Asthma and Airway Disease Research Center, University of Arizona, Tucson, Arizona.
Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
Am J Respir Crit Care Med. 2023 Oct 1;208(7):758-769. doi: 10.1164/rccm.202301-0041OC.
Club cell secretory protein (CC16) is an antiinflammatory 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. To determine ) the longitudinal association of circulating CC16 with the presence of active asthma from early childhood through adult life and ) whether CC16 in early childhood predicts the clinical course of childhood asthma into adult life. We assessed the association of circulating CC16 and asthma in three population-based birth cohorts: the Tucson Children's Respiratory Study (years 6-36; total participants, 814; total observations, 3,042), the Swedish Barn/Children, Allergy, Milieu, Stockholm, Epidemiological survey (years 8-24; total participants, 2,547; total observations, 3,438), and the UK Manchester Asthma and Allergy Study (years 5-18; total participants, 745; total observations, 1,626). 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. After adjusting for covariates, CC16 deficits were associated with increased risk for the presence of asthma in all cohorts (meta-analyzed adjusted odds ratio per 1-SD CC16 decrease, 1.20; 95% confidence interval [CI], 1.12-1.28; < 0.0001). The association was particularly strong for asthma with frequent symptoms (meta-analyzed adjusted relative risk ratio, 1.40; 95% CI, 1.24-1.57; < 0.0001), was confirmed for both atopic and nonatopic asthma, and was independent of lung function impairment. After adjustment for known predictors of persistent asthma, children with asthma in the lowest CC16 tertile had a nearly fourfold increased risk for having frequent symptoms persisting into adult life compared with children with asthma in the other two CC16 tertiles (meta-analyzed adjusted odds ratio, 3.72; 95% CI, 1.78-7.76; < 0.0001). Circulating CC16 deficits are associated with the presence of asthma with frequent symptoms from childhood through midadult 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.
肺细胞分泌蛋白 (CC16) 是一种在气道中高度表达的抗炎蛋白。CC16 缺乏与肺功能缺陷有关，但它在哮喘中的作用尚未得到明确证实。为了确定循环 CC16 与从儿童早期到成年期活跃哮喘的存在之间的纵向关联，以及 CC16 在儿童早期是否预测儿童哮喘的临床病程进入成年期。我们评估了三个基于人群的出生队列中的循环 CC16 与哮喘的关联：图森儿童呼吸研究（6-36 岁；总参与者 814 人；总观察 3042 人）、瑞典 Barn/儿童、过敏、环境、斯德哥尔摩、流行病学调查（8-24 岁；总参与者 2547 人；总观察 3438 人）和英国曼彻斯特哮喘和过敏研究（5-18 岁；总参与者 745 人；总观察 1626 人）。在所有队列中，首次调查时患有哮喘的 233 名儿童中，还测试了基线 CC16 是否与症状持续存在相关。在校正了协变量后，CC16 缺乏与所有队列中哮喘存在的风险增加相关（按每 1-SD CC16 降低的优势比进行 meta 分析，1.20；95%置信区间 [CI]，1.12-1.28；<0.0001）。该关联对于频繁出现症状的哮喘尤为强烈（meta 分析调整后的相对风险比，1.40；95%CI，1.24-1.57；<0.0001），对于特应性和非特应性哮喘均得到证实，且独立于肺功能损害。在校正了持续哮喘的已知预测因素后，与其他两个 CC16 三分位数的哮喘患儿相比，处于最低 CC16 三分位数的哮喘患儿进入成年后频繁出现症状的风险增加近四倍（meta 分析调整后的优势比，3.72；95%CI，1.78-7.76；<0.0001）。循环 CC16 缺乏与儿童期至成年中期频繁出现症状的哮喘存在相关，并预测哮喘症状持续到成年期。这些发现支持 CC16 在哮喘中可能具有保护作用及其用于风险分层的潜在用途。
