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To explore the therapeutic potential of blocking thymic stromal lymphopoietin (TSLP) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), we conducted a phase 1b/2a, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of CM326, a monoclonal antibody against TSLP. We enrolled 84 eligible patients with uncontrolled CRSwNP and stratified them based on baseline tissue eosinophil count. Patients are assigned to receive CM326 220 mg ( n  = 40) or placebo ( n  = 20) every 2 weeks (Q2W) and CM326 220 mg ( n  = 20) or placebo ( n  = 4) every 4 weeks (Q4W) for 16 weeks. Subsequently, all patients continue on CM326 220 mg Q2W or Q4W for an additional 36 weeks, followed by a 12-week follow up. Primary endpoints are safety of CM326 and change from baseline in NPS at week 16 in patients with eosinophilic CRSwNP (ECRSwNP). Main secondary endpoints include the change from baseline in NPS at week 16 in non-eosinophilic CRSwNP (nonECRwNP) and pharmacodynamic markers. Throughout the 64-week study, all treatment-emergent adverse events (TEAEs) are mild or moderate. CM326 Q2W improves NPS in patients with ECRSwNP compared with placebo at week 16 (mean difference [95% CI], −1.2 [−2.3 to −0.1], P  = 0.04), with sustained benefits during the open-label and follow-up periods. Notably, peripheral blood and tissue eosinophil counts and concentrations of plasma IL-13 and IL-5 are reduced by week 16 with the treatment of CM326 Q2W versus placebo. A post-hoc analysis demonstrates that all participants with baseline TSLP > 330 fg/mL achieve a substantial reduction in NPS by week 16 with the treatment of CM326 Q2W (mean difference vs. placebo: −1.75 [95%CI, −3.06 to −0.44], P  = 0.01). Overall, CM326 is well tolerated and effective in patients with uncontrolled ECRSwNP. A baseline plasma TSLP level of 330 fg/mL may serve as a predictive marker for treatment efficacy of CM326. ClinicalTrials.gov Identifier: NCT05324137. Anti-TSLP biologics have shown promise for the clinical treatment of type 2 respiratory disease. Here the authors present a clinical trial of CM326, a monoclonal antibody against TSLP, and show the clinical effects in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP), who present with type 2-dominant inflammation.

Background Recovery of olfactory function plays a prominent role in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). While rates and timing of such recovery vary, monoclonal antibodies might yield better results which we aimed at evaluating with this study. Methodology A prospective controlled study was conducted at our tertiary otolaryngological center from April 1, 2021, to October 1, 2022, in CRSwNP patients. We included an active group (n = 60 patients) performing dupilumab treatment and a control group (n = 60 patients) treated with intranasal and oral corticosteroids. Primary endpoints were changes in smell visual analogical scale (VAS) and SS-I (Sniffin' Sticks-identification) scores, and olfactory recovery rate. The secondary efficacy endpoints were nasal obstruction, rhinorrhea, headache, SNOT-22, and nasal congestion score (NCS). Results At 6 months, the active group demonstrated better outcomes than control in SS-I scores (10.23 ± 4.21 vs.3.68 ± 3.08; p < 0.001). No significant differences were found in blood eosinophil count, SNOT-22, and NPS (p > 0.05 for all). Olfactory function in the treatment arm improved in 86.66% (52/60 cases), with normal scores in 48.33% (29/60), while the control group reported a lower recovery rate (3/60; 5%), with no normal olfaction cases. Log-rank comparison for Kaplan–Meier functions was statistically significant (p < 0.001), but no differences were found in subanalysis in the active group based on blood eosinophil count at baseline, SNOT-22, and NPS scores. Conclusions Patients who receive dupilumab treatment may experience a faster recovery of olfactory function compared to those receiving corticosteroid therapy. This result would be maintained regardless of the severity of type 2 CRSwNP inflammation, the volume of the polyps, or the patient's subjective symptomatology.

Acute rhinosinusitis (ARS) in children may be accompanied by acute otitis media (AOM) which is often associated with bacterial co-infections. These conditions are among the primary reasons that children visit hospitals and require antibiotic treatment. This study evaluated the efficacy of the nasal-spraying probiotics (LiveSpo Navax containing 5 billion Bacillus subtilis and B. clausii spores/5 mL) as a supportive treatment for dual ARS and AOM with otorrhea in a randomized, single-blind, controlled clinical trial. Eighty-two patients (41 per group), aged 1 month to 12 years, received standard care along with nasal spraying of either physiological saline (Control group) or LiveSpo Navax (Navax group), administered three times daily over a 7-day follow-up period. A total of sixty-one patients (30–31 per group) completed the trial. The Navax group experienced 68.00% and 96.77% reductions in nasal congestion (by day 3) and rhinorrhea (by day 7), respectively, which were 2.04 and 1.94-fold higher than the Control group, with odds ratios (OR) of 4.31 and 30.00 ( p  < 0.05). Endoscopic results indicated 8% and 11% higher reductions in nasal mucopurulent discharge and tympanic membrane hyperemia in the Navax group compared to the Control group. By day 3, compared to day 0, the Navax group exhibited > 1200-fold reduction in Streptococcus pneumoniae and ≥ 4-fold reduction in Haemophilus influenzae concentrations ( p  < 0.05) in both nasopharyngeal and middle ear fluid samples, whereas the Control group showed no significant reductions. Navax treatment reduced IL-6 by 1.35- to 1.74-fold and TNF-α by 1.17- to 1.45-fold, more effectively than the Control group ( p  < 0.05). These results suggest that nasal-spray Bacillus spore probiotics, with their ability to reduce bacterial load and modulate immune responses, provide a cost-effective and safe solution for alleviating symptoms of both ARS and AOM in children. Trial registration : ClinicalTrials.gov, Identifier NCT05804123 on April 7, 2023.

Although both nasal steroids and macrolide antibiotics have been recommended for the treatment of chronic rhinosinusitis without nasal polyps (CRSsNPs), whether there is any difference in their clinical efficacy remains unexplored. In addition, few studies have investigated their clinical efficacy in a Chinese population living in China, who present distinct inflammatory patterns compared with white patients in western countries. This study compares the efficacy of mometasone furoate and clarithromycin treatment in CRSsNP in Chinese adults in a preliminary prospective, open-label, randomized trial. Forty-three CRSsNP patients were randomized to receive mometasone furoate nasal spray at 200 μg (n = 21) or clarithromycin tablet at 250 mg (n = 22) once daily for 12 weeks. Patients were assessed before the treatment and after 4, 8, and 12 weeks after treatment. Subjective symptoms were scored on a visual analog scale. Endoscopy physical findings were scored according to Lanza-Kennedy scoring system. Moreover, smoking and atopic status and coexistence of allergic rhinitis (AR) and asthma were recorded. Before the treatment, no significant difference in symptoms and nasal endoscopic physical findings were found between mometasone furoate and clarithromycin group. As early as 4 weeks after dosing, a significant reduction of total symptom scores, nasal obstruction, headache, rhinorrhea and overall burden scores, and mucosal swelling and nasal discharge scores were observed in both groups. No significant difference in symptom or endoscopic scores was observed between these two groups at any posttreatment observation time point. The coexistence of AR was correlated with lower scores of mucosal edema and nasal secretion in the mometasone furoate group after 12-week treatment. Mometasone furoate and clarithromycin show a comparable clinical effect for CRSsNPs in Chinese adults. Mometasone furoate is more effective in improving edema and secretion for CRSsNP patients with concomitant AR.

The objective of this study was to determine whether postoperative additive systemic steroid administration in chronic rhinosinusitis with nasal polyps (CRSwNP) impacted selected endoscopic, subjective and objective outcome measures. This was a prospective, randomized, double-blind, placebo-controlled, noninferiority multicenter trial of n=106 patients with CRSwNP. All patients underwent primary functional endoscopic sinus surgery (FESS) followed by topical nasal steroids. Patients were randomized to a systemic steroid or placebo for 1 month. Patients were followed up for 2 years over 9 time points. The primary outcome measures were the differences between groups with respect to the nasal polyp score (NPS) and sinonasal quality of life (SNQoL). Secondary outcome measures included interactions with respect to the Lund-Kennedy score (LKS), sinonasal symptoms, general quality of life (GQoL), 16-item odor identification test scores, recurrence rates, need for revision surgery and mucus biomarker levels. 106 patients were randomized to either the placebo or the systemic steroid group (n=53 per group). Postoperative systemic steroids were not superior to placebo with respect to all primary (p= 0.077) and secondary outcome measures (p>0.05 for all). Reported adverse events were similar between the two groups. In conclusion, the addition of postoperative systemic steroids after primary FESS did not confer a benefit over topical steroid nasal spray alone with respect to NPS, SNQOL, LKS, GQOL, sinonasal symptoms, smell scores, recurrence rates, the need for revision surgery or biomarkers over a short-term follow-up of up to 9 months and a long-term follow-up of up to 24 months in CRSwNP patients. Functional endoscopic surgery did, however, show a strong effect on all outcome measures, which remained relatively stable up to the endpoint at 2 years.

IntroductionEndoscopic sinus surgery is an effective treatment for olfactory dysfunction related to chronic rhinosinusitis (CRS). However, recent studies have shown that most patients with CRS experience a return of olfactory function to preoperative levels within months to a year after surgery. Clinically, olfactory training after sinonasal surgery has been proven beneficial for olfactory recovery. The study aims to explore the effectiveness of olfactory training in treating postoperative olfactory dysfunction in patients with CRS after surgery. Additionally, conventional olfactory training (COT) devices have the drawback of insufficient deposition rates of odourants in the olfactory cleft, leading to poor treatment outcomes. This experiment employs a modified olfactory training (MOT) device based on respiratory pressure and compares its therapeutic effects with the COT device.Methods and analysisThis will be a randomised controlled trial. The aim is to investigate the effectiveness of olfactory training in treating postoperative olfactory dysfunction in patients with CRS and to compare the effects of MOT with COT. Participants will be randomly allocated in a 1:1:1 ratio to the MOT group, the COT group and the control group for 12 months. The primary outcome will be the change in the odour threshold, odour discrimination, odour identification and the total threshold, detection and identification score after 12 months of olfactory training. The secondary outcomes will include objective olfactory cleft assessment, the volumes of grey matter, white matter and cerebrospinal fluid, the volume and shape of the olfactory bulb, and the subjective olfactory assessment.Ethics and disseminationThis study protocol has been registered with ClinicalTrials.gov and has received approval from the Peking University Third Hospital Medical Science Research Ethics Committee. The results will be published in scientific peer-reviewed journals.Trial registration numberNCT06837051.

Background Managing Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) is always challenging due to the chronicity of the disease and its intractable course. Posterior nasal neurectomy (PNN) can be effective in alleviating symptoms of CRSwNP. Materials and methods The study was conducted in a tertiary care referral hospital from August 2019 to April 2022. A total of 46 patients of CRSwNP were included (23 patients in the study and 23 in the control group). Patients in the study group underwent endoscopic sinus surgery (ESS) and PNN and patients in the control group with ESS. The symptoms and quality-of-life improvement were assessed at 1, 4, 12, and 24 weeks after the surgery. Results On intragroup analysis between the preoperative and postoperative scores (SNOT-22, RSDI and LK Score), we found a significant difference for each ( p  < 0.05). When the improvement of outcome scores was compared between the two groups, a significant difference was obtained for SNOT-22 and RSDI scores at 1 week and 4 weeks ( p  < 0.05). There was no significant difference found for the duration of surgery/complications between the two groups ( p  = 1.00). Conclusion The PNN can be an effective add-on procedure in patients with CRSwNP in alleviating short-term control of the symptoms and the quality of life. A larger sample size with long-term follow-up may be required for a better understanding of the efficacy of the PNN in patients with CRSwNP.

To assess the efficacy of budesonide intrapolyp injection in chronic rhinosinusitis with nasal polyps. Ninety patients were divided into three groups; group A was given oral prednisolone, group B was given budesonide intrapolyp injection weekly for five consecutive weeks and group C was given budesonide as nasal irrigation for one month. Patients were assessed using Sino-Nasal Outcome Test 22 score, total nasal polyp score, serum immunoglobulin E, absolute eosinophilic count, and morning cortisol level before treatment, one week and three months after completing their treatment. Total nasal polyp score decreased significantly in all groups compared to those at baseline. Reduction in the oral and injection groups was greater than the wash group ( 2 = 0.004), ( 3 < 0.001), and the same trend concerning Sino-Nasal Outcome Test 22 score ( 2 < 0.001), ( 3 < 0.001). Budesonide is an effective agent used in intrapolyp injection with no documented systemic or visual side effects that has comparable results with oral steroids.

Introduction. Antimicrobial peptides and proteins (AMPs) constitute the first line of defense against pathogenic microorganisms in the airway. The association between AMPs and chronic rhinosinusitis with nasal polyps (CRSwNP) requires further investigations. This study is aimed at investigating the expression and regulation of major dysregulated AMPs in the nasal mucosa of CRSwNP. Methods. The expression of AMPs was analyzed in nasal tissue from patients with eosinophilic (E) CRSwNP and nonECRSwNP and healthy subjects using RNA sequencing. The 10 most abundant AMPs expressed differentially in CRSwNP patients were verified by real-time PCR, and of these, the expression and regulation of secretory leukoprotease inhibitor (SLPI) and clusterin (CLU) were investigated further. Results. The 10 most abundant AMPs expressed differentially in CRSwNP compared to healthy control, regardless of subtypes, included BPIFA1, BPIFB1, BPIFB2, CLU, LTF, LYZ, and SLPI, which were downregulated, and S100A8, S100A9, and HIST1H2BC, which were upregulated. ELISA and immunofluorescence confirmed the decreased expression of SLPI and CLU levels in CRSwNP. SLPI is expressed in both nasal epithelial cells and glandular cells, whereas CLU is mainly expressed in glandular cells. AB/PAS staining further demonstrated that both SLPI and CLU were mainly produced by mucous cells in submucosal glands. Furthermore, the numbers of submucosal glands were significantly decreased in nasal polyp tissue of CRSwNP compared to nasal tissue of controls. SLPI was downregulated by TGF-β1 and IL-4 in cultured nasal tissues in vitro, while CLU expression was inhibited by TGF-β1. Glucocorticoid treatment for 2 weeks significantly increased the expression of all downregulated AMPs, but not LYZ. Additionally, budesonide significantly increased the expression of SLPI and CLU in cultured nasal tissues. Conclusion. The expression of major antimicrobial proteins is significantly decreased in nasal tissue of CRSwNP. The expression of SLPI and CLU is correlated with the numbers of submucosal glands and regulated by inflammatory cytokines and glucocorticoids.

Purpose The self-crosslinked hyaluronic acid (scHA) and steroids are considered as efficient factors for postoperative management after chronic rhinosinusitis (CRS) nasal surgery. This randomized clinical trial is designed to investigate the efficacy and potential of scHA gel as a topical drug sustained release carrier for steroid of budesonide. Methods The study is performed with 30 patients of chronic rhinosinusitis with nasal polyps (CRSwNP) who underwent functional endoscopic sinus surgery (FESS). The single application of scHA was assessed in the control patient group for postoperative recovery. In the treatment patient group, the combination of scHA/budesonide was applied for postoperative management. The patients are followed up in 2 weeks, 4 weeks and 12 weeks after surgery. Results The combination of scHA/budesonide results in better endoscopic scoring and mucus evaluation than the single scHA application. Conclusion The results indicate that the combination of scHA/budesonide is a valuable treatment for the FESS postoperative management and implies the potential of scHA gel as a topical drug sustained release scaffold.