International Forum of Allergy & Rhinology最新文献

Background: Acute invasive fungal sinusitis (AIFS) is a highly fatal infection affecting immunocompromised patients. While defects in innate immunity have been studied as the primary focus in AIFS, adaptive immunity has yet to be explored in this condition.

Methods: Sinonasal biopsies from consenting surgical patients were collected from 13 AIFS patients, 8 immunocompromised patients without fungal infection, and 4 healthy controls. B- and T-cell receptor (BCR/TCR) sequences were reconstructed from bulk transcriptome sequencing. Clonal homeostasis, repertoire diversity, and V gene usage were compared for both BCRs and TCRs. Somatic hypermutation (SHM) rates, isotype distribution, and biophysical properties of BCRs were further analyzed. Lastly, bulk transcriptomic deconvolution was performed to examine the abundance of adaptive immune cells in AIFS.

Results: Both B and T cells in AIFS exhibited increased clonal expansion, coupled with decreased receptor diversity compared with control groups. V gene usage in BCRs and TCRs demonstrated immunosuppression-associated and AIFS-specific patterns. SHM was decreased in AIFS compared with both healthy and immunocompromised controls, particularly in IgG and IgA BCRs. The light and heavy chains of BCRs in AIFS were biophysically distinct from those of controls. Bulk deconvolution reveals depletion of naïve and memory B cells, as well as CD4 and CD8 T cells in AIFS compared with immunosuppressed controls.

Conclusions: Our results suggest that adaptive immunity is dysregulated in AIFS. Further studies should focus on single-cell profiling to further dissect the cellular dynamics underlying this dysregulation. Recombinant cytokine therapies to boost adaptive responses represent promising medical therapies to complement surgical debridement and antifungal medications.

Background: Regional anesthesia is effective in alleviating postoperative pain and reducing the requirement for systemic pain medications. However, optimal postoperative pain management in endoscopic sinus surgery (ESS) remains challenging. This study investigated the potential pain-reducing outcomes of general anesthesia combined with a bupivacaine injection at the sphenopalatine ganglion (SPG) and an anterior ethmoid nerve block following ESS.

Methods: A double-blind randomized controlled trial that included 80 patients (18-75 years old) with chronic rhinosinusitis who underwent ESS was conducted. Either 0.5% bupivacaine or normal saline was injected into the anterior ethmoid nerve and SPG. The visual analog scale (VAS) pain score was assessed at 0, 1, 2, 4, 6, 8, 12, and 24 h following the surgical procedure. The timing of analgesic administration and any postoperative adverse effects of 0.5% bupivacaine were recorded.

Results: The VAS scores were significantly improved in the bupivacaine group at 1 h (95% confidence interval [CI] = 0.77-3.81, p = 0.004), 2 h (95% CI = 1.00-3.47, p = 0.001), 4 h (95% CI = 0.59-2.38, p = 0.002), and 6 h (95% CI = 0.22-2.28, p = 0.0019). Overall, the results showed a significant difference (95% CI = 0.51-1.74, p < 0.001).

Conclusions: Postoperative endoscopic SPG and anterior ethmoid nerve blocks with bupivacaine effectively reduce postoperative pain and minimize analgesic requirements after ESS.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disorder frequently associated with impaired mucociliary clearance and bacterial infection. Individuals carrying a single cystic fibrosis transmembrane conductance regulator (CFTR) mutation exhibit partial CFTR dysfunction and are increasingly recognized as being at risk for CRS; however, the sinonasal phenotype and host-pathogen interactions in CF carriers remain poorly defined.

Methods: We characterized heterozygous ΔF508 CF rabbits (heterozygous, n = 6) compared with wild-type (WT) (n = 5). Baseline sinonasal structure was assessed by computed tomography and histology. CFTR function was measured by nasal potential difference (NPD) and Ussing chamber analysis of primary epithelial cultures, with or without CFTR modulators. Bacterial sinusitis was induced using Pseudomonas aeruginosa (PA14), followed by longitudinal imaging, bacterial quantification, histology, and PA14 RNA sequencing.

Results: Heterozygous rabbits demonstrated significant sinus hypoplasia compared with WT (mm³: heterozygous 77.9 vs. WT 108.1 mm³, p < 0.01) without spontaneous sinusitis. NPD revealed ∼50% reduction in chloride transport relative to WT (∆mV: heterozygous -15.5 vs. WT -35.8, p < 0.01). CFTR modulation partially restored chloride secretion in epithelial cells from heterozygous to ∼80% of WT (p < 0.0001). Following P. aeruginosa inoculation, heterozygous rabbits exhibited higher bacterial burden (p < 0.05), persistent radiographic opacification (week 4, p < 0.01), and delayed histologic recovery. PA14 RNAseq revealed a distinct transcriptional profile in the heterozygous sinonasal environment.

Conclusions: Heterozygous ΔF508 CF rabbits recapitulate key sinonasal features relevant to CF carriers, including reduced CFTR function, altered host defense, and impaired infection clearance. This model provides a translational platform for investigating CRS pathogenesis and evaluating CFTR-targeted therapies in CF carriers.

Background: Although shifts in nasal microbiota have been well-documented in inflammatory upper airway conditions, microbiota tumor-associated alterations remain uncharacterized. This study is the first to compare sinonasal microbiota profiles of patients with malignant tumors (MT), benign tumors (BT), and controls, offering insights into tumor-associated microbiomes.

Methods: This prospective, cross-sectional, observational study assessed intraoperative sinus swabs from 70 adult research participants (MT = 23, BT = 15, control = 32). Sinonasal microbial communities were characterized using 16S rRNA gene amplicon sequencing to determine if microbial community structures differed between groups.

Results: Tumor-associated sinonasal microbiota profiles showed clear dysbiosis, with reduced relative abundance of beneficial microbes and increased putative pathogenic taxa. Both MT and BT had significantly lower microbial diversity and distinct compositions compared to controls. MT samples had significantly higher relative abundance of Firmicutes and reduced relative abundance of Actinobacteria. These phylum-level alterations were accompanied by elevated proinflammatory microbial taxa, paired with reduced relative abundance of keystone, beneficial taxa consistent with healthy nasal microbiomes. Microbial communities in BT and MT samples were similar, but Alcaligenes was more abundant, and Corynebacterium was less abundant in MT than in BT.

Conclusion: This study observed that sinonasal microbial communities in MT exhibited marked dysbiosis with a reduction in the relative abundance of putative sinonasal commensal taxa compared to controls. These alterations were present to a lesser extent in BT. Future investigations should aim to determine whether these microbial shifts contribute to tumor development or represent secondary effects, with an aim to quantify their impact on outcomes and guide therapeutic strategies.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is managed after sinus surgery with topical corticosteroids. Given limited distribution of nasal steroid sprays, patients have the option of either steroid nasal irrigation (SNI) or exhalation delivery system with fluticasone (EDS-FLU). This study evaluates the cost-effectiveness of EDS-FLU compared to SNI for CRSwNP.

Methods: A cohort-style Markov decision-tree economic model with a 33-year time horizon was developed in TreeAgePro. Because EDS-FLU is not currently covered by Medicare, costs of medications were estimated using retail pricing. A willingness-to-pay threshold of $50,000/quality adjusted life year (QALY) was used to determine cost-effectiveness. One-way and probabilistic sensitivity analysis was conducted using 10,000 Monte Carlo simulations.

Results: EDS-FLU had an incremental benefit of 0.41 QALYs compared to SNI. In base case analysis, EDS-FLU costs $140,966.63 after the study period, whereas SNI costs $40,817.50. With an ICER of $244,185.37/QALY, SNI is the more cost-effective strategy. Probabilistic sensitivity analysis reported SNI as the cost-effective strategy in 98.50% of simulations.

Conclusions: Compared to EDS-FLU, SNI is the cost-effective strategy for treating CRSwNP following FESS. Changes in drug pricing and improvements in patient selection may cause adjustments in the most cost-effective strategy for CRSwNP management.

Background: The indication for nasal irrigation with corticosteroids after sinus surgery in patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is well established, as surgery facilitates distribution throughout the sinonasal cavity. However, it remains unknown whether this approach could also provide therapeutic benefit prior to surgery. This study aims to compare the effect of budesonide versus saline nasal irrigation in surgically naive CRSwNP patients.

Methods: A randomized, double-blind, placebo-controlled parallel-group study was conducted in 52 patients with diffuse type 2 CRSwNP with no previous sinus surgery. Patients were randomized to receive either 1 mg budesonide or saline nasal irrigation twice daily for four weeks. The primary outcome was the change in the 22-item Sinonasal Outcome Test (SNOT-22). Secondary outcomes included the Visual Analogue Scale (VAS), Nasal Polyp Score (NPS), and the Connecticut (CCCRC) olfactory test.

Results: A total of 52 patients were randomized (mean age 50.1 ± 12.9 years; 51.9% female). The intention-to-treat (ITT) analysis showed that the budesonide nasal irrigation group demonstrated a significantly greater improvement in SNOT-22 (mean difference: 18.1 points [95% CI: 3.4 to 32.8; p = 0.017]), VAS (mean difference 2.24 points [95% CI: 0.35 to 4.13; p = 0.018]) and NPS (mean difference: 0.73 points [95% CI: 0.25 to 1.21]; p = 0.003). No significant differences were observed between groups in CCCRC.

Conclusion: Budesonide nasal irrigation may be an important tool for controlling sinonasal symptoms in patients with CRSwNP who are not candidates for sinus surgery or while awaiting surgical treatment.

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.