基于潜在类别分析的表皮生长因子受体酪氨酸激酶抑制剂相关性皮疹的中医证候特征研究

Study on Traditional Chinese Medicine Syndromes of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-related Rash: based on Latent Class Analysis

目的 基于潜在类别分析探讨表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)相关性皮疹的证候规律。方法 纳入EGFR-TKIs相关性皮疹的非小细胞肺癌患者123例。收集患者的一般资料和皮疹表现特征[包括皮损形态、颜色、光泽、渗液,虚实及其他症状(瘙痒、疼痛)],并将患者根据使用EGFR-TKIs情况分为:第一代(吉非替尼、厄洛替尼、埃克替尼)、第二代(阿法替尼、达克替尼)、第三代(奥希替尼)。采用潜在类别分析方法对皮疹表现进行数据挖掘分析,包括模型参数化、参数估计、模型识别、模型评价、潜在分类和结果解释。结果 123例患者中男性63例、女性60例,使用EGFR-TKIs第一代52例、第二代57例、第三代14例,使用各代EGFR-TKIs的患者在基因分布类型方面差异有统计学意义(P<0.05)。丘疹伴渗液、水疱、湿热、血虚夹痰、湿痒在使用各代EGFR-TKIs的患者中分布差异有统计学意义(P<0.05)。潜类别分析结果显示,当潜类别数为3时,贝叶斯信息准则(BIC)最小(BIC=3657.74),结合临床实际,包含3个潜类别的模型认为是较为理想的模型。对3个不同类别进行中医辨证分型,类别1符合阴虚内热证,类别2符合湿热痰结证,类别3符合肺经风热证。经过后验概率进行分组,最终得到123例患者的分类结果是:阴虚内热证43例(占35.0%),湿热痰结证45例(占36.6%),肺经风热证35例(占28.5%)。应用不同EGFR-TKIs患者在3个潜在类别分布显示,第一代以阴虚内热和肺经风热证最为常见(32.69%和38.46%),第二代以阴虚内热证和湿热痰结证最为常见(40.35%和35.09%),第三代以湿热痰结证最为常见(71.43%)。结论 EGFR-TKIs相关性皮疹常见的临床辨证分型为阴虚内热证、湿热痰结证、肺经风热证三种证型。

ObjectiveTo explore characteristics of traditional Chinese medicine(TCM)syndromes of syndromes of epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)-related rash based on latent class analysis.MethodsWe included 123 non-small cell lung cancer patients with EGFR-TKIs-related rash in the study. The general data and the appearance of the rash including the shape,color,luster,and exudation of the skin lesion,deficiency and excess,and other symptoms such as pruritus and pain were collected. EGFR-TKIs were grouped into first generation(gefitinib,erlotinib,icotinib),second generation(afatinib,dacomitinib),and third generation(osimertinib). Latent class analysis was used to analyze the data on the appearance of the rash,including model parameterization,parameter estimation,model identification,model evaluation,latent classification,and interpretation of results.ResultsTotally,123 patients(63 male and 60 female)were included. The number of cases treated by first,second and third generation of EGFR-TKIs was 52,57 and 14,respectively,and significant difference in gene types was found among the groups(P<0. 05). There were statistically significant differences in the proportion of papules with exudate,blisters,damp heat,blood deficiency with phlegm,and itching due to damp among patients using different generations of EGFR-TKIs(P<0. 05). Latent class analysis showed that when the number of latent classes is 3,the Bayesian Information Criterion(BIC) is smallest(BIC=3657. 74),and the model of three latent classes is considered to be an relatively ideal one based on the clinical experience. Judged with syndrome differentiation,classⅠ corresponds to yin deficiency and internal heat syndrome,while classⅡ and Ⅲ correspond to damp-heat-phlegm retention syndrome,and lung channel wind-heat syndrome,respectively. Calculated by posterior probability,123 patients were grouped into 43 cases of class I(35%),45 cases of classⅡ(36. 6%),and 35 cases of classⅢ(28. 5%). For patients treated by the first generation of EGFR-TKIs,yin deficiency and internal heat syndrome and lung channel wind-heat syndrome were mostly common(32. 69% and 38. 46%);yin deficiency and internal heat syndrome and damp-heat-phlegm retention syndrome were the most common types among people treated by second generation of EGFR-TKIs(40. 35% and 35. 09%),while damp-heat-phlegm retention syndrome was mostly seen in those given third generation of EGFR-TKIs(71. 43%).ConclusionThree common types of EGFR-TKIsrelated rash are yin deficiency and internal heat syndrome,damp-heat-phlegm retention syndrome,and lung channel wind-heat syndrome.