunity-driven pathogenesis of one subtype of CRS, eosinophilic CRS with nasal polyps (eCRSwNP), by secreting chemokines that recruited eosinophils, monocytes and T helper 2 (TH2) cells. An inhibitor of ALOX15 reduced the release of proinflammatory chemokines in human macrophages and inhibited the overactivation of type 2 immunity in a mouse model of eosinophilic rhinosinusitis. Our findings advance the understanding of the heterogeneous immune microenvironment and the pathogenesis of CRS subtypes and identify potential therapeutic approaches for the treatment of CRS and potentially other type 2 immunity-mediated diseases.

Three T2 inflammatory diseases in adolescents: asthma, eosinophilic esophagitis, and chronic polypous rhinosinusitis (Clinical Case)

It has long been known that comorbid diseases such as chronic polypous rhinosinusitis and obesity adversely affect the pathophysiology of asthma, impair response to therapy and reduce the quality of life of patients. Identification and effective treatment of comorbidities will improve asthma control and reduce the frequency of exacerbations. There are more and more studies that indicate a close pathophysiological relationship with allergic diseases of eosinophilic esophagitis. According to the latest data in the development of allergic diseases (asthma, allergic rhinitis, atopic dermatitis, food allergy), chronic polypous rhinosinusitis, and eosinophilic esophagitis, the key is the T2 immune response (T2 inflammation) in both children and adults.&#x0D; Timely diagnosis of inflammatory states of T2 inflammation can help in choosing the optimal treatment for such patients. Here we describe the comorbid conditions that occur in an adolescent with controlled asthma and discuss the features of their clinical course.&#x0D; The purpose of this work is to raise the awareness of practitioners about comorbid diseases — eosinophilic esophagitis and chronic polypous rhinosinusitis in children with bronchial asthma. Each of these comorbid diseases has clear diagnostic criteria, although they are underdiagnosed by medical specialists.

S100A8 enhances IL-1β production from nasal epithelial cells in eosinophilic chronic rhinosinusitis

BackgroundChronic rhinosinusitis is classified into eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS). ECRS is a refractory allergic disease involving a variety of immune and epithelial cells. S100A8 is a damage-associated molecular pattern that is closely related to allergic inflammation. However, the pathological implications of S100A8 in ECRS have not been clarified. MethodsWe evaluated the role of S100A8 in the pathogenesis of ECRS. Gene expression profiles of nasal polyps obtained from patients with ECRS or NECRS were evaluated using RNA sequencing. ResultsS100A8 was identified as a significantly upregulated gene in nasal polyps associated with ECRS. Immunohistochemistry consistently revealed intense S100A8 staining in nasal polyps from patients with ECRS. Human nasal epithelial cells expressed the receptor for advanced glycation end products and Toll-like receptor 4. Recombinant S100A8 protein induced interleukin-1β secretion in human nasal epithelial cells. ConclusionsOur data demonstrate that S100A8 results in production of interleukin-1β in the nasal epithelium, which may be involved in the pathogenesis of ECRS.

Periostin is an aggravating factor and predictive biomarker of eosinophilic chronic rhinosinusitis

BackgroundPatients with eosinophilic chronic rhinosinusitis (ECRS) respond poorly to many treatment modalities. Overproduction of periostin in the nasal mucosa is reported to contribute to polyp formation. This study examined periostin levels in patients with ECRS in comparison with levels in patients with non-ECRS. MethodsFifty-nine patients with chronic rhinosinusitis were grouped into those with ECRS and those with non-ECRS. We compared the relationships between peripheral blood eosinophil level, serum periostin level, histopathological findings, clinical and laboratory findings, nose findings, diagnostic score of the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study, and postoperative recurrence of nasal polyps in each group. ResultsIn the ECRS group, a positive correlation was found between peripheral blood eosinophil level and serum periostin level (rs = 0.49, P < 0.01: Spearman's rank correlation coefficient). ROC curve analysis was used to evaluate the serum periostin level that could predict postoperative recurrence of nasal polyps in the ECRS group: the area under the curve (AUC) was 0.95, sensitivity was 92%, and specificity was 100%; the serum periostin cutoff value for postoperative recurrence of nasal polyps was 130 ng/ml. In ROC curve analysis to evaluate peripheral blood eosinophil level, the AUC was 0.73, sensitivity was 69.2%, and specificity was 85.0%; the cutoff value was 8.8%. Conclusionsperiostin was implicated in the pathophysiology of ECRS. Periostin shown to be a more useful biomarker than eosinophils in ECRS. Periostin was shown to likely be an important biomarker for pathological severity of ECRS and postoperative recurrence of nasal polyps.

Sweet taste receptor agonists attenuate macrophage IL-1β expression and eosinophilic inflammation linked to autophagy deficiency in myeloid cells.

BackgroundEosinophilic inflammation is a hallmark of refractory chronic rhinosinusitis (CRS) and considered a major therapeutic target. Autophagy deficiency in myeloid cells plays a causal role in eosinophilic CRS (ECRS) via macrophage IL‐1β overproduction, thereby suggesting autophagy regulation as a potential therapeutic modality. Trehalose is a disaccharide sugar with known pro‐autophagy activity and effective in alleviating diverse inflammatory diseases. We sought to investigate the therapeutic potential of autophagy‐enhancing agent, trehalose, or related sugar compounds, and the underlying mechanism focusing on macrophage IL‐1β production in ECRS pathogenesis.MethodsWe investigated the therapeutic effects of trehalose and saccharin on macrophage IL‐1β production and eosinophilia in the mouse model of ECRS with myeloid cell‐specific autophagy‐related gene 7 (Atg7) deletion. The mechanisms underlying their anti‐inflammatory effects were assessed using specific inhibitor, genetic knockdown or knockout, and overexpression of cognate receptors.ResultsUnexpectedly, trehalose significantly attenuated eosinophilia and disease pathogenesis in ECRS mice caused by autophagy deficiency in myeloid cells. This autophagy‐independent effect was associated with reduced macrophage IL‐1β expression. Various sugars recapitulated the anti‐inflammatory effect of trehalose, and saccharin was particularly effective amongst other sugars. The mechanistic study revealed an involvement of sweet taste receptor (STR), especially T1R3, in alleviating macrophage IL‐1β production and eosinophilia in CRS, which was supported by genetic depletion of T1R3 or overexpression of T1R2/T1R3 in macrophages and treatment with the T1R3 antagonist gurmarin.ConclusionOur results revealed a previously unappreciated anti‐inflammatory effect of STR agonists, particularly trehalose and saccharin, and may provide an alternative strategy to autophagy modulation in the ECRS treatment.

"Who is it?" in rhinology.

"Who is it?" in rhinology.

Reply to Letter to the editor concerning "Determining a cut-off value for eosinophilic chronic rhinosinusitis".

Reply to Letter to the editor concerning "Determining a cut-off value for eosinophilic chronic rhinosinusitis".