Is Chronic Asthma Associated with Shorter Leukocyte Telomere Length at Midlife?
Is Chronic Asthma Associated with Shorter Leukocyte Telomere Length at Midlife?
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DOI：
10.1164/rccm.201402-0370oc
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发表时间：
2014-08-15
影响因子：
24.7
通讯作者：
Caspi, Avshalom
中科院分区：
文献类型：
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作者：
Belsky, Daniel W.;Shalev, Idan;Caspi, Avshalom
基本原理：哮喘与年龄相关的慢性疾病和死亡率有前瞻性的相关性，提示哮喘可能与加速老化的一般多系统表型有关的假说。目的：检验慢性哮喘是否与加速老化的生物标志物白细胞端粒长度有关。在达尼丁多学科健康与发展研究队列（n = 1，037）中，通过9次面对面评估（年龄范围为9-38岁）前瞻性确定哮喘。白细胞端粒长度在26岁和38岁时测量。哮喘被分类为生命过程持续性、儿童期发作不符合持续性标准和青少年/成人发作。我们用回归模型检验哮喘和白细胞端粒长度之间的关系。我们使用协变量调整检验了哮喘与白细胞端粒长度相关性的混杂因素。我们测试了血清C-反应蛋白和白色血细胞计数作为潜在的介质的哮喘白细胞端粒长度associations.Measurements和主要结果：研究成员与生命过程中持续性哮喘有较短的白细胞端粒长度相比，性别和年龄匹配的同龄人没有报告的哮喘。相比之下，儿童期发作和青少年/成人发作哮喘的研究成员中的白细胞端粒长度与未报告哮喘的同龄人中的白细胞端粒长度没有差异。调整肥胖和吸烟的生活史并没有改变结果。研究对象中的终生持续性哮喘患者的血嗜酸性粒细胞计数升高。血液嗜酸性粒细胞计数介导的29%的生命过程中持续性哮喘白细胞端粒长度association.Conclusions：生命过程中持续性哮喘与加速衰老的生物标志物有关，可能通过全身性嗜酸性粒细胞炎症。哮喘的生活史可以为衰老研究提供信息。
Rationale: Asthma is prospectively associated with age-related chronic diseases and mortality, suggesting the hypothesis that asthma may relate to a general, multisystem phenotype of accelerated aging.Objectives: To test whether chronic asthma is associated with a proposed biomarker of accelerated aging, leukocyte telomere length.Methods: Asthma was ascertained prospectively in the Dunedin Multidisciplinary Health and Development Study cohort (n = 1,037) at nine in-person assessments spanning ages 9-38 years. Leukocyte telomere length was measured at ages 26 and 38 years. Asthma was classified as life-course-persistent, childhood-onset not meeting criteria for persistence, and adolescent/adult-onset. We tested associations between asthma and leukocyte telomere length using regression models. We tested for confounding of asthma-leukocyte telomere length associations using covariate adjustment. We tested serum C-reactive protein and white blood cell counts as potential mediators of asthma-leukocyte telomere length associations.Measurements and Main Results: Study members with life-course-persistent asthma had shorter leukocyte telomere length as compared with sex- and age-matched peers with no reported asthma. In contrast, leukocyte telomere length in study members with childhood-onset and adolescent/adult-onset asthma was not different from leukocyte telomere length in peers with no reported asthma. Adjustment for life histories of obesity and smoking did not change results. Study members with life-course-persistent asthma had elevated blood eosinophil counts. Blood eosinophil count mediated 29% of the life-course-persistent asthma-leukocyte telomere length association.Conclusions: Life-course-persistent asthma is related to a proposed biomarker of accelerated aging, possibly via systemic eosinophilic inflammation. Life histories of asthma can inform studies of aging.