Benralizumab-resistant mucus plugs in severe asthma complicated by eosinophilic chronic rhinosinusitis.

It is an absolute necessity to achieve complete control of comorbidities to obtain optimal asthma control. Importantly, type 2 asthma and ECRS share the same inflammatory pathophysiology and are common co-morbidities. If the initial biologic is insufficiently effective, it is worth considering an alternative biologic.

The benefit of dupilumab as a postoperative short-term adjuvant therapy for chronic rhinosinusitis with nasal polyps: A preliminary study.

Introduction: Recent evidence recommends the use of biologics in patients with severe uncontrolled type 2 chronic rhinosinusitis with nasal polyp (CRSwNP) owing to its propensity for recurrence after functional endoscopic sinus surgery (FESS). Among the type 2 biologics used for the treatment of nasal polyps, dupilumab (Dupi, anti-IL-4) exhibited superior efficacy and safety in indirect comparison studies. Objective: This study aimed to evaluate the objective and subjective outcomes of patients with CRSwNP treated with and without adjuvant Dupi therapy after FESS. Methods: Adult patients with type 2 CRSwNP who underwent FESS with adjuvant Dupi after surgery were enrolled. A matched control group without adjuvant Dupi therapy were recruited during the same period. All patients underwent nasal endoscopy and completed the sinonasal outcome test-22 questionnaire evaluations at baseline and 3 months after surgery. Results: A total of 10 patients who received postoperative adjuvant therapy with Dupi and 20 patients who underwent surgery only were included. Patients with add-on Dupi therapy had significantly higher eosinophil cationic protein levels in the serum, eosinophil counts in peripheral blood, prevalence of asthma, and nasal polyp score at baseline. Both treatments were effective in reducing the patient's symptoms by SNOT-22 at 3 months postoperatively. However, patients with adjuvant Dupi therapy exhibited significantly better endoscopic scores than those with surgery only (p = .022). Conclusion: Surgery plays an important role in treating patients with CRSwNP, and adjuvant Dupi use may facilitate objective mucosal recovery postoperatively. Level of Evidence: 4.

An unusual presentation of craniopharyngioma in an adult with nasal bloackade.

Early biopsy and multidisciplinary collaboration with imaging and physical examination are crucial for the diagnosis of such rare tumor presenations. Highlighting the importance of maintaining a broad differential for intra-nasal lesions given the rare presentation of craniopharyngioma as nasal mass.

Blood eosinophilia and a higher ethmoid sinus/maxillary sinus score ratio predict new-onset asthma in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUD: Presently, the impact of Chronic rhinosinusitis with nasal polyps (CRSwNP) on asthma onset is unknown. AIMS: To evaluate the role of CRSwNP in asthma onset. MATERIALS AND METHODS: A total of 3107 CRSwNP patients were retrospectively screened from 1 January 2018, to 31 May 2021; 624 patients were enrolled. Clinical data regarding nasal symptoms, Lund-Mackay scores, blood eosinophil percentage, and onset of asthma were analyzed. Patients were divided into different groups according to past history of nasal polyps, Lund-Mackay score, and the extent of blood eosinophilia. Asthma-free rates between these subgroups were analyzed by Kaplan-Meier curves and Cox regression models. RESULTS: The prevalence of asthma was 10.90% in patients with CRSwNP, and new-onset asthma occurred in 3.14% of these patients. Higher Lund-Mackay scores for ethmoid sinus and maxillary sinus (E/M) and blood eosinophil percentages were two independent risk factors for new-onset asthma, with hazard ratios of 1.267 (95%CI, 1.155-1.390) and 1.224 (95%CI, 1.054-1.422), respectively. CRSwNP patients with an E/M ratio > 2.33 or a blood Eos percentage > 5.5% were at risk for asthma onset. CONCLUSIONS AND SIGNIFICANCE: Blood eosinophilia and a higher E/M score ratio were associated with new-onset asthma in patients with CRSwNP.

Endotype and Phenotype Related Postoperative Effects of Bacterial Lysate in Chronic Rhinosinusitis.

OBJECTIVES: Chronic rhinosinusitis (CRS) endotypes have demonstrated clinical value in guiding treatment decisions. Bacterial lysates are immunomodulators that have shown beneficial effects in various respiratory inflammatory diseases. This study aimed to evaluate the effect of postoperative bacterial lysate therapy on different CRS endotypes. METHODS: Patients diagnosed with CRS who underwent endoscopic sinus surgery were recruited. Bacterial lysates were administered postoperatively for 10 days per month for 3 months to the experimental group comprising patients with a history of frequent upper respiratory infections without adverse reactions. The remaining participants were allocated to the control group. The results of the postoperative 3-, 6-, and 12-month assessments, including the modified Lund-Kennedy (mLK) endoscopic and Sinonasal Outcome Test (SNOT) 22 scores, for the groups were compared. The tissue samples obtained from the participants were evaluated to detect the presence of relevant inflammatory mediators. RESULTS: Among the 92 participants, 47 started bacterial lysate therapy 2 weeks after the surgery. The tissue cytokine profiles and clinical parameters, such as the disease severity and blood eosinophil percentage, of the bacterial lysate and control groups were comparable before treatment. The mLK endoscopic and SNOT-22 scores did not differ after 3, 6, and 12 months of follow-up. The subgroup analysis revealed that the bacterial lysate group had significantly lower mLK endoscopic scores than the control group for CRS without nasal polyps, while there was a tendency toward significance for the interleukin (IL)-5 negative group after 6 months. CONCLUSION: Postoperative bacterial lysate therapy has some beneficial effects on the endoscopic findings of patients with CRS without nasal polyps or those who are negative for IL-5.

Systematic Review of Long Term Sinonasal Outcomes in CRSwNP after Endoscopic Sinus Surgery: A call for Unified and Standardized Criteria and Terms.

PURPOSE OF REVIEW: To present current evidence in long-term (> 5 years) results after endoscopic sinus surgery (ESS) focusing on Patients Reported Outcome Measures (PROMs) and other sinonasal outcomes while assessing the role of ESS in the treatment of CRSwNP, and identifying outcomes which affect the results of ESS and defining recommendations for future studies. RECENT FINDINGS: Long-term results of ESS in CRSwNP can be branched in PROMs and other objective measurements. Despite the heterogeneity of reported outcomes make it difficult to perform comparisons and meta-analysis, ESS improves PROMs, including symptoms, QOL and olfaction. Objectives outcomes such as NPS, LMS, type of surgery, or recurrence and revision surgery don't have a clear role in long-term results. Clustering patients suggest asthma, N-ERD, allergy, eosinophil count and IL-5 could have a role in predicting recurrence and severe disease. Long-term studies of CRSwNP treated with ESS are scarce. There is a significant need to standardize the report of results. The use of tools as SNOT-22, NPS, validated smell tests, defined criteria for disease recurrence and control and ESS extension in a unified systematic way could allow better comparisons between treatments in the new era of biologics.

Factors for predicting the outcome of surgery for non-eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Despite the large patient base in Asia, the prognostic factors of patients with non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) remain largely undetermined. OBJECTIVE: We aimed to systematically investigate the predictive value of clinical and biological variables for non-eosinophilic CRSwNP. METHODS: Fifty-one patients with non-eosinophilic CRSwNP who underwent functional endoscopic surgery were recruited. Clinical information and assessment were comprehensively collected before and after surgery. A broad spectrum of biomarkers was measured in tissue homogenates using multiple assays. A random forest algorithm and stepwise logistic regression were used to construct clinical, biological, and combined models. RESULTS: A total of 41.2% of non-eosinophilic CRSwNP patients were uncontrolled more than 6 months after surgery. We identified one clinical variable (22-item Sino-Nasal Outcome Test score) and four biomarkers (programmed cell death ligand 1, platelet-derived growth factor subunit B [PDGF-ß], macrophage inflammatory protein-3b, and PDGF-α) that were significantly predictive of the surgical outcome. The clinical, biological, and combined models showed predictive ability with areas under the curve of 0.78, 0.83, and 0.89, respectively. PDGF-ß and programmed cell death ligand 1 were identified as independent biomarkers for the prognosis of patients with CRSwNP without considerable eosinophilic infiltration. CONCLUSION: This study shows that clinical and biological factors, such as the 22-item Sino-Nasal Outcome Test score and PDGF-ß, are predictive of the post-functional endoscopic surgical prognosis of non-eosinophilic CRSwNP patients.

Rare case of poorly differentiated squamous cell cancer of HPV etiology in a nasal polyp presenting as chronic sinusitis.

Malignant tumors of the nasal cavity are rare, accounting for 0.2% to 0.5% of all human cancers and 3% to 5% of all head and neck cancers in the United States. Here, we report a rare case of poorly differentiated nonkeratinizing squamous cell carcinoma with human papillomavirus pathology in a unilateral nasal polyp, presenting as chronic sinusitis in a diabetic woman. Although symptomatology initially presented as an episode of sinusitis, its unilateral and persistent nature underscores the importance of considering malignant nasal cavity cancer in patients, even when devoid of typical risk factors and symptoms. Improved prognosis with early stage malignant neoplasm of the nasal cavity demonstrates the importance of early detection.

Spending, utilization, and coverage for chronic rhinosinusitis with nasal polyposis therapies among Medicare Advantage beneficiaries.

KEY POINTS: CRSwNP-specific mean total annual spending ranged from $5,837 (EDS-FLU) to $28,058 (dupilumab). Most CRSwNP patients receiving biologics had comorbid asthma and did not undergo sinus surgery. While biologics were covered by most Medicare Part D plans, only 37% of plans covered EDS-FLU.

Comparison of Proliferating Cell Nuclear Antigen (PCNA) Expression among Nasal Polyp and Chronic Rhinosinusitis.

BACKGROUND AND OBJECTIVE: Chronic rhinosinusitis is a common inflammatory disorder in sinonasal mucosa that could be developed with or without nasal polyps. Cellular proliferation is suggested as a possible mechanism of nasal polyp development. However, conducted studies in this context are limited. So, the present study's aim is the comparison of Proliferating cell nuclear antigen (PCNA) expression in nasal polyps and chronic rhinosinusitis. MATERIALS AND METHODS: In this cross-sectional study, 70 nasal polyp and 60 chronic rhinosinusitis samples from patients referred to Mostafa Khomeini Hospital, Tehran from 2017 to 2022 were immunohistochemically stained by PCNA marker. The percentage of PCNA nuclear expression was determined in two groups and its association with the type of pathological lesion and the patient's age and sex was analyzed by SPSS statistic software version 24 statistical software (IBM Statistics, USA). RESULTS: The mean expression of PCNA in nasal polyp and chronic rhinosinusitis samples was 16.55% ±â€¯13.66 and 17.58% ±â€¯12.68 respectively (ranging from 0 to 57% in both groups) however, there was no significant statistical difference between the two groups (p = 0.479). No relationship was found between PCNA expression with age and sex in none of the chronic rhinosinusitis and nasal polyp groups. CONCLUSION: Proliferative activity of the nasal epithelial cell is similar in chronic rhinosinusitis with and without nasal polyps and it is considered that the increase of epithelial cell proliferative activity probably has no role in nasal polyp development in patients with chronic rhinosinusitis.

IL-4Rα signaling promotes barrier-altering oncostatin M and IL-6 production in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a severe disease involving dysregulated type 2 inflammation. However, the role other inflammatory pathways play in AERD is poorly understood. OBJECTIVE: We sought to broadly define the inflammatory milieu of the upper respiratory tract in AERD and to determine the effects of IL-4Rα inhibition on mediators of nasal inflammation. METHODS: Twenty-two AERD patients treated with dupilumab for 3 months were followed over 3 visits and compared to 10 healthy controls. Nasal fluid was assessed for 45 cytokines and chemokines using Olink Target 48. Blood neutrophils and cultured human mast cells, monocytes/macrophages, and nasal fibroblasts were assessed for response to IL-4/13 stimulation in vitro. RESULTS: Of the nasal fluid cytokines measured, nearly one third were higher in AERD patients compared to healthy controls, including IL-6 and the IL-6 family-related cytokine oncostatin M (OSM), both of which correlated with nasal albumin levels, a marker of epithelial barrier dysregulation. Dupilumab significantly decreased many nasal mediators, including OSM and IL-6. IL-4 stimulation induced OSM production from mast cells and macrophages but not from neutrophils, and OSM and IL-13 stimulation induced IL-6 production from nasal fibroblasts. CONCLUSION: In addition to type 2 inflammation, innate and IL-6-related cytokines are also elevated in the respiratory tract in AERD. Both OSM and IL-6 are locally produced in nasal polyps and likely promote pathology by negatively affecting epithelial barrier function. IL-4Rα blockade, although seemingly directed at type 2 inflammation, also decreases mediators of innate inflammation and epithelial dysregulation, which may contribute to dupilumab's therapeutic efficacy in AERD.

Immature Teratoma of Ethmoid Sinus Masquerading as Antrochoanal Polyp: A Rare Case Report with Literature Review.

Teratomas are rare neoplasms that arise from totipotent stem cells. Teratomas of the head and neck are extremely rare, constituting about 10% of all cases and usually present in the neonatal period. Extensive literature search has shown that there are only two cases reportedof teratoma of the ethmoid sinus; one as a mature teratoma in a neonate and another was histologically immature teratoma in an adult male (Mwang'ombe et al. in East Afr Med J 79(2):106-107, 2002; Aggarwal et al. in J Postgrad Med 59(2):138-141, 2013). We hereby report the second case of immature teratoma of ethmoid sinus origin in an adult male.

Retinoic Acid Treatment Mitigates PM2.5-Induced Type 2 Inflammation: Insights into Modulation of Innate Immune Responses.

Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin-CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.

Nasal polyp syndrome: a patient-centred term for CRSwNP by EUFOREA.

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a chronic inflammatory disease of the nose and paranasal sinus cavities that significantly affects well-being and social function, particularly in young adults and middle-aged populations. CRSwNP is a common health condition in the Western world, with an estimated prevalence of 3%. Despite worldwide evidence-based treatment guidelines such as the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 and the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) chronic rhinosinusitis (CRS) pocket guide, a significant number of patients remain undiagnosed and/or uncontrolled with repeated oral corticosteroids (OCS) treatments and/or (multiple) endoscopic sinus surgeries (ESS).

Galectin-10 in serum extracellular vesicles reflects asthma pathophysiology.

BACKGROUND: Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes. OBJECTIVE: We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs). METHODS: We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps. RESULTS: We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo. CONCLUSION: Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.

Clinical Utility of Machine Learning Methods Using Regression Models for Diagnosing Eosinophilic Chronic Rhinosinusitis.

Objective: Machine learning methods using regression models can predict actual values of histological eosinophil count from blood eosinophil levels. Therefore, these methods might be useful for diagnosing eosinophilic chronic rhinosinusitis, but their utility still remains unclear. We compared 2 statistical approaches, and investigated the utility of machine learning methods for diagnosing eosinophilic chronic rhinosinusitis. Study Design: Retrospective study. Setting: Medical center. Methods: Data, including eosinophilic levels, obtained from blood and sinonasal samples of 264 patients with chronic rhinosinusitis (257 with and 57 without nasal polyps) were analyzed. We determined factors affecting histopathological eosinophil count in regression models. We also investigated optimal cutoff values for blood eosinophil percentages/absolute eosinophil counts (AECs) through receiver operating characteristic curves and machine-learning methods based on regression models. A histopathological eosinophil count ≥10/high-power field was defined as eosinophilic chronic rhinosinusitis. Results: Blood eosinophil levels, nasal polyp presence, and comorbid asthma were factors affecting histopathological eosinophil count. Cutoffs between the 2 statistical approaches differed in the group with nasal polyps, but not in one without nasal polyps. Machine-learning methods identified blood eosinophil percentages ≥1% or AEC ≥100/µL as cut-offs for eosinophilic chronic rhinosinusitis with nasal polyps, while ≥6% or ≥400/µL for one without nasal polyps. Conclusion: Cut-offs of blood eosinophil levels obtained by machine-learning methods might be useful when suspecting eosinophilic chronic rhinosinusitis prior to biopsy because of their ability to adjust covariates, dealing with overfitting, and predicting actual values of histological eosinophil count.

Desmoid Fibromatosis of Maxillary Sinus Masquerading as Nasal Polyp: A Case Report.

Desmoid fibromatosis is also known as aggressive fibromatosis. It is a neoplastic monoclonal proliferation of fibroblasts, with an incidence of 2 to 4 per million per year. Its incidence peaks at 8 years of age and in the third/fourth decades of life. Here we discussed a patient in third decade of life who presented with unilateral nasal blockage with a picture suggestive of sinonasal polyposis on examination. On histopathology, he was diagnosed with Desmoid fibromatosis. Though a rare entity, Desmoid fibromatosis should be kept in mind as a differential diagnosis for appropriate patient management. As per our knowledge, in India this is the first documented case of desmoid fibromatosis arising from maxillary sinus.

Murine model of eosinophilic chronic rhinosinusitis with nasal polyposis inducing neuroinflammation and olfactory dysfunction.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory condition affecting the nasal and paranasal sinus mucosa, often accompanied by olfactory dysfunction. Eosinophilic CRS with nasal polyps (ECRSwNP) is a subtype of CRS characterized by eosinophilic infiltration. Animal models for ECRSwNP with olfactory dysfunction are necessary for exploring potential therapeutic strategies. OBJECTIVE: The aim of this study was to establish a mouse model of ECRSwNP combined with olfactory dysfunction in a shorter time frame using intranasal ovalbumin and Aspergillus protease (AP) administration. The efficacy of the model was validated by evaluating sinonasal inflammation, cytokine levels, olfactory function, and neuroinflammation in the olfactory bulb. METHODS: Male BALB/c mice were intranasally administered ovalbumin and AP for 6 and 12 weeks to induce ECRSwNP. The resultant ECRSwNP mouse model underwent histologic assessment, cytokine analysis of nasal lavage fluid, olfactory behavioral tests, and gene expression profiling to identify neuroinflammatory markers within the olfactory bulb. RESULTS: The developed mouse model exhibited substantial eosinophil infiltration, increased levels of inflammatory cytokines in nasal lavage fluid, and confirmed olfactory dysfunction through behavioral assays. Furthermore, olfactory bulb inflammation and reduced mature olfactory sensory neurons were observed in the model. CONCLUSION: This study successfully established a validated mouse model of ECRSwNP with olfactory dysfunction within a remarkably short span of 6 weeks, providing a valuable tool for investigating the pathogenesis and potential therapies for this condition. The model offers an efficient approach for future research in CRS with nasal polyps and olfactory dysfunction.