Chronic Eosinophilic Sinusitis Research Articles

The value of combined detection of specific immunoglobulin E, interleukin-6 and regulatory T cells in predicting the risk of postoperative recurrence in patients with eosinophilic chronic rhinosinusitis and nasal polyps

Background: To investigate the predictive value of specific immunoglobulin E (sIgE), interleukin-6 (IL-6) and regulatory T cells (Treg) on the risk of postoperative recurrence in patients with eosinophilic chronic sinusitis with nasal polyps (EcRswNP). Methods: A total of 198 patients with EcRswNP collected to our Hospital from January 2019 to December 2021 were selected as the research subjects. All patients underwent functional endoscopic sinus surgery. The patients were selected to recurrence group (RG, n = 48) and non-recurrence group (NRG, n = 150) on the basis of the recurrence after 1 year of follow-up. The related factors of postoperative recurrence of EcRswNP were analyzed.. The ROC was used to analyze the dangerous of sIgE, IL-6 and Treg in predicting postoperative recurrence of EcRswNP patients. Results: The proportion of asthma patients, nasal congestion VAS score and peripheral blood Eos% content in the RG were exceed than the NRG, and the Organization Neu % and peripheral blood Neu% levels were less than those in the NRGp (P all < 0.05). The serum sIgE and serum IL-6 in the RG were exceed than the NRG, and the level of peripheral blood Treg was less than the NRG (P < 0.05). Logistic regression analysis showed that high levels of serum sIgE, serum IL-6 and low Treg levels were risk factors for postoperative recurrence (P < 0.05). ROC showed that the AUC of peripheral blood sIgE level, IL-6 and Treg levels alone in predicting the dangerous of postoperative recurrence in patients with EcRswNP were 0.786, 0.707 and 0.636, respectively (all P < 0.05); The AUC of combined prediction of peripheral blood sIgE, IL-6 and Treg levels for postoperative recurrence dangerous in patients with EcRswNP was 0.973, indicating that the efficacy of jointed prediction was exceed than that of single prediction (P < 0.05). Conclusions: The high levels of sIgE, IL6 and low Treg levels in patients with EcRswNP before operation will increase the risk of postoperative recurrence, which is a risk factor affecting postoperative recurrence, and the three indicators have good predictive value for predicting postoperative recurrence in patients with EcRswNP, and the combination of the three indicators has better value in predicting postoperative recurrence.

The predicting role of postoperative changes in self-reported symptoms in patients with recurrence eosinophilic chronic sinusitis with nasal polyps

Objective:To investigate whether changes in postoperative symptoms and signs in patients can predict the recurrence of ECRS after nasal endoscopic sinus surgery. Methods:A total of 70 adult patients with ECRS were enrolled for ESS surgery from June 2020 to March 2022 in a single center. There were 50 males and 20 females, with an average age of （46.9±14.5） years. Follow-up after ESS was at least 52 weeks. Patients undergo peripheral blood tests, CT of the sinuses, olfactory T&T test, visual analogue scale of symptoms（VAS）, and endoscopic scoring. Results:VAS scores and endoscopic scores were analyzed at preoperative and 6th week, 12th week, 24th week and 52th week postoperative. After 12th week postoperatively, there was a clear correlation between symptom scores and endoscopic scores. Moreover, olfactory disorder and nasal discharge were the two most obvious symptoms. There were differences in the expression of multiple preoperative clinical inflammatory indicators between the symptom-controled group and the symptom-uncontrolled group（previous surgical history, concomitant asthma, nasal smear eosinophil, serum EOS%, total IgE, CT score, olfactory score, and symptom score, all with P<0.05）, while there was no difference in baseline endoscopic score（P>0.05）. At 12th week postoperative, the two groups of patients showed significant differences in both symptom scores and endoscopic scores. The symptoms and endoscopic score at the 12th week point of follow-up were used as predictive indicators for recurrence, with sensitivity and specificity of 62.5% and 83.3%, respectively. Conclusion:The changes in postoperative symptom score and endoscopic score in ECRSwNP patients indicated that the recurred ECRS. In the symptom-uncontrolled group, symptomatic and endoscopic scores showed consistent increased scores; In the symptom-controlled group, conflicting results between increased endoscopic scores and stable symptoms suggest that the presence of asymptomatic recurrence must be considered. The changes in symptoms and signs at the 12th week point of follow-up can serve as clinical indicators for preventing disease recurrence.

Effect of TFF3 on tight junction protein in eosinophilic chronic sinusitis and its related mechanism

Objective: To study the effect of trefoil factor family (TFF) 3 on the expression of tight junctions (TJs) in the nasal mucosa epithelium of eosinophilic chronic rhinosinusitis (eCRS) and its mechanism. Methods: From September to December 2020, eligible patients from the Department of Otorhinolaryngology of the First Affiliated Hospital of Nanchang University were recruited, including 11 control patients and 37 patients with chronic rhinosinusitis with nasal polyps (CRSwNP), from whom nasal mucosa and nasal polyp tissue samples were collected. Immunohistochemistry (IHC) was used to detect the localization and expression intensity of TFFs (TFF1, TFF2 and TFF3) and TJs (occudin, claudin-1 and ZO-1) in nasal mucosa. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) were used to detect the mRNA and protein expression. A cell model of tight junction injury in human nasal epithelial cells (HNECs) through stimulation with interleukin (IL)-13 was also established. The optimal modeling concentration and time for HNECs were determined, which were subsequently treated with TFF3 and/or a phosphoinositide 3-kinase (PI3K)-specific inhibitor (LY294002). Finally, RT-qPCR and WB were used to assess the effects of TFF3 on tight junctions and the PI3K/serine/threonine kinase (Akt) signaling pathway. Data were analyzed statistically using GraphPad Prism 7 software. Results: IHC results showed that the expression of TFF1 and TFF3 in nasal mucosa of eCRS group was significantly higher than that of control group (t=4.62, P=0.002; t=5.89, P<0.001), respectively, mainly expressed in goblet cell. The expression of occludin, claudin-1 and ZO-1 in the nasal mucosa of the eCRS group was lower than that of the control group (occludin t=3.98, P=0.019; claudin-1 t=5.15, P=0.002; ZO-1 t=5.42, P=0.001), respectively. WB results showed that the expression of TFF3 in non-eosinophilic chronic sinusitis (Non-eCRS) group and eCRS group was higher than that in the control group (t=3.62, P=0.036; t=5.93, P<0.001). The expression of occludin, claudin-1 and ZO-1 in eCRS group was lower than that in the control group (occludin t=5.14, P=0.002; claudin-1 t=6.35, P<0.001; ZO-1 t=6.64, P<0.001), respectively. The RT-qPCR results showed that compared with the control group, the levels of TFF1 and TFF3 mRNA were increased in the nasal mucosal epithelium of the Non-eCRS and eCRS groups (TFF1 t=3.98, P=0.046, t=4.89, P=0.002; TFF3 t=3.50, P=0.044, t=6.78, P<0.001). There was no statistically significant difference in TFF2 mRNA levels between the Non-eCRS and eCRS groups (t=1.34, P=0.061; t=3.37, P=0.055). Compared with the control group, Non-eCRS and eCRS groups showed a decrease in the mRNA levels of occludin, claudin-1 and ZO-1 (occludin t=4.27, P=0.011, t=5.61, P=0.007; claudin-1 t=3.62, P=0.036, t=6.80, P<0.001; ZO-1 t=3.47, P=0.047, t=7.86, P<0.001). The mRNA levels of TFF3 and TJs in eCRS nasal mucosa tissue showed a moderate positive correlation (occludin r=0.661, claudin-1 r=0.614, ZO-1 r=0.548, all P<0.001); TFF1 showed a low degree of positive correlation with the expression of occludin, claudin-1 and ZO-1 (occludin r=0.467, P=0.040; claudin-1 r=0.362, P=0.012; ZO-1 r=0.425, P=0.025). The establishment of cell models showed that compared with normal HNECs, the mRNA expression of TFF3 was most significantly increased at a concentration of 50 ng/ml stimulated by IL-13 (t=3.72, P=0.013); The mRNA expression of occludin, claudin-1 and ZO-1 decreased (occludin t=3.18, P=0.031; claudin-1 t=3.86, P=0.010; ZO-1 t=5.16, P=0.002). The expression of TFF3 mRNA increased most significantly after 15 hours of IL-13 stimulation (t=3.14, P=0.034); The mRNA expression of occludin, claudin-1 and ZO-1 decreased (occludin t=3.97, P=0.010; claudin-1 t=4.78, P=0.004; ZO-1 t=5.16, P=0.004). TJs damage model could be established by treating HNECs with 50 ng/ml IL-13 for 15 hours. Intervention experiments showed that compared with the IL-13 group, the IL-13+TFF3 group showed an increase in TJs mRNA expression (occludin t=6.10, P=0.009; claudin-1 t=5.90, P=0.013; ZO-1 t=9.44, P=0.007). Compared with the IL-13 group, the expression of TJs protein in the IL-13+TFF3 group increased (occludin t=3.23, P=0.013; claudin-1 t=9.40, P=0.017; ZO-1 t=2.23, P=0.032); The expression of TJs protein decreased in the IL-13+TFF3+LY294002 group (occludin t=4.73, claudin-1 t=8.77, ZO-1 t=3.51, all P<0.001). Compared with the IL-13+TFF3 group, the IL-3+TFF3+LY294002 group showed a decrease in PI3K and p-Akt/Akt protein expression (PI3K t=13.29, p-Akt/Akt t=10.30, all P<0.001). The increased mRNA and protein expression of occludin, claudin-1 and ZO-1 induced by TFF3 were also inhibited by LY294002. Conclusion: TFF3 can up-regulate the expression of occludin, claudin-1, and ZO-1 through PI3K/Akt pathway, and has a certain protective effect on the nasal mucosal epithelial barrier, providing a new idea for treating eCRS.

Correlation between chronic sinusitis subtypes and basophil levels in peripheral blood

Objective:To explore the clinical correlation between peripheral blood basophil levels and chronic sinusitis （CRS） subtypes. Methods:One hundred and twenty-six patients with CRS and 103 healthy cases from physical examination admitted to the First Affiliated Hospital of Soochow University from January 2021 to October 2022 were retrospectively analyzed. According to the histopathological classification, CRS patients were divided into eosinophilic chronic sinusitis （eCRS） group （47 cases） and non eosinophilic chronic sinusitis （non-eCRS） group （79 cases）. The differences among the three groups in peripheral blood inflammation cell counts, eosinophils-to-basophils ratio（bEBR）, basophils-to-neutrophils ratio（BNR）, basophils-to-lymphocytes ratio（BLR）, basophils-to-monocytes ratio（BMR） were compared, and study the correlation between each index and Lund-Mackay score, and the correlation between basophils in peripheral blood and other inflammatory cells. Results:The counts of basophils in the peripheral blood of the healthy control group, eCRS group and non-eCRS group were 0.03±0.01, 0.04±0.02, 0.03±0.02, respectively, the eosinophils-to-basophils ratio（bEBR） were 5.64±4.22, 8.38±5.95, 4.55±3.90, the basophils-to-neutrophils ratio（BNR） were 0.01±0, 0.01±0.01, 0.01±0.01, and the basophils-to-lymphocytes ratio（BLR） were 0.01±0.01, 0.02±0.01, and 0.02±0.01, respectively, the basophils-to-monocytes ratio（BMR） were 0.08±0.04, 0.11±0.06, and 0.08 ±0.04 respectively. There was a statistically significant difference between eCRS group and healthy control group, non-eCRS group（P<0.01）, while there was no statistically significant difference between non-eCRS group and healthy control group（P>0.05）. Basophil counts （r=0.185 5, P<0.05）, BLR（r=0.226 9, P<0.05）, BMR（r=0.228 1, P<0.01） in patients with CRS were positively correlated with Lund Makey score. In addition, basophils were also positively correlated with eosinophils（r=0.479 2, P<0.01）, lymphocytes（r=0.259 4, P<0.01）, and monocytes（r=0.256 4, P<0.01） in patients with CRS. Conclusion:The peripheral blood basophil count, BLR and BMR were significantly increased in eCRS, and were significantly positively correlated with Lund -Makey score. It has the potential to develop into disease biomarkers and new therapeutic targets of eCRS.

The influence of two kinds of transnasal endoscopic surgery on the outcome status of sinus cavity in patients with eosinophilic chronic rhinosinusitis with nasal polyps

Objective: To investigate the trend of postoperative cavity status in patients with eosinophilic chronic sinusitis with nasal polyps (eCRSwNP) who underwent total nasalization surgery and partial reboot surgery. And to discuss the relationship between tissue eosinophil counts and status of postoperative cavity. Methods: Patients with eCRSwNP in four tertiary medical centers (Longgang ENT Hospital, Xiamen Humanity Hospital, Guangdong Clifford Hospital and the First Affiliated Hospital of Sun Yat-Sen University) from March 2018 to October 2021 were divided into 2 groups. The group without previous surgery history was performed for the nasalization surgery, and another group with previous surgery history underwent the part-reboot surgery. The follow-up time after operation was defined as the following 5 stages: 6, 12, 20-24, 36 and more than 42 months. According to FESS-95 Guangzhou standard, status of sinus cavity was assessed and classified into 3 categories: good, better and bad. The association between the sinus cavity status and tissue eosinophil counts in the above 5 stages was analyzed by one-way ANOVA, and P<0.05 was considered statistically significant. Results: A total of 72 eCRSwNP patients finished the follow-up in this study. There were 47 males and 25 females in these patients, aged from 11 to 67 years. A total of 50 cases underwent nasalization surgery and 22 cases underwent partial reboot surgery. With the follow-up time from 6 to 48 months, there were 72 cases (100.0%) who completed 6 months and 12 months follow up, 46 cases (63.9%) for 20-24 months, 36 cases (50.0%) for 32-36 months and 16 cases (22.2%) with the follow-up time more than 42 months. No matter what kind of surgery, there was no "bad" situation of the surgical cavity status 6 months after the operation, and the differentiation gradually occurred more than 12 months after the surgery. Moreover, the rates of "good" cavity status for the 5 stages in the group of nasalization surgery were 78.0%, 66.0%, 56.7%, 47.6% and 42.9%, and were 63.6%, 45.5%, 25.0%, 20.0% and 11.1% in the partial reboot surgery group, respectively, suggesting that the status of nasal cavity in nasalization surgery group was always better than that in partial reboot surgery group in every period. In addition, the "bad" rate was 0, 8.0%, 10.0%, 14.3% and 28.6% in the group of nasalization surgery, and was 0, 27.3%, 18.8%, 33.3% and 55.6% in the partial reboot surgery group, respectively. The average percentage of tissue eosinophil counts in the 72 cases was 42.1%, which had no obvious effect on the status of the surgical cavity (P>0.05). Conclusions: For eCRSwNP patients, the operative cavity status in the patients without previous operation history treated with nasalization surgery is good. The time of 1-2 years after surgery is the main period for sinus lesions. The counts of tissue eosinophils has no significant influence on surgical sinus cavity status in the eCRSwNP patients.

Application of nasal nitric oxide in primary diffuse chronic rhinosinusitis

Objective:This study aimed to investigate whether nasal nitric oxide（nNO） could be used to identify the main clinical phenotypes of primary diffuse chronic sinusitis（CRS） and reflect the severity of sinus mucosal lesions. Methods:A total of 57 patients with primary diffuse CRS were included as the case group in this study. And the patients were divided into eosinophilic CRS（EosCRS） group and non-EosCRS group according to the percentage of eosinophils in peripheral blood. At the same time, 32 healthy volunteers were selected as the control group. According to whether there is nasal polyps under nasal endoscopy, the EosCRS group was classified into EosCRS with nasal polyps（EosCRSwNP） and EosCRS without nasal polyps（EosCRSsNP）. In the same way, the non-EosCRS group was assigned to non-EosCRS with nasal polyps（non-EosCRSwNP） and non-EosCRS without nasal polyps（non-EosCRSsNP）. The levels of nNO were detected by single nostril air extraction with 10 mL/s flow rate and soft palate closure. The severity of sinus lesions were evaluated by Lund-Mackay score. The difference of nNO levels were compared by the Rank sum test. The correlation between nNO levels and Lund-Mackay score was analyzed by Pearson correlation analysis. Results:①The levels of nNO in EosCRS group [315.00（88.00, 446.50） ×10⁻⁹] and non-EosCRS group [419.00（181.00, 469.00） ×10⁻⁹] were significantly lower than those in the control group [457.00（431.00, 493.75） ×10⁻⁹]（P<0.01）. ②The levels of nNO in EosCRSwNP group [260.00（71.75, 391.50） ×10⁻⁹] were significantly lower than that in EosCRSsNP group [557.00（442.50, 619.75） ×10⁻⁹], and that in non-EosCRSwNP group [210.00（159.75, 434.25） ×10⁻⁹] were significantly lower than non-EosCRSsNP group [455.00（425.00, 481.00） ×10⁻⁹]（P<0.05）. ③There was a medially negative correlation between the levels of nNO and the total score of Lund-Mackay score in the EosCRS group（r=-0.567, P<0.01）. Conclusion:The levels of nNO can be used to determine whether primary diffuse CRS is accompanied by nasal polyps and reflect the severity of nasal sinus mucosal lesions, instead of identifying the main clinical phenotypes of primary diffuse CRS.

Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis.

Background: Eosinophilic chronic sinusitis (ECRS) is a subtype of CRS with nasal polyps (CRSwNP) that is frequently comorbid with asthma. Notably, ECRS patients often show a high recurrence of NPs after surgical resection. Leptin is a hormone produced by adipocytes that has been implicated in airway inflammatory diseases. However, to date, the role of leptin in ECRS has not been investigated. Objective: To determine whether the serum levels of leptin are altered in patients with ECRS. Methods: In total, 40 patients with ECRS, 15 patients with non-eosinophilic CRS (non-ECRS), and 12 individuals without CRS (control) were included in this study. Patient’s serum leptin levels were assessed, and the number of eosinophils in their NPs were measured through a histological evaluation of the three densest areas with cellular infiltrate beneath the epithelial surface. Finally, nasal fibroblast cultures established from NPs were stimulated with varying concentrations of recombinant leptin in vitro to determine whether leptin affects eotaxin-3 (Chemokine (C-C motif) ligand 26 :26: CCL26) expression. Results: The serum leptin levels in both the ECRS and non-ECRS groups were significantly higher than those in the control subjects (p < 0.0001 vs. ECRS; p < 0.05 vs. non-ECRS). Furthermore, ECRS patients displayed significantly elevated serum leptin levels compared to non-ECRS patients (p < 0.001), although there was no difference in body mass index between the groups. Notably, serum leptin levels were correlated with the proportion of eosinophils in peripheral blood (r = 0.3575, p < 0.01) and the number of eosinophils in NPs (r = 0.5109, p < 0.0001). Serum leptin levels were also correlated with eotaxin-3 mRNA expression in NPs (r = 0.5374, p < 0.01). Finally, leptin significantly augmented eotaxin-3 expression in nasal fibroblasts established in vitro from NPs in a leptin receptor-dependent manner (p < 0.05). Conclusion: Leptin levels are elevated in ECRS patients and may both promote and indicate the severity of ECRS as well as systemic type 2-biased inflammatory responses. Combined, these data indicate that circulating leptin may play a significant role in the development of eosinophilic inflammation in NPs.

ATYPICAL CASE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a multi-organ vasculitis. However, the hallmarks of the disease are eosinophilia, chronic sinusitis, and asthma. Vasculitic organ involvement might be absent early on, making the diagnosis challenging1. We present the case of a patient with atypical presentation and serology for EGPA. CASE PRESENTATION: A 71-year-old male with a history of non-asthmatic eosinophilic bronchitis, chronic sinusitis, and peripheral eosinophilia (peak 936 cells/uL; 17.6%) was admitted to the hospital with dyspnea and rapidly progressive acute hypoxemic respiratory failure requiring transfer to the intensive care unit. He was started on high flow nasal cannula (60LPM; FiO2 90%-100%). Bilateral crackles noted with no pitting edema. Chest CT showed bilateral airspace disease and ground glass opacities. He tested negative twice for SARS-CoV-2. White blood cell count, kidney function, and brain natriuretic peptide were normal. Autoimmune workup was ordered. He was started on empiric broad-spectrum antibiotic, and gently diuresed. As his presentation was suggestive of eosinophilic lung disease, and in light of significant oxygen requirement, the decision was made to hold on bronchoscopy and start solumedrol at 125mg/day. On ICU Day 3, autoimmune workup showed elevated anti-nuclear antibody titer of 1:160 with a speckled pattern, elevated anti-myeloperoxidase (MPO) antibody titer of 49.4 (p-ANCA), and elevated anti-proteinase-3 (anti-PR3) antibody titers of 18.8 (c-ANCA). Infectious workup was negative. The patient was diagnosed with possible EGPA. He was started on cyclophosphamide in addition to steroids. Oxygen requirement continued to improve. He was discharged home on oxygen at 4LPM and oral steroid with a plan for monthly cyclophosphamide infusion. Follow-up in 2 months with repeat chest CT showed marked improvement. DISCUSSION: The manifestations of EGPA are dynamic, with a few manifestations presenting earlier than others2. With the temporal spacing of signs and symptoms, it is often diagnosed late when more clues are evident. In 1990, the American College of Rheumatology (ACR) established a set of 6 criteria: asthma, peripheral eosinophilia >10%, mononeuropathy or polyneuropathy, migratory pulmonary infiltrates, paranasal sinus abnormality, and biopsy containing blood vessel with extravascular eosinophils2. At least 4 out of six of these criteria must be met to have a diagnosis of EGPA with a specificity of 99.7%. p-ANCA (anti-MPO) is present in around 70% of patients with active EGPA, whereas c-ANCA (anti-PR3) is nearly absent3. Our patient met 3 out of the 6 criteria, and his serology was atypical, showing high titers for both p-ANCA and c-ANCA. CONCLUSIONS: EGPA diagnosis in our patient was not a robust one. However, establishing a presumed diagnosis early and starting immunosuppressive therapy likely saved his life. REFERENCE #1: Guillevin L, Cohen P, Gayraud M, et al. Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore) 1999; 78:26. REFERENCE #2: Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990; 33:1094. REFERENCE #3: Sablé-Fourtassou R, Cohen P, Mahr A, et al. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med 2005; 143:632 DISCLOSURES: No relevant relationships by Tony Abdo, source=Web Response No relevant relationships by Ahel El Haj Chehade, source=Web Response No relevant relationships by Ahmad Hassan, source=Web Response

Asthma and nasal polyposis: Are biological treatments effective?

Chronic rhinosinusitis with nasal polyps often accompanies severe asthma. Uncontrolled nasal polyp does not only impair the quality of life, but also makes it difficult to control the accompanying asthma. Eosinophilic chronic sinusitis dominated by type 2 inflammation is phenotypically manifested by nasal polyps. In recent years, approaches towards phenotype and endotype have developed in patients with chronic sinusitis as well as in asthma; biological treatments come into question in uncontrolled patients with appropriate endotype. Randomized controlled trials conducted on treatments that antagonize the Ig-E, IL-5, and IL-4a pathways in these patients are promising. The effectiveness of biological treatments, which we think will be more involved in clinical practice in the management of nasal polyp patients in the near future, will become clear with the increase in real life data in the literature.

Mepolizumab for eosinophilic chronic sinusitis with nasal polyposis: real-life experience

Mepolizumab for eosinophilic chronic sinusitis with nasal polyposis: real-life experience

Correlation analysis between modified nasal endoscopic score and ELR value and subtype of chronic sinusitis with nasal polyps

Objective:To analyze the correlation between the modified nasal endoscopic score and ELR value and the subtype of chronic sinusitis with nasal polyps. Method:The clinical data of 119 patients of chronic sinusitis with nasal polyps were retrospectively analyzed. According to the postoperative pathological results, they were divided into two groups: eosinophilic chronic sinusitis with nasal polyps（eCRSwNP） and non-eosinophilic chronic sinusitis with nasal polyps（neCRSwNP）. All patients underwent modified nasal endoscopic examination scores, according to clinical features and anatomical features into the part of the middle nasal meatus and the part of olfactory fissure, and the scores were calculated in two areas respectively; History of asthma, allergic rhinitis and the percentage of eosinophils（EO%）, the absolute value of eosinophils（EO#）, the absolute neutrophil（N）, the absolute lymphocyte（R）, the total IgE were recorded at the same time. Calculate the NLR value and ELR value. This study used SPSS 19.0 for statistical analysis of relevant data. Result:According to the modified nasal endoscopic scoring criteria, the eCRSwNP group had significantly higher olfactory fissure area scores while middle nasal meatus area scores were significantly lower than the neCRSwNP group; ELR value, EO% and EO# were significantly higher in the eCRSwNP group than in the control group, while NLR value and N value were higher in the neCRSwNP group（P<0.05）; There was no significant difference in age, gender, R value and total IgE between the two groups. Compared with EO#, the ELR value was more stability and sensitivity. Therefore, the olfactory fissure area polyps and ELR value are more significant for pre-diagnosis. Conclusion:The modified nasal endoscopic score and ELR value are more correlated with the subtype of CRSwNP. Higher ELR value ,lower NLR value, and association with allergic rhinitis, asthma can be used as prediagnostic indicators for eCRSwNP before invasive pathological results and CT examination.

Type 2 inflammation suppression by T-regulatory cells attenuates the eosinophil recruitment in mucosa of chronic sinusitis.

Type 2 inflammation and eosinophilic infiltration are prominent pathologic features of chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of the present study was to determine the roles of Tregs in controlling type 2 inflammation and inhibiting eosinophilic infiltration in CRSwNP. A total of 134 nasal polyps, 67 ostiomeatal complex from chronic rhinosinusitis (CRS) and 62 normal nasal tissues from controls were collected to study the enumeration and function of Tregs cells and the expressions of cytokine profiles via immunofluorescence staining, flow cytometry, qRT-PCR, ELISA, and/or H&E staining. The effects of Tregs on type2 and type3 inflammations were determined in an eosinophilic chronic sinusitis (ECRS) mice model. It was confirmed that the CRSwNP displayed the features of Th2 and Th17 cells-mediated inflammation, accompanying by an increased level of eosinophilic infiltration and the eosinophil cationic protein (ECP), with a decreased frequency of Treg cells. Furthermore, the percentages of CD4+CD25+CD127lowTreg and CD4+CD25+Foxp3+Treg were only decreased in the polyps of CRSwNP but not in the paired peripheral blood. The CRSwNP possessed the decreased Nrp1+Tregs, Helios+Treg, and low TGF-β and interleukin (IL)-10 expressions in Tregs. The ECRS mice showed similar inflammatory characteristics to CRSwNP patients. The adoptive transfer of CD4+CD25+Foxp3+ Treg cells significantly decreased the inflammatory cytokines, eosinophilic chemotactic factors in the mucosa of the ECRS mice without alteration of the immune balance in the peripheral blood and spleen. In conclusion, CRSwNP showed high type 2 and type3 inflammation and defective Tregs. The induced regulatory T cell (iTreg) may correct the imbalance between immune tolerance and effect via limiting the eosinophil recruitment of mucosa in CRSwNP.

Two Cases of Allergic Fungal Sinusitis with Differing Postoperative Course

Allergic fungal sinusitis (AFS) often develops in unilateral paranasal sinuses, which must be differentiated from tumors. When AFS develops on both sides, however, it must be differentiated from eosinophilic chronic sinusitis with evident eosinophilic infiltration at nasal/paranasal sinus mucosa; both conditions are highly recurrent and commonly considered intractable paranasal sinusitis. Surgical correction is the primary treatment method for AFS, as it is essential to connect the paranasal sinus communication to ensure exhaustive resection of the pathologic mucosa and for nasal steroids to reach each paranasal sinus. We recently encountered two AFS cases with differing postoperative courses. Case 1 showed evident exacerbation in the computed tomography findings, which suggests progression to eosinophilic sinusitis. Case 2 showed a benign prognosis without recurrence. Close long-term follow-up should be mandatory after surgery for the treatment of AFS.

Expression of amphiregulin in different types of nasal polyps and its correlation with tissue remodeling

Objective: To explore the expression of amphiregulin (AREG) in nasal polyps patients with different degrees of eosinophil infiltration, and to analyze the correlation between AREG and tissue remodeling. Methods: Forty-eight patients underwent endoscopic sinus surgery in the Department of Otorhinolaryngology Head and Neck Surgery, Remin Hospital, Wuhan University from July 2017 to August 2018 were recruited, including 40 males and 8 females, aged from 16 to 60 years old. The subjects were divided into three groups: control group (n=14), eosinophilic chronic sinusitis with nasal polyps (ECRSwNP) group (n=19) and noneosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) group (n=15). The relative expression of AREG in nasal mucosa was detected by Western blot assay and immunohistochemical staining. Tissue remodeling was detected by HE staining, AB-PAS staining and Masson staining. Kruskal-Wallis test was used for comparison among multiple groups, and Spearman correlation analysis was conducted between the expression level of AREG and the related indexes of tissue remodeling. Results: The expression of AREG in ECRSwNP group was significantly higher than that in non-ECRSwNP group and control group (median protein expression of Western blot was 1.592 vs 0.617 vs0.582, all P<0.05). The degree of epithelial injury and goblet cell metaplasia in ECRSwNP group was significantly higher than that in control group (all P<0.05), the percentage of collagen fibrosis area in ECRSwNP group was significantly lower than that in control group (P=0.01). In chronic rhinosinusitis with nasal polyps (CRSwNP) patients, the area of mucous glands was negatively correlated with the expression of AREG (r=-0.616, P<0.05), and the percentage of collagen fibrosis area was negatively correlated with the expression of AREG (r=-0.738, P<0.05). Conclusion: The expression of AREG is higher in ECRSwNP patients, which is related to the process of tissue remodeling.

Successful management of severe asthma in a young boy with eosinophilic chronic rhinosinusitis who received omalizumab: a case report

BackgroundThe incidence of chronic rhinosinusitis with nasal polyps has recently increased in Japan and other East Asian countries, and this disease is called eosinophilic chronic sinusitis (ECRS) in Japan. ECRS usually occurs in adults and is frequently accompanied by refractory bronchial asthma. However, its occurrence in children under 10 years of age is rare. Here, we present an unusual case of ECRS complicated by intractable asthma in an 8-year-old boy.Case presentationOral administration of prednisolone (10 mg/day) initially relieved the ECRS and bronchial asthma, but both returned during prednisolone dose reduction. Because nasal cavity-opening surgery was ineffective, oral administration prednisolone at 10 mg/day was continued. Pancytopenia was observed 16 months after the start of treatment, and the patient was admitted to our hospital. He was diagnosed with refractory cytopenia in childhood, but gradually improved after cyclosporine treatment. Although the dose of cyclosporine was therapeutic for asthma, it did not alleviate the asthma attacks, and the patient’s quality of life markedly decreased. We administered omalizumab even though its use was contraindicated by negative results in an inhalable antigen test. After the third administration of omalizumab, the asthma was better controlled and respiratory function improved; however, the nasal symptoms of ECRS persisted. Attempts to relieve these symptoms by increasing the therapeutic dose of omalizumab were only partially successful. We replaced omalizumab with mepolizumab; doing so slightly improved the sinusitis symptoms, but quality of life remained unsatisfactory. We repeated the nasal cavity-opening surgery. After surgery, the asthma and sinusitis were unchanged.ConclusionsOmalizumab effectively treated the severe combined asthma in a young patient, but its effect on sinusitis was insufficient. More cases and long-term follow-up data are needed to better evaluate the effectiveness of mepolizumab for treatment of ECRS.

Clinical characteristics of non-eosinophilic and eosinophilic chronic sinusitis with nasal polyps

Objective:To investigate the clinical characteristics of non-eosinophilic and eosinophilic chronic sinusitis with nasal polyps.Method:Ninty-two patients with chronic sinusitis with nasal polyps were collected and divided into eosinophilic chronic sinusitis with nasal polyps(EOS CRSwNP) and non-eosinophilic chronic sinusitis with nasal polyps(NONEOS CRSwNP) by pathological classification. The clinical characteristics between the two types were compared. Result:NONEOS CRSwNP is more common in northern area of Fujian province(84.8%). NONEOS CRSwNP had the following clinical characteristics: one most nasal discharge was purulent; two more pyocysts can be seen in nasal polyps; three the proportion of eosinophils in the peripheral blood was mostly normal. Four mainly maxillary sinus lesions. EOS CRSwNP had the following characteristics: one most nasal discharge was mucous purulent; two bilateral sinus lesions were more common, mainly ethmoid sinus lesions; three the proportion of blood eosinophilic cells in peripheral blood was often increased. Ouroften accompanied by asthma, postoperative nasal polyps are prone to relapse, systemic steroid hormone is effective in the treatment of recurrent polyps.Conclusion:There are differences in clinical characteristics between eosinophilic and non-eosinophilic chronic sinusitis with nasal polyps. The ratio of eosinophils in peripheral blood, preoperative endoscopy and CT evaluation are helpful for the classification of chronic sinusitis with nasal polyps.

Different phenotypes in patients with chronic sinusitis with bilateral nasal polyps

Objective: To investigate the clinical features of patients with chronic sinusitis with bilateral nasal polyps. Method: The data of 134 patients with chronic sinusitis with bilateral nasal polyps were analyzed, retrospectively. Based on the results of the histopathological examination, patients were divided into eosinophilic chronic sinusitis with bilateral nasal polyps(ECRSwBNP) group and noneosinophilic chronic sinusitis with bilateral nasal polyps(nonECRSwBNP) group. The clinical data including medical history collection, skin prick test, nasal secretion examination, serum total IgE level, peripheral blood test, nasal endoscopy, and sinus CT examination were analyzed and compared. Result: The rate of concomitant with asthma(19.0%, 0), atopy(26.6%, 9.1%), NP recurrence rate(54.4%, 30.9%), the ratio of EOS in peripheral blood(4.8%, 1.9%), the ratio of EOS in nasal secretions(10.0%, 2.0%) and total serum IgE levels(82.15 IU/L, 25.80 IU/L) were significantly(P<0.05 ) different between two groups. In the sinus CT score, posterior ethmoid sinus(2.0, 1.0), total ethmoid sinus(5.0, 4.0), sphenoid sinus(3.0, 2.0), Olfactory cleft(OC)(4.0, 2.0), the ratio of thee thmoid sinus/maxillary sinus(2.0, 1.0) was statistically significant(P<0.05), while the rest were not statistically significant. The OC score, the ratio of EOS in peripheral blood, the ratio of the posterior ethmoid sinus/ anterior ethmoid sinus, and the ratio of the ethmoid sinus/maxillary sinus can be used for subtype in CRSwBNP patients (AUC> 0.5), while the OC score under the ROC curve is the largest area with the highest diagnostic value. When the OC score is 3 or higher, the predicted value specificity is 80.9% and the sensitivity is 52.1%. Conclusion: Patients with chronic sinusitis with bilateral nasal polyps often comorbid asthma and atopy, while these patients are trend to recurrence. The patients with ECRSwBNP comorbid asthma mainly characterized by eosinophil infiltration in tissues are more likely to recurrence. Targeted treatment based on phenotype should be considered in the clinic.

Efficacy of Reslizumab in Eosinophilic Chronic Sinusitis with Nasal Polyposis

Efficacy of Reslizumab in Eosinophilic Chronic Sinusitis with Nasal Polyposis

Diagnostic significance of serum periostin in eosinophilic chronic sinusitis with nasal polyps

Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease. Eosinophilic CRSwNP (ENP) exhibits a strong tendency for recurrence after surgery. Given that the treatment strategy of ENP differs from that of non-eosinophilic CRSwNP (nENP), clinical diagnostic criteria that distinguish ENP from nENP are needed.Methods: In total, 94 CRSwNP patients were enrolled in the cohort. Factors associated with ENP were determined with regression analysis, and optimal cutoff points of the predictors were determined by a receiver operating characteristic curve.Results: Serum periostin levels, blood eosinophils and basophils counts significantly differed between ENP and nENP. A combination of the cut-off values for the three predictors, including absolute blood eosinophil and basophil counts, yielded a sensitivity of 79.2% and 70.8%, and a specificity of 84.8% and 73.9%, respectively. Serum periostin levels yielded a sensitivity of 72.9% and a specificity of 60.9% for the diagnosis of ENP. The predicted probability of periostin in combination with blood eosinophils and basophils counts (AUC, 0.872) exhibited moderate accuracy. In addition, patients with ENP displayed an increased prevalence of smoking.Conclusions: Periostin in combination with blood eosinophils and basophils counts has the potential to better refine current CRSwNP phenotypes.

The Role of Periostin in the Occurrence and Progression of Eosinophilic Chronic Sinusitis with Nasal Polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with different host defence responses. However, whether periostin and vascular endothelial growth factor (VEGF) are similarly impaired in patients with eosinophilic CRSwNP (ENP) and those with non-eosinophilic CRSwNP (nENP) remains unclear. We sought to evaluate the expression and possible modulation of periostin and VEGF, regulated on activation normal T expressed and secreted (RANTES) and eotaxin-2 in the polyp tissues from 30 patients with ENP and from 36 patients with nENP and in middle turbinate tissues from 12 control subjects. We found that ENP tissues exhibited a significantly increased expression of periostin and VEGF compared with tissues from patients with nENP and control subjects (P < 0.05, respectively). Accordingly, the expression of VEGF, RANTES, and eotaxin-2 in ENP fibroblasts was significantly up-regulated after stimulation with up-regulated periostin in vitro, but the expression of VEGF and RANTES was significantly inhibited by stimulation with down-regulated periostin. Our findings suggest that periostin might play an important role in the occurrence and progression of ENP and might be a potential therapeutic target.