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Objectives: To investigate the value of secretions Eosinophilic cationic protein (ECP) detection in the diagnosis of endotypes of Chronic rhinosinusitis (CRS) and its correlation with clinical symptoms, so as to provide guidance for the clinical application of EOS and ECP detection in secretions., Methods: Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their EOS% and ECP levels were measured. Correlation analysis was performed for EOS% and ECP levels in secretions and tissues, respectively. The correlation between secretions EOS% and ECP and clinical symptom scores (symptomatic visual analog scale (VAS) scores, Lanza-kennedy scores from nasal endoscopy and Lund-Mackay scores from sinus CT) was further analyzed. Receiver operating characteristic curves were used to assess the predictive potential of EOS% and ECP in nasal secretions., Results: Eosinophilic chronic rhinosinusitis (ECRS) patients had higher concentrations of ECP in nasal secretions than healthy subjects and NECRS (non-eosinophilic CRS) (p < 0.0001;0.0001); EOS% in nasal secretions was higher in ECRS than healthy subjects (p = 0.0055), but the differences between ECRS and NECRS were not statistically significant (p = 0.0999). Correlation analysis showed that tissue EOS% was correlated with ECP concentration and EOS% in nasal secretions (R = 0.5943;0.2815). There was a correlation between EOS% in secretions with a total LM score (R = 0.3131); ECP concentration in secretions with a total LK score (R = 0.3792). To diagnose ECRS, the highest area under the curve (0.8230) was determined for ECP in secretions; the highest area under the curve (0.6635) was determined for EOS% in secretions., Conclusion: Measurement of ECP in nasal secretions is useful for non-invasive diagnosis of ECRS., Level of Evidence: 3 Laryngoscope, 133:3304-3312, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To explore associations between inflammatory endotypes and clinical presentations in CRS. To investigate the value of secretions myeloperoxidase (MPO) and eosinophilic cationic protein (ECP) detections in the diagnosis of endotypes of chronic rhinosinusitis (CRS), so as to provide guidance for the clinical application of MPO and ECP detection in secretions., Methods: We collected clinical symptom scores from patients with CRS and examined the differences between endotypes in clinical features. Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their NEU number, EOS%, MPO and ECP levels were measured. Correlation analysis was performed for these biomarkers in secretions and tissues, respectively. Receiver operating characteristic curves were used to assess the predictive potential of the biomarkers mentioned above in nasal secretions., Results: Patients with Eos+Neu+ and Eos+Neu-CRS scored highest in most clinical symptom scores, while Eos-Neu+ and Eos-Neu-CRS scored lowest. Correlation analysis showed that tissues NEU number was correlated with NEU number and MPO level in nasal secretions (R = 0.4088; 0.6613); tissues EOS % was correlated with EOS% and ECP level in nasal secretions (R = 0.2344; 0.5774). To diagnose Neu+CRS, the highest area under the curve (AUC) (0.8961) was determined for MPO in secretions; the highest AUC (0.7400) was determined for NEU number in secretions. To diagnose Eos+Neu-CRS from Eos-Neu-CRS in Neu-CRS, the highest AUC (0.8801) was determined for ECP in secretions., Conclusions: Clinical presentations are directly associated with CRS endotypes. Measurement of MPO and ECP in nasal secretions is useful for the endotypes diagnosis of CRS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Severe nasal polyposis and mucosal inflammation, in patients with chronic rhinosinusitis (CRS) may include a dysregulated eicosanoid profile, but a clinical role for eicosanoids in CRS with nasal polyps (NP; CRSwNP) remains to be elucidated. This study focused on assessing levels and clinical implications of inflammatory mediators in nasal secretions and urine from patients with different NP severity or Aspirin Exacerbated Respiratory Disease (AERD). Levels of leukotrienes E 4 and B 4 , prostaglandins D 2 and E 2 as well as 15(S)-hydroxyeicosatetraenoic acid were measured with enzyme immunoassays and cytokines with magnetic bead immunoassays. Patients with CRSwNP were subdivided based on NP score; CRSwNP-low (NP score ≤ 4, n = 11) or CRSwNP-high (NP score ≥ 5, n = 32) and compared to CRS without polyps (CRSsNP, n = 12), CRSwNP-AERD (n = 11) and individuals without CRS (n = 25). Smell test score, fractional exhaled nitric oxide (FeNO), blood eosinophils and Sinonasal outcome test-22 were assessed as clinical markers. Leukotriene E 4 , prostaglandin D 2 and 15(S)-hydroxyeicosatetraenoic acid in nasal secretions correlated with NP score. Nasal leukotriene E 4 also correlated with FeNO and smell test score, with highest levels found in CRSwNP-AERD. Levels of prostaglandin D 2 in nasal secretion as well as urinary levels of the prostaglandin D 2 metabolite 11β-prostaglandin F 2α differed between CRSNP-high and CRSwNP-low. Urinary 11β-prostaglandin F 2α was associated with asthma comorbidity whereas a similar association with prostaglandin D 2 in nasal secretions was not observed. In conclusion, subdividing patients based on NP severity in combination with analysis of eicosanoids in non-invasively collected nasal secretions, may have clinical implications when assessing CRS disease severity., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2-mediated inflammatory disease associated with significant clinical, social, and economic burdens and high unmet therapeutic need. Dupilumab, a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, demonstrated efficacy and acceptable safety in CRSwNP and other type 2 diseases (eg, atopic dermatitis and asthma). We now report the local effects of dupilumab on type 2 inflammatory biomarkers in nasal secretions and nasal polyp tissues of patients with CRSwNP in a randomized, placebo-controlled, phase 2 trial (NCT01920893)., Methods: Cytokines, chemokines, and total immunoglobulin E (IgE) levels were measured using immunoassay techniques in nasal secretions and nasal polyp tissue homogenates of CRSwNP patients receiving dupilumab 300 mg or placebo weekly for 16 weeks., Results: With dupilumab, type 2 biomarker concentrations decreased in nasal secretions (least squares mean area under the curve from 0 to 16 weeks for the change from baseline) vs placebo for eotaxin-3 (-30.06 vs -0.86 pg/mL; P = 0.0008) and total IgE (-7.90 vs -1.86 IU/mL; P = 0.022). Dupilumab treatment also decreased type 2 biomarker levels in nasal polyp tissues at Week 16 vs baseline for eosinophilic cationic protein (P = 0.008), eotaxin-2 (P = 0.008), eotaxin-3 (P = 0.031), pulmonary and activation-regulated chemokine (P = 0.016), IgE (P = 0.023), and IL-13 (P = 0.031)., Conclusions: Dupilumab treatment reduced multiple biomarkers of type 2 inflammation in nasal secretions and polyp tissues of patients with CRSwNP, demonstrating that antagonism of IL-4Rα signaling suppresses IL-4-/IL-13-dependent processes, such as mucosal IgE formation, as well as the expression of chemokines attracting inflammatory cells to the nasal mucosa., (© 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Objective: Eosinophil recruitment to the nasal mucosa involves a number of chemokines. The aim of this study was to evaluate nasal secretion levels of macrophage inflammatory protein-1 alpha (MIP-1α) and MIP-1β and to correlate these levels with clinical characteristics and degree of eosinophilia in nonallergic and allergic patients with nasal polyposis (NP)., Methods: Fourteen nonatopic and 14 atopic patients with NP were recruited for this cross-sectional study. Fourteen healthy subjects were included as controls. The concentrations of MIP-1α and MIP-1β in nasal secretions were measured by flow cytometry. Eosinophil counts were performed by cytological examination of the scraped nasal mucosa. We scored each of the 28 patients according to the nasal symptom score, endoscopic score, and computed tomography (CT) score., Results: We found significantly higher concentrations of MIP-1α in nasal fluid of nonallergic and allergic NP patients compared to control subjects. In nonallergic patients, we found positive correlations between MIP-1α levels and endoscopic score, CT score, and the percentage of eosinophils., Conclusion: MIP-1α may play a role in eosinophil recruitment in NP. Our results suggest that the measurement of MIP-1α in nasal secretions could be useful in evaluating the degree of eosinophil inflammation and severity of disease in nonallergic patients., (© The Author(s) 2014.)

Analysis of immune markers in nasal secretions has become crucial in the study of nasal diseases. We proposed the cotton piece method, a modified method, for the collection and processing of nasal secretions. The nasal secretions of 31 healthy control participants and 32 patients with nasal diseases were collected by the traditional sponge method and the cotton piece method, respectively. The concentrations of 14 cytokines and chemokines related to nasal diseases were detected. The properties of nasal secretions collected by the cotton piece method were more uniform than the sponge method. The concentration of IL-6 in the disease group collected by the cotton piece method was significantly higher than that in the control group (P = 0.002), and the cotton piece method could distinguish the positive detection rates of IL-1β (P = 0.031) and TNF-α (P = 0.001) between the control and disease groups. The levels of inflammatory mediators in nasal secretions could preliminarily distinguish different nasal diseases. The cotton piece method is a noninvasive and reliable method for collecting nasal secretions, which is beneficial for detecting local inflammatory and immune responses of the nasal mucosa. [ABSTRACT FROM AUTHOR]

Background: The EPOS guidelines promote cellular analysis as a primary goal in endotyping chronic rhinosinusitis (CRS). Current analysis is mainly based on biopsy or operative tissue collection, whereas the use of sinonasal secretions for inflammatory endotyping is not advocated in clinical practice. Early endotyping is crucial though, especially regarding the increasing evidence of patient-tailored therapy. We aimed to investigate the diagnostic value and reproducibility of sinonasal secretions sampling. Methods: First, preoperative secretion analysis of 53 Caucasian CRS patients was compared to subsequent operative tissue analysis. Second, secretion analysis at two different time points was compared for 10 postoperative Caucasian CRS patients with type 2 (T2) inflammation and 10 control participants. Secretions were collected by both endoscopic aspiration and nasal blown secretions in all participants. Results: The sensitivity to detect T2 inflammation was higher in nasal aspiration samples (85%) compared to nasal blow secretions (32%). A specificity of 100% for both techniques was obtained. A 90% reproducibility for T2 eosinophil detection was found by sampling at different time points regardless of the technique. Of the T2 patients, 60% showed no T2 inflammatory pattern more than one year after endoscopic sinus surgery. Conclusions: Nasal secretion sampling, especially aspiration of nasal secretions, is useful in the detection of T2 inflammation in CRS pathology. We proposed a structured histopathology analysis to be useful in daily clinical practice, which includes Congo red staining sensitive for eosinophilic cells and free eosinophil granules. Analysis of nasal secretions enables endotyping in an early stage, allowing more directed therapy.

Introduction: Charcot-Leyden crystal (CLC) protein has been regarded as a hallmark of eosinophilic inflammation. Objective: The purpose of this study was to investigate the role and levels of CLC protein in patients with nonallergic rhinitis with eosinophilia syndrome (NARES). Methods: Overall, 39 NARES patients and 19 controls were recruited. The severity of nasal symptoms was measured by visual analogue scale and serum and local specific immunoglobulin E were determined in all patients. Nasal eosinophilia was assessed by semiquantitative analysis of eosinophils in nasal scrapings. Nasal secretion CLC protein concentrations were evaluated by ELISA. Results: CLC protein concentrations were significantly higher in NARES patients than in controls (p < 0.0001). Nasal secretion CLC protein levels were significantly correlated with the degree of eosinophilia in nasal scrapings (rs = 0.331; p = 0.04) in NARES patients. Patients with high CLC protein concentrations displayed more severe nasal symptoms than patients with low CLC protein concentrations (p = 0.0080), particularly, nasal itching (p = 0.0029). Pilot study in 8 NARES patients demonstrated that treatment for 1 month with intranasal fluticasone propionate significantly decreased the nasal secretion CLC protein concentrations from baseline levels (p = 0.0335) and markedly attenuated the degree of swelling of inferior turbinate. Conclusions: CLC protein levels are significantly higher in nasal secretions of NARES patients and associated with the degree of nasal eosinophilia and the severity of nasal symptoms. Significantly, nasal secretion CLC protein levels obviously decreased after treatment with intranasal corticosteroids, suggesting its possible role in evaluating the medical treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the cytokine levels in nasal fluid in subjects with nasal polyposis (NP) and co-morbid asthma and NP patients without asthma and to correlate these levels with clinical parameters of severity of disease. Forty NP patients (20 asthmatic and 20 nonasthmatic) were enrolled. Nasal secretion samples were collected from nasal cavities of all 40 subjects. The levels of Th1 cytokines IL-2, IL-12 and IFN-γ, Th2 cytokines IL-4, IL-5, IL-6, and IL-10, chemokine IL-8, and proinflammatory cytokines IL-1β, TNF-α and TNF-β were measured using flow cytometric method. Each of the 40 patients was staged clinically according to global nasal symptom score, endoscopic score, and Lund-Mackay computed tomography (CT) score. The concentrations of Th2 cytokines IL-5, IL-6 and IL-10 were significantly higher ( P < 0.01, P < 0.01, P < 0.05) in patients with NP and asthma compared with NP patients without asthma. Positive correlations were observed between concentration of IL-2 in nasal secretions and global nasal symptom score, endoscopic score, and Lund-Mackay score only in NP patients without asthma. We also found positive correlation between CT score and the levels of IL-8, IL-4, and IL-1β in nonasthmatic patients. Finally, our results showed a positive correlation between IL-5 levels in nasal fluid and endoscopic score only in asthmatic patients. NP in asthmatic patients have different immunological patterns compared to those without asthma. We also concluded that concentrations of cytokines measured in nasal fluid were not sensitive enough to determine the severity of disease. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis has complex pathophysiological features. The role of anatomic variations in the development of sinusitis remains unclear. We describe a rare manifestation of this disease, a polyp inside the pneumatized concha polyposa. A 23-year-old male patient had been suffering from headache, nasal obstruction, loss of the sense of smell, and postnasal discharge. Computed tomographic scans of the sinuses showed bilateral concha bullosae, with a polyp inside the left one. Therapy included endoscopic nasal surgery and postoperative topical corticosteroid and macrolide treatment. We discuss the influence of sinusitis on the phenomenon of "sinus headache." We also comment on the use of topical corticosteroids and macrolides in preoperative and postoperative treatment of chronic rhinosinusitis with nasal polyposis. [ABSTRACT FROM AUTHOR]

Background: Nasal polyposis (NP) frequently complicates the course of cystic fibrosis (CF). The aim of this study was to determine the pattern of inflammatory cells and mediators in nasal secretions from patients with or without NP compared to patients with idiopathic NP and healthy controls. Methods: Eighteen CF patients with NP (NP+ group: 6 untreated, 12 treated with nasal steroids), and 15 without NP (NP− group) were included in this prospective study and compared to 9 patients with idiopathic NP and 12 healthy controls. Differential cell count eosinophil cationic protein (ECP), interleukin-5 (IL-5) and IL-8 were determined in nasal lavage fluids. Results: The total cell count, the number and the percentage of neutrophils and eosinophils, the levels of IL-8, IL-5 and ECP were significantly higher in nasal secretions from both NP+ and NP− as compared with controls. No difference was found between untreated and treated CF patients with NP. No difference was found between NP+ and NP− groups. Compared to idiopathic NP group, both NP+ and NP− groups had higher percentage of neutrophils and lower percentage of eosinophils. There were no differences according to the use of topical steroids, systemic antibiotherapy, or the type of mutation. CF patients with positive nasal culture had a higher percentage of neutrophils than those with negative culture. CF patients with atopy had a higher percentage of eosinophils than non-atopic patients. Conclusion: Our results demonstrate that nasal inflammation is a prominent feature in patients with CF and does not differ according to the presence of NP. IL-8 and IL-5 may play crucial roles in recruitment and activation of neutrophils and eosinophils in upper airways of CF patients. [Copyright &y& Elsevier]