Dupilumab-related late adverse events in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Anti-IL-4 receptor α antibody (dupilumab) has demonstrated favorable sinonasal outcomes for chronic rhinosinusitis with nasal polyps (CRSwNP), which is mainly caused by type 2 inflammation. Although increased blood eosinophil levels and injection site symptoms are frequently observed as acute adverse events (AEs) of dupilumab, limited knowledge is available regarding the late AEs of dupilumab for CRSwNP. OBJECTIVES: We investigated the late AEs following the initiation of dupilumab treatment for CRSwNP. MATERIAL AND METHODS: Fifty-one patients with CRSwNP treated with dupilumab for > 3 months were enrolled, and their clinical data were collected from their medical records. RESULTS: Six (11.8%) patients experienced late AEs. One case of eczema with pruritus, one case of psoriasis-like dermatitis, two cases of severe rash, one case of malignant lymphoma, and one case of alopecia areata were observed. Skin disorders were the most common late AEs in this study. It is a Th1-inflammatory disease, and its mechanism is thought to be due to the immune imbalance caused by dupilumab. We could not confirm whether malignant lymphoma in our case was caused by dupilumab use. CONCLUSIONS AND SIGNIFICANCE: Skin disorders are often late AEs associated with dupilumab; therefore, careful monitoring after dupilumab initiation should be considered.

Oncostatin M promotes epithelial barrier dysfunction in patients with eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Oncostatin M (OSM) may be involved in the promotion of mucosal epithelial barrier dysfunction in patients with eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) by inducing matrix metalloproteinase (MMP) -1 and -7. The aim was to evaluate the roles and mechanisms of action of OSM on MMP-1 and -7 synthesis from nasal epithelial cells (NECs). METHODS: OSM, OSM receptor (OSMR), MMP-1 and -7 expression was evaluated in nasal mucosa or primary NECs from scrapings by quantitative polymerase chain reaction (qPCR), immunofluorescence and immunohistochemistry. OSM and other cytokines were used to stimulate air-liquid interface (ALI) cultured NECs. qPCR, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence were used to evaluate the expression of OSMR, MMP-1, -7 and occludin in NECs. RESULTS: Elevated levels of OSMRß, MMP-1 and -7 were found in the tissues and scraped NECs of Eos CRSwNP in comparison to them obtained from the inferior turbinate (IT) and control subjects. The levels of OSM and OSMRß mRNA in tissues were positively correlated with the levels of MMP-1 and -7. OSM stimulation of NECs increased the expression of MMP-1 and -7, and the responses were suppressed by a STAT3 inhibitor, and a PI3K inhibitor respectively. In parallel studies, we found that stimulation with OSM disrupted the localization of occludin, a tight junction protein in NECs. The response was suppressed by a pan-MMP inhibitor. CONCLUSION: OSM induces the synthesis and release of MMP-1 and -7 in NECs. Furthermore, MMP-1 and -7 promote mucosal epithelial barrier dysfunction in patients with Eos CRSwNP.

Alterations of gut microbiome in eosinophilic chronic rhinosinusitis.

PURPOSE: A growing body of evidence has elucidated that the gut microbiota has a crucial impact on the pathophysiological process of atopic diseases. Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is a local atopic disease of the systemic immune response. Alterations in the gut microbiome in eCRSwNP patients remain largely undefined. METHODS: 16S rRNA gene sequencing was performed in a cross-sectional study of 17 eCRSwNP patients, 9 noneCRSwNP patients and 13 healthy controls, and gut microbiota DNA sequencing between each pair of groups was compared using bioinformatic methods. RESULTS: Compared with that of healthy controls, the gut microbiomes of eCRSwNP patients were characterised by a distinct overall microbial composition. However, no significant differences were found in the alpha diversity of the gut microbiota between patients and healthy controls. The distinct differences in microbial composition were significantly correlated with the severity of disease. At the genus level, the abundance of Faecalibacterium positively correlated with Lund-Mackay CT scores. Similarly, the abundance of Turicibacter positively correlated with the percentage of tissue eosinophils. CONCLUSIONS: We found alterations in the gut microbiome in eCRSwNP patients, and the alterations in the gut microbiome were correlated with the severity of disease.

The value of combined detection of specific immunoglobulin E, interleukin-6 and regulatory T cells in predicting the risk of postoperative recurrence in patients with eosinophilic chronic rhinosinusitis and nasal polyps.

Background: To investigate the predictive value of specific immunoglobulin E (sIgE), interleukin-6 (IL-6) and regulatory T cells (Treg) on the risk of postoperative recurrence in patients with eosinophilic Chronic rhinosinusitis with nasal polyps (EcRswNP). Methods: A total of 198 patients with EcRswNP collected to our Hospital from January 2019 to December 2021 were selected as the research subjects. All patients underwent functional endoscopic sinus surgery. The patients were selected to recurrence group (RG, n = 48) and nonrecurrence group (NRG, n = 150) on the basis of the recurrence after 1 year of follow-up. The related factors of postoperative recurrence of EcRswNP were analyzed. The ROC was used to analyze the dangerous of sIgE, IL-6 and Treg in predicting postoperative recurrence of EcRswNP patients. Results: The proportion of asthma patients, nasal congestion VAS score, and peripheral blood Eos% content in the RG exceeded that in the NRG, and the Organization Neu % and peripheral blood Neu% levels were less than those in the NRGp (P all < 0.05). The serum sIgE and serum IL6 in the RG were higher than those in the NRG, while the level of peripheral blood Treg was lower than that in the NRG (P < 0.05). Logistic regression analysis showed that high levels of serum sIgE, serum IL-6 and low Treg levels were risk factors for postoperative recurrence (P < 0.05). ROC showed that the AUC of peripheral blood sIgE level, IL-6 and Treg levels alone in predicting the dangerous of postoperative recurrence in patients with EcRswNP were 0.786, 0.707 and 0.636, respectively (all P < 0.05); The AUC of combined prediction of peripheral blood sIgE, IL-6 and Treg levels for postoperative recurrence dangerous in patients with EcRswNP was 0.973, indicating that the efficacy of jointed prediction was exceed than that of single prediction (P < 0.05). Conclusions: The high levels of sIgE, IL6 and low Treg levels in patients with EcRswNP before operation will increase the risk of postoperative recurrence, which is a risk factor affecting postoperative recurrence, and the three indicators have good predictive value for predicting postoperative recurrence in patients with EcRswNP, and the combination of the three indicators has better value in predicting postoperative recurrence.

Activation of the PGE2-EP2 pathway as a potential drug target for treating eosinophilic rhinosinusitis.

Current treatments of eosinophilic chronic rhinosinusitis (ECRS) involve corticosteroids with various adverse effects and costly therapies such as dupilumab, highlighting the need for improved treatments. However, because of the lack of a proper mouse ECRS model that recapitulates human ECRS, molecular mechanisms underlying this disease are incompletely understood. ECRS is often associated with aspirin-induced asthma, suggesting that dysregulation of lipid mediators in the nasal mucosa may underlie ECRS pathology. We herein found that the expression of microsomal PGE synthase-1 (encoded by PTGES) was significantly lower in the nasal mucosa of ECRS patients than that of non-ECRS subjects. Histological, transcriptional, and lipidomics analyses of Ptges-deficient mice revealed that defective PGE2 biosynthesis facilitated eosinophil recruitment into the nasal mucosa, elevated expression of type-2 cytokines and chemokines, and increased pro-allergic and decreased anti-allergic lipid mediators following challenges with Aspergillus protease and ovalbumin. A nasal spray containing agonists for the PGE2 receptor EP2 or EP4, including omidenepag isopropyl that has been clinically used for treatment of glaucoma, markedly reduced intranasal eosinophil infiltration in Ptges-deficient mice. These results suggest that the present model using Ptges-deficient mice is more relevant to human ECRS than are previously reported models and that eosinophilic inflammation in the nasal mucosa can be efficiently blocked by activation of the PGE2-EP2 pathway. Furthermore, our findings suggest that drug repositioning of omidenepag isopropyl may be useful for treatment of patients with ECRS.

Is the measurement of ethmoid sinus dominance in eosinophilic chronic rhinosinusitis accurate?

OBJECTIVE: An ethmoid-dominant shadow on computed tomography is an indicator of type 2 inflammation, and is one of the main items used to diagnose and classify the severity of eosinophilic chronic rhinosinusitis in the Japanese diagnostic criteria. Ethmoid sinus dominance is examined using the Lund-Mackay scoring system and may be overestimated due to scoring characteristics. We aim to investigate the accuracy of evaluations of ethmoid dominance using the conventional scoring system and the possibility of conducting an objective evaluation using a more detailed other scoring system. METHODS: Patients diagnosed with eosinophilic chronic rhinosinusitis and who underwent bilateral endoscopic sinus surgery were enrolled in the present study. Computed tomography was performed preoperatively on all subjects. The bilateral anterior and posterior ethmoid sinuses and bilateral maxillary sinus were scored, and the ethmoid-to-maxillary ratio was calculated using 3 different scoring systems: Lund-Mackay (each sinus score ranges between 0 and 2), simplified Zinreich (score ranging between 0 and 3), and Zinreich (score ranging between 0 and 5). RESULTS: A total of 149 patients were eligible for the present study. Significant differences were observed in ethmoid-to-maxillary ratio evaluated by the 3 different scoring systems (2.4 ±â€¯0.7, 3.0 ±â€¯1.1, and 3.7 ±â€¯2.2). Only 2 patients were negative for ethmoid dominance by the Lund-Mackay scoring system, while 14 were negative by the simplified-Zinreich and Zinreich scoring systems. Severity changed from the initial grade in 12 patients. CONCLUSIONS: The present results confirmed a potential overestimation when only the Lund-Mackay scoring system was used to assess ethmoid dominance. Ethmoid dominance has been identified as one of the main predictive factors for the long-term postoperative outcomes of eosinophilic chronic rhinosinusitis and is included in the Japanese diagnostic criteria. A detailed evaluation of ethmoid dominance is desirable for more accurate evaluations of the severity and prognosis of eosinophilic chronic rhinosinusitis.

A Case of Pott's Puffy Tumor in a Patient With Eosinophilic Chronic Rhinosinusitis.

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory type 2 inflammation-based airway allergic disease that is prone to complications such as bronchial asthma. Pott's puffy tumor (PPT) is a rare clinical entity characterized by osteomyelitis of the frontal bone accompanied by a subperiosteal abscess. A 56-year-old female with a history of cranial surgery and bronchial asthma presented to an otolaryngology clinic with nasal obstruction and loss of smell, later developing swelling and redness on her forehead. She was diagnosed and treated for ECRS and was thought to have developed PPT during her course. Nasal endoscopy reveals bilateral polyp formation originating from the middle meatus. Paranasal computed tomography (CT) indicates substantial swelling extending from the opening of the frontal sinus to the adjacent subcutaneous tissue, accompanied by a defect in the frontal bone and osteolysis at the base of the frontal skull. Her management included conservative antibiotic therapy adjusted due to a drug eruption and, subsequently, endoscopic sinus surgery (ESS). The case was complicated by the patient's medical history and the absence of detailed surgical records, which limited the use of enhanced imaging techniques. This underscores the complexity of diagnosing and managing PPT in adults, particularly those with prior surgeries, emphasizing the need for a tailored diagnostic and therapeutic approach that integrates detailed patient history with current clinical indicators to effectively guide treatment. This case contributes to the limited literature on adult PPT and underscores the critical need for careful patient monitoring and detailed surgical history.

Feasibility of continued treatment with dupilumab in patients with type 2 inflammatory disease who developed eosinophilic pneumonia: 3 case reports.

Several reports have described dupilumab-induced eosinophilic pneumonia (EP) after treatment with dupilumab in patients with type 2 inflammatory disease. Other reports have suggested the efficacy of dupilumab for chronic EP (CEP). Whether dupilumab can be continued in patients with type 2 inflammatory disease who develop EP during dupilumab treatment remains unclear. We present herein three cases with different clinical presentations involving dupilumab and EP. In Case 1, dupilumab was discontinued because of dupilumab-induced EP during the treatment of asthma. In Case 2, although pre-existing idiopathic EP worsened during the treatment of eosinophilic chronic rhinosinusitis (ECRS), dupilumab was continued. In Case 3, CEP and ECRS were successfully treated with dupilumab and corticosteroids were discontinued. In conclusion, treatment with dupilumab in patients with type 2 inflammatory disease and idiopathic EP is worth considering if the benefits are deemed to outweigh the risks and careful attention is given to the clinical course.

Common Characteristics of Sinonasal Inflammation Associated with IgG4-Related Disease and Other Chronic Inflammatory Diseases: A Retrospective Observational Study.

INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4, tissue infiltration of IgG4-positive cells, and fibrosis. Although a number of IgG4-RD patients show sinonasal involvement, there is little known about sinonasal inflammation associated with IgG4-RD. This study aimed to describe the clinicopathological features of sinonasal inflammation associated with IgG4-RD and to compare with other inflammatory diseases, such as eosinophilic chronic rhinosinusitis (ECRS) and granulomatosis with polyangiitis (GPA). METHODS: A retrospective analysis of clinicopathological features of patients with sinonasal lesions and high serum IgG4 was performed. Patient data were reviewed to determine whether they fulfilled the diagnostic criteria for other inflammatory diseases. RESULTS: Six of 7 patients were diagnosed with IgG4-RD, while 1 patient was diagnosed with GPA. In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and nasal crusting in the 3 patients (50%). Computed tomography showed ethmoid sinus involvement in 5 patients (83%). Five of the 6 patients (83%) were diagnosed with IgG4-RD based on nasal biopsy, whereas 1 patient (17%) was diagnosed based on lacrimal gland biopsy. Four patients fulfilled the Japanese epidemiological survey of refractory ECRS (JESREC) criteria. However, none of the patients showed eosinophil infiltration. Although the patient with GPA showed high levels of serum IgG4 and tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient showed common clinical features of GPA. CONCLUSION: Patients with sinonasal inflammation associated with IgG4-RD had similar clinical characteristics with ECRS and GPA. Histopathological findings of the nasal biopsy from clinically diagnosed GPA was consistent with that of IgG4-RD. Sinonasal inflammation associated with IgG4-RD should be diagnosed based not only on tissue infiltration of IgG4-positive cells but in conjunction with clinical findings such as local nasal characteristics, involvement of other organs, and serum antineutrophil cytoplasmic antibody levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration.

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.

Functional 2D Nanoplatforms Alleviate Eosinophilic Chronic Rhinosinusitis by Modulating Eosinophil Extracellular Trap Formation.

The therapeutic outcomes of patients with eosinophilic chronic rhinosinusitis (ECRS) remain unsatisfactory, largely because the underlying mechanisms of eosinophilic inflammation are uncertain. Here, it is shown that the nasal secretions of ECRS patients have high eosinophil extracellular trap (EET) and cell-free DNA (cfDNA) levels. Moreover, the cfDNA induced EET formation by activating toll-like receptor 9 (TLR9) signaling. After demonstrating that DNase I reduced eosinophilic inflammation by modulating EET formation, linear polyglycerol-amine (LPGA)-coated TiS2 nanosheets (TLPGA) as functional 2D nanoplatforms with low cytotoxicity, mild protein adsorption, and increased degradation rate is developed. Due to the more flexible linear architecture, TLPGA exhibited higher cfDNA affinity than the TiS2 nanosheets coated with dendritic polyglycerol-amine (TDPGA). TLPGA reduced cfDNA levels in the nasal secretions of ECRS patients while suppressing cfDNA-induced TLR9 activation and EET formation in vitro. TLPGA displayed exceptional biocompatibility, preferential nasal localization, and potent inflammation modulation in mice with eosinophilic inflammation. These results highlight the pivotal feature of the linear molecular architecture and 2D sheet-like nanostructure in the development of anti-inflammation nanoplatforms, which can be exploited for ECRS treatment.

Analysis of the Construction of a Predictive Model for Eosinophilic Chronic Rhinosinusitis.

Purpose: This study aimed to determine indices to diagnose and predict eosinophilic chronic rhinosinusitis (ECRS) during the initial clinic visit. Patients and Methods: We retrospectively analyzed 116 patients with chronic rhinosinusitis who underwent endoscopic sinus surgery and were classified according to the postoperative pathological diagnosis. General data and various clinical indicators were analyzed, and indicators with statistically significant differences between groups were further incorporated into a multivariate logistic regression to establish a comprehensive prediction model. The receiver operating characteristic (ROC) curve was used to compare the two significant valuable single factors from previous studies, the difference in CT scores between the ethmoid sinus and the sum difference of the maxillary sinus (EM difference) and the absolute value of peripheral blood eosinophil (bEOS), with a comprehensive prediction model. Results: There were significant differences in history of allergic asthma (p < 0.001), visual analog scale (VAS) score (p=0.005), sino-nasal outcome test-22(SNOT-22) scale score (p=0.004), Lund-Mackay scale score (p=0.017), EM difference (p=0.002), percentage of bEOS (%)(p=0.001), and absolute value of bEOS (×109/L) (p=0.000) between the two groups (p< 0.05). The history of allergic disease, VAS and bEOS were screened out and included in the comprehensive prediction model. The area under the curve (AUC) of the comprehensive prediction model (0.804)> the AUC of the absolute value of the bEOS (0.764)>the AUC of the EM difference (0.655). The AUC of the EM difference and the comprehensive prediction model were statistically different (P=0.025). There was no statistical difference between the absolute value of bEOS and the AUC of the comprehensive prediction model. Conclusion: The comprehensive prediction model covering the three aspects of allergic asthma history, VAS score, and bEOS count had the highest AUC compared to the other predictors and had good predictive power for the diagnosis of ECRS.

Eosinophil extracellular traps in eosinophilic chronic rhinosinusitis induce Charcot-Leyden crystal formation and eosinophil recruitment.

Eosinophil extracellular traps (EETs) are implicated in various eosinophil-associated diseases; however, their role in chronic rhinosinusitis (CRS) remains unclear. In the present study, 57 CRS patients were enrolled, and immunofluorescence was used to analyze EETs in eosinophilic (eCRS) and non-eosinophilic (Non-eCRS) tissues. MSD was used to examine IL-4, IL-5, and IL-13 concentrations in tissue homogenates. Charcot-Leyden crystals (CLCs) protein expression was detected in PMA, PMA+DNase I, and blank control eosinophils using ELISA. Eotaxin-3 mRNA and protein levels were measured in human nasal epithelial cells (HNECs) cultured with EETs, EETs+DNase I, DNase I, and unstimulated eosinophils using PCR and ELISA. EETs were significantly increased in eCRS tissues compared with Non-eCRS (P<0.001), and correlated with VAS and Lund-Mackay CT scores. IL-5 expression was related to EETs formation (r = 0.738, P<0.001). PMA-stimulated eosinophils exhibited higher CLCs protein levels (P<0.01). Co-culturing HNECs with EETs significantly increased eotaxin-3 mRNA and protein levels (P<0.0001, P<0.001) compared with other groups. The study suggests EETs formation is elevated in eCRS patients and is involved in CLCs formation and chemokine secretion, promoting eosinophilic inflammation.

Assessment of serum soluble CD40 ligand levels in patients with chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a disease highly associated with abnormal regulation of T and B cells. The underlying pathophysiology of inflammatory pathways has critical implications for the diagnosis and management of CRS. Soluble CD40-ligand (sCD40L) is a cleaved form of CD40L present in plasma which functions the same way as CD40L, which has been observed as an inflammatory biomarker in many diseases. CD40L-positive cells control B-cell maturation, proliferation, apoptosis, and antibody production by binding to its receptor CD40 on B-cells. And our results show for the first time that patients with CRS have lower serum sCD40L levels compared to healthy subjects and that decreased sCD40L levels in patients correlate with increased CD40L-positive cell counts in the sinonasal mucosa. In addition, eosinophilic chronic rhinosinusitis (eCRS) patients tend to exhibit more CD40L-positive cells in the sinonasal mucosa compared to non-eCRS patients. This supports the notion that local blockade of CD40/CD40L may suppress pathogenic T/B cell responses and reduce tissue inflammation. Significantly, sCD40L and CD40L may be involved in the development and progression of CRS by impairing peripheral blood B-cell function and enhancing the local inflammatory response in the sinonasal mucosa.

Association between peripheral eosinophilia, JESREC score, and olfactory dysfunction in patients with chronic rhinosinusitis.

Objective: The purpose was to evaluate the relationship between peripheral eosinophilia, Japan Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score, and olfactory dysfunction in chronic rhinosinusitis (CRS) patients and to explore the accuracy and specific cut points of the JESREC score in predicting olfactory dysfunction. Methods: In this cross-sectional, retrospective study, olfactory function was assessed by the Sniffin' Sticks 12-item test and multivariate logistic regression analyses were carried out. Receiver operating characteristic curves were plotted to derive accuracy and cutoff values for the JESREC scores of the olfactory dysfunction criterion. Results: A total of 354 patients [mean (SD) age, 50.0 (14.9) years; 41.8% women] were included in the final analysis. The prevalence of olfactory dysfunction was 46.3%. Individuals who had olfactory dysfunction were more likely to be male (64.6% vs. 52.6%), have eosinophilic chronic rhinosinusitis (ECRS) (39.0% vs. 7.9%), have a longer course of CRS (2.3 years vs. 1.5 years), have higher JESREC scores (8.5 vs. 4.5), and have higher proportions of nasal polyps (78.7% vs. 18.9%) and peripheral eosinophilia (3.3% vs. 1.4%). In logistic analysis, the percentage of eosinophils (1.25, 1.13-1.37), JESREC score (1.31, 1.22-1.40), bilateral lesion (2.06, 1.25-3.41), nasal polyps (15.83, 9.23-27.16), CT shadow (2.73, 1.69-4.43), and ECRS (6.86, 3.68-12.80) were associated with olfactory dysfunction in CRS patients after controlling for covariates, while peripheral neutrophils were not significant. In addition, the area under the curve was 0.778 and the cutoff value for JESREC score for olfactory dysfunction was defined as 5.5. Conclusions: Peripheral eosinophilia and high JESREC scores were significantly associated with the risk of olfactory dysfunction in CRS patients, and special attention should be paid to patients with a JESREC score ≥6.

A case of recurrent chronic eosinophilic pneumonia after switching from benralizumab to dupilumab.

Dupilumab inhibits interleukin-4Rα and suppresses type 2 inflammation. Careful administration of dupilumab is required because it increases the blood eosinophil count secondary to a decrease in local eosinophil counts, sometimes resulting in eosinophilic complications. We herein report a case of recurrent chronic eosinophilic pneumonia after switching from benralizumab to dupilumab. A 54-year-old man with a history of eosinophilic pneumonia presented to our hospital with symptoms of cough, fever, and phlegm production six months after beginning dupilumab administration for recurrent chronic rhinosinusitis. When using dupilumab, it is essential to carefully monitor patients' eosinophil trends and pulmonary symptoms.

Residual nasal polyp tissue following dupilumab therapy is associated with periostin-associated fibrosis.

PURPOSE: Dupilumab, an anti-interleukin-4 receptor alpha monoclonal antibody, is a new treatment for severe uncontrolled chronic rhinosinusitis with nasal polyps. However, data on the effect of dupilumab on histological changes in nasal polyp tissue are lacking. We aimed to investigate the effect of dupilumab on real-life clinical conditions and nasal polyp tissues from patients with eosinophilic chronic rhinosinusitis (ECRS), which is a refractory subtype. METHODS: We conducted an open-label, prospective, observational, single-centre study on 63 patients with refractory ECRS on the basis of the criteria of the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study. These patients had a history of surgery and received dupilumab for 24 weeks. Patient-reported sinonasal symptoms, T&T olfactometry and nasal polyp scores were prospectively evaluated. In 23 patients with residual nasal polyps following dupilumab treatment, changes in systemic and local periostin expression, and total collagen deposition in nasal polyp tissues were investigated before and after dupilumab administration. RESULTS: Dupilumab rapidly improved sinonasal symptoms and reduced the nasal polyp score 24 weeks after initiation. 40 (63.5%) patients had resolution of nasal polyps, but the reduction was limited in the remaining 23 (36.5%) patients. Periostin expression in serum and nasal lavage fluid was decreased, whereas periostin and the total collagen deposition area in subepithelial tissues in residual nasal polyps were enhanced after dupilumab administration. CONCLUSION: Dupilumab improves sinonasal symptoms and reduces the nasal polyp score in refractory ECRS. Periostin-associated tissue fibrosis may be involved in the differential effect of dupilumab on nasal polyp reduction.

Bacteriology of Different Phenotypes of Chronic Rhinosinusitis.

OBJECTIVES: Chronic rhinosinusitis (CRS) reduces the health-related quality of life and subsequently causes a tremendous socio-economic impact. Although many studies have been conducted, few have identified a relationship between bacteriological characteristics and different phenotypes or endotypes. Therefore, this study aimed to elucidate the recent trends in bacterial cultures from different types of CRS in the Asian population. METHODS: This retrospective case-control study recruited patients diagnosed with CRS who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. The patients were classified into those with chronic rhinosinusitis with nasal polyps (CRSwNP)/chronic rhinosinusitis without nasal polyps (CRSsNP), eosinophilic chronic rhinosinusitis (eCRS)/non-eosinophilic chronic rhinosinusitis (NECRS), and central compartment atopic disease (CCAD)/lateral-dominant nasal polyp (LDNP) groups. The demographic data and bacteriological characteristics of the groups were analyzed. RESULTS: We included 503 patients, identifying no significant difference between CRSwNP and CRSsNP for several common bacteria in CRS. The number of Staphylococcus epidermidis isolates in culture was significantly higher in the NECRS group (50.46% vs. 32.56%, p = 0.0003) than that in the eCRS group. The number of methicillin-resistant Staphylococcus aureus (MRSA; 8.51% vs. 2.35%, p = 0.0221) positive isolates was significantly higher in the CCAD group than that in the LDNP group. CONCLUSIONS: This was the first study in Asia to analyze the relationship between bacteriological characteristics and CCAD. MRSA is significantly higher in the CCAD group than that in the LDNP group. Recognizing the unique microbiology of CRSwNP, eCRS, and CCAD is crucial when selecting antimicrobial therapy to lessen the socio-economic impact. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1071-1076, 2024.

The current findings in eosinophilic chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a persistent inflammatory disease of the nasal cavity and paranasal sinuses. Traditional classification is denoted by the presence (CRSwNP) or absence of nasal polyps (CRSsNP). Particularly, CRSwNP is distinguished by the presence of infiltrating cells and inflammatory markers in the nasal mucosa. Patients with CRSwNP in Western countries predominantly display a type 2 endotype, whereas those in Asian regions display a mixed type 2 endotype. Nevertheless, recent transcriptome analyses have revealed two types of nasal polyps - type 2 and non-type 2 polyps, suggesting that geographical differences in endotypes likely resulted from the different proportions of each endotype. Moreover, various endotypes of CRSsNP have been identified, making phenotype a crucial factor for predicting treatment efficacy. Type 2 endotypes, designated as eosinophilic CRS (ECRS) in Japan, are characterized by severe eosinophilic infiltration into the paranasal sinus tissue and are particularly refractory. In this review, we discuss the latest developments in ECRS. We also provide recent findings on the involvement of nasal epithelial cells in pathogenesis.