International Forum of Allergy & Rhinology最新文献

Background: Post hoc analyses of clinical trials have characterized dupilumab's adverse effects, yet the real-world impact in chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma is not well described. This study aims to characterize the risks of lymphoma, cardiovascular events, eosinophilia, joint pain, inflammatory arthritis, and sleep apnea in dupilumab-treated CRSwNP and/or asthma patients compared to those not taking dupilumab, and to other biologics.

Methods: This retrospective cohort study used TriNetX, a de-identified database containing over 100 million patient records. Demographics and adverse effects associated with immunotherapy use were collected.

Results: We identified 21,249 dupilumab-treated CRSwNP and/or asthma patients. After matching for demographics, comorbid conditions, and medication use, dupilumab was associated with a lower risk of acute myocardial infarction (RR 0.538, 95% CI 0.435-0.665), pulmonary embolism (RR 0.639, 95% CI 0.500-0.817), cerebral infarction (RR 0.716, 95% CI 0.580-0.884), venous thrombosis (RR 0.625, 95% CI 0.511-0.763), cardiovascular disease (RR 0.733, 95% CI 0.678-0.791), and sleep apnea (RR 0.891, 95% CI 0.818-0.970), with a higher risk of eosinophilia (RR 3.157, 95% CI 2.606-3.826), versus no biologic. Dupilumab was associated with a similar risk of lymphoma and musculoskeletal outcomes. Compared to omalizumab and mepolizumab, dupilumab showed a more favorable musculoskeletal and cardiovascular profile, while it demonstrated a largely similar profile to tezepelumab.

Conclusions: Despite eosinophilia, dupilumab was associated with decreased risk of major cardiovascular, thromboembolic, and sleep apnea outcomes in CRSwNP and asthma. These findings suggest dupilumab may confer protection against adverse outcomes beyond respiratory symptom control.

Background: Central compartment atopic disease (CCAD) has recently been recognized as a distinct phenotype within the spectrum of type 2-dominant chronic rhinosinusitis (CRS). Although international guidelines highlight polypoid changes in the central nasal cavity, standardized diagnostic and classification criteria are still lacking. This study aims to develop and internally validate a consensus-based classification system through expert agreement.

Methods: A two-round modified Delphi study was conducted with 10 international rhinology experts. Participants evaluated the need for a specific grading framework, the relative diagnostic value of nasal endoscopy versus radiology, and the clarity and applicability of the proposed criteria (Grades 0-IV). Six representative endoscopic and radiologic cases were used in each round to assess interpretive accuracy and interobserver agreement. Consensus was predefined as ≥ 80% of ratings in the top two categories (4-5) on a 5-point Likert scale.

Results: Eighty percent of experts identified nasal endoscopy as the primary diagnostic tool in the first Delphi round. The interpretive accuracy of the preliminary grading system was high, with all panelists correctly recognizing the proposed distinctions. Interobserver agreement was substantial (κ = 0.72). In the second round, refined definitions improved overall consensus and reproducibility. Endoscopy was reaffirmed as the cornerstone of diagnosis, while radiology played a complementary role. Diagnostic clarity and agreement increased, reaching κ = 0.80.

Conclusion: The consensus process confirmed nasal endoscopy as the key diagnostic method for CCAD, supported by substantial interobserver reproducibility. The refined definitions improved clarity and agreement, facilitating differentiation from other CRS phenotypes and establishing a reliable framework for future research.

Introduction: Chronic rhinosinusitis (CRS) is an inflammatory condition of the sinonasal mucosa. While physical activity is known to modulate systemic inflammation, its role in CRS prevention remains unclear. This study evaluates the association between moderate to vigorous physical activity (MVPA) and CRS using longitudinal Fitbit data.

Methods: We conducted a retrospective cohort study within the All of Us Research Program using Fitbit-derived activity data linked to electronic health records. Adults with ≥ 1 year of valid data were eligible. MVPA was averaged across "strict weeks" (7 valid days, > 100 steps/day) and categorized as < 75, 75-150, 150-225, 225-300, or > 300 min. CRS was defined using ICD-10 coding. Propensity score matching was performed on demographics, obesity, and smoking status. Kaplan-Meier curves, Cochran-Mantel-Haenszel odds ratios, and fixed-effects models assessed associations between MVPA and CRS.

Results: The matched cohort included 583 CRSsNP cases and 583 controls. Kaplan-Meier survival analysis demonstrated significant separation across MVPA groups (p = 0.0099), with higher activity associated with lower cumulative incidence. Participants exercising 75-150 min/week had nearly twice the odds of CRS compared with those exercising 150-225 min (OR = 1.95, 95% CI 1.07-3.55). Timing models showed earlier diagnoses among the least active group (- 152 weeks, 95% CI - 169 to - 134) and later diagnoses among those exercising > 300 min/week (+ 260 weeks, 95% CI + 200 to + 320). Continuous modeling revealed an inverse dose-response with a plateau beyond 300 min.

Conclusion: Regular MVPA is associated with reduced CRS incidence and prolonged disease-free years, supporting physical activity as a possible modifiable risk factor for CRS.

Background: Appropriate medical therapy (AMT) is first-line treatment for patients with chronic rhinosinusitis (CRS). We evaluated inflammatory structure, treatment-induced changes, and biomarker-outcome associations in AMT-managed patients.

Methods: Fifty-one CRS patients were evaluated before and after AMT which included a combination of oral antibiotics, oral steroids, or intranasal steroids tailored to CRS phenotype and severity. At each visit, patients completed the SNOT-22, CRS-PRO, Brief Smell Identification Test (BSIT), CT scan (Lund-Mackay Score [LM]), and endoscopy (Modified Lund-Kennedy Score [MLK]). Middle-meatal mucus was analyzed for IL-1b, IL-5, IL-13, IFN-g, and MIP1a using Luminex and ELISA. Principal components analysis (PCA) was performed on baseline cytokine data to identify key biomarker axes. Paired-sample Wilcoxon tests compared cytokine changes, and Spearman's correlation assessed relationships between biomarkers and disease measures.

Results: PCA revealed two major components: PC-1 (inflammation severity) dominated by ECP and MIP1a, and PC-2 (endotype axis) with positive weighting of IL-5 and IL-13 (T2) and negative weighting of IFN-g and IL-1b (T1/3). AMT significantly reduced inflammatory severity and T2 biomarker burden, driven by decreases in IL-5, IL-13, ECP, and MIP1a (all p < 0.01), while T1/3 biomarker remained unchanged. Clinical outcomes, including MLK, SNOT-22, CRS-PRO, and BSIT, improved and showed stronger correlations with T2 than T1/3 biomarkers.

Conclusion: AMT for CRS is associated with reduction in index biomarkers across inflammatory severity and T2 endotype with minimal effects on T1/3 inflammation. T2-driven inflammation appears to be the most AMT-responsive axis found in this study, aligning with measurable improvements in endoscopic, patient reported, and nasal airflow outcomes.

Background: The management of moderate-to-severe allergic rhinitis (AR) is challenging given numerous advanced therapies. A comparative, evidence-based treatment hierarchy to guide the selection of biologics, allergen immunotherapy (AIT), and advanced pharmacotherapies is critically lacking due to a paucity of head-to-head trials. This network meta-analysis established a treatment hierarchy for moderate-to-severe AR by comparing the efficacy and safety of biologics, AIT, and key pharmacotherapies.

Methods: We analyzed 28 randomized controlled trials (13,312 participants), which evaluated the efficacy and safety of biologics (anti-IgE, anti-IL-4Rα therapies), AIT (evaluated within a 6-month time frame to ensure comparability), and key pharmacotherapies (intranasal corticosteroids alone or combined with antihistamines) for moderate-to-severe AR. Efficacy was assessed by changes in the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS), and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). A treatment hierarchy was established using surface under the cumulative ranking curve (SUCRA) probabilities.

Results: For the TNSS, anti-IL-4Rα therapy was most effective, followed by anti-IgE therapy and AIT, which surpassed all pharmacotherapies. The combination of intranasal corticosteroid and intranasal antihistamine ranked the highest for ocular symptoms. Anti-IL-4Rα therapy was also superior for improving the RQLQ. Overall, all treatments demonstrated a favorable safety profile. Biologics and AIT did not show a significant increase in adverse events risk compared to placebo.

Conclusions: This network meta-analysis establishes the first comprehensive treatment hierarchy for moderate-to-severe AR. Our findings demonstrate that biologics, particularly anti-IL-4Rα therapy, are the most effective interventions for nasal symptom control, ranking superior to AIT and pharmacotherapies, thus providing a robust, data-driven framework to personalize patient care.

Key points: Most state Medicaid programs granted omalizumab (91.4%) and dupilumab (59.5%) preferred drug status. Omalizumab was the most commonly prescribed therapy among Medicaid patients between 2015 and2024.

Background: The role of epithelial dysregulation is poorly understood in fungal sinusitis. We aimed to examine differential gene expression and quantify protease expression in sinonasal tissue from distinct patient cohorts, those with and without invasive fungal sinusitis (IFS). We hypothesized that abnormal epithelial integrity in the sinonasal mucosa of immunosuppressed IFS patients may allow for tissue invasion.

Methods: Bulk RNA sequencing was performed on tissue from eight patients from two cohorts: immunosuppressed patients with and without IFS. Evaluation of protein expression for select proteases and their inhibitors was performed on all sinonasal tissues using multiplex western blotting. To expand upon these findings, protein expression of proteases and their inhibitors was evaluated in sinonasal tissue from eight patients with non-invasive fungal sinusitis (fungal ball).

Results: Bulk RNA sequencing identified 33 genes that were differentially regulated in immunosuppressed IFS tissue compared to those without IFS. Multiplex western blot revealed several proteases, including matrix metalloproteinases (MMPs), with increased expression in the immunosuppressed IFS cohort compared to the cohorts without IFS. Tissue inhibitors of MMPs (TIMPs) were proportionally lower in IFS patient tissue compared to the control cohorts, resulting in several abnormal IFS-related MMP/TIMP ratios. In the non-invasive fungal sinusitis cohort, unique MMP/TIMP ratios were dysregulated.

Conclusions: Several proteases with increased expression in immunosuppressed IFS patients may be responsible for both an appropriate immune response to the pathogen as well as epithelial barrier breakdown and subsequent fungal invasion.