循环CC16与支气管哮喘：一项从童年早期到成人期间基于人群、多中心研究
2023/08/28
摘要
背景：CC16是一种在气道中高度表达的抗炎蛋白。CC16缺乏与肺功能缺陷相关，但其在支气管哮喘（以下简称哮喘）中的作用尚未确定。
目的：本研究旨在确定1）循环CC16与从童年早期到成年期活动性哮喘发生的纵向相关性，以及2）童年早期CC16是否可预测儿童哮喘到成年期的临床过程。
方法：本研究在三个基于人群的出生队列中评估了循环CC16与哮喘的关系：TCRS（6-36岁；参与者N=814，观察者N=3042）、BAMSE（8-24岁；N=2547、3438）和MAAS（5-18岁，Ns=745、1626）。在任一队列的233名首次调查时患有哮喘的儿童中，还检测了基线CC16以明确与症状持续性的关联。
结果：1）在校正协变量后发现，CC16缺陷与所有队列中哮喘风险的增加相关（每1-SD CC16减少的荟萃分析校正后OR为1.20[95%CI 1.12-1.28]；P<0.0001）。对于症状频繁的哮喘，这种关联性尤其强（荟萃分析校正后RR为1.40[1.24-1.57]；P<0.00001），且在特应性和非特应性哮喘中均得到证实，同时与肺功能损伤无关。2） 在对持续性哮喘的已知预测因素进行校正后，与其他两个CC16三分位数的哮喘儿童相比，CC16处于最低三分位数中的哮喘儿童出现持续到成年生活的频繁发作的风险增加了近4倍（荟萃分析校正后OR为3.72[1.78-7.76]；P<0.0001）。
结论：循环CC16缺陷与哮喘的发生有关，即哮喘从儿童期到中年期发作频繁，并可预测哮喘症状持续至成年。上述发现支持CC16在哮喘中的可能保护作用及其在风险分层中的潜在用途。
Circulating CC16 and Asthma: A Population-Based, Multi-Cohort Study from Early Childhood Through Adult Life
Voraphani N, Stern DA, Ledford JG, Spangenberg AL, Zhai J, Wright AL, Morgan WJ, Kraft M, Sherrill DL, Curtin JA, Murray CS, Custovic A, Kull I, Hallberg J, Bergström A, Herrera-Luis E, Halonen M, Martinez FD, Simpson A, Melén E, Guerra S.
Abstract
BACKGROUND:CC16 is an anti-inflammatory protein highly expressed in the airways. CC16 deficiency has been associated with lung function deficits, but its role in asthma has not been established conclusively.
OBJECTIVE:To determine 1) the longitudinal association of circulating CC16 with the presence of active asthma from early childhood through adult life and 2) whether CC16 in early childhood predicts the clinical course of childhood asthma into adult life.
METHODS:We assessed the association of circulating CC16 and asthma in three population-based birth cohorts: TCRS (years 6-36; N-participants=814, N-observations=3042), BAMSE (years 8-24; Ns=2547, 3438), and MAAS (years 5-18, Ns=745, 1626). Among 233 children who had asthma at the first survey in any of the cohorts, baseline CC16 was also tested for association with persistence of symptoms.
REsults:1) After adjusting for covariates, CC16 deficits were associated with increased risk for the presence of asthma in all cohorts (meta-analyzed adjOR per 1-SD CC16 decrease: 1.20[95%CI 1.12-1.28];P<0.0001). The association was particularly strong for asthma with frequent symptoms (meta-analyzed adjRRR: 1.40[1.24-1.57];P<0.0001), was confirmed for both atopic and non-atopic asthma, and was independent of lung function impairment. 2) After adjustment for known predictors of persistent asthma, asthmatic children in the lowest CC16 tertile had a nearly 4-fold increased risk for having frequent symptoms persisting into adult life, compared with asthmatic children in the other two CC16 tertiles (meta-analyzed adjOR: 3.72[1.78-7.76];P<0.0001).
conclusions:Circulating CC16 deficits are associated with the presence of asthma with frequent symptoms from childhood through mid-adult life and predict the persistence of asthma symptoms into adulthood. These findings support a possible protective role of CC16 in asthma and its potential use for risk stratification
背景：CC16是一种在气道中高度表达的抗炎蛋白。CC16缺乏与肺功能缺陷相关，但其在支气管哮喘（以下简称哮喘）中的作用尚未确定。
目的：本研究旨在确定1）循环CC16与从童年早期到成年期活动性哮喘发生的纵向相关性，以及2）童年早期CC16是否可预测儿童哮喘到成年期的临床过程。
方法：本研究在三个基于人群的出生队列中评估了循环CC16与哮喘的关系：TCRS（6-36岁；参与者N=814，观察者N=3042）、BAMSE（8-24岁；N=2547、3438）和MAAS（5-18岁，Ns=745、1626）。在任一队列的233名首次调查时患有哮喘的儿童中，还检测了基线CC16以明确与症状持续性的关联。
结果：1）在校正协变量后发现，CC16缺陷与所有队列中哮喘风险的增加相关（每1-SD CC16减少的荟萃分析校正后OR为1.20[95%CI 1.12-1.28]；P<0.0001）。对于症状频繁的哮喘，这种关联性尤其强（荟萃分析校正后RR为1.40[1.24-1.57]；P<0.00001），且在特应性和非特应性哮喘中均得到证实，同时与肺功能损伤无关。2） 在对持续性哮喘的已知预测因素进行校正后，与其他两个CC16三分位数的哮喘儿童相比，CC16处于最低三分位数中的哮喘儿童出现持续到成年生活的频繁发作的风险增加了近4倍（荟萃分析校正后OR为3.72[1.78-7.76]；P<0.0001）。
结论：循环CC16缺陷与哮喘的发生有关，即哮喘从儿童期到中年期发作频繁，并可预测哮喘症状持续至成年。上述发现支持CC16在哮喘中的可能保护作用及其在风险分层中的潜在用途。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(Am J Respir Crit Care Med. 2023 Jul 31. doi: 10.1164/rccm.202301-0041OC.)
(Am J Respir Crit Care Med. 2023 Jul 31. doi: 10.1164/rccm.202301-0041OC.)
Circulating CC16 and Asthma: A Population-Based, Multi-Cohort Study from Early Childhood Through Adult Life
Voraphani N, Stern DA, Ledford JG, Spangenberg AL, Zhai J, Wright AL, Morgan WJ, Kraft M, Sherrill DL, Curtin JA, Murray CS, Custovic A, Kull I, Hallberg J, Bergström A, Herrera-Luis E, Halonen M, Martinez FD, Simpson A, Melén E, Guerra S.
Abstract
BACKGROUND:CC16 is an anti-inflammatory protein highly expressed in the airways. CC16 deficiency has been associated with lung function deficits, but its role in asthma has not been established conclusively.
OBJECTIVE:To determine 1) the longitudinal association of circulating CC16 with the presence of active asthma from early childhood through adult life and 2) whether CC16 in early childhood predicts the clinical course of childhood asthma into adult life.
METHODS:We assessed the association of circulating CC16 and asthma in three population-based birth cohorts: TCRS (years 6-36; N-participants=814, N-observations=3042), BAMSE (years 8-24; Ns=2547, 3438), and MAAS (years 5-18, Ns=745, 1626). Among 233 children who had asthma at the first survey in any of the cohorts, baseline CC16 was also tested for association with persistence of symptoms.
REsults:1) After adjusting for covariates, CC16 deficits were associated with increased risk for the presence of asthma in all cohorts (meta-analyzed adjOR per 1-SD CC16 decrease: 1.20[95%CI 1.12-1.28];P<0.0001). The association was particularly strong for asthma with frequent symptoms (meta-analyzed adjRRR: 1.40[1.24-1.57];P<0.0001), was confirmed for both atopic and non-atopic asthma, and was independent of lung function impairment. 2) After adjustment for known predictors of persistent asthma, asthmatic children in the lowest CC16 tertile had a nearly 4-fold increased risk for having frequent symptoms persisting into adult life, compared with asthmatic children in the other two CC16 tertiles (meta-analyzed adjOR: 3.72[1.78-7.76];P<0.0001).
conclusions:Circulating CC16 deficits are associated with the presence of asthma with frequent symptoms from childhood through mid-adult life and predict the persistence of asthma symptoms into adulthood. These findings support a possible protective role of CC16 in asthma and its potential use for risk stratification
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