Departments of Allergy and of Research and Evaluation, Kaiser Permanente Southern California, San Diego and Pasadena, Calif.
Departments of Allergy and of Research and Evaluation, Kaiser Permanente Southern California, San Diego and Pasadena, Calif.
J Allergy Clin Immunol. 2014 Jun;133(6):1549-56. doi: 10.1016/j.jaci.2013.10.006. Epub 2013 Dec 4.
Asthma phenotyping can facilitate understanding of disease pathogenesis and potential targeted therapies.
To further characterize the distinguishing features of phenotypic groups in difficult-to-treat asthma.
Children ages 6-11 years (n = 518) and adolescents and adults ages ≥12 years (n = 3612) with severe or difficult-to-treat asthma from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study were evaluated in this post hoc cluster analysis. Analyzed variables included sex, race, atopy, age of asthma onset, smoking (adolescents and adults), passive smoke exposure (children), obesity, and aspirin sensitivity. Cluster analysis used the hierarchical clustering algorithm with the Ward minimum variance method. The results were compared among clusters by χ(2) analysis; variables with significant (P < .05) differences among clusters were considered as distinguishing feature candidates. Associations among clusters and asthma-related health outcomes were assessed in multivariable analyses by adjusting for socioeconomic status, environmental exposures, and intensity of therapy.
Five clusters were identified in each age stratum. Sex, atopic status, and nonwhite race were distinguishing variables in both strata; passive smoke exposure was distinguishing in children and aspirin sensitivity in adolescents and adults. Clusters were not related to outcomes in children, but 2 adult and adolescent clusters distinguished by nonwhite race and aspirin sensitivity manifested poorer quality of life (P < .0001), and the aspirin-sensitive cluster experienced more frequent asthma exacerbations (P < .0001).
Distinct phenotypes appear to exist in patients with severe or difficult-to-treat asthma, which is related to outcomes in adolescents and adults but not in children. The study of the therapeutic implications of these phenotypes is warranted.
哮喘表型分析有助于了解疾病发病机制和潜在的靶向治疗方法。
进一步描述治疗困难的哮喘中表型组的特征。
这项事后聚类分析评估了来自哮喘的流行病学和自然史：结局和治疗方案（TENOR）研究的 6-11 岁儿童（n=518）和青少年及成年患者（n=3612）严重或治疗困难的哮喘患者。分析变量包括性别、种族、特应性、哮喘发病年龄、吸烟（青少年和成年人）、被动吸烟暴露（儿童）、肥胖和阿司匹林敏感性。聚类分析采用层次聚类算法和 Ward 最小方差法。通过 χ(2)分析比较聚类间的差异；在聚类间有显著差异（P<0.05）的变量被认为是鉴别特征候选者。通过调整社会经济状况、环境暴露和治疗强度，在多变量分析中评估聚类与哮喘相关健康结局之间的关联。
在每个年龄组中都确定了 5 个聚类。性别、特应性和非白色人种是两个年龄组的鉴别变量；儿童中被动吸烟暴露是鉴别变量，而青少年和成年中阿司匹林敏感性是鉴别变量。聚类与儿童的结局无关，但两个成年和青少年聚类，一个通过非白色人种区分，另一个通过阿司匹林敏感性区分，表现出较差的生活质量（P<0.0001），且阿司匹林敏感聚类经历更频繁的哮喘恶化（P<0.0001）。
在严重或治疗困难的哮喘患者中似乎存在不同的表型，这与青少年和成年患者的结局有关，而与儿童无关。有必要研究这些表型的治疗意义。
