Prevalence and predictors of depression and anxiety in patients with chronic rhinosinusitis: a systematic review and meta-analysis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a persistent inflammation of the sinuses. As a result of long-term discomfort, patients may experience symptoms of common mental disorders such as anxiety and depression. This may affect the quality of life and disease progression. However, there is still uncertainty about the extent of the problem. OBJECTIVE: This meta-analysis aimed to determine the prevalence of depression and anxiety symptoms in patients with CRS. SEARCH STRATEGY: We searched PubMed, Embase, Web of Science, Cochrane Library, and CBM databases for relevant studies published before 15 July 2022 in patients with CRS with concomitant depression and anxiety symptoms. DATA COLLECTION AND ANALYSIS: Two authors independently performed screening and quality assessment using validated tools. Extraction of data using predefined standardised data collection spreadsheets. Heterogeneity and inconsistency were checked using the I² statistic. RESULTS: The meta-analysis included 32 articles involving 56 933 patients. The prevalence of depression and anxiety symptoms was estimated at 24.7% (95% CI, 21.3% to 28. 1%) and 29.7% (95% CI, 19.3% to 40.2%). Subgroup analysis revealed the following: (1) CRS without nasal polyps (CRSsNP): 26.2% (95% CI, 21.9% to 30.5%), CRS with nasal polyps(CRSwNP): 20% (95% CI, 15.9% to 24%); (2) Female patients: 36. 1% (95% CI, 25.3% to 46.9%), male patients: 24.3% (95% CI, 12. 1% to 36.6%); and (3) The average age≤50 years patients: 29.8% (95% CI, 21.3% to 38.2%), the average age>50 years patients: 22. 1% (95% CI, 17.1% to 27%). CONCLUSION: A significant proportion of people with CRS have symptoms of depression and anxiety, and early screening for depression and anxiety in people with CRS is critical. And, more attention needs to be given to females and patients with CRSsNP during screening. PROSPERO REGISTRATION NUMBER: CRD42022345959).

The Effectiveness of Biological Agents on Chronic Rhinosinusitis with Nasal Polyposis in Patients with Comorbid Asthma: A Multicenter Real-Life Study from Türkiye.

Background and Objectives: Real-life data on the efficacy of biologic agents (BAs) on asthma-comorbid CRSwNP are needed. Our primary goal is to investigate the effects of BAs on CRSwNP symptoms, as well as endoscopic and tomography scores. Our secondary goal is to show a reduction in the frequency of acute sinusitis exacerbations and the need for surgery. Materials and Methods: We conducted a multicenter, retrospective, real-life study. We screened the patients with asthma-comorbid CRSwNP treated with omalizumab or mepolizumab. A total of 69 patients (40 F/29 M; omalizumab n = 55, mepolizumab n = 14) were enrolled. We compared the visual analog scale (VAS), sinonasal outcome test-22 (SNOT-22), nasal congestion score (NCS), Lund-Mackay computed tomography score (LMS), and total endoscopic polyp scores (TPS) before and after BAs. We evaluated the endoscopic sinus surgery (ESS) and acute exacerbations of chronic rhinosinusitis (AECRS) frequencies separately, according to the BAs. Results: The overall median (min-max) age was 43 (21-69) years. The median (min-max) of biologic therapy duration was 35 (4-113) months for omalizumab and 13.5 (6-32) for mepolizumab. Significant improvements were seen in VAS, SNOT-22, and NCS with omalizumab and mepolizumab. A significant decrease was observed in TPS with omalizumab [95% CI: 0-4] (p < 0.001), but not with mepolizumab [95% CI: -0.5-2] (p = 0.335). The frequency of ESS and AECRS were significantly reduced with omalizumab [95% CI: 2-3] (p < 0.001) and [95% CI: 2-5] (p < 0.001); and mepolizumab [95% CI: 0-2] (p = 0.002) and [95% CI: 2-8.5] (p < 0.001), respectively. There was no significant difference in LMS with either of the BAs. Conclusions: Omalizumab and mepolizumab can provide a significant improvement in the sinonasal symptom scores. BAs are promising agents for CRSwNP patients with frequent exacerbations and multiple surgeries.

Comorbidities associated with adult asthma: a population-based matched cohort study in Finland.

BACKGROUND: Asthma is a common chronic disease characterised by variable respiratory symptoms and airflow limitation, affecting roughly 4%-10% of the adult population. Adult asthma is associated with higher all-cause mortality compared to individuals without asthma. In this study, we investigate the comorbidities that may affect the management of asthma. METHODS: Total of 1648 adults with asthma and 3310 individuals without asthma aged 30-93 were matched with age, gender and area of residency, and followed from 1 January 1997 to 31 December 2013. Baseline information was collected with questionnaires 1997 and follow-up register data from the national discharge registry Finnish Institute for Health and Welfare. Data included diagnoses from outpatient care and day surgery of specialised health care, and data from inpatient care of specialised and primary health care. We included all main diagnoses that had at minimum 200 events and number of diagnoses based on their common appearance with adult asthma. RESULTS: The mean follow-up time varied between 14.2 and 15.1 years, and age at the time of enrolment was 53.9 years for subjects without asthma and 54.4 years for patients with asthma. Chronic obstructive pulmonary disease was 10 times more common among asthmatics. Risk of acute rhinosinusitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis and vocal cord dysfunction was fourfold and risk of pneumonia, and chronic rhinosinusitis was 2.5 times more common among asthmatics. Sleep apnoea, gastro-oesophageal reflux disease, diabetes, allergic rhinitis and dysfunctional breathing were twofold and cataract nearly twofold higher in the asthmatic group. Adult asthma was also significantly associated with musculoskeletal diseases, incontinence and bronchiectasis. CONCLUSIONS: The most common and most severe comorbidity of adult asthma in this study was chronic obstructive pulmonary disease. Other common comorbidities of adult asthma include acute rhinosinusitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, allergic rhinitis, dysfunctional breathing, diabetes, pneumonia, sleep apnoea and gastro-oesophageal reflux disease.

Is generative pre-trained transformer artificial intelligence (Chat-GPT) a reliable tool for guidelines synthesis? A preliminary evaluation for biologic CRSwNP therapy.

INTRODUCTION: Biologic therapies for Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) have emerged as an auspicious treatment alternative. However, the ideal patient population, dosage, and treatment duration are yet to be well-defined. Moreover, biologic therapy has disadvantages, such as high costs and limited access. The proposal of a novel Artificial Intelligence (AI) algorithm offers an intriguing solution for optimizing decision-making protocols. METHODS: The AI algorithm was initially programmed to conduct a systematic literature review searching for the current primary guidelines on biologics' clinical efficacy and safety in treating CRSwNP. The review included a total of 12 studies: 6 systematic reviews, 4 expert consensus guidelines, and 2 surveys. Simultaneously, two independent human researchers conducted a literature search to compare the results. Subsequently, the AI was tasked to critically analyze the identified papers, highlighting strengths and weaknesses, thereby creating a decision-making algorithm and pyramid flow chart. RESULTS: The studies evaluated various biologics, including monoclonal antibodies targeting Interleukin-5 (IL-5), IL-4, IL-13, and Immunoglobulin E (IgE), assessing their effectiveness in different patient populations, such as those with comorbid asthma or refractory CRSwNP. Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, demonstrated significant improvement in nasal symptoms and quality of life in patients with CRSwNP in several randomized controlled trials and systematic reviews. Similarly, mepolizumab and reslizumab, which target IL-5, have also shown efficacy in reducing nasal polyp burden and improving symptoms in patients with CRSwNP, particularly those with comorbid asthma. However, additional studies are required to confirm the long-term efficacy and safety of these biologics in treating CRSwNP. CONCLUSIONS: Biologic therapies have surfaced as a promising treatment option for patients with severe or refractory CRSwNP; however, the optimal patient population, dosage, and treatment duration are yet to be defined. The application of AI in decision-making protocols and the creation of therapeutic algorithms for biologic drug selection, could offer fascinating future prospects in the management of CRSwNP.

Patterns of Olfactory Impairment Among Patients with Uncontrolled Chronic Rhinosinusitis.

OBJECTIVES: Self-reported olfactory dysfunction is an assessment component criterion for chronic rhinosinusitis (CRS) disease control of the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS). No studies have objectively explored olfactory function across different psychophysical olfactory domains among patients with uncontrolled CRS. We aimed to investigate the patterns of olfactory impairment in patients with uncontrolled CRS with Sniffin' Sticks test. METHODS: A total of 79 patients with CRS were prospectively recruited and assessed for disease control based on the EPOS criteria. Sniffin' Sticks test scores, olfactory cleft computed tomography (CT) scores, olfactory cleft endoscopy scale (OCES), questionnaire of olfactory disorders-negative statements (QOD-NS), and sinonasal outcome test-22 (SNOT-22) were obtained. Multiple logistic regression was applied to explore risk factors of uncontrolled CRS. RESULTS: Twenty-six percent of patients with CRS presented with uncontrolled status. The odor threshold (OT) (p = 0.005), odor identification (OI) (p = 0.041), and thresholds-discrimination-identification (TDI) (p = 0.029) scores were significantly lower in patients with uncontrolled CRS when compared with patients with controlled CRS. Furthermore, patients with uncontrolled CRS presented with a significantly increased percentage of anosmia (p = 0.014), olfactory cleft CT score (p = 0.038), OCES (p = 0.016), QOD-NS(p = 0.008), and SNOT-22 (p < 0.001) scores than patients with controlled CRS. After adjusting for patient demographics, as for the subdomain of olfaction, only the OT score was an independent risk factor for uncontrolled CRS (odds ratio = 0.604; p = 0.030). The OT scores less than 5.950 were the best predictor of uncontrolled CRS. CONCLUSION: Patients with uncontrolled CRS demonstrated distinct patterns of olfactory impairment, and a reduced olfactory threshold was highly associated with uncontrolled CRS. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2341-2348, 2024.

[Decision-making in the treatment of chronic rhinosinusitis with nasal polyps in the era of biologics]. / Entscheidungsfindung bei der Behandlung der chronischen Rhinosinusitis mit Nasenpolypen in der Ära der Biologika.

Chronic rhinosinusitis is one of the most common chronic diseases in the population. Chronic rhinosinusitis with nasal polyps (CRSwNP) in adults is predominantly characterized by a type 2 inflammatory endotype. If sufficient control cannot be achieved through primary drug therapy, surgical intervention is usually recommended as the next stage of treatment. Nowadays, various biologics are available that have been or will be approved for use in these patients. This review summarizes the presentations from the 29th Congress of the European Rhinologic Society in Sofia 2023 and the latest findings on decision-making in the treatment of CRSwNP. Standard therapy with medication and sinus surgery fails in some patients with CRSwNP. Biologics that act on the type 2 inflammatory pathway led to a reduction in the nasal polyp score (NPS), an improvement in nasal obstruction, and an improvement in quality of life without significant side effects. Biomarkers such as total IgE, serum eosinophils, and Osteoprotegerin (OPG) can provide indications of the success of the treatment. In summary, it can be said that for many patients with recurrent CRSwNP, a combination of paranasal sinus surgery and treatment with a biologic that is precisely tailored to the patient's endotype is the best option. However, the question of which surgical approach and which biologic at which time and for which patient is still ongoing and requires further studies.

Adherence to guidelines prior to endoscopic sinus surgery in patients with chronic rhinosinusitis and asthma.

INTRODUCTION: Optimal care for patients with simultaneous chronic rhinosinusitis (CRS) and asthma is often complicated due to interaction between these conditions. This study depicts the lack of attention to asthma within the otorhinolaryngological field, and the relationship between CRS and asthma, including the risk of revision surgery in such patients. METHODS: A retrospective cohort study was conducted on patients undergoing functional endoscopic sinus surgery (FESS) because of CRS with nasal polyps (CRSwNP) and without nasal polyps in a five-year period. Patients were examined for adherence to guidelines, asthma, revision FESS, allergies and septo-/turbinoplasty. Results were compared to international reports. RESULTS: A total of 589 patients had FESS because of CRS of whom 203 (34.5%) had co-existing asthma. A higher risk of asthma (relative risk (RR) = 1.82 (95% confidence interval (CI): 1.29-2.56), p less-than 0.001) and revision FESS (RR = 2.20 (95% CI: 1.33-3.65), p less-than 0.001) was found in patients with CRSwNP. Attention to asthma was poor in patients with no asthma diagnosis before referral. CONCLUSIONS: Asthma was lower in the study population than in the literature. Danish national guidelines on CRS management are insufficient regarding attention to asthma. Results call attention to the need for more multidisciplinary team management. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Utilizing Histopathology to Predict Success with Macrolide Therapy in CRS Patients.

There is currently interest regarding CRSsNP patients with refractory symptomatology following functional endoscopic sinus surgery, and which of these patients can derive benefit from low-dose macrolide therapy. In the present study, we analyze a cohort of over fifty CRSsNP patients on macrolide therapy; structured histopathological findings at the time of surgery were analyzed against the success of macrolide treatment. Independently, fibrosis, absence of squamous metaplasia, absence of eosinophilia, presence of neutrophilic infiltrate, and lymphoplasmocytic predominance were all associated with objective success of macrolide treatment; these findings may allow clinicians to more appropriately select patients for this therapy.

MicroRNA-125b Is a Potential Predictor of Surgical Outcomes in Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND: Despite advances in surgical techniques, recurrence rates after endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) remain high and difficult to predict. OBJECTIVE: This study aimed to evaluate the potential role of microRNA 125b (miR-125b) in predicting disease evolution following ESS. METHODS: We conducted a prospective study including patients undergoing first ESS for CRSwNP in our department between January 2020 and November 2021. We determined miR-125b levels from nasal polyps and pursued a standardized follow-up for at least 18 months for each patient. RESULTS: A total of 86 patients were included in the study. Higher postoperative endoscopy scores were associated with more severe disease at presentation on computed tomography scan, presence of concomitant asthma, and higher values of miR-125b. Even after multivariate repeated measures analysis and adjustments for confounders, miR-125b remained statistically significant. Moreover, miR-125 was the most important factor in predicting disease evolution at 18 months. CONCLUSION: A clear, robust relation between nasal polyp control evaluated through objective measures and miR-125b values was observed. This finding indicates the potential role of miR-125b in predicting the course of the disease following ESS.

Deep learning in computed tomography to predict endotype in chronic rhinosinusitis with nasal polyps.

BACKGROUND: As treatment strategies differ according to endotype, rhinologists must accurately determine the endotype in patients affected by chronic rhinosinusitis with nasal polyps (CRSwNP) for the appropriate management. In this study, we aim to construct a novel deep learning model using paranasal sinus computed tomography (CT) to predict the endotype in patients with CRSwNP. METHODS: We included patients diagnosed with CRSwNP between January 1, 2020, and April 31, 2023. The endotype of patients with CRSwNP in this study was classified as eosinophilic or non-eosinophilic. Sinus CT images (29,993 images) were retrospectively collected, including the axial, coronal, and sagittal planes, and randomly divided into training, validation, and testing sets. A residual network-18 was used to construct the deep learning model based on these images. Loss functions, accuracy functions, confusion matrices, and receiver operating characteristic curves were used to assess the predictive performance of the model. Gradient-weighted class activation mapping was performed to visualize and interpret the operating principles of the model. RESULTS: Among 251 included patients, 86 and 165 had eosinophilic or non-eosinophilic CRSwNP, respectively. The median (interquartile range) patient age was 49 years (37-58 years), and 153 (61.0%) were male. The deep learning model showed good discriminative performance in the training and validation sets, with areas under the curves of 0.993 and 0.966, respectively. To confirm the model generalizability, the receiver operating characteristic curve in the testing set showed good discriminative performance, with an area under the curve of 0.963. The Kappa scores of the confusion matrices in the training, validation, and testing sets were 0.985, 0.928, and 0.922, respectively. Finally, the constructed deep learning model was used to predict the endotype of all patients, resulting in an area under the curve of 0.962. CONCLUSIONS: The deep learning model developed in this study may provide a novel noninvasive method for rhinologists to evaluate endotypes in patients with CRSwNP and help develop precise treatment strategies.

Single-cell RNA sequencing reveals the epithelial cell, fibroblast, and key gene alterations in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the nasal mucosa, and epithelial-mesenchymal transition (EMT) is thought to be an essential process in the pathogenesis of CRSwNP. However, the mechanisms of epithelial and fibroblastic changes at the single-cell level are unclear. In this study, we investigated the epithelial cell, fibroblast, and key gene alterations in the development of CRSwNP. We revealed major cell types involved in CRSwNP and nasal mucosal inflammation formation, then mapped epithelial and fibroblast subpopulations. We showed that the apical and glandular epithelial cells and the ADGRB3+ and POSTN+ fibroblasts were the key cell subtypes in the progression of CRSwNP. Pseudotime and cell cycle analysis identified dynamic changes between epithelial cells and fibroblasts during its development. WFDC2 and CCL26 were identified as the key marker genes involved in the development of CRSwNP and were validated by IHC staining, which may provide a potential novel target for future CRSwNP therapy. ScRNA-seq data provided insights into the cellular landscape and the relationship between epithelial cells and fibroblasts in the progression of CRSwNP. WFDC2 and CCL26 were identified as the key genes involved in the development of CRSwNP and may be the potential markers for gene therapy.

Adverse events associated with budesonide nasal irrigation reported to the US Food and Drug Administration: 2007 to 2022.

KEYPOINTS: Between 2007 and 2022, the FDA received 119 US-based reports mentioning budesonide nasal irrigation. Most reports were submitted by patients and alerted FDA to off-label usage of budesonide. Notable adverse events reported to the FDA included headache, dyspnea, and blurred vision.

Chronic rhinosinusitis with nasal polyps (CRSwNP) treated with omalizumab, dupilumab, or mepolizumab: A systematic review of the current knowledge towards an attempt to compare agents' efficacy.

BACKGROUND: The heterogeneity of existing studies, along with the fact that there are no published head-to-head trials, are the main reasons for the lack of guidelines regarding the selection of the proper biologic in treatment of chronic rhinosinusitis (CRS) with nasal polyps. The aim of this study is to summarize the current knowledge regarding the efficacy of omalizumab, dupilumab, and mepolizumab in CRS treatment. We also attempt to proceed to an indirect comparison of the agents and try to answer the tricky question: which agent to select and why? METHODS: An extensive search in English literature was conducted in PubMed/Medline, Embase, Google Scholar, and Cochrane Database/Library. Eligibility criteria included papers with full text published in English, adult population studies, clearly described intervention protocol, and documented primary and secondary outcomes. RESULTS: The studies included numbered 37. All agents provided significant improvement in polyp size, sinuses opacification, severity of symptoms, need for surgery and systemic corticosteroids use. Analysis of available systematic reviews, meta-analyses and indirect treatment comparison studies showed that dupilumab appeared to be the most beneficial agent, in terms of primary and secondary outcomes. However, these results are of relatively low level of evidence due to several methodological limitations. CONCLUSIONS: Although the present analysis showed a moderate supremacy of dupilumab, there is still no evidence-based answer to the question "which biologic agent is the most effective in CRS treatment?" Improved statistical methodology, head-to-head trials, and real-life studies could lead to more robust conclusions, establishing the real role of the specific biologic agents.

Eosinophil Peroxidase: A Biomarker for Eosinophilic Chronic Rhinosinusitis Agnostic of Polyp Status.

OBJECTIVE: To evaluate eosinophil peroxidase (EPX) as a biomarker for tissue levels of eosinophilia, cytokines, and chemokines within chronic rhinosinusitis (CRS). METHODS: Twenty-eight subjects undergoing sinonasal surgery were prospectively enrolled. Ethmoid tissue was analyzed with an in-house EPX immunoassay and a 48-plex cytokine-chemokine array. Clinical severity was assessed using SNOT-22 and Lund-Mackay scores. Subjects were grouped as follows: controls, polyp status (CRS with [CRSwNP] and without nasal polyps [CRSsNP]), tissue eosinophilia (eosinophilic CRS [eCRS], non-eosinophilic CRS [neCRS]), or combinations thereof (eCRSwNP, eCRSsNP, neCRSsNP). eCRS was defined as >10 eosinophils per high power field (HPF). Subjects without CRS or asthma were enrolled as controls. RESULTS: EPX was elevated in CRSwNP compared to control (p = 0.007), in eCRS compared to neCRS (p = 0.002), and in eCRSwNP along with eCRSsNP compared to neCRSsNP (p = 0.023, p = 0.015, respectively). eCRS displayed elevated IL-5 compared to neCRS (p = 0.005). No significant differences in EPX or IL-5 were observed between eCRSwNP and eCRSsNP. IL-5 was elevated in eCRSwNP (p = 0.019) compared neCRSsNP. Area under the receiver operator characteristic curve was 0.938 (95% CI, 0.835-1.00) for EPX and tissue eosinophilia, with an optimal cut-point of 470 ng/mL being 100% specific and 81.25% sensitive for tissue eosinophilia. Linear regression revealed a strong correlation between EPX and IL-5 (R2 = 0.64, p < 0.001). Comparing EPX and IL-5, only EPX displayed significant correlation with SNOT-22 (p = 0.04) and Lund-Mackay score (p = 0.004). CONCLUSION: EPX is associated with tissue eosinophilia in CRS patients regardless of polyp status. EPX correlates with IL-5 and could be potentially considered a biomarker for anti-IL-5 therapies. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:69-78, 2024.

Omalizumab improves sinonasal outcomes in patients with chronic rhinosinusitis with nasal polyps regardless of allergic status.

BACKGROUND: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have atopic comorbidities, including elevated IgE levels and comorbid asthma. Omalizumab, an IgE monoclonal antibody, is an effective treatment for CRSwNP, but the impact of allergy or asthma status on response to omalizumab in patients with CRSwNP has not been well studied. OBJECTIVE: To evaluate the impact of allergy and asthma status on omalizumab treatment in patients with CRSwNP, this posthoc exploratory analysis assessed sinonasal outcomes from subgroups of patients included in POLYP 1 and POLYP 2 and the open-label extension (OLE) trials. METHODS: Patients (N = 249) were grouped by the presence/absence of comorbid allergy (≥ 1 physician-reported allergic rhinitis, allergic sinusitis, food allergy, or atopic dermatitis), presence/absence of comorbid asthma, baseline serum total IgE (≥ 150 or <150 IU/mL), and baseline blood eosinophil levels (>300 or ≤ 300 cells/µL). Sinonasal outcomes were the nasal polyps score, nasal congestion score, and sino-nasal outcome test-22. RESULTS: During POLYP 1 and POLYP 2 and the OLE, omalizumab treatment improved the nasal polyps score, nasal congestion score, and sino-nasal outcome test-22 score in patients with/without physician-reported allergic comorbidities, with/without asthma, with higher/lower total IgE levels, and with higher/lower blood eosinophil counts. In the OLE, the pattern of improvement was similar in patients who continued or switched to omalizumab. CONCLUSION: In patients with CRSwNP, omalizumab improved sinonasal outcomes independent of allergic status, which suggests that a wide range of patients with different endotypes and phenotypes of CRSwNP may benefit from omalizumab treatment. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03280550, NCT03280537, NCT03478930.

The influence of inhibitors of apoptosis proteins (IAPs) on chronic rhinosinusitis with nasal polyps.

BACKGROUND: Inhibitors of apoptosis proteins (IAPs) modulate the inflammatory process, and may facilitate the formation of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to observe if IAPs were differently expressed between patients with CRSwNP and controls, and to correlate the expression of IAPs with some inflammatory markers, as with the response to nasal corticosteroids in patients with CRSwNP. METHODOLOGY: We obtained nasal biopsies from patients with CRSwNP (n=27) and controls (n=16). qRT-PCR measured the expression of IAPs and caspases, while Luminex assay measured the concentration of cytokines. Unpaired parametric tests and Principal Component Analysis (PCA) were used for statistical analysis. RESULTS: We observed lower expression of IAP genes (XIAP, BIRC2/IAP1, and BIRC3/IAP2) in CRSwNP patients compared to controls, and we identified that patients with bad response to corticosteroids presented lower levels of BIRC2/IAP1, XIAP, BCL2, CASP9, and IL-17, and higher levels of CASP7 and TGF-B. CONCLUSIONS: IAPs expression was downregulated in CRSwNP, and was associated with poorer response to nasal corticosteroids. The present findings suggest the importance of IAPs as a link between environment and the host inflammatory responses, and this pathway could be explored as a potential new target therapy for patients with CRSwNP.

Effectiveness of dupilumab versus endoscopic sinus surgery for the treatment of type-2 chronic rhinosinusitis with nasal polyps: a preliminary report.

PURPOSE: Historically managed with intranasal corticosteroids (INCS) and endoscopic sinus surgery (ESS), type-2 Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) treatment was revolutionized by the introduction of dupilumab but universally accepted guidelines are still lacking. METHODS: Patients treated at our University Hospital for type-2 CRSwNP were enrolled. Demographic data were collected, as well as laboratory (eosinophils, total IgE), endoscopic [nasal polyps score (NPS), modified Lund-Kennedy score (mLKS)], radiological [Lund-Mackay score (LMS) at CT scan], SNOT-22, and olfactory [Sniffin' Sticks identification test (SSIT)] features. Patients were treated with dupilumab or ESS and re-evaluated after 3 and 12 months. RESULTS: At 3 and 12 months, patients undergoing ESS achieved a higher reduction of NPS and mLKS, while patients receiving dupilumab experienced a higher improvement at SNOT-22 and SSIT with a greater positive variation in the prevalence of anosmia (- 57.7% vs - 42.9%) and normosmia (+ 37.8 vs + 28.5%). Mean mLKS and LMS were quite similar. Results were independent of clinical features known to contribute to CRSwNP severity, except for patients with ≥ 2 prior ESS who had a significantly lower smell improvement. CONCLUSION: ESS and dupilumab were effective at reducing CRSwNP inflammatory burning. CRSwNP smell impairment cannot be attributed only to olfactory cleft obstruction and other mechanisms may be involved. Dupilumab acts systemically with poor correlation with NPS. As of today, dupilumab appears to be more suitable for elderly patients with anesthesiological contraindications and/or several previous surgeries, while ESS may represent the first-line choice in surgery-naive patients.