American Journal of Rhinology & Allergy最新文献

Background: Patients with aspirin-exacerbated respiratory disease (AERD) have difficult-to-treat asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and often require treatment with biologic therapy for asthma or CRSwNP. Healthcare utilization in patients with AERD has not been well described since the advent of respiratory biologics.

Objective: To determine real-world healthcare utilization and quality of life among patients with AERD and to understand the impact of dupilumab, a monoclonal antibody targeting the interleukin 4 receptor, on patient-reported health outcomes and healthcare utilization.

Methods: We conducted a longitudinal survey study of 98 patients with AERD recruited from the Brigham and Women's Hospital AERD registry. Patients completed online questionnaires describing their medication history, healthcare utilization, and quality of life every 3 months for 2 years.

Results: At the end of 24 months, participants who were on dupilumab at the start of the study and those who started dupilumab had a significant reduction in the number of reported poor health days in the preceding month compared to patients not on dupilumab (P < .001 and P < .01, respectively). Participants on dupilumab and those who started dupilumab also had significantly lower overall sinonasal outcome test-22 and asthma control test scores compared to those not on dupilumab over 24 months (P < .05 for both groups).

Conclusion: Dupilumab therapy significantly improves health-related quality of life in patients with AERD, specifically as it pertains to patient assessment of days of overall poor health and quality of life related to sinonasal and asthma symptoms.

Objective: Conductive olfactory losses mainly involve obstruction of the olfactory cleft (OC) and diminished OC airflow. This study investigated the association between abnormal nasal structure and OC airflow.

Methods: A systematic search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis to identify studies on the effect of the nasal structure on the OC airflow and olfaction.

Results: A total of 11 studies were included. Nasal vestibule morphological variabilities directly impact the transport of molecules in odorant-laden air to the OC. A greater airflow vortex and a narrower vestibule region intensified the airflow vortex toward the olfactory region. Middle turbinectomy significantly increased the average flux to the OC. The location of the major airflow and airflow velocity maxima shifted towards the OC in patients with septal deviation. The airflow has been redirected into the upper part of the nasal airway in patients with inferior turbinate hypertrophy. For patients with unilateral cleft lip, unilateral nasal airflow on the cleft side has a lower rate and flow. The mean velocity in the posterior OC correlated well with olfaction compared to that in the anterior OC. The nasal polyps (NP) within the middle meatus increased the olfactory airflow but did not enhance the olfaction. NP in the olfactory region or anterior to the olfactory region significantly decreased the olfactory airflow and olfaction. Furthermore, obstruction of the OC did not change the nasal patency. When the OC shape presented with a stenotic slit or lumen structure among patients with conductive olfactory dysfunction without NP, the inspiratory velocity and flow rate within OC were significantly lower than in the healthy control group.

Conclusion: Various nasal structural factors affect patterns of OC airflow and olfaction. Identifying the related airflow-limiting structures may promote the comprehensive evaluation of conductive olfactory losses in patients with olfactory dysfunction.

Background: Viral infections have long been implicated in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Given widespread exposure to the common cold coronavirus 229E (HCoV229E), we sought to investigate how HCoV-229E is cleared and stimulates interferon pathways in air-liquid interface (ALI) cultures from patients with CRSwNP.

Objective: The objective of this study was to identify whether viral clearance and ISG expression is different in ALI cultures from donors with CRSwNP compared with controls.

Methods: Plaque assays were used to quantify infectious virus released by infected air-liquid interface (ALI) cultures derived from patients with CRSwNP compared to patients without CRS (controls). Additionally, mock and induced levels of Interferon Stimulated Genes (ISGs) mRNA following HCoV-229E infection were quantified by RT-qPCR.

Results: Quantification of infectious virus by plaque assay reveals that CRSwNP ALI cultures were equally susceptible to HCoV-229E infection, and surprisingly viral titers dropped significantly faster than in the control ALI cultures. We further demonstrate that this accelerated viral clearance correlates with increased mRNA expression of at least 4 ISGs following viral infection in the CRSwNP ALIs compared to the control ALIs.

Conclusion: This study paradoxically demonstrates that ALI cultures from patients with CRSwNP are more efficient at clearing the common cold HCoV-229E virus compared to controls. We also demonstrate significantly increased ISG mRNA expression following HCoV-229E infection in CRSwNP. These findings call for further investigation into the effect of unimpaired interferon signaling on the type 2 inflammatory environment in patients with CRSwNP.

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.

Objective: Allergic rhinitis (AR) is a growing public health problem worldwide. Respecting the significance of the modified Lund-Kennedy (MLK) score in rhinitis assessment, we delved into its evaluation value on the sublingual immunotherapy (SLIT) efficacy in AR patients.

Methods: Totally 100 AR patients were enrolled, with pre- and post-SLIT MLK score, total nasal symptoms score (TNSS), total medication score (TMS), visual analogue scale (VAS), inflammatory cytokines, and immune function-related parameters compared. The correlations of MLK score with TNSS/TMS/VAS, as well as with IL-4/INF-γ/eosinophil (EOS)/percentage/specific immunoglobulin (sIgE)/sIgG were assessed by Spearman correlation analysis. The value of MLK score on assessing SLIT efficacy in AR patients was analyzed.

Results: SLIT treatment reduced MLK/TNSS/TMS/VAS scores, abated IL-4 level/EOS percentage/sIgE, and elevated INF-γ/sIgG levels. MLK score was positively correlated with pre- and post-SLIT TNSS score (r_{pre-treatment}= 0.592, r_{post-treatment}= 0.756), TMS score (r_{pre-treatment}= 0.385, r_{post-treatment}= 0.718), VAS score (r_{pre-treatment}= 0.369, r_{post-treatment}= 0.704), IL-4 (r_{pre-treatment}= 0.553, r_{post-treatment}= 0.639), EOS percentage (r_{pre-treatment}= 0.511, r_{post-treatment}= 0.632), and sIgE (r_{pre-treatment}= 0.472, r_{post-treatment}= 0.524), and negatively with INF-γ (r_{pre-treatment}= -0.418, r_{post-treatment}= -0.578) and sIgG4 (r_{pre-treatment}= -0.460, r_{post-treatment}= -0.613). The MLK score had an area under curve of 0.846 (77.01% sensitivity, 76.92% specificity, 4 cut-off value) and 0.944 (91.67% sensitivity, 92.11% specificity, 2 cut-off value) for assessing SLIT treatment as effective and markedly effective for the patients, respectively.

Conclusion: The MLK score had good evaluation value on the efficacy of SLIT treatment in AR patients.

Objectives: Studies suggest that transplant patients are at a higher risk of developing chronic rhinosinusitis (CRS). However, there is a dearth of studies describing the factors that may be linked to the development of CRS in this population. Our objective is to identify the risk factors associated with the development of CRS in transplant recipients.

Study design: Retrospective cohort.

Setting: Tertiary care center.

Methods: This cohort included 3347 transplant recipients seen between 2017 and 2022. Of these, 2128 patients met the inclusion criteria and were grouped according to whether they were diagnosed with CRS during the post-transplant period. The analysis included both univariate and multivariate analysis to ascertain the odds ratio (OR) and predictive factors.

Results: Of the 2128 patients, 649/2128 (30.4%) had CRS. CRS patients had an increased prevalence of previous endoscopic sinus surgery, allergic rhinitis, and recurrent acute rhinosinusitis in the pre-transplant period compared to the non-CRS group. According to the multivariate analysis, patients with primary immunodeficiency and additional transplant were 1.9 and 3.1 times more likely to develop CRS during the posttransplant period (95% CI: 1.3-2.6, p < .0001), (95% CI: 1.3 -7.3, p = .01), respectively. Sirolimus use was also associated with the development of CRS (OR = 1.4, 95% CI: 1.1-1.9, p = .01).

Conclusion: This study is the largest cohort aimed at determining the predictive factors associated with the development of CRS. Patients with pretransplant rhinologic conditions, hematologic deficiencies, and the utilization of specific immunosuppressants were found to have a higher likelihood of developing CRS following transplantation.