Chronic Rhinosinusitis With Nasal Polyposis Patients Research Articles

[Does aspirin therapy after desensitization still have a role in treatment of chronic rhinosinusitis with nasal polyposis in the era of biologics?]

The prevalence of analgesic intolerance syndrome (AIS), internationally known as NSAID-exacerbated respiratory disease (NERD), is reported to be 0.5-5.7% in the general population. The disease often begins with nasal symptoms, which are later joined by chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and respiratory hypersensitivity reactions following use of nonsteroidal anti-inflammatory drugs (NSAIDs). In the setting of chronic respiratory disease, the type2 inflammatory endotype is predominant in approximately 80% of patients with CRSwNP, rendering biologics directed against interleukin (IL)-4, IL‑5, IL-13, and IgE of high clinical interest, particularly in patients with severe CRSwNP and NERD. NERD is often associated with CRSwNP and asthma. Patients with CRSwNP and NERD have been treated, among other therapies, with aspirin therapy after desensitization (ATAD). With the approval of monoclonal antibodies for CRSwNP and asthma, the question arises as to what extent ATAD, which is associated with undesirable side effects, is still useful in the treatment of CRSwNP. In this manuscript, the use of ATAD in CRSwNP patients is discussed from different medical and socioeconomic points of view, both alternatively to or in combination with monoclonal antibodies. Accordingly, both ATAD and biologics continue to play asupporting role in modern treatment of CRSwNP in NERD patients, and should be used judiciously to complement each other.

Histopathologic features of biologic therapy nonresponders in chronic rhinosinusitis with nasal polyposis.

Biologics are effective for chronic rhinosinusitis with nasal polyposis (CRSwNP) by reducing type 2 inflammation. Nonresponders often require functional endoscopic sinus surgery (FESS) and represent a challenging population potentially due to non-type 2 pathophysiology. This study characterizes the histopathologic features of biologic nonresponders. A retrospective review of 257 CRSwNP patients undergoing FESS was conducted. The biologic nonresponder group included patients with prior biologic therapy who exhibited persistent symptoms and polyp burden. Those with CRSwNP not prescribed biologic therapy were selected as controls. Demographics, comorbidities, and structured histopathology consisting of 13 variables were collected. Of 257 CRSwNP patients, 20 were on biologics prior to FESS. Fourteen patients (70.0%) received dupilumab, one (5.0%) received mepolizumab, one (5.0%) received omalizumab, and four (20.0%) tried multiple biologics. The mean age for the biologic nonresponder group was 45.8 years compared to 50.4 years for the controls. Nonresponders had a significantly increased incidence of reduced tissue eosinophilia, defined as<5 per high power field (55%vs. 31.2%, p=0.044) and increased basement membrane thickening (100%vs. 78.1%, p=0.017). The remaining 11 variables did not reach statistical significance. Histopathologic analysis of biologic nonresponders demonstrates decreased eosinophilia and thickened basement membranes. These findings, particularly low tissue eosinophils, are consistent with a non-type 2 CRSwNP that may be recalcitrant to biologic therapies. Histopathologic analysis done in conjunction with FESS may aid clinicians in understanding response to biologic therapies in patients with CRSwNP who have persistent symptom burden necessitating FESS.

Targeting IL-4 and IL-13 Receptors on Eosinophils in CRSwNP Patients: The Clinical Efficacy of Dupilumab.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease linked to type 2 inflammation. Several biologics have demonstrated therapeutic potential for the treatment of this pathology in which IL-4, IL-5 and IL-13 represent the major cytokines involved in the control of eosinophilic respiratory inflammation. 25% of CRSwNP patients relapse after the use of oral glucocorticoids or after surgery and often require several surgeries during their lifetime. In our study we enrolled 14 patients, 11 male and 3 female. The inclusion criteria were: age ≥ 18 years; confirmed diagnosis of chronic rhinosinusitis with severe nasal polyposis; disease severity with NPS Nasal Polyposis Endoscopic Score total score ≥ 5 and/or SNOT-22 ≥ 50; previous treatment failure due to lack of efficacy or discontinuation of systemic corticosteroid therapy and/or non-response or recurrence following surgery. The results presented in this study showed the ability of Dupilumab to improve all the parameters analysed. In particular, statistically significant data were obtained for NPS, SNOT-22, NRS, and IgE in patients exposed to Dupilumab treatment for 24 weeks, highlighting the ability of Dupilumab to produce clinical benefit in CRWwNP patients. In light of these data, the administration of dupilumab every two weeks represents a valid clinical strategy that ENT specialists can adopt for the treatment of adults with inadequately controlled CRSwNP.

Optimizing the timing of biologic and surgical therapy for patients with refractory chronic rhinosinusitis with nasal polyposis (CRSwNP).

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is often treated with endoscopic sinus surgery (ESS); however, patients may require revision surgery due to recurrence. To date, no studies have compared outcomes for combined surgery and biologic therapy for CRSwNP compared with biologic therapy alone. Retrospective case-control study of CRSwNP patients who underwent ESS while on dupilumab or mepolizumab (ESS-biologic cohort) compared with CRSwNP patients on biologic therapy (biologic-only controls). Cohorts were matched according to indication, aspirin-exacerbated respiratory disease (AERD), sinonasal outcome test-22 (SNOT-22), and total polyp scores. Sixteen patients underwent ESS while on biologic therapy (13 dupilumab and 3 mepolizumab). Sixteen patients were biologic-only controls. There were no significant differences between indication, baseline SNOT-22 scores, polyp scores, and AERD status between cohorts. Patients underwent surgery a median of 33 days after starting biologic therapy. After 12 months of follow-up, the total polyp score for the ESS-biologic cohort decreased from 4.73 to 0.09 compared with a decrease from 5.22 to 3.38 for the biologic-only controls (95% confidence interval [CI] of difference: -5.37 to -1.38, Cohen's d: 2.40, p=0.005). In the ESS-dupilumab subanalysis, the ESS-dupilumab cohort had a significant reduction in polyp burden from 4.85 to 0.00 compared with 4.88 to 3.50 for the controls (95% CI of difference: -5.68 to -1.32, Cohen's d: -1.69, p=0.009). In CRSwNP patients, combined ESS and biologic therapy results in a significant and sustained decrease in polyp burden compared with biologic therapy alone. Larger studies are warranted to further examine the impact of combined therapy.

Interleukin 5 Receptor Subunit Alpha Expression as a Potential Biomarker in Patients with Nasal Polyposis.

Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) affects the quality of life of patients suffering from it. The search for a suitable biomarker has been conducted over the last decades. Interleukin 5 receptor subunit alpha (IL-5Rα) involves the activation, maintenance, and survival of eosinophils, which are highly tied to chronic inflammatory processes of the airways, like asthma or CRSwNP. In this study, we evaluate the utility of IL5RA as a genetic biomarker in CRSwNP. IL5RA mRNA expression level was analyzed in different groups of patients by performing qPCR assays. A significant increase in IL5RA expression was observed in CRSwNP patients, especially those with asthma and atopy. We found differences in expression levels when comparing groups with or without polyposis or asthma, as well as some atypical cases related to eosinophil levels. That opens a path to future studies to further characterize groups of patients with common features in the context of pharmacogenetics and in an era towards developing a more precise personalized treatment with IL-5Rα as a therapeutic target for CRSwNP.

Olfaction Now and in the Future in CRSwNP.

Chronic rhinosinusitis (CRS) is the leading cause of olfactory dysfunction in the general population. Olfactory dysfunction is more common in patients with CRS with nasal polyposis (CRSwNP) compared to those without polyps. The present review aims to summarize the current literature on the mechanism behind olfactory dysfunction in CRSwNP and the impact of therapy on olfactory outcomes in this patient population. A comprehensive review of the available literature on olfaction in CRSwNP was performed. We evaluated the most recent evidence from studies on the mechanisms behind smell loss in CRSwNP and the impact of medical and surgical therapy for CRS on olfactory outcomes. The mechanism behind olfactory dysfunction in CRSwNP is not completely understood, but evidence from clinical research and animal models suggests both an obstructive component causing conductive olfactory loss and an inflammatory response in the olfactory cleft leading to sensorineural olfactory loss. Oral steroids and endoscopic sinus surgery have both shown efficacy in improving olfactory outcomes in CRSwNP in the short term; however, the long-term response of these treatments remains uncertain. Newer targeted biologic therapies, such as dupilumab, have also shown remarkable and durable improvement in smell loss for CRSwNP patients. Olfactory dysfunction is highly prevalent in the CRSwNP population. Although significant advances have been made in our understanding of olfactory dysfunction in the setting of CRS, additional studies are needed to elucidate cellular and molecular changes mediated by type 2-mediated inflammation in the olfactory epithelium with potential downstream effects on the central olfactory system. Further identification of these underlying basic mechanisms will be vital for developing future therapies targeted to improve olfactory dysfunction in patients with CRSwNP.

Blow Me Away: Change in Exhaled Fractional Nitric Oxide (FeNO) Levels May Help to Identify Aspirin Exacerbated Respiratory Disease (AERD)

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a heterogenous disease. Aspirin-exacerbated respiratory disease (AERD) is a distinct CRSwNP phenotype with a unique therapeutic approach. Our study aimed to compare fractional exhaled nitric oxide (FeNO) and urinary leukotriene E4 (LTE4), before and after endoscopic sinus surgery (ESS) among CRSwNP patients with and without AERD.

Chronic rhinosinusitis with nasal polyps as a major comorbid disease in severe asthma patients: Evidence from severe asthma registry of Kuwait

The clinical and laboratory features of patients enrolled in the severe asthma registry in Kuwait were evaluated, with special emphasis on chronic rhinosinusitis with nasal polyposis (CRSwNP). The following information were collected from ongoing severe asthma registry from Kuwait: demographic data, clinical features, asthma control test in the previous month and treatment for severe asthma patients (ATS/ERS criteria). 311 patients with severe asthma enrolled in severe asthma registry of Kuwait and 141 patients has comorbid CRSwNP. Mean age of patients was 43.3 years, SD 12.7. Although 93.6% of patients with CRSwNP were eligible for biological therapy, 56% (79 patients) received biologic therapy. The most common biologic therapy was Dupilumab. The use of biologics significantly improved oral corticosteroid (OCS) use (frequently used in 84 CRSwNP patients (59.6%) in the previous year into 98.7% of patients with no OCS use after biologic initiation). OCS sparing is required in patients with CRSwNP or severe asthma. The use of targeted biologic therapy significantly improved treatment outcome.

130 Skin-associated side effects in patients with chronic rhinosinusitis with nasal polyposis following treatment with dupilumab

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a typical type-2 inflammation involving T-helper type-2 cells and impairing quality of life due to nasal obstruction, discharge and reduced sense of smell. Recently, the anti-IL4Ra antibody dupilumab was approved for CRSwNP and while dermatologic side effects in patients treated with dupilumab for atopic dermatitis are frequently observed, there is limited knowledge about these effects in patients with CRSwNP. We aimed to investigate frequency and characteristics of dermatologic side effects following initiation of dupilumab treatment in a cohort of Austrian CRSwNP patients.

Biologic Therapies in Chronic Rhinosinusitis with Nasal Polyposis: Overview of Systematic Reviews and Updated Systematic Review.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a highly prevalent and challenging disease to manage. Several systematic reviews (SRs) have been carried out to evaluate the efficacy and safety of biologic therapies. We aimed to evaluate the current and available evidence of the biologics in treating CRSwNP. Systematic Review of three electronic databases. Following the PRISMA Statement, the authors explored three main databases through February 2020 for pertinent SRs and meta-analyses (MAs) as well as experimental and observational studies. A Measurement Tool to Assess Systematic Reviews Version-2 (AMSTAR-2), was employed to evaluate the quality of methodology of SRs and MAs. A Total of five SRs were included in this overview. The AMSTAR-2 final summary was moderate to critically low. Although conflicting findings were reported, anti-immunoglobulin E (Anti-IgE) and anti-interleukin-4 (Anti-IL-4) were superior to placebo for improving total nasal polyp (NP) score, particularly in patients with asthma. Findings of the included reviews revealed that both sinus opacification and the Lund-Mackay (LMK) total scores significantly improved after biologics use. Subjective quality-of-life (QoL) assessment provided by general and specific questionnaires illustrated favorable results of biologics for CRSwNP, whereas no significant adverse events were reported. The current findings support the use of biologics for CRSwNP patients. However, the evidence for their use in such patients should be cautiously adopted because of the questionable evidence. The online version contains supplementary material available at 10.1007/s12070-022-03144-8.

Dupilumab-induced skin-associated side effects in patients with chronic rhinosinusitis with nasal polyposis.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a typical type-2 inflammation involving T-helper type-2 cells and impairing quality of life due to nasal obstruction, discharge and reduced sense of smell. Recently, the anti-IL4Rα antibody dupilumab was approved for CRSwNP. While dermatologic side effects in patients treated with dupilumab for atopic dermatitis are frequently observed, there is limited knowledge about these effects in patients with CRSwNP. We aimed to investigate frequency and characteristics of dermatologic side effects following initiation of dupilumab treatment in a cohort of Austrian CRSwNP patients. Therefore, CRSwNP patients presenting at the Department of Otorhinolaryngology, Head and Neck Surgery at the Vienna General Hospital were retrospectively evaluated for newly developed skin eruptions while under dupilumab treatment. Incidence was calculated and details on clinical symptoms were collected. One hundred and ninety-two CRSwNP patients receiving dupilumab treatment were included, comprising a cumulative follow-up of 89.65 years (median: 5.5, IQR: 5.9). We observed dermatologic side effects in four patients starting at a median time of 15.5 (range 4-23) weeks after dupilumab initiation corresponding to an incidence-rate of 4.46 (95%-confidence interval 1.39-11.23) events per 100 patient-years follow-up. The majority (75%, 3/4) of affected patients developed psoriasis-like dermatitis, whereas one individual experienced rosacea-like folliculitis and alopecia areata. While dupilumab dosing was reduced in 3/4 CRSwNP patients, one patient completely stopped dupilumab therapy. Our study provides the first comprehensive evaluation of both frequency and characteristics of dermatologic side effects caused by dupilumab in CRSwNP patients. All affected patients developed Th1-inflammatory associated skin disorders - previously observed only in individuals with prior affections of the skin (i.e. atopic dermatitis). Thus, individuals receiving dupilumab for CRSwNP may develop novel symptoms that require interdisciplinary management. Future studies on dupilumab in a real-world setting will be required to further explore its spectrum of side effects.

A comprehensive investigation of the demographics, treatments, comorbidities, and disease burden of chronic rhinosinusitis with nasal polyposis patients: a descriptive analysis.

BackgroundChronic rhinosinusitis with nasal polyposis (CRSwNP) is a frequently diagnosed chronic disease that has been widely recognized as a significant economic strain on society. Recently, concern about the rising prevalence of eosinophilia in CRSwNP has attracted research interest. A comprehensive understanding of the characteristics and disease burden of CRSwNP patients may contribute to improved management of these patients.MethodsWe conducted a multi-center retrospective observational study based on real-world data. Patients were filtered into three groups: CRSwNP overall group, CRSwNP surgical group, and CRSwNP patients who had a relapse after surgeries. Furthermore, we used laboratory test results of blood eosinophil percentage (EOS%) as an indicator of eosinophilia. The comorbidities and medications of patients in the high and low EOS% groups were compared. Disease burden was measured from two aspects: direct costs and loss of working days.ResultsA total of 1,724 CRSwNP patients were eligible, 527 of which were filtered into the surgical groups. Only 16 patients in this study were found to have a relapse. The mean ages of the CRSwNP non-surgical, CRSwNP surgical, and CRSwNP relapse groups were 46, 47, and 52.5 years old, respectively. Most patients sought treatment in the otolaryngology department. Among all three groups, the most prevalent comorbidities were allergic rhinitis and asthma. The most prescribed drug was intranasal/oral corticosteroids. The direct costs per person/year for the non-surgical group, surgical group, and relapse group were ¥188.60, ¥15,190.00, and ¥14,160.00, respectively. The loss of working days per person/year for the non-surgical group, surgical group, and relapse group was 10.41, 24.40, and 21.65 days, respectively.ConclusionsCRSwNP is a disease of middle age. It is frequently associated with asthma and allergic rhinitis. Eosinophilia was found to have a considerate influence on patients’ treatment patterns. Based on available data, we noted that patients in the high EOS% group were more likely to have asthma and allergic rhinitis. Intranasal/oral corticosteroids were the most frequently used drug for patients with CRSwNP, while a smaller proportion of patients in the high EOS% group used intranasal/oral corticosteroids. The disease burden of CRSwNP is posing significant challenges to both patients and society.

A Practical Clinical Protocol for Monitoring Patients with Severe Uncontrolled Chronic Rhinosinusitis with Nasal Polyposis Treated with Biologics.

Objectives:Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a pathological condition which leads to high healthcare-related costs and low quality of life for patients. The introduction of new biological therapies (monoclonal antibodies, MAbs) in CRSwNP patients has allowed new therapeutic options for non-responders to conventional therapies and Dupilumab represents the first approved biological agent. The aim of this paper is to provide a practical clinical multidisciplinary protocol which might help clinicians involved in this field to monitor the clinical outcomes.Methods:Our centre of Rhinology and Rhino-Allergology has developed a dedicated collection form to observe the outcomes of patients treated with Dupilumab. Our research started from the indications given in EPOS 2020 as main reference. We then implemented these references in an electronic database trying to apply Evidence Based Medicine (EBM) in current clinical practice.Results:The result consists of three parts: an anamnestic collection data, a clinician reported outcome and two patient reported outcomes (PROMs) questionnaire, the visual analogue scale (VAS) and the Sino-Nasal Outcome Test-22 (SNOT-22). The tables we propose should provide an adequate correlation with the patients’ adherence to therapy and their treatment outcomes. Such periodical evaluation (after a month, after 3 months, after 6 months and at one year) should quickly allow to monitor if the patient is correctly assuming the therapy and the eventual objective improvements.Conclusions:We propose a practical monitoring protocol formulated to analyse both objective and subjective aspects of patients with severe uncontrolled CRSwNP treated with MAbs, thus helping to define in future a better comparison between the clinical results of different institutes.

POSB231 How to Determine Surgical Pathway Operating Costs in Chronic Rhinosinusitis with Nasal Polyposis Patients? The Time Driven Activity-Based Costing Experiment

To analyze the absorption of economic resources related to the diagnostic, surgical and therapeutic pathway of chronic rhinosinusitis with nasal polyposis patients (CRSwNP), assuming the hospital perspective and stratifying for different patients’ characteristics.

POSB143 The Financial Burden of Surgically Managing Chronic Rhinosinusitis with Nasal Polyposis in England

Chronic rhinosinusitis with nasal polyposis (CRSwNP) characterised by type 2 inflammation imposes significant burden of illness. Many patients whose symptoms are uncontrolled by intranasal corticosteroids need repeated surgeries to alleviate rhinorrhea, nasal congestion, hyposmia and/or facial pressure. The objective of this study was to determine the financial burden due to surgically managed CRSwNP from an NHS perspective. Hospital Episode Statistics (HES) were used to capture the characteristics and costs for all CRSwNP patients with ≥1 sinus surgery in England between April 2010 and March 2020. Patients were stratified into subgroups based on the absence (NP-No Comorbidities (NC)) or presence of relevant comorbidities such as asthma only (NP-Asthma) or asthma with NSAID exacerbated respiratory disease, known as Samter’s triad (NP-ST). 101,054 patients were included in the study (64% (n=64,461) NP-NC, 31.7% (n=32,049) NP-Asthma, 4.5% (n=4,544) NP-ST). The total cost of treating these patients was £260 million, with surgery tariffs, inpatient tariffs and outpatient tariffs accounting for 66.8% (£173.8million), 11.3% (£29.3 million) and 21.9% (£57 million) respectively. The average surgery tariff for an NP-ST patient was £2,089, significantly higher than the tariff associated with the NP-Asthma (£1,755), and NP-NC (£1,676) subgroups (p<0.01). Both inpatient and outpatient average tariffs were numerically and statistically significantly higher for NP-ST and NP-Asthma patients compared to NP-NC patients. Combined inpatient and outpatient tariffs were £631 per NP-NC patient, rising to £1,103 and £2,253 for NP-Asthma and NP-ST patients respectively. Surgical management of CRSwNP constitutes a significant direct financial burden on the English healthcare system, particulary for patients with comorbidities. These patients, or those with a poor surgical prognosis, may benefit from the emerging novel biologic therapies which can reduce the clinical burden of disease. Such treatment strategies may also contribute to a reduction in the significant financial burden associated with surgical costs.

Chronic rhinosinusitis with nasal polyposis (CRSwNP): the correlation between expression of Galectin-10 and Clinical-Cytological Grading (CCG).

Chronic rhinosinusitis with nasal polyps (CRSwNP) is typically characterized by Type 2 inflammation. Several biomarkers of eosinophilic inflammation, including Galectin-10, also known as Charcot-Leyden crystal protein (CLCP), have been identified to establish eosinophilic infiltration of polyps, a reliable predictor of recurrence.Objective: We aimed to evaluate the Galectin-10 expression in nasal polyps of patients with CRSwNP and to assess the correlation of Charcot-Leyden crystals expression to the severity of CRSwNP according to Clinical-Cytological Grading (CCG). A double-label immunofluorescence was performed to evaluate the expression of Gal-10, CD15, Tryptase, and CD63 and their eventual co-localization on histological samples of 18 patients with CRSwNP. Double-positive Gal-10+CD15+ and Galectin-10+Tryptase+ inflammatory cells were counted by confocal microscopy. Galectin-10 was detectable in all examined tissues from CRSwNP patients, and its expression increased as low, medium and high CCG tissues were examined, respectively. Galectin-10 was extensively present in inflammatory cells, while limited Galectin-10 deposits were detected around mucosal epithelial cells. We showed the strong correlation between CCG and Galectin-10 expression, mainly colocalized with infiltrating eosinophils and mast-cells, in patients affected by CRSwNP.

Matrix metalloproteinases and chronic rhinosinusitis with nasal polyposis. Unravelling a puzzle through a systematic review.

The expression of metalloproteinases (MMPs) in chronic rhinosinusitis with nasal polyposis (CRSwNP) was reviewed in order to investigate their possible use as therapeutical targets and/or biomarkers. The differences between CRSwNP and normal controls or CRS without NP, as well as the effects of various treatments on MMPs, tissue inhibitors of MMPs (TIMPs) and MMP/TIMP ratios were considered as primary outcomes. Additional factors reported to affect MMP expression levels were noted as secondary outcomes. Data regarding inflammatory subtypes, patients’ clinical characteristics, controls, laboratory method(s) and origin of samples were also pooled. Studies on 10 or fewer patients or on specimens other than nasal and serum were excluded. Forty-three studies were included. Tissue sample origin, allergic rhinitis, smoking, infection, medication intake and primary or recurrent disease should be considered as confounding factors for MMP levels. MMP-1 and -7 were consistently found to be significantly higher in CRSwNP patients than controls. CRSwNP endotypes with distinctly different inflammation patterns seem to present similar MMP-related remodelling patterns. The existing literature has revealed several population and methodology related confounding factors and remains inconclusive regarding the roles of MMPs in CRSwNP pathophysiology and their possible clinical usefulness as biomarkers and therapeutical targets.

Postoperative Debridement versus No Debridement in Chronic Rhinosinusitis.

Introduction:This study aimed to assess the long-term effects of postoperative debridement on the 4th and 8th postoperative weeks versus no debridement in terms of subjective and objective outcomes.Materials and Methods:The statistical population of this study (n=80) consisted of 40 patients having chronic rhinosinusitis with nasal polyposis (CRSwNP) and 40 patients having chronic rhinosinusitis without nasal polyposis (CRSsNP). These samples were randomly divided into two groups of debridement and control. Results:According to the results, 8 weeks after endoscopic sinus surgery (ESS), the 22-item Sino-Nasal Outcome Test questionnaire score (P =0.03), Lund-Kennedy score (P<0.001), nasal blockage (P=0.02), and loss/decrease in sense of smell (P=0.02) in CRSwNP were significantly lower in the debridement group than in the control group. Moreover, 6 months after ESS, in both CRSwNP and CRSsNP, no significant difference was observed between the two groups considering the outcomes (P>0.05).Conclusion:This study showed that debridement could lead to short-term improvements in CRSwNP patients; however, no long-term benefit was observed.

Aspirin Exacerbated Respiratory Disease and Nasal Polyp Phenotyping.

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

TLR-2 expression and dysregulated human Treg/Th17 phenotype in Aspergillus flavus infected patients of chronic rhinosinusitis with nasal polyposis

BackgroundT helper (Th)17 and regulatory T (Treg) cells with toll-like receptor (TLR)-2 have been acknowledged to play a critical role in chronic rhinosinusitis with nasal polyposis (CRSwNP). However, its pathogenesis has been perplexed by conflicting reports on the role of Th17/Treg cells in patients of distinct ethnicities. We attempted to understand the role of Th responses induced during host defense against Aspergillus flavus.ResultsThe percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell populations and various cytokine profiles in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens were characterized from 50 CRSwNP cases, before and after treatment, and in 50 healthy controls. TLR-2 expression was analyzed in tissues of cases and controls for disease co-relation. The major pathogen identified in our study was A. flavus by mycological investigations. A marked immune imbalance was noted with elevated Th17 and decreased Tregs in PBMCs of CRSwNP patients after A. flavus stimulation. Comparatively, interleukin (IL)-17 and IL-10 levels were increased, with low transforming growth factor (TGF)-β levels in A. flavus stimulated PBMC supernatants of patients. The mRNA expression of TLR-2 in polyps of CRSwNP patients indicated significant (p = 0.001) upregulation in comparison to the controls.ConclusionsOur data highlights the excessive expression of TLR-2 in nasal polyps contributing to the imbalance in Th17/Tregs population in patients. After therapy, recovery of Tregs cells indicates restoration and tissue homeostasis, though high circulating CD4+CD161+ Th17 cells may continue to be a threat to patients predisposed to future recurrences. The constant exposure and tendency of A. flavus to colonize nasal cavities can lead to a Th17 driven airway inflammation. Dysregulated Th17 with TLR-2 promote resistance to treatment and progression to the chronicity of the disease.