基于多维特征的无监督聚类分析揭示慢性鼻窦炎伴鼻息肉不同内在型的临床特点及相关因素  

Unsupervised clustering analysis based on multidimensional features reveals distinct clinical characteristics and associated factors of different phenotypes in patients with chronic rhinosinusitis with nasal polyp

作　　者：黄晶煜 骆勇戈 吕浩 刘朵 王云飞 刘佩强 谭路[1] 向荣[1] 章薇[1] 许昱[1,3] Huang Jingyu;Luo Yongge;Lyu Hao;Liu Duo;Wang Yunfei;Liu Peiqiang;Tan Lu;Xiang Rong;Zhang Wei;Xu Yu(Department of Rhinology and Allergy,Otorhinolaryngology Head and Neck Surgery Center,Renmin Hospital of Wuhan University,Wuhan 430060,China;Department of Radiation and Medical Oncology,Zhongnan Hospital,WuhannUniversity,Wuhan 430071,China;ResearchInstitute of Otorhinolaryngology Head and Neck Surgery,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院耳鼻咽喉头颈外科中心鼻科及变态反应科,武汉430060 [2]武汉大学中南医院放化疗科,武汉430071 [3]武汉大学人民医院耳鼻咽喉头颈外科研究所,武汉430060

出　　处：《中华耳鼻咽喉头颈外科杂志》2024年第6期590-601,共12页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：国家自然科学基金(82271134、82071017、82201250);湖北省自然科学基金(2023AFB229);武汉大学自主科研项目(2042023kf0025);湖北省重点实验室开放项目-种子基金项目(2023KFZ011)。

摘　　要：目的:利用常规可用的临床标志物,通过对慢性鼻窦炎伴鼻息肉(CRSwNP)患者进行无监督聚类分析,揭示不同集群患者的临床特征。方法:收集2021—2023年于武汉大学人民医院接受鼻内镜手术治疗的155例CRSwNP患者(男112例,女43例,年龄7~87岁)的临床数据,包括年龄、性别、吸烟史、饮酒史、组织局部嗜酸粒细胞(EOS)计数及中性粒细胞(NEU)计数、共病变应性鼻炎(AR)、共病哮喘、是否复发、血清特异性免疫球蛋白E(IgE)、总IgE、细胞因子水平、外周血EOS计数及占比、Lund-Mackay CT评分、筛窦和上颌窦CT评分的比率(E/M比率)、视觉模拟量表(VAS)评分、Lund-Kennedy内镜评分等常见临床指标,进行无监督聚类分析,以明确每个群组对应的临床特征。采用GraphPad Prism 9.5软件对数据进行统计学分析。结果:通过临床核心指标的层次聚类分析,我们将患者分为4类(Cluster A1~A4),其主要特点是外周血细胞因子较高的轻症息肉、伴发过敏及哮喘的鼻息肉、高复发的NEU型鼻息肉亚组,以及高嗜酸性鼻息肉。核心指标及其子集的聚类结果展示了两类轻症息肉(Cluster B1~B2),其主要特点是细胞因子高表达、合并AR;以及两类重型息肉(Cluster B3~B4),临床表现为症状严重且Lund-Mackay CT评分、Lund-Kennedy内镜评分均高,其差异在于症状的复杂性、EOS浸润程度和伴发哮喘的概率。针对嗜酸性鼻息肉的进一步聚类分析,揭示了一类高度NEU浸润的复发性鼻息肉。多指标相关性分析的结果全面展示了鼻息肉常见临床参数之间的关联,为深入理解CRSwNP的临床表型提供了有价值的信息。结论:通过聚类分析,成功将CRSwNP患者分为不同亚型,深入探讨了它们在临床特征和疾病结果上的差异,为制定更精准的临床治疗方案提供了新的视角。Objective To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp(CRSwNP)through unsupervised clustering analysis.Methods The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected,including 112 males and 43 females,aged from 7 to 87 years.Unsupervised clustering analysis was conducted using various clinical parameters,including age,gender,smoking and drinking history,local eosinophil(EOS)and neutrophil(NEU)counts,comorbid allergic rhinitis(AR),comorbid asthma,recurrence status,serum-specific IgE,total IgE,cytokine levels,peripheral blood EOS count and percentage,Lund-Mackay CT score,the ratio of CT scores for the maxillary sinus and ethmoid sinus(E/M ratio),visual analogue scale(VAS)score,Lund-Kennedy endoscopic score,and other common clinical indicators to elucidate the clinical characteristics of each cluster.Statistical analysis was conducted using GraphPad Prism 9.5 software.Results Hierarchical clustering analysis identified four main clusters(Cluster A1-A4),showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels,nasal polyps accompanied by allergies and asthma,a subtype of nasal polyps with high recurrence rates dominated by neutrophils,and nasal polyps with high eosinophil levels.Further subset clustering revealed two clusters of mild polyps(Cluster B1-B2)featuring high cytokine expression and comorbid AR;and two clusters of severe polyps(Cluster B3-B4)presented with severe symptoms,high Lund-Mackay CT score,and high Lund-Kennedy endoscopic score.Variations between Cluster B3 and B4 included symptom complexity,the degree of eosinophil infiltration,and the probability of comorbid asthma.Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps.The comp

关 键 词：鼻窦炎 鼻息肉 层次聚类分析 复发 内在型 

分 类 号：R765[医药卫生—耳鼻咽喉科]