American Journal of Rhinology & Allergy最新文献

Background: Acute invasive fungal rhinosinusitis (AIFR) is a life-threatening disease mainly affecting immunocompromised patients. Early detection is therefore key to improving patient survival. To date, there are still no standard clinical criteria for AIFR diagnosis.

Objective: This study develops a predictive model that utilizes clinical presentation and computed tomography (CT) findings to diagnose AIFR.

Methods: A retrospective cohort study was conducted on patients with high risk for AIFR at King Chulalongkorn Memorial Hospital over the past 15 years (2008-2022). We constructed several multivariate logistic regression models for AIFR diagnosis based on different subsets of variables from 3 categories: signs/symptoms, endoscopy, and CT imaging.

Results: There were 67 AIFR-positive patients and 68 AIFR-negative patients. Combining variables from 3 categories, a 6-variable model (fever, visual loss, mucosal discoloration, crusting, mucosal loss of contrast, retroantral fat stranding) achieved the highest area under the receiver operating characteristic curve of 0.8900 (74.63% sensitivity, 89.71% specificity).

Conclusions: We proposed predictive models for AIFR diagnosis in high-risk patients using clinical variables. The models can be used to guide the decision for further management such as biopsy or surgical intervention.

Background: Dupilumab was first approved by the United States Food and Drug Administration in 2017 for atopic dermatitis and has since been approved for many other indications. The use of dupilumab has grown, but industry payments to physicians have yet to be explored.

Objective: The study objective is to characterize the change in payments by pharmaceutical companies to physicians for dupilumab-related promotional activities.

Methods: Data from 2017 to 2023 was extracted from the Open Payments website and filtered to determine the number of dupilumab-related payments to physicians, the amounts of these payments, the number of unique physicians that were paid, and the amount of money going towards different payment purposes.

Results: In 2017, pharmaceutical companies paid a total of $6.1 million to allergists/immunologists, dermatologists, gastroenterologists, otolaryngologists, and pulmonologists for dupilumab-related activities. This amount grew to a total of $22.6 million in 2023. These specialties all experienced an increase in the number of unique physicians paid; the number of allergists/immunologists paid increased by 1.8-fold, dermatologists by 1.4-fold, gastroenterologists by 640-fold, otolaryngologists by 95-fold, and pulmonologists by 118-fold. Across all five specialties, pharmaceutical companies paid the most money for the purpose of non-consulting, non-continuing education speaker fees.

Conclusion: From 2017 to 2023, pharmaceutical companies have paid increasing numbers of payments to increasing numbers of unique allergists/immunologists, dermatologists, gastroenterologists, otolaryngologists, and pulmonologists for dupilumab-related promotional events.

Background: Endoscopic sinus surgery (ESS) is a minimally invasive procedure indicated for medically refractory chronic sinusitis (CRS). As with any surgical procedure, there are potential risks and complications.

Objective: The purpose of this study is to report skull base, orbital, and hemorrhagic-associated complication rates following ESS.

Methods: A retrospective query on the TriNetX platform identified patients diagnosed with CRS who subsequently underwent ESS in the last 20 years. Outcomes analyses were performed to determine the incidence of skull base (cerebrospinal fluid rhinorrhea, bacterial meningitis, dural tear), orbital (diplopia, optic nerve injury, blindness, epiphora, orbital hemorrhage, canthotomy/canthoplasty), and hemorrhagic (epistaxis, carotid artery injury, blood transfusion) complications within 30 days postoperatively. Kaplan-Meier Analysis estimated survival probability from each complication type. Outcome rates were also compared between female and male patients.

Results: A total of 116 669 patients from 55 healthcare organizations fit the study criteria. The average age at surgery was 47.9 ± 17.9 years. The gender distribution of the cohort was 50% female and 48% male. The risk of skull base, orbital, and hemorrhagic complications within 30 days of the surgery was found to be 0.212%, 0.741%, and 3.00%, respectively. Kaplan-Meier Analysis revealed that survival probability from each complication type was 99.783%, 99.260%, and 96.903%, respectively. Comparison of outcome risks stratified by gender revealed no major differences for skull base and orbital complications; however, males exhibited a significantly higher risk of hemorrhagic complications (3.2% vs 2.8%, P < .0001).

Conclusions: The study supports ESS as a safe procedure for the management of CRS. Though rare, hemorrhagic complications are more common than orbital and skull base complications. Hemorrhagic complications are also more common in men than women. These findings provide insights for counseling patients about ESS risks and benefits.

Background: Computed tomography (CT) plays a crucial role in assessing chronic rhinosinusitis, but lacks objective quantifiable indicators.

Objective: This study aimed to use deep learning for automated sinus segmentation to generate distinct quantitative scores and explore their correlations with disease-specific quality of life.

Methods: From July 2021 to August 2022, 445 CT data were collected from 2 medical centers. A deep learning model based on nnU-Net was trained for automatic sinus segmentation and internally validated using 300 cases. The remaining 145 cases were split into an external testing set (74 cases) and an independent testing set (71 cases). Two quantitative scores, the quantitative Lund-MacKay score and the quantitative opacification score (QOS), were derived from the segmentation results. The quantitative scores' efficacy was assessed by comparing them with the Lund-MacKay score (LMS), the 22-item Sinonasal Outcome Test score (SNOT-22), and other clinical variables through correlation analyses. Furthermore, the relationship between quantitative scores and postoperative quality of life improvement was explored using single-factor logistic regression.

Result: The segmentation model achieved average Dice similarity coefficients of 0.993, 0.978, 0.958, and 0.871 for the training, validation, external testing, and independent testing sets, respectively. Both quantitative scores significantly correlated with the LMS (rho = 0.87 and rho = 0.70, P < .001). Neither score correlated with the total SNOT-22 score, although the modified QOS showed significant correlations with the nasal and sleep subdomains (rho = 0.26 and rho = 0.27, P < .05). No significant association was found between quantitative score and postoperative improvement in quality of life.

Conclusion: Deep learning enables the automated segmentation of sinuses on CT scans, producing quantitative scores of sinus opacification. These automatic quantitative scores may serve as tools for chronic rhinosinusitis assessment.

Purpose: Fractional nasal exhaled NO (FnNO), fractional exhaled NO (FeNO) and lung function tests were performed in children with moderate-to-severe persistent allergic rhinitis (AR) to investigate the significance of the above indices in the assessment and diagnosis of children with AR.

Methods: A total of 135 children with persistent AR were selected and divided into moderate-to-severe and mild groups; serum total immunoglobulin E (IgE), peripheral blood eosinophil counts (EOS), FnNO, FeNO, and lung function tests were performed.

Results: Children in the moderate-to-severe group had increased levels of FnNO and FeNO and decreased levels of forced expiratory flow at 75% of forced vital capacity as a percentage of the predicted value (FEF75%) and maximum mid-term expiratory flow as a percentage of the predicted value (MMEF%) . IgE in children with AR was positively correlated with FeNO and FnNO and negatively correlated with FEF75% . EOS was positively correlated with FnNO. FeNO was negatively correlated with FEF75% and forced expiratory flow at 50% of forced vital capacity as a percentage of the predicted value (FEF50%). FnNO was negatively correlated with FEF75%, FEF50%, and MMEF%.

Conclusion: FnNO, FeNO, and pulmonary function tests may help assess disease severity and level of disease control in children with persistent AR.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex immunological disease associated with significant morbidity and reduced health-related quality of life. Dupilumab is an anti-T2-inflammatory biological drug registered for chronic rhinosinusitis with nasal polyps, indicated by integrated care pathways when optimal medico-surgical treatment yields insufficient control of sinonasal symptoms.

Objective: The purpose of this study was to confirm the long-term efficacy of dupilumab in the treatment of severe uncontrolled CRSwNP.

Methods: Multicentric data collection of patients with severe uncontrolled CRSwNP treated with Dupilumab was retrospectively performed. Mixed Model Anova test was used to evaluate the effect of the biological therapy in the improvement of nasal polyp score and quality of life measured with Sinonasal Outcome Test-22 (SNOT-22) and visual analog scale (VAS) scores.

Results: The study showed a statistically significant and progressive improvement in the Nasal Polyp Score with a decrease from a median baseline value of 6 (IQR 5-6) to 0 (IQR 0-2) at 24 months. Furtherly, optimal results were found for SNOT-22 scores from baseline (62 ± 19) to 6 months (15± 11), with further variations on each successive timepoint remaining below the minimal clinically important difference. VAS scores of nasal obstruction, rhinorrhea, sleep disorders, and craniofacial pain, demonstrated consistent and significant improvements over time until one year of treatment, confirming substantial relief for the most pertinent symptoms of the condition.

Conclusions: The results of this study show high therapeutic efficacy and safety of dupilumab for severe CRswNP particularly in the first 6-12 months, with sustained benefits up to 24 months.

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: Cribriform foramina provide the openings for olfactory nerve fibers to cross from the nasal cavity to the olfactory bulb. Disruption of the olfactory nerve fibers is known to affect olfactory function, but little is known about the potential effects on the number of cribriform foramina in congenital anosmia.

Objective: This pilot study aimed to investigate whether there was a reduction in foramina in patients with acquired and congenital anosmia (including both Kallmann syndrome and isolated congenital anosmia) compared to controls with normal olfactory function.

Methods: Paranasal CT image stacks were analyzed from 20 patients with congenital anosmia (n = 6), acquired anosmia (n = 6), or normal olfactory function (n = 8). Cribriform foramina were counted by three observers from the slice revealing the crista galli and the ethmoidal slits. The two closest values for each subject were analyzed in comparison across the three groups using one-way analysis of variance.

Results: Patients with congenital, but not acquired, anosmia had significantly fewer cribriform foramina (x̄ ± SE = 10.17 ± 1.23) compared to healthy, normosmic controls (x̄ ± SE = 19.88 ± 2.01). There was no significant difference in foramina count between congenital and acquired anosmics (x̄ ± SE = 15.83 ± 3.47).

Conclusion: In this pilot study, a reduced number of cribriform foramina was found in individuals with congenital anosmia. Examination of cribriform foramina could be helpful in counseling patients with olfactory loss. Further investigation in larger studies with additional cohorts is warranted.

Background: Preoperative review of computed tomography (CT) imaging assists with endoscopic sinus surgery (ESS) planning, where trainees may benefit from a systematic approach. We have previously developed an optimized preoperative checklist for sinus CT imaging using an iterative modified Delphi method.

Objective: In this study, we assess the utility of an optimized preoperative checklist for residents performing ESS.

Methods: Resident sinus CT scan education consisted of a preintervention questionnaire, an 18-min video outlining the optimized preoperative checklist, and a delayed postintervention questionnaire; these were distributed via Qualtrics to otolaryngology residents across 5 training programs in the NY metro area. The preintervention questionnaire contained 25 survey questions and a 225-point quiz on sinus CT anatomy; the delayed postintervention questionnaire contained the same 25 survey questions and a second, distinct 225-point quiz.

Results: In total, 74 residents completed the preintervention questionnaire, 47 completed the postintervention questionnaire, and 36 completed both. Among residents completing both questionnaires, the average preintervention quiz score was 136.8 ± 24.0 and the average postintervention quiz score was 156.0 ± 23.5 (P < .001). Resident habitual utilization of a systematic preoperative CT imaging checklist increased significantly from 21.6% to 72.9% as a result of the curriculum intervention.

Conclusion: We find that an educational program centered on an iteratively optimized preoperative checklist for ESS improves the ability of trainees to identify critical sinus CT structures. Further integration of checklists and educational curricula may enhance rhinology education efforts and improve surgical anatomy competency.

Objective: To evaluate the association between smell loss and other aspects of disease, and evaluate dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate or severe smell loss.

Methods: This post-hoc analysis of the SINUS-24/52 studies (NCT02912468/NCT02898454) analyzed nasal polyp score (NPS, 0-8), nasal congestion/obstruction (NC, 0-3), Lund-Mackay CT-scan score (LMK-CT, 0-24), rhinosinusitis severity visual analog scale (RS-VAS, 0-10), and 22-item Sinonasal Outcome Test (SNOT-22, 0-110) according to baseline monthly average patient-reported loss of smell scores (LoS, 0-3) of >1 to 2 (moderate) or >2 to 3 (severe) in patients randomized to dupilumab 300 mg or placebo every 2 weeks.

Results: Of 724 patients randomized, baseline LoS was severe in 601 (83%) and moderate in 106 (15%). At baseline, severe versus moderate LoS was associated with 1-point greater severity of NC (odds ratio [OR] 6.01 [95% confidence interval, (CI) 3.95, 9.15]), 5-point greater severity of LMK-CT (OR 2.19 [1.69, 2.85]), and 8.9-point greater severity of SNOT-22 (OR 1.35 [1.20, 1.49]). At Week 24, least squares mean differences (95% CI) dupilumab versus placebo in change from baseline were: NPS -1.90 (-2.56, -1.25) and -1.95 (-2.20, -1.70) in the moderate and severe baseline LoS subgroups, respectively; NC -.35 (-.64, -.06) and -1.00 (-1.13, -.87); LMK-CT -6.30 (-7.88, -4.72) and -6.22 (-6.82, -5.63); RS-VAS -1.18 (-2.20, -.16) and -3.47 (-3.90, -3.03); and SNOT-22 -7.52 (-14.55, -.48) and -21.72 (-24.63, -18.82); all nominal P < .05 versus placebo. Improvements with dupilumab in NC, RS-VAS, and SNOT-22 were statistically greater in patients with severe versus moderate baseline LoS.

Conclusion: Significant smell impairment in severe CRSwNP is associated with significant disease (NC, RS-VAS, LMK), health-related quality of life impairment (SNOT-22), asthma, and non-steroidal anti-inflammatory drug-exacerbated respiratory disease. Dupilumab significantly improved NPS, NC, LMK-CT, RS-VAS, and SNOT-22 in subjects with moderate and severe baseline smell loss.