Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study.
Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study.
复制标题
DOI：
10.1016/s2213-2600(15)00196-4
复制
发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Martinez FD
中科院分区：
文献类型：
--
作者：
Guerra S;Halonen M;Vasquez MM;Spangenberg A;Stern DA;Morgan WJ;Wright AL;Lavi I;Tarès L;Carsin AE;Dobaño C;Barreiro E;Zock JP;Martínez-Moratalla J;Urrutia I;Sunyer J;Keidel D;Imboden M;Probst-Hensch N;Hallberg J;Melén E;Wickman M;Bousquet J;Belgrave DC;Simpson A;Custovic A;Antó JM;Martinez FD
血清中抗炎俱乐部细胞分泌蛋白（CC16）的低水平与COPD患者FEV1的加速下降有关。在普通人群中，低循环CC16是否先于肺功能缺陷和COPD发病率尚不清楚。我们使用了基于人群的TESAOD （N=960，平均随访时间：14年）、ECRHS-Sp （N=514, 11年）和SAPALDIA （N=167, 8年）研究中基线时无copd的成年人的纵向数据。从基线开始测量血清CC16，并与随后的FEV1下降和气流限制发生率相关。为了评估生命早期CC16的影响，我们还测量了4-6岁样本中的循环CC16，以预测CRS （N=427）、MAAS （N=481）和BAMSE （N=231）出生队列中随后的儿童肺功能。在成人中，在调整性别、年龄、身高、吸烟状况/强度、包龄、哮喘和初始FEV1水平后，基线CC16与TESAOD （p=0.0014）、ECRHS-Sp （p=0.023）的FEV1随后下降呈负相关，SAPALDIA中也发现了类似的趋势（p=0.052）。基线时较低的CC16也预示着TESAOD和ECRHS-Sp中发生二级气流受限事件的风险增加（即FEV1/FVC<70%加上fev1%预测< 80%）。在儿童中，4 - 6岁时CC16的最低胎率与16岁前的FEV1缺陷相关（来自出生队列调整模型的荟萃分析估计：- 68ml， p=0.0001）。结果在16岁前从不吸烟的受试者中得到证实（- 71ml, p<0.0001）。低血清CC16与随后的肺功能生长减慢和加速下降以及发展为2期气流受限的风险增加有关。美国国家心脏、肺和血液研究所和欧盟第七框架计划。有关其他资助机构的完整列表，请参阅论文的致谢部分。
Low serum levels of the anti-inflammatory club cell secretory protein (CC16) have been associated with an accelerated FEV1 decline in COPD. Whether low circulating CC16 precedes lung function deficits and incidence of COPD in the general population is unknown. We used longitudinal data from adults who were COPD-free at baseline from the population-based TESAOD (N=960, mean follow-up: 14yrs), ECRHS-Sp (N=514, 11yrs) and SAPALDIA (N=167, 8yrs) studies. CC16 was measured in serum from baseline and associated with subsequent FEV1 decline and incidence of airflow limitation. To evaluate early life CC16 effects, we also measured circulating CC16 in samples from ages 4-6yrs to predict subsequent lung function in childhood in the CRS (N=427), MAAS (N=481), and BAMSE (N=231) birth cohorts. In adults – after adjustment for sex, age, height, smoking status/intensity, pack-years, asthma, and initial FEV1 levels – baseline CC16 was inversely associated with subsequent decline of FEV1 in TESAOD (p=0.0014), ECRHS-Sp (p=0.023), and a similar trend was found in SAPALDIA (p=0.052). Low CC16 at baseline also predicted an increased risk for incident stage 2 airflow limitation (i.e., FEV1/FVC<70% plus FEV1 % predicted < 80%) in TESAOD and ECRHS-Sp. In children, the lowest tertile of CC16 at age 4–6yrs was associated with subsequent FEV1 deficits up to age 16yrs (meta-analyzed estimate from adjusted models on birth cohorts: −68ml, p=0.0001). Results were confirmed among subjects who never smoked by age 16yrs (−71ml, p<0.0001). Low serum CC16 is associated with subsequent slower growth and accelerated decline of lung function, and increased risk of developing stage 2 airflow limitation. US National Heart, Lung, and Blood Institute and EU Seventh Framework Programme. For a complete list of other funding agencies, please refer to the acknowledgements section of the paper.