International Forum of Allergy & Rhinology最新文献

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease often associated with asthma. The global airway hypothesis suggests bidirectional inflammatory interactions between upper and lower airways. Mepolizumab, an anti-IL-5 therapy, treats conditions systemically, while functional endoscopic sinus surgery (FESS) primarily addresses sinonasal disease and can improve asthma control. The combined effect on airway outcomes remains unclear. This study evaluated the global airway hypothesis with objective measures and targeted therapies.

Objective: To investigate the impact of mepolizumab, with or without FESS, on airway inflammation, lung function, and symptom burden in severe CRSwNP with or without asthma.

Methods: In this RCT, 58 patients received either mepolizumab alone or combined with FESS. Inflammation and symptom outcomes were analyzed in blood, nose, and bronchi at baseline, six, and 12 months. Patients were stratified by baseline inflammatory subgroup.

Results: Both groups showed improvements in FEV1% (MepoFESS: +3.4%, p = 0.010; Mepo Only: +3.5%, p = 0.015), FVC% (MepoFESS: +3.7%, p < 0.001; Mepo Only: +2.9%, p = 0.009), inflammation markers (FeNO, blood eosinophils, nasal polyp eosinophils), and all patient-reported outcomes. MepoFESS produced greater gains in nasal polyp score, nasal congestion, and overall symptom burden. Lung function and systemic inflammation improved similarly in both groups.

Conclusions: Mepolizumab improves upper and lower airway outcomes in CRSwNP. FESS adds localized benefits in sinonasal symptom control without further impact on lower airway inflammation. Findings support a comprehensive approach targeting systemic and local type 2 inflammation in global airway disease.

Background: Classification based on the existence and severity of blood eosinophilia via machine learning (ML) may provide novel insights into the pathophysiology of chronic rhinosinusitis (CRS).

Methods: Key features of CRS with blood eosinophilia were investigated through exploratory data analyses and ML, focusing on the existence (Setting-1: absolute eosinophil count [AEC] cutoff: 500/µL) and severity (Setting-2: AEC cutoffs: 500 and 1500/µL) of blood eosinophilia. Four ML models were tested for each setting; SHapley Additive exPlanations (SHAP) was applied to identify key classification features of the best model.

Results: Univariate analyses targeting 399 patients with CRS demonstrated significant differences for 17 and eight additional features in both settings and Setting-2, respectively. Setting-2 revealed an increased incidence of eosinophilic CRS without nasal polyps (NPs) with increasing severity. Random forest and eXtreme Gradient Boosting were the best ML models in Setting-1 and -2, respectively. Based on SHAP, the blood basophil count was one of the three most important classification features for any class. In Setting-2, high C-reactive protein levels, high blood basophil count, comorbid chronic eosinophilic pneumonia, low computed tomography (CT) scores in the maxillary sinus, and low NP scores were the five most important classification features separating an AEC ≥ 1500/µL from other classes.

Conclusion: ML classification of CRS revealed the involvement of basophils in eosinophilia in peripheral blood. Features specific for CRS with an AEC ≥ 1500/µL indicated that otolaryngologists should suspect the potential eosinophilic CRS with unique comorbidities even in the absence of NPs and the unremarkable inflammation on sinonasal CT.

Background: Precedent chronic rhinosinusitis (CRS) is associated with new-onset asthma and non-cystic fibrosis bronchiectasis (BE).

Objective: To assess if endoscopic sinus surgery (ESS) mitigates the development of lower airway diseases in patients with CRS.

Methods: This retrospective study utilized electronic medical records from an academic center. CRS patients (> 18 years old) without asthma or BE, were identified between January 2006 and December 2013. Charts were reviewed until May 2023. New diagnoses of asthma or BE were identified in patient records following ESS before December 2018 compared to patients without ESS. Lund-Mackay (LM) scores were calculated in a random subset of patients to assess disease severity. Logistic regression was used to estimate the odds of developing asthma or BE by ESS status.

Results: A total of 1877 patients underwent ESS, while 13,453 did not. CRS severity was higher in the ESS group (LM, 9.02) versus no ESS group (LM, 4.28). After up to 17 years of follow-up, 207/1877 (11%) and 40/1877 (2.1%) of patients with ESS had a new asthma or BE diagnosis, respectively. Out of 13,453 patients, 1778 (13.2%) and 293 (2.2%) patients without ESS had a new asthma or BE diagnosis. The unadjusted odds of a new asthma diagnosis were lower by 19% for ESS versus no ESS; OR (95% CI), 0.81 (0.70-0.95). After controlling for confounders (age, gender, race/ethnicity, smoking status, and chronic rhinitis), the association remained significant, with a 15% reduction in the odds of a new asthma diagnosis; OR (95% CI), 0.85 (0.73-0.99). There was no association between ESS status and a new diagnosis of BE.

Conclusions: Despite higher CRS severity, patients undergoing ESS had a lower risk of a new asthma diagnosis and did not have a higher risk of developing BE.

Objective: In the last two decades, transnasal endoscopic surgery (TES) has become pivotal in the management of sinonasal tumors. This approach involves a multiblock tumor resection, adding complexity to the interpretation of surgical margins after pathological examination. This study compares different strategies to infer subclinical local residual disease (SLRD), aiming to identify and validate the best available method for assessing SLRD after transnasal endoscopic resection of sinonasal squamous cell carcinoma (SCC) and intestinal-type adenocarcinoma (ITAC).

Methods: Three methods to estimate SLRD (as either absent-R0 - or microscopically present-R1) were applied in patients who received negative margins-aimed endoscopic resection: sole-pathologist examination, multidisciplinary evaluation, and anatomic diagram-based assessment. The primary outcome to compare methods was time-to-recurrence (TTR) stratification provided by these methods.

Results: 105 patients were included (50 SCC and 55 ITAC). All three methods resulted significantly associated with TTR in both ITAC and SCC populations. In a multivariate model, only SLRD assessed with the anatomical diagram was independently associated with time-to-local-recurrence (TTLR) in SCC and TTR in both ITAC and SCC groups. The concordance index (C-index), the area under the curve (AUC), and the incremental AUC (iAUC) were higher for the anatomical diagram method in the ITAC and SCC cohorts.

Conclusion: The anatomic diagram proved to be the best available strategy, yet with limitations, for assessing SLRD, demonstrating superior TTR stratification compared to traditional methods.