Multidisciplinary consensus on a stepwise treatment algorithm for management of chronic rhinosinusitis with nasal polyps.

Fevipiprant in CRSwNP and comorbid asthma: Wrong target population or wrong PGD2 receptor?

Biologics for chronic rhinosinusitis with nasal polyps (CRSwNP)

Objective To investigate the impact of steroid-eluting implants after endoscopic sinus surgery (ESS) on health care resource use (HCRU) in chronic rhinosinusitis patients with (CRSwNP) and without (CRSsNP) nasal polyps. Methods This retrospective, observational cohort study using real-world evidence data included adult patients with CRS who underwent ESS in 2015–2019 with at least 24 months of data before and after ESS. Patients who received implants were matched to patients who did not based on a propensity score developed using baseline characteristics and NP status. HCRU was compared between cohorts within each CRSwNP and CRSsNP subgroup using chi-square tests (binary variables). Results The implant cohort in the CRSwNP subgroup had fewer all-cause outpatient (90.0% vs. 93.9%, p < .001) and all-cause otolaryngology (64.3% vs. 76.4%, p < .001) visits as well as fewer endoscopy (40.5% vs. 47.4%, p = .005) and debridement (48.8% vs. 55.6%, p = .007) procedures than the non-implant cohort. The implant cohort in the CRSsNP subgroup had fewer all-cause outpatient (88.9% vs. 94.2%, p < .001) and all-cause otolaryngology (53.5% vs. 74.4%, p < .001) visits as well as fewer endoscopy (31.8% vs. 41.7%, p < .001) and debridement (36.7% vs. 53.4%, p <.001) procedures than the non-implant cohort. Revision sinus surgery was reduced in the implant cohort in both subgroups, and reached statistical significance in the CRSwNP subgroup (3.8% vs. 6.0%, p = .039) but not in the CRSsNP subgroup (3.6% vs. 4.2%, p = .539). Conclusions Overall, patients receiving implants had lower HCRU for 24 months after sinus surgery independent of nasal polyp status, and revision surgery was reduced in CRSwNP patients. These findings provide additional evidence that long-term reductions in HCRU may be achieved with steroid-eluting implant use during sinus surgery. What is known on this topic Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a disproportionately higher burden of disease and consume greater healthcare resources than chronic rhinosinusitis patients without nasal polyps (CRSsNP). CRSwNP patients represent approximately 30% of CRS patients who undergo surgery, but their clinical course is disproportionally complicated by disease recurrence and revision surgery. Steroid-eluting sinus implants have been shown in clinical trials to improve short-term postoperative outcomes after endoscopic sinus surgery (ESS) in CRS patients in general. A recent real-world evidence study reported that steroid-eluting sinus implants following ESS were associated with a reduction in HCRU in CRS patients followed for 18 months, but the impact of implants on HCRU in CRSwNP and CRSsNP patients separately remains unknown. What this study adds In this observational study, reduced HCRU was observed in CRSwNP and CRSsNP patients who receive steroid-eluting sinus implants. Use of implants in CRSwNP and CRSsNP patients was associated with a significant reduction in healthcare visits (all-cause outpatient, all-cause otolaryngology), and sinus procedures (endoscopy, debridement). Revision surgery was significantly reduced in the implant cohort of CRSwNP patients and trended lower in the implant cohort of CRSsNP patients. Use of implants had no significant impact on all-cause ER/urgent care visits or sinus-related imaging.

Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma

Basophils are elevated in nasal polyps of patients with chronic rhinosinusitis without aspirin sensitivity

Chronic rhinosinusitis (CRS) is an inflammatory condition of the nasal airway and paranasal sinuses that can broadly be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). The relationship between CRS and atopy to inhalant allergens remains unclear. We sought to examine the presence of atopy in patients failing medical therapy for both types of CRS. The objective of this research was to analyze the frequency and distribution of allergen sensitivity in patients failing medical therapy for CRSwNP and CRSsNP in comparison to rhinitis patients without CRS and the general population. A prospectively collected database of 334 consecutive CRS patients who had surgery after failing maximal medical therapy was queried to identify those who met inclusion criteria: a sinus computed tomography (CT), an endoscopy consistent with CRS, and skin-prick testing with 24 common inhalant allergens in 8 classes at our institution (n = 125). Additionally, data from these CRS patients were compared to a group of 50 patients diagnosed with rhinitis who had similar symptoms but radiologically normal CT scans, as well as published normative population skin-prick testing data obtained from the National Health and Nutrition Examination Study III (NHANES III). The relationship between atopy, as assessed by the frequency of skin test positivity, and radiological disease severity, was assessed for several allergen classes in CRSwNP, CRSsNP and rhinitis patients. One or more positive skin results were observed in 103 of 125 (82.4%) CRS patients who underwent surgery--a prevalence significantly higher than that found in the NHANES III study (p < 0.05) but not different from the rhinitis control group (36/50, 72.0%). The most prevalent positive skin test results were to dust mites and ragweed in CRSwNP, CRSsNP, and rhinitis patients. Comparing these 3 patient groups, there were no significant differences in the rates of positive skin-test results to any single allergen. However, the median number of skin test–positive results was higher in CRSwNP patients compared to CRSsNP and rhinitis patients. Consistent with other studies, we found that CRSwNP patients were more likely to be male and have concurrent asthma. In our series of patients failing medical therapy for CRS, we found higher rates of atopy compared with the general population but not compared with rhinitis patients. CRSwNP patients with medically refractory sinusitis were more likely to have multiple positive skin tests and asthma as compared to the general population or patients with either CRSsNP or rhinitis. Host barrier dysfunction may play a role in enabling multisensitization.

Profiling the immunological characteristics of exacerbation of chronic rhinosinusitis with nasal polyps.

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a chronic inflammatory condition of the nasal and paranasal sinus mucosa with nasal polyp formation. This systematic review evaluated the efficacy and safety of biological therapies, including omalizumab, mepolizumab, and benralizumab, compared with endoscopic sinus surgery (ESS) in CRSwNP management. A literature search using the PubMed, Scopus, and Web of Science databases identified five studies that met the inclusion criteria. The studies included randomized controlled trials and observational studies assessing biological therapies or ESS in adults with CRSwNP. The primary outcomes were nasal polyp score (NPS), nasal congestion score, Sinonasal Outcome Test (SNOT-22), and adverse events. Omalizumab showed significant improvements in NPS, nasal congestion score, and SNOT-22 scores compared to placebo, with sustained effects in an open-label extension study. Mepolizumab significantly reduced SNOT-22 scores, improved lung function, and decreased blood eosinophil counts and systemic corticosteroid use in patients with severe eosinophilic asthma and CRSwNP. Benralizumab improved NPS and nasal blockage scores compared to placebo, with effects varying by comorbidities and baseline characteristics. ESS with medical therapy showed better SNOT-22 scores than medical therapy alone, though not reaching the minimal clinically important difference. Biological therapies and ESS were well tolerated, with adverse events comparable to those of the placebo. This review demonstrates the effectiveness of biological therapies and ESS in managing CRSwNP, particularly in severe cases of the disease. Further research is needed to evaluate the long-term efficacy, safety, and cost-effectiveness of these interventions in CRSwNP management.

Evidence regarding long-term postoperative follow-up of chronic rhinosinusitis with nasal polyps (CRSwNP) patients is scarce in the literature. The objective of the present study was to report long-term 12-year postoperative outcomes for CRSwNP patients. CRSwNP patients were prospectively followed after endoscopic sinus surgery. Sinonasal symptoms, nasal polyp score (NPS), Barcelona Smell Test 24 (BAST-24), Lund-Mackay Score (LMS), and Medical Outcome Study Short Form-36 (SF-36) questionnaire were assessed before and 12 years after surgery. At long-term follow-up (median, 12 years), a strong improvement was noted for all patients (N=76) in nasal symptoms score, NPS, BAST-24, and LMS scores compared with baseline. No long-term improvement in SF-36 was found. Patients with CRSwNP have a long-term 12-year postoperative improvement in nasal symptoms, polyp size, computed tomography, and olfaction.

Biologics and the treatment of chronic rhinosinusitis

Outside of SINUS-24 (A Controlled Clinical Study of Dupilumab in Patients With Bilateral Nasal Polyps) and SINUS-52 (Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps), there are limited data on the efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The objective was to compare dupilumab with functional endoscopic sinus surgery (FESS) in patients with CRSwNP by assessing the change in nasal polyp and Sino-Nasal Outcome Test (SNOT-22) scores postintervention. A retrospective matched cohort study compared 54 patients who had CRSwNP treated with dupilumab with 54 patients who had CRSwNP treated with FESS; both cohorts were treated with topical corticosteroids. The primary end points were change in nasal polyp score and overall SNOT-22 score. Secondary end points were change in SNOT-22 domain scores and SNOT-22 olfaction score. Patients who underwent FESS had a greater improvement in nasal polyp score (5.18±2.01) compared with patients treated with dupilumab (4.27±1.98, p=0.02). There was no significant difference in terms of the change in overall SNOT-22 score. Patients treated with dupilumab had greater improvement in the extranasal rhinologic SNOT-22 domain scores (4.87±3.91) compared with patients treated with FESS (2.93±4.32, p=0.02). There was a greater improvement in the SNOT-22 olfaction scores for patients treated with dupilumab (2.35±2.17) compared with patients treated with FESS (1.48±2.24, p=0.04). Patients taking dupilumab were followed on average for 12.20months and patients treated with FESS were followed for 17.90months. Overall, both therapies are effective at reducing symptoms in patients with CRSwNP according to SNOT-22. Patients treated with dupilumab reported improved olfaction and decreased cough, postnasal drainage, and thick nasal drainage as compared with patients treated with FESS, while patients treated with FESS had a greater reduction in polyp burden.

This study was undertaken to assess the association between the likelihood of surgical recurrence and serum ECP and TIgE levels in chronic rhinosinusitis with nasal polyps (CRSwNP). Clinical information was gathered retrospectively from 166 cases of surgically treated CRSwNP as well as 60 cases of chronic rhinosinusitis without nasal polyps (CRSsNP). A comparative analysis on serum levels of total immunoglobulin E (TIgE) and eosinophil cationic protein (ECP) was carried out between the two groups. The CRSwNP patients were assigned into recurrence and non-recurrence groups based on the absence/presence of disease recurrence after a 2-year follow-up. An analysis was conducted on the correlation between the patients' clinical data and their serum ECP and TIgE levels. Receiver operating characteristic (ROC) curves were utilized to assess the clinical utility of these two biomarkers. The CRSwNP participants had higher serum levels of ECP and TIgE (4.28 ± 0.81 > 3.58 ± 0.77 ng/L, P < 0.001; 52.99 ± 8.62 > 15.65 ± 3.25 KU/L, P < 0.001) compared to CRSsNP participants. Univariate analysis indicated that neutrophil ratio, lymphocyte ratio, Lund-Kennedy score, Lund-Mackay score, SNOT-22 score, olfactory function score, and postoperative recurrence were significantly correlated with serum ECP and TIgE levels. Higher serum levels of TIgE and ECP (4.89 ± 0.79 < 4.11 ± 0.72, P < 0.001; 58.74 ± 8.27 < 51.40 ± 8.04, P < 0.001) were detected in the recurrence groups vs. the non-recurrence group. Multivariate analysis showed that serum ECP and TIgE were independent risk factors for recurrence of CRSwNP. Serum ECP and TIgE levels were found to be predictive of postoperative recurrence risk in CRSwNP patients (AUC: 0.77, 0.74, 0.84; P < 0.05) according to ROC curve analysis. Significant differences were not observed in any general clinical data. The findings suggest that elevated serum ECP and TIgE levels in patients with CRSwNP can be as good predictors for the risk of recurrence after endoscopic sinus surgery.

B cell-activating Factor of the TNF Family (BAFF) and a Proliferation-inducing Ligand (APRIL) Expression in Chronic Rhinosinusitis

Background The association between objective imaging findings and subjective symptoms remains undefined. Aims To investigate the correlation between objective imaging findings and symptom severity in the overall chronic rhinosinusitis with nasal polyps (CRSwNP) population as well as its subendotypes according to the eosinophilic inflammation. Methods Patients with CRSwNP undergoing endoscopic sinus surgery were included. All participants completed the Sino-Nasal Outcome Test (SNOT-22) questionnaire. The Lund-Mackay (LM) CT scores was also obtained. Spearman correlation analysis was performed to evaluate the correlation between CT scores and SNOT-22 scores. Results Forty-four non-eosinophilic CRSwNP(neCRSwNP) and 93 eosinophilic CRSwNP (eCRSwNP) patients were recruited. There was significant association between LM total score and nasal subdomain of SNOT-22 in the overall CRSwNP patients. The nasal symptom of SNOT-22 was significantly associated with maxillary, frontal, sphenoid, anterior drainage, and posterior drainage in all CRSwNP patients. In eCRSwNP and neCRSwNP patients, the sense of smell/taste was associated with sphenoid and posterior drainage. Thick nasal discharge was positively correlated with maxillary, frontal, and anterior drainage only in eCRSwNP patients. Conclusions The high score of sphenoid and posterior drainage may suggest the occurrence of loss of sense of smell/taste, while high score of maxillary sinus may indicate suffering from thick nasal discharge in eCRSwNP patients.

BackgroundA disintegrin and metalloproteinase 8 (ADAM8) has been implicated in eosinophilic inflammation; however, its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains to be elucidated. This study aimed to investigate the predictive significance of ADAM8 levels in nasal secretions for the endotypes and disease control status of CRSwNP.MethodsA cohort comprising 120 CRSwNP patients and 45 healthy controls (HCs) was assembled, delineating 53 non-eosinophilic CRSwNP (neCRSwNP) and 67 eosinophilic CRSwNP (eCRSwNP) patients. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were utilized to measure ADAM8 levels in nasal mucosal tissues and secretions from all participants. The receiver operating characteristic (ROC) curves and Pearson correlation analysis were employed to assess the predictive capability of ADAM8 levels in predictiving CRSwNP endotypes and disease control status.ResultsADAM8 levels in nasal secretions were elevated in CRSwNP patients compared to HCs, with a more pronounced increase observed in eCRSwNP patients. Elevated ADAM8 concentrations in nasal secretions were positively correlated with peripheral blood eosinophil counts and percentages, tissue eosinophil counts, serum total IgE, Lund–Mackay scores, and Lund-Kennedy scores. Ultimately, 103 CRSwNP patients completed the follow-up protocol, with 72 classified as the controlled group and 31 as the uncontrolled group. Uncontrolled CRSwNP patients exhibited significantly higher ADAM8 levels in nasal secretions compared to the controlled group. The ROC curves indicated that ADAM8 in nasal secretions exhibits robust discriminatory capacity for eCRSwNP and postoperative disease control status.ConclusionADAM8 in nasal secretions emerges as a potential novel biomarker for the prognostication of CRSwNP endotypes and the postoperative disease control status.