American Journal of Rhinology & Allergy最新文献

Background: Sinonasal inverted papilloma (SNIP) is a benign epithelial tumor with distinctive histopathological features. However, the role of inflammation in SNIP remains poorly characterized.

Objectives: This study aimed to compare the histopathological patterns and inflammatory characteristics of SNIP with those of chronic rhinosinusitis with nasal polyps (CRSwNPs) or normal ethmoid sinus mucosa.

Methods: Fifty-eight tissue biopsies were prospectively collected from 38 patients with SNIPs, 12 CRSwNPs, and 8 normal ethmoid sinus mucosae. SNIP was histopathologically divided into four grades based on the extent of epithelial remodeling. The immunohistochemical characteristics of epithelial remodeling (p63, CK5) and infiltration of inflammatory cells (eg, eosinophils, neutrophils, and macrophages) and cytokines (eg, interleukin-1β, interleukin-6, and tumor necrosis factor-α) were analyzed.

Results: Among the 38 SNIPs, 21.1%, 36.8%, 23.7%, and 18.4% were grades I, II, III, and IV, respectively. The expression levels of p63 and CK5 were significantly higher in SNIP than in the other two groups (both, p < 0.05). Neutrophil and macrophage infiltration was more pronounced in SNIP and with differences among the four grades. The expression levels of inflammatory cytokines were significantly higher in the SNIP group than in the CRSwNP group. A positive correlation between the expression levels of p63 and inflammatory cytokines was observed in both SNIPs and CRSwNPs.

Conclusion: Excessive epithelial remodeling is an important histological feature of SNIP; it is accompanied by sinonasal mucosal inflammation.

Background: Elevated nitric oxide (NO) levels have been linked to a heightened risk of recurrence in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, the precise influence of NO on CRSwNP recurrence remains unclear.

Objective: This study seeks to elucidate the relationship between NO levels and the risk of CRSwNP recurrence.

Methods: A protein chip array analysis was conducted to identify differentially expressed inflammatory mediators in the nasal tissues between patients with CRSwNP and healthy controls (HC). Differentially expressed proteins were analyzed, and bioinformatics analysis was used to predict the potential functions and pathways of these proteins. Western blotting (WB) and immunohistochemistry were employed to validate the candidate proteins in 2 independent cohorts. Receiver-operating characteristic (ROC) curves were employed to assess the abilities of target proteins for predicting the postoperative recurrence of CRSwNP.

Results: Twelve differentially expressed proteins were identified between the CRSwNP and HC groups. Notably, differentially expressed proteins exhibited high expression of the biological process term "positive regulation of nitric oxide-mediated signal transduction" (P < .05). WB and immunohistochemistry results demonstrated that guanylate cyclase 1 soluble subunit alpha 1 (GUCY1A1), GUCY1A2, nitric oxide synthase 1 adaptor protein, epidermal growth factor receptor, and insulin were found to be upregulated in the CRSwNP group compared to the HC group (P < .05). Moreover, elevated levels of GUCY1A2 and GUCY1A1 were observed to be associated with an increased risk of CRSwNP recurrence (P < .05), and ROC curve analysis confirmed their effectiveness as predictors for postoperative recurrence (P < .05).

Conclusion: Our findings revealed that CRSwNP exhibited a distinct tissue protein profile, with soluble guanylate cyclase dysfunction and the nitric oxide pathway implicated in the underlying pathological mechanisms. The discovery-validation results suggested that GUCY1A1 and GUCY1A2 were promising predictors for postoperative recurrence in patients with CRSwNP.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) remains challenging to manage effectively, with high symptom recurrence rates and significant impacts on quality of life, prompting a need to evaluate the real-world use of biologics and optimize treatment strategies.

Objective: To assess the real-world application and perspectives of American Rhinologic Society (ARS) members on biologic treatments and surgical interventions for CRSwNP, focusing on clinical practice patterns, adoption of biologics, and their impact on surgical practices.

Methods: A standardized questionnaire evaluated clinical practice patterns of biologics prescriptions and surgery in treating CRSwNP between July 2022 and August 2023. Data collected from 162 ARS members were analyzed.

Results: Of 162 participants, a substantial majority (95.06%, n = 154) reported prescribing biologics in their practice. Notably, 45.45% (n = 70) found biologics easily accessible, although accessibility challenges remained for some. The impact of biologics on surgical practices was significant, with 36.36% (n = 56) observing a marked reduction in revision sinus surgeries. Among the participants, 47.16% (n = 71) agreed that aspirin-exacerbated respiratory disease (AERD) was the highest phenotype that tended to increase the possibility of biological treatment by more than 20%. Adopting Patient-Reported Outcome Measures (PROMs) was prevalent, with 57.79% (n = 89) utilizing them in patient management.

Conclusion: The study highlights the evolving landscape in managing CRSwNP, with a marked trend toward integrating biological treatments into clinical practice. It underscores the necessity for continued research, updates to clinical guidelines, and enhanced practitioner education to optimize treatment outcomes for CRSwNP patients.

Background: Posterior nasal neurectomy (PNN) has been shown to reduce the symptom burden of patients with perennial moderate and severe allergic rhinitis (AR).

Objectives: To evaluate the long-term safety and effectiveness of PNN for the treatment of perennial moderate and severe AR.

Methods: A prospective 3-year single-arm study was conducted in which the reflective total nasal symptom score (rTNSS) and total non-nasal symptom score (rTNNSS) were collected preoperatively and at 3 months, 6 months, 1 year, 2 years, and 3 years postoperatively.

Results: A total of 213 patients with AR were recruited and received PNN, of whom 154 patients completed the 3-year follow-up. The mean rTNSS of the long-term follow-up patients improved from 7.74 (95% confidence interval [CI] 7.507-7.974) at baseline to 2.604 (95% CI 2.221-2.986), P < .001, at 6 months and showed sustained improvement to 3.156 (95% CI 2.806-3.506), P < .001, at 3 years. The mean rTNNSS ranged from 1.301 (95% CI 1.112-1.491) at baseline to 0.564 (95% CI 0.441-0.688) (P < .001) at 6 months and showed sustained improvement to 0.641 (95% CI 0.533-0.749) (P < .001) at 3 years. The rTNSS subscores (sneezing, congestion, rhinorrhea, and itching) and rTNNSS subscores (lacrimation, eye itching, postnasal drip, and cough) remained significantly improved from the baseline at all follow-up time points (all P < .001).

Conclusion: Posterior nasal neurectomy significantly and sustainably alleviated nasal and non-nasal symptoms of perennial moderate and severe AR and improved patient quality of life through 3 years postprocedure.

Background: The Th2 cell polarization is a crucial factor in the pathogenesis of allergic diseases. The underlying mechanism requires further investigation. Telomerase has an immune-regulating ability. The aim of this study is to elucidate the association between telomerase and Th2 cell polarization in patients with allergic rhinitis (AR).

Methods: CD4⁺ T cells were isolated from blood samples collected from AR patients and healthy control subjects. RNA sequencing was employed to analyze RNA samples extracted from CD4⁺ T cells. An AR mouse model was established using the ovalbumin-alum protocol.

Results: High telomerase gene activity and high endoplasmic reticulum (ER) stress status were observed in CD4⁺ T-cells in patients with AR. Positive correlation between the telomerase reverse transcriptase (TERT) gene expression in CD4⁺ T cells and AR response in patients with AR. TERT facilitated the degradation of Foxp3 proteins in CD4⁺ T cells, resulting in the polarization of Th2 cells. Sensitization with the ovalbumin-alum protocol enhanced the Tert expression in CD4⁺ T cells by exacerbating ER stress. Conditional inhibition of the Tert or eukaryotic translation initiation factor 2-α (Eif2a) expression in CD4⁺ T cells effectively attenuated experimental AR in mice.

Conclusions: Elevated amounts of telomerase in CD4⁺ T cells were found in CD4⁺ T cells of subjects with AR. Telomerase promoted Th2 cell polarization by inducing Foxp3 protein degradation and promotes GATA3 activation. Inhibition of TERT or eIF2a alleviated experimental AR.

Background: Current treatment paradigms recommend surgical intervention when conventional medical management proves ineffective in resolving chronic rhinosinusitis with nasal polyposis.

Objectives: To assess and compare the efficacy of dupilumab and functional endoscopic sinus surgery (FESS) for the treatment of chronic rhinosinusitis with nasal polyp (CRSwNP) over time.

Methods: Studies comparing CRSwNP patients who received dupilumab with those who underwent FESS were included. Outcome measures included the nasal congestion score (NCS), Sino-nasal Outcome Test-22 (SNOT-22), University of Pennsylvania Smell Identification Test-40 (UPSIT-40), and nasal polyp score (NPS). The risk of bias was evaluated using the Newcastle-Ottawa Scale.

Results: A total of 4 studies with 724 participants were included. The dupilumab group had a superior NCS, but an inferior NPS, compared to the FESS group during the follow-up period. The SNOT-22 score of the dupilumab group was inferior to that of the FESS group until 6 months posttreatment, but the scores were similar at around 1 year. A similar trend was observed for the UPSIT-40 score, but the score of the dupilumab group was higher at around 1 year.

Conclusion: Functional endoscopic sinus surgery was more effective than dupilumab for several months after treatment. However, at 1 year after treatment, the effects of the 2 treatments became similar, with greater olfactory improvement seen in the dupilumab group.

Background: Malva sylvestris L. (commonly known as mallow) has been widely used in traditional Tibetan formulations to treat allergic rhinitis (AR), and malvidin is a key anti-inflammation constituent of this plant.

Objective: The present study aimed to evaluate the potential therapeutic effect and mechanism of malvidin in an AR mouse model.

Methods: Malvidin's efficacy was evaluated in an AR mouse model induced by ovalbumin (OVA) sensitization and challenge. The factors, such as nasal symptoms, serum OVA-specific immunoglobulin E (IgE) levels, histological changes in the nasal mucosa, and expressions of Th1, Th2, Th17, and Tregs and their cytokines, were assessed. Western blotting was used to analyze the effect of malvidin on signal transducer and activator of transcription 6 (STAT6) and GATA3 expression levels.

Results: Malvidin reduced the allergic symptoms and serum levels of OVA-specific IgE in the AR model. Histological analysis indicated that malvidin alleviates nasal mucosal edema, eosinophil infiltration, and goblet cell proliferation. In addition, it altered the expression of Th1/Th2/Th17-related cytokines, enhanced the Treg population, and reduced Th2-mediated immunity by suppressing the phosphorylation of STAT6 and expression of the GATA3 protein.

Conclusions: Malvidin significantly improved allergic symptoms in an OVA-induced AR mouse model by modulating Th1/Th2 immune responses and suppressing the STAT6/GATA3 pathway, indicating its potential as a naturally sourced agent for AR management.

Background: Despite National Institutes of Health and American Medical Association recommendations to publish online patient education materials at or below sixth-grade literacy, those pertaining to endoscopic skull base surgery (ESBS) have lacked readability and quality. ChatGPT is an artificial intelligence (AI) system capable of synthesizing vast internet data to generate responses to user queries but its utility in improving patient education materials has not been explored.

Objective: To examine the current state of readability and quality of online patient education materials and determined the utility of ChatGPT for improving articles and generating patient education materials.

Methods: An article search was performed utilizing 10 different search terms related to ESBS. The ten least readable existing patient-facing articles were modified with ChatGPT and iterative queries were used to generate an article de novo. The Flesch Reading Ease (FRE) and related metrics measured overall readability and content literacy level, while DISCERN assessed article reliability and quality.

Results: Sixty-six articles were located. ChatGPT improved FRE readability of the 10 least readable online articles (19.7 ± 4.4 vs. 56.9 ± 5.9, p < 0.001), from university to 10th grade level. The generated article was more readable than 48.5% of articles (38.9 vs. 39.4 ± 12.4) and higher quality than 94% (51.0 vs. 37.6 ± 6.1). 56.7% of the online articles had "poor" quality.

Conclusions: ChatGPT improves the readability of articles, though most still remain above the recommended literacy level for patient education materials. With iterative queries, ChatGPT can generate more reliable and higher quality patient education materials compared to most existing online articles and can be tailored to match readability of average online articles.

Background: Intranasal trigeminal function is important in detecting environmental stimuli. The impact of age-associated chemosensory dysfunction upon taste and olfaction is well described, but an understanding of trigeminal loss (chemesthesis) is lacking.

Objective: The goal of this study was to characterize trigeminal function in a cohort of older adults and explore potential impacts.

Methods: Twenty-eight participants over 50 years of age were recruited from the community as part of an aging cohort study. This nested cohort completed chemosensory questionnaires, patient-reported outcome measures (PROMs), and psychophysical testing for taste (taste strips), olfaction (Sniffin' Sticks), and trigeminal function (eucalyptol lateralization). Data were analyzed for associations between trigeminal function, olfactory, and taste psychophysical performance, patient-reported metrics, and demographic risk factors.

Results: Patient-reported trigeminal impairment is less severe than other chemosensory loss, with mean visual analog scores (VAS, rated 0-100 from least to most severe) for smell (32.9 ± 34.2), taste (20.6 ± 28.4), and trigeminal sensation (9.5 ± 12.8). Despite low VAS scores, psychophysical trigeminal dysfunction was present in 10 (35.7%) subjects. Psychophysical olfactory and taste dysfunction were present in 16 (57.1%) and eight (28.6%) participants respectively. Hypercholesterolemia was associated with psychophysical trigeminal dysfunction (mean lateralization performance in hypercholesterolemia 57.7% ± 17.1 vs. 74.1% ± 10.4, p = .008).

Conclusion: Intranasal trigeminal impairment is present in nearly one-third of aging adults when assessed by psychophysical methods but is under-recognized. Hyperlipidemia may be associated with trigeminal impairment. Future inquiries should better characterize these findings in larger and prospective cohorts.