James Bates, Joshua Liaw, Kathryn Girling, Alecia Banks, Sean Gannon, James Earnshaw, Abigail Walker
Background
Botulinum toxin type A is a potent neurotoxin and was first approved for use in 1989; since there has been a surge in its uses. The latest international trend is the unapproved use of botulinum toxin for allergic and nonallergic rhinitis, being advertised as “Haytox.”
Methods
A single-group open-label non-randomized Phase 1 clinical trial was completed. Rhinitis and nonallergic rhinitis were confirmed via formalized examination and testing with total IgE and radioallergosorbent test (RAST). Participants received 40 units of botulinum toxin type A, administered topically intranasally, 20 units per nostril, using the LMA MAD Nasal Intranasal Mucosal Atomization Device. Safety of the intervention was assessed with adverse event tracking logs. Symptom scores were used to assess symptom reduction, including total nasal symptom score (TNSS), visual analog scale (VAS) measurements at Weeks 0, 2, 4, and 12. In addition, peak nasal inspiratory flow (PNIF) was measured at Weeks 0 and 4, with the minimum clinically important difference (MCID) being used to demonstrate any clinically significant change in the TNSS score.
Results: A total of
15 participants enrolled, of which 14 participants received treatment, with no serious adverse or related adverse events reported. There was a statistically and clinically significant reduction in TNSS and a statistically significant reduction in VAS from Weeks 0 to 12.
Conclusion
In this Phase 1 trial, topical application of botulinum toxin via spray was shown to be safe, without any significant adverse events. It reduced the TNSS and VAS across the cohort. However, the treatment efficacy should be taken in context as there was no blinding, alternative dosing, or comparison against placebo or recognized active treatment options. This safety data should embolden future research trials.
{"title":"A Phase 1 Research Trial to Evaluate the Safety and Effectiveness of Intranasal Botulinum Toxin Type A Spray for Patients With Rhinitis","authors":"James Bates, Joshua Liaw, Kathryn Girling, Alecia Banks, Sean Gannon, James Earnshaw, Abigail Walker","doi":"10.1002/alr.70058","DOIUrl":"10.1002/alr.70058","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Botulinum toxin type A is a potent neurotoxin and was first approved for use in 1989; since there has been a surge in its uses. The latest international trend is the unapproved use of botulinum toxin for allergic and nonallergic rhinitis, being advertised as “Haytox.”</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A single-group open-label non-randomized Phase 1 clinical trial was completed. Rhinitis and nonallergic rhinitis were confirmed via formalized examination and testing with total IgE and radioallergosorbent test (RAST). Participants received 40 units of botulinum toxin type A, administered topically intranasally, 20 units per nostril, using the LMA MAD Nasal Intranasal Mucosal Atomization Device. Safety of the intervention was assessed with adverse event tracking logs. Symptom scores were used to assess symptom reduction, including total nasal symptom score (TNSS), visual analog scale (VAS) measurements at Weeks 0, 2, 4, and 12. In addition, peak nasal inspiratory flow (PNIF) was measured at Weeks 0 and 4, with the minimum clinically important difference (MCID) being used to demonstrate any clinically significant change in the TNSS score.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results: A total of</h3>\u0000 \u0000 <p>15 participants enrolled, of which 14 participants received treatment, with no serious adverse or related adverse events reported. There was a statistically and clinically significant reduction in TNSS and a statistically significant reduction in VAS from Weeks 0 to 12.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this Phase 1 trial, topical application of botulinum toxin via spray was shown to be safe, without any significant adverse events. It reduced the TNSS and VAS across the cohort. However, the treatment efficacy should be taken in context as there was no blinding, alternative dosing, or comparison against placebo or recognized active treatment options. This safety data should embolden future research trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>TGA number: CT-2024-CTN-02905-1; ANZCTR number: ACTRN12624000772549</p>\u0000 </section>\u0000 </div>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":"16 2","pages":"162-169"},"PeriodicalIF":6.8,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jamie R. Oliver, Naomi C. Wang, Cole W. VandeVelde, Nathan Farrokhian, Jennifer A. Villwock
{"title":"Systemic Estrogen Therapy Is Associated With Lower Surgical Intervention Rates for Nasal Obstruction","authors":"Jamie R. Oliver, Naomi C. Wang, Cole W. VandeVelde, Nathan Farrokhian, Jennifer A. Villwock","doi":"10.1002/alr.70041","DOIUrl":"10.1002/alr.70041","url":null,"abstract":"","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":"15 12","pages":"1429-1432"},"PeriodicalIF":6.8,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chandler Rygalski, Nanda Nayak, Christina Dorismond, Rory Lubner, Daniel Lofgren, Ping Li, Katherine N. Cahill, Mason Krysinski, Rakesh Chandra, Justin Turner, Naweed Chowdhury
<p>Chronic rhinosinusitis (CRS) is among the most common chronic upper airway diseases in the United States, with evidence suggesting chronic air pollutant exposure, such as fine particulate matter 2.5 (PM<sub>2.5</sub>), has implications in both its development and severity [<span>1-4</span>]. In the current study, we hypothesized that chronic PM<sub>2.5</sub> exposure could adversely impact quality-of-life (QoL) outcomes after endoscopic sinus surgery (ESS) in CRS patients and sought to quantify this effect.</p><p>Patients undergoing ESS were enrolled in a single-center prospective observational cohort study of CRS and followed for at least 6 months. Home addresses were converted into latitude and longitude coordinates for exposure estimation using the <i>geocoder</i> tool in DeGAUSS [<span>5</span>]. A validated open-source high-resolution spatiotemporal PM<sub>2.5</sub> exposure model was used to estimate daily exposure and averaged to obtain an exposure summary measure in the year prior to surgery [<span>6</span>]. The 22-item Sino-Nasal Outcome Test (SNOT-22) was completed at baseline and subsequent follow-up appointments at 6, 12, 18, and 24 months to allow longitudinal evaluation of QoL outcomes. Survey results were also divided into the five underlying subdomains to allow analysis by symptom group (rhinologic, extra-nasal rhinologic, ear/facial symptoms, psychological, and sleep) [<span>7</span>]. Minimal clinically important differences (MCID) for each subdomain (3.8, 2.4, 3.2, 3.9, and 2.9 points, respectively) were used to evaluate for clinically meaningful changes in postoperative scores [<span>8</span>]. Multivariate linear regression models were used for the overall CRS cohort and the subpopulations of CRS with and without nasal polyps (CRSwNP, CRSsNP, respectively) to estimate the association between average preoperative 12-month PM<sub>2.5</sub> exposures and postoperative QoL outcomes after adjusting for sociodemographic variables known to be associated with PM<sub>2.5</sub> exposure, including RUCA scores and income. All analyses were conducted in R version 4.2.1 (R Core Team, Vienna, Austria) on the Vanderbilt Advanced Computing Cluster for Research and Education (ACCRE). A prespecified alpha threshold of 0.05 was used to determine statistical significance.</p><p>A total of 226 CRS patients met inclusion criteria and had sufficient follow-up of at least 6 months, with 113 patients in both subpopulations of CRSwNP and CRSsNP (Table S1). Mean 12-month PM<sub>2.5</sub> levels for the group were estimated at 8.2 µg/m<sup>3</sup>, with a range of 6.5–13 µg/m<sup>3</sup>. The mean (SD) baseline total SNOT-22 score for the overall CRS cohort was 43.7 (19.9), indicative of a moderately severe level of QoL impairment. The mean overall postoperative change in SNOT-22 scores in our patient population was −21.4 ± 21.5 points, demonstrating a notable QoL improvement after ESS. The most common follow-up length was 6 months (31%), with decre
慢性鼻窦炎（CRS）是美国最常见的慢性上呼吸道疾病之一，有证据表明，慢性空气污染物暴露，如细颗粒物2.5 (PM2.5)，对其发展和严重程度都有影响[1-4]。在当前的研究中，我们假设慢性PM2.5暴露可能会对CRS患者内窥镜鼻窦手术（ESS）后的生活质量（QoL）结果产生不利影响，并试图量化这种影响。接受ESS的患者被纳入一项CRS的单中心前瞻性观察队列研究，并随访至少6个月。使用DeGAUSS[5]中的地理编码器工具将家庭地址转换为纬度和经度坐标，以便进行暴露估计。使用一个经过验证的开源高分辨率时空PM2.5暴露模型来估计每日暴露量，并取其平均值以获得手术前一年的暴露总测量值。22项鼻-鼻预后测试（SNOT-22）在基线时完成，随后在6、12、18和24个月随访，以便对生活质量结果进行纵向评估。调查结果还分为五个潜在的子域，以便根据症状组（鼻、鼻外、耳/面部症状、心理和睡眠）进行分析。每个子域的最小临床重要差异（MCID）（分别为3.8、2.4、3.2、3.9和2.9分）用于评估术后评分[8]的临床意义变化。在调整已知与PM2.5暴露相关的社会人口学变量（包括RUCA评分和收入）后，对CRS总体队列和伴有和不伴有鼻息肉的CRS亚群（分别为CRSwNP和CRSsNP）使用多元线性回归模型来估计术前平均12个月PM2.5暴露与术后生活质量结果之间的关联。所有的分析都是在Vanderbilt Advanced Computing Cluster for Research and Education （ACCRE）上的R 4.2.1版本（R Core Team, Vienna, Austria）中进行的。采用预先设定的alpha阈值0.05来确定统计学显著性。共有226例CRS患者符合纳入标准，并进行了至少6个月的随访，其中113例患者属于CRSwNP和CRSsNP亚群（表S1）。该组的12个月平均PM2.5水平估计为8.2微克/立方米，范围为6.5-13微克/立方米。总体CRS队列的平均（SD）基线总SNOT-22评分为43.7(19.9)，表明生活质量受损的中度严重水平。在我们的患者群体中，术后SNOT-22评分的平均总体变化为- 21.4±21.5分，表明ESS后的生活质量显著改善。最常见的随访时间为6个月（31%），随着随访时间间隔的缩短，随访时间为24个月的患者占总人数的19%。表1和表2分别显示了CRSwNP和CRSsNP对ESS后SNOT-22总和子域变化评分与12个月PM2.5平均水平的多元回归建模结果。在CRSwNP中，PM2.5暴露与术后改善程度之间存在显著关联（β = 8.25, p = 0.036），暴露程度越高，SNOT-22总分改善程度越低。从亚组来看，心理领域总分（β = 3.68, p = 0.013）和睡眠领域总分（β = 2.57, p = 0.037）的变化有显著相似的相关性。值得注意的是，CRSsNP亚组术后SNOT-22总分或子域评分与12个月PM2.5暴露之间没有统计学上的显著关联。本研究结果表明，慢性PM2.5暴露是CRSwNP患者ESS后生活质量改善降低的潜在危险因素。我们的多元回归结果表明，12个月PM2.5暴露量每增加1 μ g/m3，术后整体SNOT-22改善幅度下降约8个点，接近公布的MCID 8.9分。在心理和睡眠子域中，在12个月的PM2.5暴露中，每增加1微克/立方米，总体变化幅度就会下降约3和2个点，接近这些子域的MCID值（分别为3.2和2.9点）。这些结果表明，在整个SNOT-22评分及其子域中，暴露增加1-1.5µg/m3可能会影响术后结果，其临床意义为[8]。值得注意的是，受PM2.5暴露影响最大的两个snt -22子域是心理和睡眠域，这两个子域通常被认为是CRS的次要影响，而不是临床综合征的主要标志。 先前的研究表明，在心理和睡眠领域的基线得分较高的患者更有可能寻求手术治疗，尽管术后这些症状的改善最小。根据我们的研究，慢性PM2.5暴露可能会进一步减弱这些改善，并成为难治性症状的驱动因素，这突出了术前预期咨询和对这些症状进行多方面管理的必要性。这项研究有几个重要的局限性。首先，我们的人口主要由位于小地理区域的白人患者组成，限制了其普遍性。此外，虽然家庭住址在每次预约时都得到确认，但由于混杂因素，如职业暴露或术前期间的多个地址，我们的估计可能无法准确反映个人暴露情况。由于其收集的可靠性较低，吸烟状况也未包括在内。最后，虽然SNOT-22评分被用来衡量长期术后结果，但这通常是一个嘈杂的指标，容易在受试者内部发生变化，这些变化基于药物依从性、急性加重和季节性因素，而这些因素没有被考虑在内。尽管存在这些局限性，但目前的研究进一步证明了空气污染物暴露的重要性及其与较差的术后结果的关联，值得在更广泛的地理范围内进行更大规模的多机构研究，并有可能使用可穿戴传感器进行个性化暴露计算。Katherine N. Cahill曾在AstraZeneca、Sanofi、Genentech、Regeneron、Novartis的科学顾问委员会任职，担任Eli Lilly的顾问，报告来自UpToDate的版税，并报告来自Novo Nordisk的研究支持。Rakesh Chandra是Sanofi， Regeneron, Optinose， Lyra Therapeutics的顾问。所有其他作者声明无利益冲突。
{"title":"The Impact of Chronic Particulate Matter Exposure on Quality-of-Life Outcomes After Endoscopic Sinus Surgery","authors":"Chandler Rygalski, Nanda Nayak, Christina Dorismond, Rory Lubner, Daniel Lofgren, Ping Li, Katherine N. Cahill, Mason Krysinski, Rakesh Chandra, Justin Turner, Naweed Chowdhury","doi":"10.1002/alr.70051","DOIUrl":"10.1002/alr.70051","url":null,"abstract":"<p>Chronic rhinosinusitis (CRS) is among the most common chronic upper airway diseases in the United States, with evidence suggesting chronic air pollutant exposure, such as fine particulate matter 2.5 (PM<sub>2.5</sub>), has implications in both its development and severity [<span>1-4</span>]. In the current study, we hypothesized that chronic PM<sub>2.5</sub> exposure could adversely impact quality-of-life (QoL) outcomes after endoscopic sinus surgery (ESS) in CRS patients and sought to quantify this effect.</p><p>Patients undergoing ESS were enrolled in a single-center prospective observational cohort study of CRS and followed for at least 6 months. Home addresses were converted into latitude and longitude coordinates for exposure estimation using the <i>geocoder</i> tool in DeGAUSS [<span>5</span>]. A validated open-source high-resolution spatiotemporal PM<sub>2.5</sub> exposure model was used to estimate daily exposure and averaged to obtain an exposure summary measure in the year prior to surgery [<span>6</span>]. The 22-item Sino-Nasal Outcome Test (SNOT-22) was completed at baseline and subsequent follow-up appointments at 6, 12, 18, and 24 months to allow longitudinal evaluation of QoL outcomes. Survey results were also divided into the five underlying subdomains to allow analysis by symptom group (rhinologic, extra-nasal rhinologic, ear/facial symptoms, psychological, and sleep) [<span>7</span>]. Minimal clinically important differences (MCID) for each subdomain (3.8, 2.4, 3.2, 3.9, and 2.9 points, respectively) were used to evaluate for clinically meaningful changes in postoperative scores [<span>8</span>]. Multivariate linear regression models were used for the overall CRS cohort and the subpopulations of CRS with and without nasal polyps (CRSwNP, CRSsNP, respectively) to estimate the association between average preoperative 12-month PM<sub>2.5</sub> exposures and postoperative QoL outcomes after adjusting for sociodemographic variables known to be associated with PM<sub>2.5</sub> exposure, including RUCA scores and income. All analyses were conducted in R version 4.2.1 (R Core Team, Vienna, Austria) on the Vanderbilt Advanced Computing Cluster for Research and Education (ACCRE). A prespecified alpha threshold of 0.05 was used to determine statistical significance.</p><p>A total of 226 CRS patients met inclusion criteria and had sufficient follow-up of at least 6 months, with 113 patients in both subpopulations of CRSwNP and CRSsNP (Table S1). Mean 12-month PM<sub>2.5</sub> levels for the group were estimated at 8.2 µg/m<sup>3</sup>, with a range of 6.5–13 µg/m<sup>3</sup>. The mean (SD) baseline total SNOT-22 score for the overall CRS cohort was 43.7 (19.9), indicative of a moderately severe level of QoL impairment. The mean overall postoperative change in SNOT-22 scores in our patient population was −21.4 ± 21.5 points, demonstrating a notable QoL improvement after ESS. The most common follow-up length was 6 months (31%), with decre","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":"15 12","pages":"1425-1428"},"PeriodicalIF":6.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alr.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sidharth K. Sengupta, Jess C. Mace, Kara Y. Detwiller, Timothy L. Smith, Mathew Geltzeiler, Vivek C. Pandrangi
{"title":"Olfactory Dysfunction and Mental Health Disparities Within a US Population","authors":"Sidharth K. Sengupta, Jess C. Mace, Kara Y. Detwiller, Timothy L. Smith, Mathew Geltzeiler, Vivek C. Pandrangi","doi":"10.1002/alr.70049","DOIUrl":"10.1002/alr.70049","url":null,"abstract":"","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":"15 12","pages":"1419-1424"},"PeriodicalIF":6.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jakob L. Fischer, Tyler J. Gallagher, Matthew E. Lin, Ian Kim, Bozena B. Wrobel, Daniel M. Beswick, Jivianne T. Lee, Marilene B. Wang, Jeffrey D. Suh
{"title":"Reassessment of Age-Group Subanalyses in Sinus Surgery Complications in a TriNetX Database","authors":"Jakob L. Fischer, Tyler J. Gallagher, Matthew E. Lin, Ian Kim, Bozena B. Wrobel, Daniel M. Beswick, Jivianne T. Lee, Marilene B. Wang, Jeffrey D. Suh","doi":"10.1002/alr.70053","DOIUrl":"10.1002/alr.70053","url":null,"abstract":"","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":"15 12","pages":"1448-1452"},"PeriodicalIF":6.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Konstantinos Garefis, Susanne Weise, Pauline Hanslik, Coralie Mignot, Halina B. Stanley, Maxime Fieux, Camille Ferdenzi, Evangelia Tsakiropoulou, Clémentine Lipp, Arnaud Bertsch, Moustafa Bensafi, Iordanis Konstantinidis, Thomas Hummel
{"title":"Response to Dr. Hyun Jin Min's Letter Regarding “Electrical Stimulation of Trigeminal Nerve at the Anterior Nasal Septum in Healthy Individuals and Patients With Olfactory Dysfunction”","authors":"Konstantinos Garefis, Susanne Weise, Pauline Hanslik, Coralie Mignot, Halina B. Stanley, Maxime Fieux, Camille Ferdenzi, Evangelia Tsakiropoulou, Clémentine Lipp, Arnaud Bertsch, Moustafa Bensafi, Iordanis Konstantinidis, Thomas Hummel","doi":"10.1002/alr.70055","DOIUrl":"10.1002/alr.70055","url":null,"abstract":"","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":"15 11","pages":"1338-1339"},"PeriodicalIF":6.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Age-Group Subanalyses in TriNetX: A Critique and Re-Analysis","authors":"Ming-Chin Lan, Joshua Wang","doi":"10.1002/alr.70057","DOIUrl":"10.1002/alr.70057","url":null,"abstract":"","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":"15 11","pages":"1327-1328"},"PeriodicalIF":6.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dipesh Gyawali, Thomas Mundy, Majid Hosseini, Morteza Bodaghi, Akio Fujiwara, Sejal Shyam Bhatia, Kayla Baker, Elena Bartolone, Dhara Patel, Henry Chu, Raju Gottumukkala, Jonathan Bidwell, Edward D. McCoul
Background
Sinusitis is a prevalent disease for which nasal endoscopy (NE) is an optimal diagnostic modality. However, NE accuracy is limited by inter-operator variability in landmark identification and localization of mucus that is necessary for sinusitis diagnosis. We sought to develop a novel multi-class machine learning (ML) framework that detects anatomical landmarks and structures for sinusitis assessment as supported by clinical best practices.
Methods
A total of 3513 NE images from 452 patients were manually annotated by four physicians for three classes: middle turbinate (MT), inferior turbinate (IT), and mucus. A YOLOv11-nano model was trained for multi-class detection and segmentation. We developed a rule-based logic for middle meatus localization, implementing a clinical algorithm that applies anatomy Intersection over Union (IoU) and conditional logic for sinusitis diagnosis. The system was validated on 178 images from 50 patients with chronic rhinosinusitis without polyps (CRSsNP) with benchmarking of real-time performance.
Results
The multi-class detection and segmentation model achieved > 75% F1 score for detecting turbinates with mucus. The clinical algorithm achieved 75.0% sensitivity, 76.0% specificity, and 75.2% accuracy for sinusitis classification, with a F1 score of 81.8%, approaching the accuracy of a trained otolaryngologist. The framework achieved near real-time performance at > 20fps on GPU device, demonstrating suitability for integration into live clinical workflows.
Conclusion
This novel ML-driven diagnostic framework with a rule-based clinical algorithm enhances decision-making for diagnosing sinusitis with NE. By reducing inter-operator variability, achieving performance comparable to otolaryngologists, and enabling real-time processing for non-specialists, this work holds potential for standardizing care and improving patient outcomes. Future research will focus on expanding to different sinusitis phenotypes and prospective real-time implementation in clinical settings.
{"title":"Machine Learning-Enhanced Clinical Decision Support for Diagnosing Sinusitis With Nasal Endoscopy","authors":"Dipesh Gyawali, Thomas Mundy, Majid Hosseini, Morteza Bodaghi, Akio Fujiwara, Sejal Shyam Bhatia, Kayla Baker, Elena Bartolone, Dhara Patel, Henry Chu, Raju Gottumukkala, Jonathan Bidwell, Edward D. McCoul","doi":"10.1002/alr.70045","DOIUrl":"10.1002/alr.70045","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sinusitis is a prevalent disease for which nasal endoscopy (NE) is an optimal diagnostic modality. However, NE accuracy is limited by inter-operator variability in landmark identification and localization of mucus that is necessary for sinusitis diagnosis. We sought to develop a novel multi-class machine learning (ML) framework that detects anatomical landmarks and structures for sinusitis assessment as supported by clinical best practices.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 3513 NE images from 452 patients were manually annotated by four physicians for three classes: middle turbinate (MT), inferior turbinate (IT), and mucus. A YOLOv11-nano model was trained for multi-class detection and segmentation. We developed a rule-based logic for middle meatus localization, implementing a clinical algorithm that applies anatomy Intersection over Union (IoU) and conditional logic for sinusitis diagnosis. The system was validated on 178 images from 50 patients with chronic rhinosinusitis without polyps (CRSsNP) with benchmarking of real-time performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The multi-class detection and segmentation model achieved > 75% F1 score for detecting turbinates with mucus. The clinical algorithm achieved 75.0% sensitivity, 76.0% specificity, and 75.2% accuracy for sinusitis classification, with a F1 score of 81.8%, approaching the accuracy of a trained otolaryngologist. The framework achieved near real-time performance at > 20fps on GPU device, demonstrating suitability for integration into live clinical workflows.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This novel ML-driven diagnostic framework with a rule-based clinical algorithm enhances decision-making for diagnosing sinusitis with NE. By reducing inter-operator variability, achieving performance comparable to otolaryngologists, and enabling real-time processing for non-specialists, this work holds potential for standardizing care and improving patient outcomes. Future research will focus on expanding to different sinusitis phenotypes and prospective real-time implementation in clinical settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":"16 2","pages":"152-161"},"PeriodicalIF":6.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12863022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yeong-In Jo, Jee Won Moon, Joo-Hoo Park, Hwa Eun Yang, Subin Cho, Hyeongguk Son, Hyun-Woo Yang, Il-Ho Park
Background
Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is characterized by persistent sinonasal inflammation and marked eosinophilic infiltration. Although the relationship between eosinophils and NP formation has been extensively studied, the mechanisms governing eosinophil transepithelial migration into the nasal mucosa remain poorly understood. Cadherin-26 (CDH26), an epithelial adhesion molecule that binds to integrins α4 (ITGA4) and αE, has been implicated in eosinophilic inflammation and may play a critical role in eosinophil recruitment and tissue infiltration.
Objective
This study aimed to investigate the role and underlying mechanism of CDH26 in facilitating eosinophil transepithelial migration in patients with eCRSwNP.
Methods
Single-cell ribonucleic acid (RNA) sequencing and immunohistochemistry (IHC) were performed on nasal tissues from patients with eCRSwNP, non-eCRSwNP, chronic rhinosinusitis without nasal polyps (CRSsNP), and healthy controls to evaluate CDH26 expression. Human primary nasal epithelial cells (hPNECs) were stimulated in vitro with interleukin-4 (IL-4) or IL-13, and CDH26 expression was assessed via reverse transcription polymerase chain reaction (RT-PCR), western blotting, and IHC. The effect of IL-4 receptor blockade using Dupilumab was evaluated in monolayer cultures. ITGA4 expression in EoL-1 eosinophil-like cells was measured by flow cytometry, and their interaction with recombinant CDH26 was evaluated using cell adhesion and Transwell migration assays.
Results
CDH26 expression was significantly upregulated in eCRSwNP tissues compared to that in other groups. IL-4 and IL-13 stimulation induced CDH26 expression in hPNECs, which was dose-dependently inhibited by Dupilumab. EoL-1 cells expressed ITGA4 and adhered to recombinant CDH26 in vitro. Th2 cytokine stimulation enhanced EoL-1 cell transepithelial migration, which was significantly reduced by CDH26 knockdown or Dupilumab treatment.
Conclusion
Th2 cytokine-induced upregulation of epithelial CDH26 facilitates eosinophil transepithelial migration, potentially via ITGA4 interaction. Thus, CDH26 may represent a novel therapeutic target for managing eCRSwNP.
{"title":"Cadherin-26 Facilitates Transepithelial Migration of Eosinophils in Eosinophilic Chronic Rhinosinusitis","authors":"Yeong-In Jo, Jee Won Moon, Joo-Hoo Park, Hwa Eun Yang, Subin Cho, Hyeongguk Son, Hyun-Woo Yang, Il-Ho Park","doi":"10.1002/alr.70044","DOIUrl":"10.1002/alr.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is characterized by persistent sinonasal inflammation and marked eosinophilic infiltration. Although the relationship between eosinophils and NP formation has been extensively studied, the mechanisms governing eosinophil transepithelial migration into the nasal mucosa remain poorly understood. Cadherin-26 (CDH26), an epithelial adhesion molecule that binds to integrins α4 (ITGA4) and αE, has been implicated in eosinophilic inflammation and may play a critical role in eosinophil recruitment and tissue infiltration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to investigate the role and underlying mechanism of CDH26 in facilitating eosinophil transepithelial migration in patients with eCRSwNP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-cell ribonucleic acid (RNA) sequencing and immunohistochemistry (IHC) were performed on nasal tissues from patients with eCRSwNP, non-eCRSwNP, chronic rhinosinusitis without nasal polyps (CRSsNP), and healthy controls to evaluate CDH26 expression. Human primary nasal epithelial cells (hPNECs) were stimulated in vitro with interleukin-4 (IL-4) or IL-13, and CDH26 expression was assessed via reverse transcription polymerase chain reaction (RT-PCR), western blotting, and IHC. The effect of IL-4 receptor blockade using Dupilumab was evaluated in monolayer cultures. ITGA4 expression in EoL-1 eosinophil-like cells was measured by flow cytometry, and their interaction with recombinant CDH26 was evaluated using cell adhesion and Transwell migration assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CDH26 expression was significantly upregulated in eCRSwNP tissues compared to that in other groups. IL-4 and IL-13 stimulation induced CDH26 expression in hPNECs, which was dose-dependently inhibited by Dupilumab. EoL-1 cells expressed ITGA4 and adhered to recombinant CDH26 in vitro. Th2 cytokine stimulation enhanced EoL-1 cell transepithelial migration, which was significantly reduced by CDH26 knockdown or Dupilumab treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Th2 cytokine-induced upregulation of epithelial CDH26 facilitates eosinophil transepithelial migration, potentially via ITGA4 interaction. Thus, CDH26 may represent a novel therapeutic target for managing eCRSwNP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13716,"journal":{"name":"International Forum of Allergy & Rhinology","volume":"16 2","pages":"138-151"},"PeriodicalIF":6.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12863020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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