International Forum of Allergy & Rhinology最新文献

Background: Pseudomonas aeruginosa is an opportunistic pathogen in cystic fibrosis-related chronic rhinosinusitis (CF-CRS) that produces phenazine metabolites pyocyanin and 1-hydroxyphenazine (1-HP), which may have detrimental effects on mitochondria, reactive oxygen species (ROS), Ca²⁺ signaling, and apoptosis. However, prior studies utilized lung cancer cells or dissociated animal cells. We sought to better define human nasal epithelial responses to phenazines, including the role of Ca²⁺.

Methods: Live cell imaging was used to measure Ca²⁺ and mitochondrial function in RPMI2650 nasal carcinoma cells and primary human nasal epithelial cells (HNECs) cultured in submersion and at air-liquid interface (ALI). Gene expression was measured by quantitative PCR. Ciliary beat frequency (CBF) was quantified by high-speed imaging.

Results: Pyocyanin, but not 1-HP, increased mitochondrial Ca²⁺ dependent on phospholipase C and endoplasmic reticulum (ER) Ca²⁺ release, correlating with protein kinase C activation. Mitochondrial membrane potential decreased and mitochondrial ROS increased with both pyocyanin and 1-HP in a Ca²⁺-independent manner. Both pyocyanin and 1-HP decreased viability of RPMI2650s and other squamous carcinoma cell lines over 24 h, whereas HNECs survived, possibly due to differential regulation of protein homeostasis genes, including activating transcription factor 6 (ATF6). Mitochondrial ROS was enhanced in CF-CRS ALIs, which may explain why pyocyanin reduced CBF in CF but not non-CF ALIs.

Conclusions: Ca²⁺ signaling is not required for phenazine mitochondrial toxicity. The greater sensitivity of cancer cells to phenazine cytotoxicity necessitates use of primary cells when studying host responses to bacterial phenazines. Enhanced ROS production and ciliotoxicity in CF-CRS may contribute to susceptibility to P. aeruginosa infection.

Background: EPOS 2020 defined chronic rhinosinusitis (CRS) disease control using patient symptoms and medication usage but endoscopic findings were considered optional. The effect of adding endoscopic features, an appropriate threshold, and their association with present or future symptom control have not been studied.

Methods: A prospective cohort study of 188 adult CRS patients undergoing bilateral endoscopic sinus surgery from 2017 to 2023 was conducted. Patients were assessed at 6-12 months (V1) and 18-60 months (V2) postoperatively. Individual patient symptoms from the SNOT-22, endoscopic findings (modified Lund-Kennedy [MLK] score), and medication usage were recorded. CRS control status was classified as controlled or suboptimal control (EPOS partly/un-controlled) based on EPOS 2020 criteria without endoscopic features. The predictive role of endoscopic findings was analyzed.

Results: Endoscopic findings were weakly associated with concurrent control status but the total MLK (V1 AUC = 0.631, p < 0.001; V2 AUC = 0.620, p < 0.05) outperformed any individual MLK component in strength of association. Adding MLK to V1 control status using a threshold of MLK ≥ 3 marginally improved prediction accuracy for V2 control compared to V1 control status defined without endoscopic features (AUC = 0.744 vs. 0.721, respectively, both p < 0.001).

Conclusion: While endoscopic findings are only weakly associated with concurrent control status, their addition enhances prediction of subsequent V2 CRS outcomes. Our study provides the first real-world evidence supporting the value of endoscopic findings as predictors for CRS disease progression, with an MLK threshold ≥ 3 showing moderate predictive accuracy for future maintenance of control.

Background: Although the therapeutic effects of acupuncture and sphenopalatine ganglion (SPG) needling for allergic rhinitis (AR) are well established, evidence for the efficacy of their combination remains limited.

Methods: In this multicenter, randomized, parallel-controlled trial, 260 patients with persistent moderate-to-severe AR were assigned to 8 weeks of pharmacotherapy (MED; loratadine 10 mg/day), acupuncture (ACU; 3 sessions/week), sphenopalatine ganglion needling (SPG-N; 1 session/week), or combination therapy (COM, which received both acupuncture and SPG needling). The primary outcome was the response rate (≥30% reduction in total nasal symptom score [TNSS]) at Week 8. Secondary outcomes included changes in TNSS, total non-nasal symptom score (TNNSS), rhinoconjunctivitis quality of life questionnaire (RQLQ), and visual analogue scale (VAS) scores from baseline to Weeks 2, 4, 8, and the 4-week follow-up.

Results: At Week 8, response rates differed significantly among groups (COM: 82.54%; ACU: 71.43%; SPG-N: 55.74%; MED: 45.31%; p < 0.001) and were sustained at the 4-week follow-up. The COM showed the earliest significant improvement at Week 2 (63.49%, p < 0.001). Compared to MED, both COM (relative risk [RR] = 1.90, 95% confidence interval [CI], 1.40-2.58; p < 0.001) and ACU (RR = 1.61, 95% CI, 1.18-2.21; p = 0.003) were associated with significantly higher response rates at Week 8, whereas SPG-N was not (RR = 1.27, 95% CI, 0.90-1.79; p = 0.17).

Conclusion: This study demonstrated that acupuncture combined with SPG needling provides more rapid, robust, and sustained symptomatic improvement in AR, offering an evidence-based non-pharmacologic alternative for AR management.

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.