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This review article aims to outline what is known in the pathophysiology of chronic rhinosinusitis with nasal polyposis (CRSwNP) and describe the mechanism of the biologic agents being investigated for this disease. Chronic rhinosinusitis with nasal polyposis is an inflammatory disease of the nasal and paranasal mucosa, which causes symptoms of nasal obstruction, hyposmia, and rhinorrhea. Conventional therapy for CRSwNP includes intranasal corticosteroids (INCS) and polypectomy, but INCS offer only modest benefits, and recurrence after surgery is common. Therefore, effective pharmacologic therapies for CRSwNP are being actively sought. Monoclonal antibodies have been successful in other chronic diseases involving eosinophilic inflammation, such as chronic urticaria and asthma. Thus, researchers have begun expanding their scope and investigating the efficacy of these drugs in the treatment of nasal polyposis. The monoclonal antibodies under investigation (omalizumab (anti IgE), dupilumab (anti IL-4/IL-13), and reslizumab and mepolizumab (both anti IL-5), benralizumab (anti IL-5Rα), and etokimab (anti IL-33)) target key players in the pathophysiology of nasal polyposis (NP). Dupilumab has just completed phase III trials for CRSwNP with positive results, while omalizumab, mepolizumab, and benralizumab are currently in phase III trials for this indication. At this time, while there are no FDA-approved biologics for use in NP, research has highlighted the contributions of IL-4, IL-5, IL-13, and IgE as disease mediators in the pathogenesis of NP. The current FDA-approved treatment of intranasal steroids does not provide significant relief for many patients; therefore, these phase III trials of monoclonal antibodies bring hope for an exciting new treatment option.

ABSTRACT Objective: To compare the efficacy of two different methods of topical corticosteroid delivery techniques; conventional nasal spray versus high volume nasal irrigation with squeeze bottle, post-operatively in patients of nasal polyposis. Study Design: Quasi-experimental study. Place and Duration of Study: Department of Ear Nose Throat, Combined Military Hospital, Kohat Pakistan, from Sep 2021 to Aug 2022. Methodology: A total of 80 patients diagnosed with nasal polyposis were recruited for this study. Selected patients were divided into two equal groups. Pre-operatively all patients were carefully assessed with the help of Sino-nasal outcome test 22 (SNOT 22) and Lund Kennedy Endoscopy score for severity of symptoms. Post-operatively, Group-A received Betamethasone via high volume irrigation by squeeze bottle whereas Group-B received the Beclomethasone via conventional nasal spray. This treatment plan continued for 3 months. Post-operatively, SNOT 22 and Lund Kennedy Endoscopy score assessment was carried out at 3 months. Results: Both groups were comparable with respect to demographic data. In Group-A pre-op median and interquartile range for SNOT score was 68 and 10 respectively and it was reduced to 14 and 5 post-operatively, whereas in Group-B, it was 68 and 10; 27 and 5.5 pre and post-operatively. Post-operative difference was significant (p-value=0.001). Similarly, in Group-A, pre and post-operative median and interquartile range for LKE score 6 and 1 respectively and 2 and 0, whereas in Group-B it was 6.22 and 0.4 and 1.5 with statistically significant post-operative difference (p-value=0.001). Conclusion: High volume irrigation with squeeze bottle is more effective method of delivering the drug to target tissue in comparison to conventional nasal spray after nasal polyposis surgery.

Nasal polyps are benign inflammatory growth of sinonasal mucosa, often associated with chronic rhinosinusitis. This condition prevalent among adults, significantly impacts the quality of life. Eosinophil plays a crucial role in the pathogenesis of nasal polyposis. Hence, this study was carried out to compare the relationship between tissue eosinophilia and radiological findings in nasal polyposis. This observational study was conducted at a tertiary care centre, involving 30 patients with nasal polyposis underwent endoscopic sinus surgery. All patients underwent pre operative CT scan and Lund MacKay score were calculated. Excised polyp tissues were examined, and eosinophil count was calculated per high power field (400 X). Eosinophil count was categorized as low (≤ 10 E/HPF) and high (> 10 E/HPF). The study population had a mean age of 41.65 ± 11.43 years, with a male predominance (80%). Hypertension was the most common comorbidity (26.67%). The mean Lund MacKay score was 18.03 ± 4.3 with the majority of patients (60%) had Lund-Mackay scores between 17–24, indicating significant sinus involvement. Patients with higher eosinophil counts (> 10 E/HPF) showed more severe disease, reflected by higher Lund-Mackay scores ( p  < 0.0001). A moderate positive correlation ( r  = 0.005) was observed between tissue eosinophil count and Lund-Mackay scores. This study found moderate positive correlation between the Lund Mackay score and tissue eosinophil count. The correlation between tissue eosinophil count and disease severity underscores its potential as a prognostic marker in nasal polyposis.

Introduction Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease, which is usually type 2-mediated in the western hemisphere, associated with severe therapeutic and socioeconomic challenges. The first targeted systemic treatment option for severe uncontrolled CRSwNP is a human monoclonal antibody against the interleukin-4 receptor α (IL-4Rα) subunit called dupilumab, which was approved for subcutaneous administration in Germany in October 2019. The purpose of this study is to investigate the efficacy of dupilumab in real life in patients treated with dupilumab in label according to license in our department in 2019–2021. Materials and methods Since October 2019, we have investigated 40 patients (18 men, 22 women) treated with dupilumab in a single-center, retrospective single-arm longitudinal study. The following parameters were collected before treatment (baseline), at 1 month, 4 months, 7 months, 10 months, and 13 months: the Sino-Nasal Outcome Test-22 (SNOT-22), the forced expiratory pressure in 1 s (FEV-1), the olfactometry using Sniffin' Sticks-12 identification test (SSIT), a visual analog scale of the total complaints, the Nasal Polyp Score (NPS), histologic findings as well as total serum IgE, eosinophilic cationic protein in serum and blood eosinophils. Results The average age was 52.7 years (± 15.3). The follow-up period was 13 months. The SNOT-22 average was 60 points (± 22.2) at the first visit, 28.2 points (± 17.1) after 4 months and 20.8 points (± 17.7) after 13 months. The NPS was 4.3 points (± 1.5), after 4 months 2.1 points (± 1.3) and after 13 months 1.4 points (± 1.1). Olfactometry showed 3.2 points (± 3.7) at the baseline, 7.0 points (± 4.0) after 4 months and 7.8 points (± 3.5) after 13 months. The other parameters also improved. Most parameters showed linear dependence in the slopes under therapy ( p  < 0.001). Adverse side effects were mostly only mild, and no rescue therapy was needed. Conclusion There is a clear improvement in the medical condition and symptoms in all categories mentioned under therapy with dupilumab, as well as a reduction in the need for systemic glucocorticoids and revision surgery as rescue treatment. Our results show that dupilumab tends to be an effective therapy alternative for severe CRSwNP.

Approximately 5-10% of asthmatic patients worldwide suffer from severe asthma. Experimental and clinical studies have demonstrated that IL-13 is an important cytokine in chronic airways inflammation. IL-13 is involved in Th2 inflammation and has been identified as a possible therapeutic target in the treatment of asthma. Two different human monoclonal antibodies (mAbs) anti-IL-13 (tralokinumab and lebrikizumab) block binding and signaling of IL-13 to its receptors, IL-13Rα1 and IL-13Rα2. Several randomized, double-blind, placebo-controlled multicenter studies have evaluated the safety and efficacy of tralokinumab and lebrikizumab in the treatment of adult patients with severe asthma, but all have failed to meet their primary endpoints. No serious adverse events related to the treatment with these anti-IL-13 mAbs have been reported in these studies. These negative clinical results contrast with positive findings from blocking IL-13 signaling in experimental models of asthma, raising doubts about the transferrable value of some models. Interestingly, dupilumab, a mAb which blocks both IL-4 and IL-13 signaling reduces exacerbation rates and improves lung function in severe asthmatics. These results suggest that IL-4 and IL-13 share some, but not all functional activities in airway inflammation. Tralokinumab might show efficacy in a highly selected cohort of asthmatics characterized by overexpression of IL-13.

Nasal polyps (NPs) develop in 20% to 30% of patients with chronic rhinosinusitis. Severe forms of chronic rhinosinusitis with nasal polyposis (CRSwNP) may be treated with systemic corticosteroids (SCSs), which increase the risk for adverse clinical outcomes. This study compared the incidence of SCS-related adverse outcomes and health care resource utilization and costs between patients with CRSwNP who had SCS exposure and those who did not have SCS exposure. This retrospective cohort study used health care claims data from adult patients with CRSwNP identified in the IBMⓇ MarketScanⓇ Databases between January 2003 and June 2019. The first SCS prescription date in SCS users or a matched date in SCS nonusers (controls) represented the index date. Enrollment for ≥1 year before and after the index date was required. SCS-related adverse outcomes and costs were compared between all SCS users and controls, and among subgroups of patients who had claims for 1–3 and ≥4 SCS prescriptions in the 12-month postindex period. Comparisons were also made among SCS users and controls who previously had and did not have NP surgery, and those with and without comorbid asthma. Inverse probability of treatment weights was applied to all comparisons, which were evaluated for a variable-length follow-up period. SCS users (n = 37,740) had a greater risk for any adverse outcome than controls (n = 7032) (incidence rate ratio [IRR] = 1.10; 95% CI, 1.05–1.16). The risk for adverse outcomes was highest in the subgroups that did not have NP surgery and that had ≥4 SCS claims (n = 2993) versus controls who did not have NP surgery (n = 5078) (IRR = 1.30; 95% CI, 1.18–1.44). Similarly, patients with asthma and ≥4 SCS claims (n = 4195) had a greater risk for SCS-related outcomes versus controls with asthma (n = 1226) (IRR = 1.36; 95% CI, 1.19–1.55). SCS users incurred 60% higher all-cause costs versus non-SCS users (P < 0.001). In patients with CRSwNP, SCS use was associated with a higher risk for adverse outcomes and with increased health care costs compared with controls without SCS exposure. Alternative treatment strategies that avoid and/or reduce SCS use may decrease health care costs and the risk for adverse outcomes among patients with CRSwNP.

Biological therapies are available for the treatment of the severe allergic asthma (SAA) with blood eosinophil count ≥ 0.3 × 109/L. Several of them also showed benefits on nasal polyps (NP), one of the most frequent comorbidities of the severe asthma, but comparative studies on their effectiveness in the association SAA-NP are currently lacking. The aim of this study is to compare the effectiveness of benralizumab, mepolizumab and omalizumab in patients with SAA-NP in real-life settings. A retrospective, observational, multicenter real-life study was realized including patients with SAA-NP treated by benralizumab, mepolizumab or omalizumab for 6 months. We analysed the nasal and respiratory symptoms, the number of asthma attacks and salbutamol use/week, acute sinusitis and severe exacerbation rates, the asthma control score, the lung function parameters, the NP endoscopic score, the sinus imaging and the blood eosinophil count 6 months before and after treatment. Seventy-two patients with SAA-NP were included: 16 treated by benralizumab, 21 by mepolizumab and 35 by omalizumab. After 6 months of treatment, almost all studied parameters were improved (except sinus imaging) with a greater effect of omalizumab on the nasal pruritus (p = 0.001) and more benefits of benralizumab on exacerbations rate, asthma attacks per week and lung function (all p < 0.05). Benralizumab and mepolizumab were more effective to improve the NP endoscopic score and the blood eosinophil count (both p < 0.001). All three biological therapies showed effectiveness by improving asthma and nasal outcomes in patients with SAA-NP. Several differences have been found that should be confirmed by larger comparative studies.

Background: Severe eosinophilic asthma is frequently associated to chronic rhinosinusitis and nasal polyposis (CRSwNP) that contribute to poor asthma control. Mepolizumab is an anti-IL-5 monoclonal antibody, approved for the treatment of severe eosinophilic asthma. A limited number of studies have assessed the efficacy of mepolizumab on CRSwNP in severe asthmatics. We aim to evaluate the efficacy of mepolizumab on sino-nasal symptoms, polyp growth and asthma control in severe eosinophilic asthma patients with CRSwNP in real life. Methods: In this study 44 severe eosinophilic asthma patients with CRSwNP were treated with mepolizumab (100 mg q4w) for 1 year. The following outcomes were assessed before (T0), after 6 (T6) and 12 months (T12) of treatment: sino/nasal outcome test (SNOT-22), Total Endoscopic Nasal Polyp Score (TENPS), %FEV1 (FEV1/FEV1 predicted) and Asthma control test (ACT). Blood eosinophil count, exhaled nitric oxide (FENO) and prednisone intake were measured. In a subgroup of patients, nasal cytology was performed before (T0), after 6 (T6) and after 12 months (T12) of treatment with mepolizumab. Results: We reported a significant reduction of SNOT-22 [from 51.5 ± 21.2 at baseline (T0) to 31.70 ± 17.36 at T6 and 29.7 ± 21.5 at T12 (T0–T12 p < 0.001)] and a decrease of TENPS (from 2.88 ± 3.07 to 1.70 ± 2.37 and 1.77 ± 2.56 at T0, T6 and T12, respectively, T0–T12 p = 0.99). A significant improvement of %FEV1, ACT and a decrease in blood eosinophils and mean prednisone intake were also reported. No statistically significant decreasing trend was measured for FENO. Nasal cytology findings suggest a significant reduction of eosinophil percentage following mepolizumab treatment (from 16.8 ± 7.2% to 3.6 ± 6.2% and 0.8 ± 2.4% at T0, T6 and T12 respectively, T0 to T12: p < 0.001). Conclusions: Mepolizumab improves sino-nasal and asthma symptoms and reduces polyp growth in patients with severe eosinophilic asthma and concomitant CRSwNP in real life. The reviews of this paper are available via the supplemental material section.

Chronic rhinosinusitis (CRS) is a broad clinical syndrome that is characterized by prolonged mucosal inflammation of the nose and paranasal sinuses, and is typically divided into two subtypes based on the presence or absence of nasal polyps. The etiology and pathogenesis of both forms remain areas of active research. Over the last 15 years, a number of hypotheses have been proposed to explain all or part of the clinical CRS spectrum. These hypotheses reflect the concept that CRS results from a dysfunctional interplay between individual host characteristics and factors exogenous to the host. Six broad theories on CRS etiology and pathogenesis are discussed as follows: (1) the “fungal hypothesis,” (2) the “superantigen hypothesis,” (3) the “biofilm hypothesis,” and (4) the “microbiome hypothesis,” all of which emphasize key environmental factors, and (5) the “eicosanoid hypothesis” and (6) the “immune barrier hypothesis,” which describe specific host factors. These theories are reviewed, and the evidence supporting them is critically appraised.