International Forum of Allergy & Rhinology最新文献

Background: The purpose of this randomized controlled trial (RCT) was to demonstrate that posterior nasal nerve ablation treatment with the NEUROMARK System is superior to a sham control procedure in patients with chronic rhinitis.

Methods: In this prospective, multicenter, single-blinded, superiority RCT, 132 participants were randomized 2:1 to the active treatment arm (88) and sham control arm (44). The primary endpoint was the comparison of the reflective Total Nasal Symptom Score (rTNSS) responder rate between study arms at 90-day follow-up. Secondary efficacy outcomes included postnasal drip, chronic cough, Nasal Obstruction Symptom Evaluation (NOSE), mini-Rhinoconjunctivitis Quality of Life Questionnaire (mini-RQLQ), and Patient Health Questionnaire-9 (PHQ-9) (a depression assessment).

Results: The responder rate was significantly higher for the active treatment arm: 73.3% (95% confidence interval [CI], 64.0%-82.7%) compared to the sham control arm: 35.0% (95% CI, 20.2%-49.8%; p < 0.001). The primary endpoint was met, demonstrating the active treatment arm is superior to the sham control arm. The active treatment arm had significantly greater decreases (improvements) in the rTNSS (-4.0 vs. -1.2, p < 0.0001), postnasal drip (-1.1 vs. -0.3, p < 0.001), cough (-0.9 vs. -0.1, p < 0.001), NOSE score (-32.2 vs. -8.0, p < 0.0001), mini-RQLQ (-1.7 vs. -0.5, p < 0.0001), and PHQ-9 (-3.0 vs. -0.7, p = 0.028), compared to the sham control arm. The NOSE responder rate and mini-RQLQ responder rate were significantly higher for the active treatment arm than the sham control arm (p = 0.001 and p < 0.0001, respectively).

Conclusion: Treatment for chronic rhinitis with the NEUROMARK System is superior to sham control.

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.