International Forum of Allergy & Rhinology最新文献

Most physicians hold antithrombotic medication prior to surgery, regardless of drug class Physicians rely on the cardiologist or their own experience for perioperative decision making There was no consensus on antithrombotic perioperative medication timing across drug classes.

Background: Staphylococcus aureus biofilms play a crucial role in chronic rhinosinusitis (CRS), leading to the persistence of symptoms. Severe CRS patients are frequently infected with S. aureus strains that exhibit higher biofilm properties (e.g., biomass, exoprotein production) compared to S. aureus from controls. S. aureus biofilms resist antibiotic treatment; however, the relationship between bacterial biofilm properties, antibiotic susceptibility, and CRS severity has not yet been defined and is the subject of this study.

Methods: S. aureus clinical isolates and reference strains, and matched clinical datasets were collected from CRS patients and controls (n  =  35). Antimicrobial susceptibility of the isolates to clindamycin, mupirocin, clarithromycin, doxycycline, and amoxicillin-clavulanic acid was determined by minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC).

Results: S. aureus MBEC values (n  =  35) were significantly higher (up to 11 times) than the MIC for all five antibiotics (p < 0.001). Among the various antibiotics tested, mupirocin had the strongest antibiofilm activity and amoxicillin-clavulanic acid the weakest: at antibiotic concentrations that are deemed to indicate susceptibility or intermediate resistance when testing in planktonic form, 80% biofilm eradication was reached for all isolates using mupirocin and only 5/35 isolates using amoxicillin-clavulanic acid. The biofilm metabolic activity, biomass, colony-forming units, and exoprotein production were positively correlated with the MBEC values for amoxicillin-clavulanic acid and clarithromycin, but not for the other antibiotics. Lund-Mackay and Lund-Kennedy disease severity scores showed positive correlations with the MBEC values of clarithromycin.

Conclusion: These findings show that whilst severe CRS patients are frequently infected with S. aureus strains that exhibit higher biofilm-mediated virulence, these biofilms are also more difficult to control with standard of care antibiotics. Better personalized therapies are required to manage biofilm-mediated infections in severe CRS patients.

Background: Loss of smell is a principal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP), affecting health-related quality of life and posing a safety hazard.

Methods: WAYPOINT (NCT04851964), a phase 3, multicenter trial in adults with uncontrolled CRSwNP, randomized patients 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Changes from baseline in biweekly mean Nasal Polyposis Symptom Diary (NPSD) loss of smell item, University of Pennsylvania Smell Identification Test (UPSIT), and 22-item Sino-Nasal Outcome Test (SNOT-22) loss of smell/taste item scores, as well as anosmia (UPSIT score ≤18) prevalence, were assessed over 52 weeks.

Results: Among 408 patients (tezepelumab [n = 203]; placebo [n = 205]), significant improvements with tezepelumab versus placebo in NPSD loss of smell item, UPSIT, and SNOT-22 loss of smell/taste item scores were seen at week 4 (least-squares mean [LSM] treatment difference [95% CI]: -0.36 [-0.46, -0.27]; 6.03 [4.72, 7.34]; and -1.01 [-1.22, -0.80], respectively) and week 52 (-1.01 [-1.18, -0.83]; 9.50 [7.84, 11.16]; and -1.90 [-2.20, -1.61]); all nominal p < 0.0001. Between-treatment differences in daily NPSD loss of smell item score were evident from day 7 (LSM treatment difference: -0.08 [95% CI: -0.15, -0.02]; nominal p < 0.01). Improvements in NPSD loss of smell, UPSIT, and SNOT-22 loss of smell/taste item scores were observed across multiple prespecified subgroups. Anosmia prevalence was lower with tezepelumab than placebo at week 4 (43.0% [n/N = 64/149] vs. 80.3% [n/N = 106/132]) and week 52 (31.5% [n/N = 47/149] vs. 75.8% [n/N = 100/132]).

Conclusions: Tezepelumab provides early and sustained improvements in sense of smell among patients with uncontrolled CRSwNP.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) often coexists with asthma. Endoscopic sinus surgery (ESS) improves asthma morbidity, but the impact of early surgery (< 6 months from diagnosis) versus later surgery (1-3 years) is unclear. We examined whether early ESS is associated with improved asthma outcomes compared with delayed surgery.

Methods: We conducted a retrospective cohort study using the TriNetX Research Network, including adults with CRSwNP who underwent ESS. Patients were grouped as early surgery (≤ 6 months after diagnosis) or late surgery (1-3 years). Outcomes over 5 years included asthma diagnoses by severity, exacerbations, and medication use (long-acting β2-agonists [LABA], corticosteroids, biologics). Propensity score matching was performed 1:1 (N = 3683 per group) based on demographics, baseline asthma severity, and asthma medication usage.

Results: After matching, groups were well balanced. Early ESS was associated with lower risk of moderate (11.5% vs. 13.5%; odds ratio [OR] = 0.84; p = 0.012) and severe persistent asthma (6.5% vs. 8.4%; OR = 0.76; p = 0.003). Rates of mild intermittent or persistent asthma and overall new asthma diagnoses did not differ. Early surgery patients had fewer associated asthma exacerbations (6.4% vs. 8.1%; OR = 0.78; p = 0.005) and were less likely to require LABAs (23.7% vs. 29.4%; OR = 0.75; p < 0.0001), steroids (63.7% vs. 67.4%; OR = 0.85; p = 0.0009), and biologics (7.7% vs. 10.1%; OR = 0.74; p = 0.0004).

Conclusion: Early ESS for CRSwNP is associated with reduced progression to moderate/severe asthma, fewer exacerbations, and lower reliance on oral steroids, LABAs, and biologics. These findings suggest early surgery may alter asthma trajectory and reduce treatment burden in CRSwNP patients.

Background: Microplastics and nanoplastics (MNPs) have emerged as ubiquitous environmental contaminants; these particles have been detected in mucus and irrigation fluids, and at greater concentrations in patients with sinusitis and allergic rhinitis. Emerging evidence at other mucosal surfaces, including the gut and lung, suggests that MNPs exacerbate epithelial barrier dysfunction and induce inflammatory responses. Despite their relevance, the impact of inhaled plastics on the nasal epithelium, the initial point of contact for airborne plastics, remains underexplored.

Methods: Submerged RPMI 2650 nasal epithelial cultures and air-liquid interface (ALI) cultures of primary human nasal epithelial cells were dosed with polystyrene (PS) MNPs, with a focus on the effects of 100 nm nanoplastics and surface charge alterations. Analyses of secreted cytokines, transcriptomic changes, epithelial integrity, and histologic appearance were performed.

Results: Note that 100 nm PS nanoplastics caused transcriptomic inflammatory and oxidative stress pathway activation in RMPI 2650 submerged cultures, with conserved inflammatory gene signatures in the ALI exposure model as well. Dose-dependent elevations in IL-8 and TNFα were observed after ALI exposure to 1 µm PS microplastics, and 100 nm PS nanoplastics elicited early elevations in IL-6, IL-8, and TNF, with more pronounced effects from amine-modified particles, while no cytotoxicity, barrier disruption, or type-2 alarmin induction was observed. Scanning electron microscopy revealed ciliary disruption and particle adherence.

Conclusions: PS MNPs cause inflammatory cytokine responses in nasal epithelial cells over even a short timeframe, in addition to ciliary blunting and transcriptional evidence of significant inflammation and stress response. This sinonasal model can help answer critical questions about the pathogenicity of plastic exposures.

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.