Impact of elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy on rates of endoscopic sinus surgery in cystic fibrosis.

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI), a combination cystic fibrosis transmembrane receptor (CFTR) modulator, has demonstrated improved pulmonary outcomes in individuals with cystic fibrosis (CF). However, ETI's impact on functional endoscopic sinus surgery (FESS) remains unclear. METHODS: The TriNetX Analytics Research Network, consisting of 120 million global de-identified electronic medical records, was queried from 2012 to 2023 for subjects with CF who underwent sinus surgery.1 Patients on ETI prior to FESS (n = 6,056) were propensity score matched to control individuals with CF not on CFTR modulators (n = 37,906) and those on other FDA-approved CFTR modulators (tezacaftor/ivacaftor, lumacaftor/ivacaftor, and ivacaftor) (n = 2437) based on relevant factors. The primary outcome was the absolute risk reduction (ARR) of undergoing FESS. Secondary outcomes included ARR of CF-related pulmonary exacerbations and hospital admission from 0 to 6, 6 to 12, and 12 to 24 months following FESS. RESULTS: ETI use demonstrated a significant ARR for FESS when compared to CF patients not on CFTR modulators (2.12%; 95% confidence interval [CI] 1.5-2.75; p-value < 0.0001) and those on other CFTR modulators (4.7%; 95% CI 3.54-5.85; p-value < 0.0001). No significant differences occurred in secondary outcomes between ETI and non-CFTR modulator groups, except for reduced CF-related pulmonary exacerbations from 0 to 6 months post-FESS. Additionally, a significant reduction in pulmonary exacerbations was observed at all time points and hospital admissions within 6 months following FESS compared to those using other CFTR modulators. CONCLUSIONS: In a large dataset, CF patients on ETI demonstrated significantly reduced risk of FESS, pulmonary exacerbations, and hospital admission compared to patients not on CFTR modulators or those on other CFTR modulators, suggesting improved sinonasal disease and overall health status in CF.

The role of revision sinus surgery in the initiation of dupilumab therapy: A real-world study of molecular and cellular features.

KEY POINTS: A persistent type 2 endotype signature exists in recalcitrant chronic rhinosinusitis with nasal polyps mucosa on dupilumab. Revision sinus surgery immediately prior to dupilumab reduces long-term interleukin (IL)-4/IL-13 tissue mRNA. Pre-dupilumab revision surgery is associated with reduced tissue eosinophils and GATA-3+ cells.

Inhalational exposure history is associated with differential sinonasal gene expression profiles and clinical outcomes in chronic rhinosinusitis patients: A pilot study.

KEY POINTS: Inhalational exposure (IE) history assessment is important and may guide chronic rhinosinusitis disease management. Combined exposure status was the most significant factor across differential gene expression analyse IE history was associated with pro-inflammatory transcriptome changes and worse clinical outcomes.

CHI3L1 on fibrinolytic system imbalance in chronic rhinosinusitis with nasal polyp.

Background: Chronic rhinosinusitis (CRS) is an inflammatory disease affecting more than 10% of the global adult population. It is classified into Th1, Th2, and Th17 endotypes and eosinophilic and non-eosinophilic types. Th2-based inflammation and eosinophilic CRS (ECRS) are associated with tissue remodeling and fibrinolytic system impairment. Objective: To elucidate the role of eosinophils in inducing fibrin deposition in CRS nasal polyp tissues and explore potential regulatory mechanisms. Methods: We analyzed the expression of genes related to the serpin family and fibrinolytic system using Gene Expression Omnibus and Next-generation sequencing data. Differentially expression genes (DEGs) analysis was used to compare control and nasal polyp tissues, followed by KEGG and Gene ontology (GO) analysis. We measured the expression and correlation of plasminogen activator-1 (PAI-1), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and urokinase plasminogen activator surface receptor (u-PAR) in CRS tissues, and evaluated the effect of eosinophils on the fibrinolytic system using a cytokine array and co-culture. Results: Nasal polyp tissues showed upregulated PAI-1, u-PA, and u-PAR expression and downregulated t-PA expression. Fibrinolytic system-related genes positively correlated with Th2 cytokines, except for t-PA. Eosinophil-derived Chitinase-3-like protein 1 (CHI3L1) increased PAI-1 expression and decreased t-PA levels in fibroblasts and epithelial cells. The inhibition of CHI3L1 suppresses these alterations. Conclusion: CHI3L1 contributes to fibrin deposition by impairing the fibrinolytic system during nasal polyp formation. The regulation of CHI3L1 expression may inhibit fibrin deposition and edema in ECRS, presenting a potential treatment for this condition.

Suppressor of Cytokine Signaling Proteins 3 and 5 Potentially Delineate Polarization of Th cells in Chronic Rhinosinusitis.

Background: Chronic rhinosinusitis (CRS) is an inflammatory condition classified into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). Th cells manage inflammatory cells in CRS. Suppressor of Cytokine Signaling (SOCS) proteins regulate Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in Th cells by polarizing toward Th1, Th2, and Th17 cells. This study evaluated the levels of SOCS1,3,5 in CRS patients to find associations with Th cells. Methods: In this cross-sectional study, 20 CRSwNP patients, 12 CRSsNP patients, and 12 controls participated. The infiltration of CD4+ T cells was determined using immunohistochemistry. The expression of specific transcription factors and SOCS proteins was assessed using real-time PCR. Cytokine levels were evaluated using ELISA. SOCS protein levels were investigated using western blot analysis. Results: The expression of SOCS3 increased in the CRSwNP group compared to CRSsNP and control groups (p <0.001). SOCS3 protein levels increased in the CRSwNP group compared to CRSsNP (p <0.05) and control (p <0.001) groups. Although there was a significant difference in SOCS5 expression between CRSsNP and control groups, SOCS5 protein levels were significantly different between CRSsNP and control (p <0.001) and CRSwNP (p <0.05) groups. Conclusions: Targeted therapies may be suggested for CRS by modulating SOCS3 and SOCS5 proteins that are responsible for polarization of Th cells toward Th2 or Th1 cells, respectively. JAK-STAT pathway targeting, which encompasses numerous cells, can be limited to SOCS proteins to more effectively orchestrate Th cell differentiation.

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

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

Efficacy of dupilumab for severe chronic rhinosinusitis with nasal polyps and asthma: A prospective study.

BACKGROUND: Dupilumab exerts clinical effects, including improved sinus opacification, olfactory function, and quality of life, in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). Meanwhile, only a few studies have reported its effects on nasal airway resistance and olfactory function, particularly in the Japanese population. Predictors of response remain unclear. OBJECTIVE: In this prospective, observational study, we assessed the comprehensive efficacy and therapeutic response to dupilumab in severe CRSwNP patients with comorbid asthma. METHODS: In 16 adult severe CRSwNP patients with comorbid asthma, the efficacy of 48-week dupilumab treatment, including olfactory function measured by a T&T olfactometer, nasal airway resistance measured by rhinomanometry, nasal polyp score, Lund-Mackay computed tomography score (LMS), and 22-item Sinonasal Outcome Test (SNOT-22), was assessed. Regarding asthma, the annualized rate of exacerbations, 7-item Asthma Control Questionnaire (ACQ-7), and spirometry were assessed. Treatment responsiveness was analyzed. RESULTS: With 48-week dupilumab treatment, olfactory function, nasal airway resistance, nasal polyp score, LMS, and SNOT-22 scores improved significantly. Regarding comorbid asthma, the rate of exacerbations decreased, and ACQ-7 scores and lung function improved significantly. According to the European Position Paper on Rhinosinusitis and Nasal Polyps 2022/European Forum for Research and Education in Allergy and Airway Diseases criteria, 15 patients (94%) were moderate-to-excellent responders at 48 weeks of treatment. Patients with higher SNOT-22 scores, ACQ-7 scores, rates of asthma exacerbation in the previous year, and blood eosinophil counts benefited more from treatment. CONCLUSION: Dupilumab improved upper and lower airway outcomes especially in severe CRSwNP patients with comorbid, poorly controlled asthma.

[Research on the classification model of chronic sinusitis based on VGG].

Objective:To build a VGG-based computer-aided diagnostic model for chronic sinusitis and evaluate its efficacy. Methods:①A total of 5 000 frames of diagnosed sinus CT images were collected. The normal group consisted of 1 000 frames（250 frames each of maxillary sinus, frontal sinus, septal sinus, and pterygoid sinus）, while the abnormal group consisted of 4 000 frames（1 000 frames each of maxillary sinusitis, frontal sinusitis, septal sinusitis, and pterygoid sinusitis）. ②The models were trained and simulated to obtain five classification models for the normal group, the pteroid sinusitis group, the frontal sinusitis group, the septal sinusitis group and the maxillary sinusitis group, respectively. The classification efficacy of the models was evaluated objectively in six dimensions: accuracy, precision, sensitivity, specificity, interpretation time and area under the ROC curve（AUC）. ③Two hundred randomly selected images were read by the model with three groups of physicians（low, middle and high seniority） to constitute a comparative experiment. The efficacy of the model was objectively evaluated using the aforementioned evaluation indexes in conjunction with clinical analysis. Results:①Simulation experiment: The overall recognition accuracy of the model is 83.94%, with a precision of 89.52%, sensitivity of 83.94%, specificity of 95.99%, and the average interpretation time of each frame is 0.2 s. The AUC for sphenoid sinusitis was 0.865（95%CI 0.849-0.881）, for frontal sinusitis was 0.924（0.991-0.936）, for ethmoidoid sinusitis was 0.895（0.880-0.909）, and for maxillary sinusitis was 0.974（0.967-0.982）. ②Comparison experiment: In terms of recognition accuracy, the model was 84.52%, while the low-seniority physicians group was 78.50%, the middle-seniority physicians group was 80.50%, and the seniority physicians group was 83.50%; In terms of recognition accuracy, the model was 85.67%, the low seniority physicians group was 79.72%, the middle seniority physicians group was 82.67%, and the high seniority physicians group was 83.66%. In terms of recognition sensitivity, the model was 84.52%, the low seniority group was 78.50%, the middle seniority group was 80.50%, and the high seniority group was 83.50%. In terms of recognition specificity, the model was 96.58%, the low-seniority physicians group was 94.63%, the middle-seniority physicians group was 95.13%, and the seniority physicians group was 95.88%. In terms of time consumption, the average image per frame of the model is 0.20 s, the average image per frame of the low-seniority physicians group is 2.35 s, the average image per frame of the middle-seniority physicians group is 1.98 s, and the average image per frame of the senior physicians group is 2.19 s. Conclusion:This study demonstrates the potential of a deep learning-based artificial intelligence diagnostic model for chronic sinusitis to classify and diagnose chronic sinusitis; the deep learning-based artificial intelligence diagnosis model for chronic sinusitis has good classification performance and high diagnostic efficacy.

Chitosan-based crosslinking for controlled topical drug release in rhinosinusitis.

KEY POINTS: Chitosan is a promising drug delivery vector for therapeutics owing to its biocompatibility. Once crosslinked with chitosan, prolonged drug release was noted regardless of hydrophilicity. Hydrophilic drugs may require different strategies to obtain a sustained release profile.

EUFOREUM Berlin 2023: Optimizing care for type 2 inflammatory diseases from clinic to AI: A pediatric focus.

The European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual forum EUFOREUM in Berlin in November 2023. The aim of EUFOREUM 2023 was to highlight pediatric action plans for prevention and optimizing care for type 2 inflammatory conditions starting in childhood, with a focus on early-stage diagnosis, ensuring neither under- nor overdiagnosis, optimal care, and suggestions for improvement of care. EUFOREA is an international not-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic respiratory diseases through the implementation of optimal patient care via educational, research, and advocacy activities. The inclusive and multidisciplinary approach of EUFOREA was reflected in the keynote lectures and faculty of the virtual EUFOREUM 2023 (www.euforea.eu/euforeum) coming from the pediatric, allergology, pulmonology, ENT, dermatology, primary health care fields and patients around the central theme of type 2 inflammation. As most type 2 inflammatory conditions may start in childhood or adolescence, and most children have type 2 inflammation when suffering from a respiratory or skin disease, the moment has come to raise the bar of ambitions of care, including prevention, remission and disease modification at an early stage. The current report provides a comprehensive overview of key statements by the faculty of the EUFOREUM 2023 and the ambitions of EUFOREA allowing all stakeholders in the respiratory field to be updated and ready to join forces in Europe and beyond.

Rare and common manifestation of musculoskeletal and sinonasal sarcoidosis: A case report.

Sarcoidosis is a systemic granulomatous disease that can affect multiple organ systems. Although many sarcoidosis patients are asymptomatic, the variable clinical progression of symptomatic patients and the nonspecific presentation make diagnosis difficult in certain cases. Musculoskeletal and sinonasal involvement of sarcoidosis are uncommon manifestations, and they are often only seen in patients with widespread disease. Diagnosis of osseous sarcoidosis, sarcoid arthropathy, and sarcoid rhinosinusitis are typically based on a combination of clinical history, radiological findings, and pathologic specimens. Although there are classic image findings, such as lacelike honeycomb appearance of small bones of the hands or hilar/mediastinal lymphadenopathy, sole reliance on image findings for the diagnosis of sarcoidosis is unreasonable as many findings are nonspecific. However, failure to include sarcoidosis in the differential diagnosis often leads to a delay in recognition of musculoskeletal or sinonasal involvement and results in ineffective treatment plan. Even in patients with biopsy-proven sarcoidosis, some image findings in isolation that may represent granulomatous infiltrates are disregarded as nonspecific without raising the possibility of sarcoidosis due to its rare occurrence. Here we discuss a case of multisystemic sarcoidosis in a 42-year-old female with a constellation of classic and rare findings of biopsy-proven sarcoidosis.

Childhood infections, asthma and allergy trajectories, and chronic rhinosinusitis in middle age: A prospective cohort study across six decades.

INTRODUCTION: Evidence on the early life risk factors of adult CRS, and the history of asthma and allergies across the life course, is limited. AIM: To investigate relationships between respiratory infective/allergic conditions in childhood, and asthma and allergies across the life course and CRS in middle age. METHODS: Data were from the population-based Tasmanian Longitudinal Health Study (TAHS) cohort, first studied in 1968 when aged 6-7 years (n = 8583) and serially followed into middle age (n = 3609). Using a well-accepted epidemiological definition, participants were assigned a CRS-severity subtype at age 53: no sinusitis/CRS (reference); past doctor diagnosis only; current symptoms without doctor diagnosis; and doctor-diagnosed CRS with current symptoms. Relationships with infective/allergic respiratory illnesses at age 7, and previously published asthma-allergy trajectories from 7 to 53 years, were examined using multinominal regression. RESULTS: In middle age, 5.8% reported current CRS symptoms with 2.5% doctor-diagnosed. Childhood conditions associated with symptomatic doctor-diagnosed CRS included frequent head colds (multinomial odds ratio [mOR] = 2.04 (95% confidence interval [95% CI]: 1.24, 3.37)), frequent tonsillitis (mOR = 1.61 [95% CI: 1.00, 2.59]) and current childhood asthma (mOR = 2.23 [95% CI: 1.25, 3.98]). Life course trajectories that featured late-onset or persistent asthma and allergies were associated with all CRS subtypes in middle age; early-onset persistent asthma and allergies (mOR = 6.74, 95% CI: 2.76, 16.4); late-onset asthma allergies (mOR = 15.9, 95% CI: 8.06, 31.4), and late-onset hayfever (mOR = 3.02, 95% CI: 1.51, 6.06) were associated with symptomatic doctor-diagnosed CRS. CONCLUSION: Current asthma, frequent head colds and tonsillitis at age 7 could signal a susceptible child who is at higher risk for CRS in mid-adult life and who might benefit from closer monitoring and/or proactive management. Concurrent asthma and allergies were strongly associated and are potential treatable traits of adult CRS.

Outcomes of biological therapy in patients with severe asthma with chronic rhinosinusitis in Saudi Arabia: patients with nasal polyps versus those without nasal polyps.

BACKGROUND: This study's purposes were to evaluate the impact of biological therapies on outcomes in patients with severe asthma (SA) and chronic rhinosinusitis (CRS) and to compare these effects among those with NP (CRSwNP) versus those without NP (CRSsNP) in the "real-world" setting in Saudi Arabian patients. METHODS: From March to September 2022, a retrospective observational cohort study was undertaken at the severe asthma clinics of the Armed Forces Hospital-Southern Region (AFHSR) and King Khalid University Hospital, Abha, Saudi Arabia, to delineate the effects of dupilumab therapy. Outcomes were assessed, including clinical outcomes, FEV1, and laboratory findings before and one year after dupilumab. Post-therapy effects were compared between CRSwNP and CRSsNP. RESULTS: Fifty subjects were enrolled, with a mean age of 46.56. There were 27 (54%) females and 23(46%) males. Significant improvements in clinical parameters (frequency of asthma exacerbations and hospitalizations, the use of OCs, anosmia, SNOTT-22, and the ACT), FEV1, and laboratory ones (serum IgE and eosinophilic count) were observed 6 and 12 months after using dupilumab (p < 0.001), respectively. However, after 12 months of dupilumab therapy, there were no significant differences between those with and without NP with regards to clinical (anosmia, ACT, and OCs use), laboratory (eosinophilic count, serum IgE level) parameters, and FEV1%. CONCLUSIONS: Patients with CRS experienced significant improvements in clinical, FEV1, and laboratory outcomes after dupilumab therapy. However, these improvements were not maintained when comparing CRSwNP with CRSsNP. There were no significant differences between those with and without NP regarding ACT and OCs use or laboratory (eosinophilic count, serum IgE level) parameters. Further prospective multicenter studies are warranted.

Impact of sociodemographic status and sex on chronic rhinosinusitis and olfaction in people with cystic fibrosis.

BACKGROUND: Sociodemographic status (SDS) including race/ethnicity and socioeconomic status as approximated by education, income, and insurance status impact pulmonary disease in people with cystic fibrosis (PwCF). The relationship between SDS and chronic rhinosinusitis (CRS) remains understudied. METHODS: In a prospective, multi-institutional study, adult PwCF completed the 22-Question SinoNasal Outcome Test (SNOT-22), Smell Identification Test (SIT), Questionnaire of Olfactory Disorder Negative Statements (QOD-NS), and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Lund-Kennedy scores, sinus computed tomography, and clinical data were collected. Data were analyzed across race/ethnicity, sex, and socioeconomic factors using multivariate regression. RESULTS: Seventy-three PwCF participated with a mean age of 34.7 ± 10.9 years and 49 (67.1%) were female. Linear regression identified that elexacaftor/tezacaftor/ivacaftor (ETI) use (ß = â€’4.09, 95% confidence interval [CI] [‒6.08, ‒2.11], p < 0.001), female sex (ß = â€’2.14, 95% CI [‒4.11, ‒0.17], p = 0.034), and increasing age (ß = â€’0.14, 95% CI [‒0.22, ‒0.05], p = 0.003) were associated with lower/better endoscopy scores. Private health insurance (ß = 17.76, 95% CI [5.20, 30.32], p = 0.006) and >16 educational years (ß = 13.50, 95% CI [2.21, 24.80], p = 0.020) were associated with higher baseline percent predicted forced expiratory volume in one second (ppFEV1). Medicaid/Medicare insurance was associated with worse endoscopy scores, CFQ-R respiratory scores, and ppFEV1 (all p < 0.017), and Hispanic/Latino ethnicity was associated with worse SNOT-22 scores (p = 0.047), prior to adjustment for other cofactors. No other SDS factors were associated with SNOT-22, QOD-NS, or SIT scores. CONCLUSIONS: Differences in objective measures of CRS severity exist among PwCF related to sex, age, and ETI use. Variant status and race did not influence patient-reported CRS severity measures or olfaction in this study. Understanding how these factors impact response to treatment may improve care disparities among PwCF. CLINICAL TRIALS: NCT04469439.

Predicting Adherence to Topical Medications in Chronic Rhinologic Disease: A Systematic Review.

OBJECTIVE: To determine risk factors of medical adherence and describe strategies to increase adherence in patients with chronic rhinologic disease. DATA SOURCES: PubMED, SCOPUS, CINAHL, and Cochrane. REVIEW METHODS: Systematic review of 4 databases (PubMED, SCOPUS, CINAHL, Cochrane) from inception of databases to September 1, 2022 to identify studies that evaluated factors related to and affected by medical adherence in patients with chronic rhinologic disease. RESULTS: Of 1491 studies screened, 25 studies met inclusion criteria. Of these, 7 studies described how sensory attributes of intranasal sprays affect adherence, including odor, taste, aftertaste, and side effects. Five studies described record keeping diaries/notification systems to improve adherence, with demonstration of web-based platforms to send reminders as well as keep record of medication usage to improve adherence. Eight studies described patient-specific risk factors to nonadherence, with demonstration of increased age and conscientious personalities correlating with medical adherence. Five studies looked at pediatric patients specifically, with adherence rates in children parallelling that of adults. Additionally, nonadherence in children may have greater implications for school performance. CONCLUSION: Overall, adherence to topical medical therapy in patients with chronic rhinologic disease is affected by patient-related and medication-specific factors which should be considered when counseling patients. Web-based diary or notification systems may help increase adherence. Additionally, children are equally adherent to topical medical therapy as adults and nonadherence may have negative implications for school performance.

Antibody-based therapeutics for chronic rhinosinusitis with nasal polyps.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory condition with heterogenous underlying endotypes, the most common being type 2 mediated inflammation. Several biologics have been developed to target specific pro-inflammatory cytokines and their receptors with proven efficacy in both quantitative and qualitative outcomes in patients with severe uncontrolled disease. However, there is an ongoing debate on the role of biologics relative to conventional therapies for CRSwNP and their efficacy in patient subgroups with non-polyp type 2 disease. AREAS COVERED: This review examines the evidence on the efficacy and safety of biologics in CRSwNP, recommendations for their use, and discusses the broader economic factors influencing their application in clinical practice. EXPERT OPINION: Emerging real-life data demonstrating the variable efficacy of the available biologics for patients with CRSwNP, coupled with the high cost compared to conventional therapies such as surgery, renders biologics to be considered as an add-on therapy in the majority of cases. However, ongoing research into increasing biologic dose intervals and novel therapies targeting alternative pathways may offer a more cost-effective and sustainable option in future.

ChatGPT as a New Tool to Select a Biological for Chronic Rhino Sinusitis with Polyps, "Caution Advised" or "Distant Reality"?

ChatGPT is an advanced language model developed by OpenAI, designed for natural language understanding and generation. It employs deep learning technology to comprehend and generate human-like text, making it versatile for various applications. The aim of this study is to assess the alignment between the Rhinology Board's indications and ChatGPT's recommendations for treating patients with chronic rhinosinusitis with nasal polyps (CRSwNP) using biologic therapy. An observational cohort study involving 72 patients was conducted to evaluate various parameters of type 2 inflammation and assess the concordance in therapy choices between ChatGPT and the Rhinology Board. The observed results highlight the potential of Chat-GPT in guiding optimal biological therapy selection, with a concordance percentage = 68% and a Kappa coefficient = 0.69 (CI95% [0.50; 0.75]). In particular, the concordance was, respectively, 79.6% for dupilumab, 20% for mepolizumab, and 0% for omalizumab. This research represents a significant advancement in managing CRSwNP, addressing a condition lacking robust biomarkers. It provides valuable insights into the potential of AI, specifically ChatGPT, to assist otolaryngologists in determining the optimal biological therapy for personalized patient care. Our results demonstrate the need to implement the use of this tool to effectively aid clinicians.

Real-Life Evidence of Mepolizumab Treatment in Chronic Rhinosinusitis with Nasal Polyps: A Multicentric Study.

Background: The introduction of biological drugs in the management of chronic rhinosinusitis with nasal polyps (CRSwNP) is allowing new and increasingly promising therapeutic options. This manuscript aims to provide a multicenter trial in a real-life setting on Mepolizumab treatment for severe uncontrolled CRSwNP with or without comorbid asthma. Methods: A retrospective data analysis was jointly conducted at the Otolaryngology-Head and Neck Surgery departments of La Sapienza University and San Camillo Forlanini Hospital in Rome. Both institutions participated by sharing clinical information on patients with CRSwNP treated with Mepolizumab. Patients were evaluated before starting Mepolizumab, at six months and at twelve months from the first drug administration. During follow-up visits, patients underwent endoscopic evaluation, quality of life assessment, nasal symptoms assessment, and blood tests to monitor mainly neutrophils, basophils, eosinophils, and IgG, IgA, and IgE assay. Results: Twenty patients affected by CRSwNP and treated with Mepolizumab were enrolled (12 females and 8 males with a mean age of 63.7 years). Sixteen patients (80%) had concomitant asthma. During follow-up, a gradual improvement in nasal polyp score, quality of life and nasal symptoms, assessed by SNOT-22 and VAS and loss of smell measured by olfactory VAS, was found. Regarding blood tests, eosinophils decreased gradually, while other blood parameters showed no statistically significant changes. Conclusions: Mepolizumab has been shown to be effective in the therapeutic management of patients with CRSwNP. Further studies are needed to support our findings and better understand the underlying immune pathways to predict patients' response to biological treatment in CRSwNP.

Correlation of Eosinophils and Type 2 Inflammatory Mediators with Osteitis in Chronic Rhinosinusitis with Nasal Polyps.

Objective: Osteitis is more prevalent in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), making the disease refractory and prone to recurrence. However, the pathophysiologic mechanism of osteitis formation in CRS has not been fully elucidated, and this study aimed to further elucidate the association of eosinophils and type 2 inflammatory mediators with osteitis in patients with CRSwNP. Methods: This retrospective study collected clinical data on 125 cases of CRSwNP. The participants were categorized into two groups based on the presence or absence of osteitis in their sinus CT scan. The groups were classified as the osteitis group and the non-osteitis group. The clinical baseline data, type 2 inflammatory mediators, and eosinophils were compared between the two groups. The correlation between these factors and the Global Osteitis score scale (GOSS) was also evaluated. Results: There were 69 cases in the osteitis group and 56 cases in the non-osteitis group of CRSwNP patients. The prevalence of concomitant asthma (P=0.009), SNOT-22 score, LUND-MAKAY score, and LUND-KEDENY score were significantly higher in the osteitis group than in the non-osteitis group (All P values were < 0.001); the absolute values of IL-13 (P<0.001), periosteal proteins (P<0.001), and tissue eosinophils (P < 0.05) were significantly higher in the osteitis group as compared with the non-osteitis group. Logistic regression analysis showed that IL-13 and periosteal proteins were risk factors for CRSwNP osteitis (P<0.001). ROC curve analysis revealed that IL-13 had the highest predictive value (AUC=0.786) with a cut-off value of 5.8059 pg/mL, the sensitivity of 58.0%, and a specificity of 89.3% respectively. Conclusion: Osteitis could indicate the more severe symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), and elevated IL-13, periosteal proteins, and tissue eosinophils are risk factors for osteitis formation in patients with CRSwNP.

Cystic fibrosis pathogens persist in the upper respiratory tract following initiation of elexacaftor/tezacaftor/ivacaftor therapy.

Elexacaftor/tezacaftor/ivacaftor (ETI) therapy has revolutionized the treatment of cystic fibrosis (CF) for most affected individuals but the effects of treatment on sinus microbiota are still unknown. Changes to the airway microbiota in CF are associated with disease state and alterations to the bacterial community after ETI initiation may require changes to clinical management regimens. We collected sinus swab samples from the middle meatus in an observational study of 38 adults with CF and chronic rhinosinusitis (CRS) from 2017 to 2021 and captured the initiation of ETI therapy. We performed 16S and custom amplicon sequencing to characterize the sinus microbiota pre- and post-ETI. Real-time quantitative PCR (RT-qPCR) was performed to estimate total bacterial abundance. Sinus samples from people with CF (pwCF) clustered into three community types, dependent on the dominant bacterial organism: a Pseudomonas-dominant, Staphylococcus-dominant, and mixed dominance cluster. Shannon's diversity index was low and not significantly altered post-ETI. Total bacterial load was not significantly lowered post-ETI. Pseudomonas spp. abundance was significantly reduced post-ETI, but eradication was not observed. Staphylococcus spp. became the dominant organism in most individuals post-ETI and we showed the presence of methicillin-resistant Staphylococcus aureus (MRSA) in the sinus both pre- and post-ETI. We also demonstrated that the sinus microbiome is predictive of the presence of Pseudomonas spp., Staphylococcus spp., and Serratia spp. in the sputum. Pseudomonas spp. and Staphylococcus spp., including MRSA, persist in the sinuses of pwCF after ETI therapy, indicating that these pathogens will continue to be important in CF airway disease management in the era of highly effective modulator therapies (HEMT).IMPORTANCEHighly effective modulator therapies (HEMT), such as elexacaftor/tezacaftor/ivacaftor (ETI), for cystic fibrosis (CF) have revolutionized patient care and quality of life for most affected individuals. The effects of these therapies on the microbiota of the airways are still unclear, though work has already been published on changes to microbiota in the sputum. Our study presents evidence for reduced relative abundance of Pseudomonas spp. in the sinuses following ETI therapy. We also show that Staphylococcus spp. becomes the dominant organism in the sinus communities of most individuals in this cohort after ETI therapy. We identified methicillin-resistant Staphylococcus aureus (MRSA) in the sinus microbiota both pre- and post-therapy. These findings demonstrate that pathogen monitoring and treatment will remain a vital part of airway disease management for people with cystic fibrosis (pwCF) in the era of HEMT.