Association Between T2-related Comorbidities and Effectiveness of Biologics in Severe Asthma.

Rationale: Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents. Objectives: To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA). Methods: This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV1% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis. Measurements and Main Results: Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%; P < 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%; P < 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV1% predicted improvement of 3.2% (95% CI, 1.0-5.3; P = 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed. Conclusions: These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.

Staphylococcus aureus lysate induces an IgE response via memory B cells in nasal polyps.

BACKGROUND: Locally increased IgE levels plays a pathologic role in chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: This study aimed to investigate whether Staphylococcus aureus could induce aberrant IgE synthesis in CRSwNP and the potential mechanisms involved. METHODS: Total IgE, IL-4, IL-5, and IL-13 concentrations in the supernatants of the cultures stimulated with S aureus lysate were assessed by ELISA. S aureus-induced cellular responses were investigated by single-cell RNA sequencing. Flow cytometry and quantitative reverse transcription PCR were used to analyze B-cell subsets and stimulated cell ε-germline transcript expression, respectively. IgE-positive B-cell and germinal center localization were assessed by immunohistochemistry and immunofluorescence. RESULTS: S aureus lysate induced IgE production in the supernatants of nasal polyp (NP) tissues but not in those of healthy nasal mucosa. Moreover, IgE levels increased from days 2 to 4 after stimulation, paralleling the enhanced ε-germline transcript, IL-5, and IL-13 expression. Single-cell RNA sequencing revealed that there were increased IL-5 and IL-13 in group 2 innate lymphoid cells and identified a clonal overlap between unstimulated memory B cells and S aureus-stimulated plasma cells. The enriched IgE within NPs was mainly produced by IgE-negative memory B cells. Cellular evidence indicated that the IgE memory response to S aureus might also exist in the peripheral blood of CRSwNP patients. The S aureus-induced IgE memory response was associated with elevated IgE levels in NPs, asthma, and postoperative CRSwNP recurrence. CONCLUSIONS: S aureus induced an IgE response via IgE-negative memory B cells in CRSwNP patients, possibly contributing to CRSwNP development.

Sleep quality burden in chronic rhinosinusitis with nasal polyps and its modulation by dupilumab.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with a substantial burden on patients' quality of life and impaired sleep quality. The most common CRSwNP endotype is characterized by type 2 inflammation, with enhanced production of interleukin (IL)-4, IL-5, and IL-13. Dupilumab is a monoclonal antibody against IL-4 receptor-α, which inhibits both IL-4 and IL-13 signaling, and was recently approved for treatment of CRSwNP. OBJECTIVE: We investigated the effect of dupilumab on the sleep quality of patients with CRSwNP in a real-life setting. METHODS: Patients were evaluated at baseline and after 1 and 3 months of dupilumab treatment by means of the Epworth sleepiness scale (ESS), insomnia severity index (ISI), Pittsburgh sleep quality index (PSQI), and sinonasal outcome test 22 (SNOT-22) sleep domain. RESULTS: A total of 29 consecutive patients were enrolled, and their baseline sleep quality assessment were as follows: ESS of 7.9 (± 4.5); ISI of 13.1 (± 6.2); PSQI of 9.2 (± 3.7); and SNOT-22 sleep domain of 12.1 (± 4.2). Excessive daily sleepiness, insomnia, and globally impaired sleep quality were present in 24.1%, 79.3%, and 93.1% respectively. Treatment with dupilumab was associated with significant improvement in ESS, ISI, PSQI, and SNOT-22 sleep domain with concomitant reduction of the proportion of patients with insomnia and globally impaired sleep quality. CONCLUSION: CRSwNP was associated with a significant impact on global sleep quality, in particular, insomnia, and treatment with dupilumab induced a rapid improvement (after 1 single month of treatment) in all the sleep quality parameters, suggesting that sleep disturbances should be more carefully evaluated as an additional outcome in these patients.

Remission in Type 2 Inflammatory Diseases: Current Evidence, Unmet Needs, and Suggestions for Defining Remission in Chronic Rhinosinusitis with Nasal Polyps.

PURPOSE OF REVIEW: The development of biological therapies for type 2 inflammatory diseases raises the possibility of addressing remission in those dis-immune conditions. No consensus exists for a definition of remission in chronic rhinosinusitis with nasal polyps (CRSwNP). This review aims to critically evaluate the published data to provide the basis for defining remission in CRSwNP. RECENT FINDINGS: The published evidence has yet to provide an unequivocal definition on remission in type 2 inflammatory diseases, in part reflecting differences in approaches to diagnosis and follow-up. A multidimensional evaluation is necessary when considering complete remission, including clinical, inflammatory, and histologic criteria, but how to combine or tailor the three perspectives according to disease severity at baseline or timing of assessment of treatment category is yet to reach consensus. We suggest defining remission starting from the approach taken in asthma and eosinophilic esophagitis, that is, including the resolution of symptoms and improvements in objective parameters of disease severity and/or inflammatory activity. Future studies and consensuses should provide validated criteria with cutoffs for the day-to-day definition of remission. The definition of remission in CRSwNP should include the following criteria, to be verified and maintained for a period of ≥ 12 months: absence of symptoms (nasal obstruction, loss of smell, rhinorrhea as the main ones); no impact of symptoms on quality of life; no need of surgery; no chronic or rescue medications (systemic corticosteroids or antibiotics); and recovery of smell function, possibly evaluated by objective test. Assessment of underlying inflammation should also be considered once accurate and feasible biomarkers are available in clinical practice.

Breathing pattern disorder in chronic rhinosinusitis with severe asthma: nasal obstruction and polyps do not increase prevalence.

OBJECTIVES: Chronic rhinosinusitis (CRS) with severe asthma are associated with breathing pattern disorder (BPD). Mouth breathing is a sign of breathing pattern disorder, and nose breathing a fundamental part of breathing pattern retraining for BPD. The prevalence of BPD in relation to CRS subtypes and the relationship of nasal obstruction to BPD in CRS and associated severe asthma is unknown. The breathing pattern assessment tool (BPAT) can identify BPD. Our objective was to thus investigate the prevalence of BPD, nasal airflow obstruction and measures of airway disease severity in CRS with (CRSwNP) and without nasal polyps (CRSsNP) in severe asthma. METHODS: We determined whether CRS status, peak nasal inspiratory flow (PNIF) or polyp disease increased BPD prevalence. Demographic factors, measures of airway function and breathlessness in relation to BPD status and CRS subtypes were also evaluated. RESULTS: 130 Patients were evaluated (n = 69 had BPD). The prevalence of BPD in CRS with severe asthma was 53.1%. There was no difference between BPD occurrence between CRSwNP and CRSsNP. The mean polyp grade and PNIF were not statistically different between the BPD and non-BPD group. The presence of nasal polyps did not increase breathlessness. CONCLUSIONS: BPD and CRS are commonly co-associated. CRS status and nasal obstruction per se does not increase BPD prevalence.

Doxycycline may be more clinically effective in type 2 chronic rhinosinusitis nasal polyp comorbid with asthma.

OBJECTIVE: Chronic rhinosinusitis with nasal polyp (CRSwNP) is one of the major phenotypes of chronic rhinosinusitis (CRS) with a high symptom burden. Doxycycline can be used as add-on therapy in CRSwNP. We aimed to evaluate short-term efficacy of oral doxycycline on visual analog scale (VAS) and SNOT-22 (Sino-nasal outcome test) score for CRSwNP. METHODS: Visual analog score (VAS) for nasal symptoms and total SNOT-22 scores of 28 patients who applied with the diagnosis of CRSwNP and received 100 mg doxycycline for 21 days were analyzed in this retrospective cohort study. Doxycycline efficacy was also evaluated in subgroups determined according to asthma, presence of atopy, total IgE and eosinophil levels. RESULTS: After 21-day doxycycline treatment, there was a significant improvement in VAS score for post-nasal drip, nasal discharge, nasal congestion, and sneeze, and total SNOT-22 score (p = 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). No significant improvement was observed in VAS score for the loss of smell (p = 0.18). In the asthmatic subgroup, there were significant improvements in all VAS scores and total SNOT-22 score after doxycycline. In the non-asthmatic subgroup, there was no significant change in any of the VAS scores, but total SNOT-22 score was significantly improved (42 [21-78] vs. 18 [9-33]; p = 0.043). Improvement in VAS score for loss of smell is significant in only some subgroups like asthmatic patients, non-atopic patients, and patients with eosinophil >300 cell/µL. CONCLUSIONS: Doxycycline can be considered as an add-on treatment for symptom control in patients especially with CRSwNP comorbid with asthma.

Chronic invasive fungal rhinosinusitis and granulomatous invasive fungal sinusitis: A systematic review of symptomatology and outcomes.

INTRODUCTION: Chronic invasive fungal rhinosinusitis (CIFRS) and granulomatous invasive fungal sinusitis are two uncommon diseases differentiated primarily by the pathologic finding of non-caseating granulomas in GIFRS. Both share many similarities in presentation. We aim to characterize the symptomatology and outcomes of these diseases. METHODS: A comprehensive search strategy was designed to identify studies in the Cochrane, EMBASE and PubMed databases from database inception to January 2022. Inclusion criteria included all patients with a diagnosis of either CIFRS or GIFRS. All studies were screened by two reviewers. Chi-square analyses were used where appropriate. RESULTS: 51 studies were included totaling 513 patients. The majority were diagnosed with CIFRS (389, 75.8 %) compared to GIFRS (124, 24.4 %). CIFRS was more common in immunocompromised or diabetic patients (p < 0.0001; p = 0.02). Patients with CIFRS were more likely to exhibit nasal symptoms including discharge (p = 0.0001), obstruction (p = 0.03) and congestion (p = 0.001) as well as systemic symptoms including fever, which no GIFRS patient exhibited, facial pain (p = 0.007), headache (p = 0.004). Aspergillus was the most common organism identified in both groups with a slight predominance among GIFRS patients (p = 0.01). GIFRS patients were also more likely to present with no identifiable organisms (p = 0.0006). CIFRS patients were more likely to die of disease (p = 0.0008). CONCLUSIONS: CIFRS generally presents with more symptoms and is associated with poorer outcomes primarily occurring in an immunocompromised population. GIFRS likely follows a more insidious course in immunocompetent patients. Understanding the key differences in symptomatology and outcomes for these two populations is critical for appropriate diagnosis and prognostication.

Dupilumab in chronic rhinosinusitis with nasal polyps: Real life data in a multicentric Sicilian experience.

OBJECTIVE: This study aimed to evaluate the effectiveness and safety of dupilumab during the first year of treatment in a real-life setting, focusing on improvement in nasal polyp score (NPS) as well as specific symptoms, quality of life and olfactory function. METHODOLOGY/PRINCIPAL: A multicentric observational cohort study was carried out. A total of 170 patients were enrolled in the Otorhinolaryngology Unit of the three University Hospitals and considered for dupilumab therapy. All recorder characteristics were age (at the first dupilumab application visit), sex, smoke habits, previous local and systemic corticosteroid therapy, history of endoscopic sinus surgery, number of previous endoscopic sinus surgery, concomitant asthma, history of an allergic condition, immunoglobulin E (IgE), allergy to nonsteroidal anti-inflammatory drugs (NSAIDs), Aspirin Exacerbated Respiratory Disease (AERD), other comorbidities associated, blood eosinophils, nasal polyp score, sinonasal outcome test 22 (SNOT 22), sniffin' stick test, the start date of dupilumab therapy and number of doses of dupilumab and eventually, Dupilumab's adverse events related to administration. The Wilcoxon test for dependent samples was performed to compare variables. Statistical significance was assumed for p values < 0.05. RESULTS: A statistically significant reduction in SNOT-22 and NPS was shown at the 6th and 12th month compared to baseline values (p < 0.001 for both comparisons). A statistically significant increase value at the Sniffin' sticks test was shown in the 6th and 12th month compared to baseline values (p < 0.001 for both comparisons). At the 12-month follow-up, according to EUFOREA indications, all patients were considered to remain in treatment with dupilumab and continued the treatment because of a reduced NPS, improved quality of life and a reduced need for system corticosteroids. Dupilumab seemed to be well tolerated by all patients. Any adverse effect of the drug led to the quit of biological treatment. CONCLUSIONS: This multi-centric real-life study supported the effectiveness of dupilumab as an add-on therapy to intranasal corticosteroids in patients with severe uncontrolled CRSwNP in improvement of quality of life, severity of symptoms, polyp size reduction and smell function. Furthermore, our data support the safety profile of monoclonal therapy with dupilumab.

Dupilumab improves sleep quality in chronic rhinosinusitis with nasal polyps.

PURPOSE: Chronic rhinosinusitis with nasal polyps (CRSwNP) often alters sleep quality. Dupilumab emerged as an innovative and effective therapy for refractory/recurrent severe CRSwNP. The aim of this observational retrospective study was to evaluate the sleep quality in patients with CRSwNP who underwent treatment with dupilumab. MATERIALS AND METHODS: Forty-five patients treated with dupilumab for CRSwNP were enrolled. Clinical parameters (age, sex, comorbidities, Nasal Polyp Score - NPS, Asthma Control Test - ACT), nasal cytology, quality of life (Sino Nasal Outcome Test 22 - SNOT-22), sleep quality (Pittsburgh Sleep Quality Index - PSQI, Epworth Sleepiness Scale - ESS), and risk of sleep apnea (STOP-BANG) were recorded before treatment (T0), and after 3 (T1), 6 (T2), and 12 months (T3). RESULTS: NPS, ACT and SNOT-22 total score improved during treatment (p < 0.05). Meanwhile, all sleep parameters evaluated with SNOT-22, ESS and PSQI improved over time (p < 0.001), expect for PSQI Use of sleeping medications. Indeed, sleep drugs are rarely used before and during the treatment. The global sleep quality was classified as poor in 88.9 % of cases at T0 and decreased to 5.7 % at T3. A high risk of sleep apnea was revealed by the STOP-BANG in 68.9 % of cases at T0 and 2.8 % of patient at T3 (p < 0.001). CONCLUSIONS: Dupilumab improves the sleep quality and reduce the risk of sleep apnea in patients with severe CRSwNP. Its favorable effect occurs within 3 months and is maintained during the treatment.

Effectiveness and safety profile of mepolizumab in chronic rhinosinusitis with nasal polyps: Real life data in a tertiary care.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a type 2 pattern of inflammation. Mepolizumab was approved for the treatment of CRSwNP in 2021, it may be useful to evaluate its safety profile in a real-world setting. AIM: This work aimed to prospectively highlight the effectiveness and safety profile of Mepolizumab in patients with CRSwNP enrolled in the Otorhinolaryngology Unit of the University Hospital of Messina. METHODS: An observational cohort study was carried out considering all patients treated with Mepolizumab. A descriptive analysis was conducted reporting all demographic characteristics, endoscopic evaluations, and symptom conditions. RESULTS: A total of 30 patients were treated with Mepolizumab, one patient discontinued the treatment. A statistically significant reduction in the Sino-Nasal Outcome Tests-22 (SNOT-22) and nasal polyp score (NPS) was shown at the 6th and 12th months compared to baseline values (SNOT-22, -33 and - 43, p < 0.001 for both comparisons; NPS, 0 and - 1, p < 0.001 for both comparisons). The median (Q1-Q3) sniffin' sticks test score increased from 7 (6-8) at the 6th month to 11 (10-13) at the 12th month. Seven patients (24.1 %) reported pain at the injection site, accompanied by redness, warmth, and tenderness within the first 24 h post-injection with a median duration of three days from the onset. CONCLUSIONS: Given the optimal treatment response and the minimal adverse effects observed, clinicians should consider Mepolizumab a safe and effective treatment in CRSwNP patients. Further studies in real-life setting are necessary to better understand the long-term effects.

A novel technique with butterfly splint for middle turbinate stabilization in sinus surgery.

OBJECTIVE: To assess the efficacy of newly designed butterfly splint with special technique for middle turbinate stabilization in preventing adhesion following bilateral endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP). STUDY DESIGN: Prospective, double-blind, randomized controlled. SETTING: University hospitals. METHODS: Following ESS, in cases of traumatized and/or unstable middle turbinates, newly designed butterfly plastic splint was randomly inserted in the middle meatus of one nasal side, while no splint was inserted in the other (control). Patients were followed up on after 1 week, 1 month, and 6 months. Endoscopic examination and a visual analog scale were used to evaluate each side of the nasal cavity for adhesion, crusting, pus, pain, nasal obstruction, and nasal discharge. RESULTS: Thirty patients (60 nasal sides) were included. For all investigated parameters, there was no significant difference between the splinted and non-splinted sides at the first week visit. Adhesion was found significantly less in the splinted sides (3%) than the non-splinted sides (27%) after 1 month (P = 0.038). The adhesion rate in the splinted sides remained 3% at the 3 month follow-up visit, however, in the non-splinted sides, the rate increased up to 30% (P = 0.007). Throughout the follow-up visits, all other investigated parameters remained statistically insignificant between both sides. CONCLUSIONS: The newly designed butterfly plastic splints to avoid middle turbinate adhesion is safe and effective in both reducing middle meatal adhesion with low complication rate in CRSwNP patients undergoing ESS and middle turbinate stabilization in its intermediate position.

Management of patients with chronic rhinosinusitis with nasal polyps in Spain: learnings from a nationwide survey of otorhinolaryngologists.

PURPOSE: To describe the self-reported practices on the diagnosis, treatment, and follow-up of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) by ear, nose, and throat (ENT) specialists in Spain to identify potential areas for management optimization. METHODS: A cross-sectional online survey with 16 questions was carried out. Recruitment was performed by emailing registered ENT specialists in the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC). RESULTS: In total, 127 ENT specialists completed the survey. Fifty-one percent of respondents combined clinical criteria and objective evidence of mucosal inflammation to diagnose CRSwNP. Patient interview and, to a lower degree, a visual analogue scale were the most employed diagnostic tools to quantify symptom severity. Less than half (45%) routinely used the 22-item sino-nasal outcomes test (SNOT-22) to assess the impact of CRSwNP disease in quality of life. The use of patient-reported outcomes and other clinical evaluation tools showed a larger uptake among ENT specialists that worked at an ENT department with an available rhinology unit. Almost all the specialists surveyed (95%) recommended biological treatment, particularly in patients with uncontrolled CRSwNP with respiratory comorbidities (76%), as well as in candidates for revision surgery (66%). CONCLUSION: Spanish otorhinolaryngologists showed a trend toward incorporating CRSwNP guideline recommendations in their clinical practice. The observed low uptake of patient-reported outcomes and objective clinical evaluation tools in routine clinical practise have been identified as areas for optimizing the management of patients with CRSwNP.

Effectiveness and rapidity on olfatory fuction recovery in CRS patients treated with Dupilumab: a real life prospective controlled study.

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

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.

Systemic inflammation response index predicts the postoperative recurrence of chronic rhinosinusitis with nasal polyps: a retrospective study in the Chinese population.

PURPOSE: Endoscopic sinus surgery (ESS) is now frequently used to treat chronic sinusitis with nasal polyps (CRSwNP), but postoperative recurrence plagues many patients. We aimed to assess the value of the systemic inflammation response index (SIRI) and the systemic immune-inflammatory index (SII) for the prediction of postoperative recurrence in patients with CRSwNP. METHODS: A total of 143 patients with CRSwNP and 76 age- and sex-matched healthy subjects were enrolled. Patients were divided into the recurrence group and the non-recurrence group according to the recurrence of CRSwNP. Univariate and multivariate analyses showed independent risk factors for the recurrence. A receiver operating characteristic curve analysis was conducted to assess the predictive accuracy of the variables and determine the optimal cut-off values. Finally, a survival analysis was conducted. RESULTS: Univariate analysis revealed that age, sex, CRP, EOS, SIRI, SII, NLR, ELR, and Lund-Mackay CT scores were significant predictors of the recurrence of CRSwNP. Multivariate analysis confirmed that SIRI (OR = 1.310, p < 0.001) and Lund-Mackay CT scores (OR = 1.396, p < 0.001) were independent predictors. SIRI (AUC = 0.761, 95% CI: 0.685-0.836) had a certain value in predicting the recurrence of CRSwNP. CONCLUSION: SIRI is a potential predictive marker of the postoperative recurrence of CRSwNP.

Postinfectious conditions challenge disease-specificity of SNOT-22.

PURPOSE: The Sino-Nasal-Outcome-Test 22 (SNOT-22) questionnaire assesses treatment outcome and health-related quality of life (HRQOL) in patients with chronic rhinosinusitis (CRS). However, given the overlap between CRS and olfaction in terms of nasal function and the definition of CRS, a fundamental question arises: can patients with olfactory dysfunction (OD) stemming from other causes attain SNOT-22 scores similar to those seen in CRS, even in the absence of CRS? Our study aimed to explore whether OD arising from various postinfectious mechanisms challenges the disease-specificity of SNOT-22 for CRS. If so, could focus on scores within specific symptom domains of SNOT-22 prove valuable in distinguishing between different etiologies. METHODS: The study adopted an observational, retrospective cohort design based on prospectively registered patients and related variables using the REDCap platform. 460 patients experiencing OD due to either (1) simple or (2) complex post-COVID-19, (3) postinfectious non-COVID-19, and (4) CRS, were included in the analysis. RESULTS: The study revealed that the total SNOT-22 score lacks disease-specificity for CRS. This is evident, because complex postinfectious mechanisms resulting from COVID-19 can produce similar symptoms in patients. Notably, elevated total scores were primarily driven by high subdomain scores within the "sleep and cognition" domain. CONCLUSIONS: The application of SNOT-22 as a screening tool needs to be approached with caution, as the total score alone does not provide disease-specific insights. A more thorough exploration of the four symptom domains and the identification of distinctive scoring patterns within the clinical context may prove pivotal in effectively differentiating between various underlying causes.

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.

Switching of biological therapy to dupilumab in comorbid patients with severe asthma and CRSwNP.

PURPOSE: Nowadays, several efficacious biologic drugs are used for severe asthma with or without chronic rhinosinusitis with nasal polyps (CRSwNP). However, it has been observed that not all comorbid patients (asthma/CRSwNP) receiving biologic treatment for asthma experience satisfactory control of both conditions equally. METHODS: We selected 20 patients who had both severe asthma and comorbid CRSwNP under biological treatment with benralizumab, omalizumab or mepolizumab with adequate control of asthma but inadequate control of nasal symptoms. Patients were switched to dupilumab and outcomes were evaluated at baseline (T0), at 3 months (T1), at 6 months (T2), at 12 months (T3) and finally at 18 months (T4). Data were collected at each time point including blood tests measuring eosinophil levels and total IgE, SNOT22, ACT, NPS score, rhinomanometry, olfactory testing, and nasal cytology. RESULTS: The results showed an overall improvement in all the outcomes. Peripheral eosinophilia was observed consistently with existing literature. All patients registered an improvement in sinonasal outcomes, while only one patient had a worsening of asthma. Three patients interrupted the therapy due to various causes: poor asthma control, onset of psoriasis and thrombocytopenia. CONCLUSIONS: The response to a biologic treatment for CRSwNP control may be heterogenous and it seems that patients may benefit from switching improving control in equal measure in the upper and lower airway. Further studies to explore the endotype/phenotype which best fits with each biologic are mandatory to personalize the therapy.

Sleep and psychological disorders seriously affect the quality of life of chronic rhinosinusitis patients.

PURPOSE: Chronic rhinosinusitis (CRS) is a common disease that affects patients' quality of life (QoL). We aim to explore which symptoms bothered the patient most. METHODS: This is a cross-sectional study of CRS patients 2 years after endoscopic sinus surgery (ESS). The main observation indicators were SNOT-22 and visual analog scale (VAS) scores. The patients were grouped according to clinical control standard of EPOS 2020. Patients' symptom scores and postoperative medication were used for analysis. RESULTS: A total of 276 patients were included, among them, uncontrolled patients accounted for 23.9%, sense of taste/smell, fatigue, lacking of a good night's sleep, reduced concentration and reduced productivity were the most serious symptoms that troubled them. VAS and SNOT-22 scores were significantly different among all groups (P = 0.000), and had clinical significance for the diagnosis of clinical uncontrolled patients (both P < 0.0001). Furthermore, the duration of corticosteroids use and nasal saline irrigation in uncontrolled patients was significantly longer than that in other patients (P < 0.05). CONCLUSION: There are significant differences in the QoL of CRS patients with different clinical control, sleep and psychological disorders are main symptoms that affect the QoL of CRS patients, and more targeted management of sleep/psychological issues may be needed especially for uncontrolled patients.

Aberrant expressions of TAM receptors are associated with postoperative recurrence in chronic rhinosinusitis with nasal polyps.

OBJECTIVES: TAM receptors (TYRO3, AXL, and MER) play important roles in inflammatory responses, but their effects in chronic rhinosinusitis with nasal polyps (CRSwNP) remain elucidated. We aim to evaluate the values of TAM receptors in disease severity and postoperative recurrence of CRSwNP. METHODS: We initially enrolled 160 patients with CRSwNP who were treated with functional endoscopic sinus surgery (FESS) and postoperative recurrence was evaluated during the follow-up period. Circulating TAM receptor levels were detected by enzyme-linked immunosorbent assay (ELISA), and tissue expressions were measured by real-time polymerase chain reaction (RT-PCR) and immunohistochemical (IHC). The relationships between TAM receptor levels and postoperative recurrence were examined. RESULTS: A total of 150 patients completed the follow-up schedule, 49 patients experienced postoperative recurrence and the remaining 101 patients were non-recurrent. In recurrent CRSwNP patients, serum levels of TAM receptors were increased compared to those in non-recurrent patients and were positively correlated with disease severity scores (P < 0.05). Circulating TYRO3 and MER were identified as potential predictors of postoperative recurrence based on receiver operating characteristics (ROC) and Kaplan-Meier plots (P < 0.05). Furthermore, tissue TAM receptor levels, as determined by both RT-PCR and IHC, were enhanced in the recurrent group than in the non-recurrent group (P < 0.05) and were predictive of postoperative recurrence (P < 0.05). Interestingly, circulating TYRO3 and MER concentrations, as well as tissue TYRO3 expression, were found to be significantly increased in patients who experienced postoperative recurrence (P < 0.05). IHC images from the same patients revealed that TAM expressions were enhanced in the recurrent tissues compared to their baseline tissue levels. CONCLUSIONS: Our laboratory results demonstrated that TAM receptors were increased in recurrent CRSwNP patients and associated with postoperative recurrence. Moreover, the new laboratory findings suggested that measuring circulating levels of TAM receptors might serve as a promising new approach to assess disease progression and predict the risk of postoperative recurrence.