CC16在早产与成人期肺功能及哮喘关联中的作用
2025/10/11
摘要
背景：克拉拉细胞分泌蛋白（CC16）是一种具有抗炎和抗菌特性的肺特异性蛋白，其在早产儿体内水平降低。
目的：通过纵向和中介分析，探讨循环CC16在早产（<37周）与从儿童期至青年成年期肺功能及哮喘关联中的作用。
方法：利用BAMSE出生队列（n=2557名参与者，10631次纵向观察），我们评估了血浆CC16（8岁、24岁）、肺量测定（8岁、16岁、24岁、26岁）和哮喘（8岁、12岁、16岁、24岁、26岁）数据。采用纵向多变量混合模型检验早产、CC16、预计值百分比FEV1/FVC（ppFEV1/FVC）及哮喘之间的纵向关联。并检验了CC16（8-24岁）作为早产与成年期（24-26岁）支气管扩张剂使用前后ppFEV1/FVC及哮喘关系的中介因素。
结果： 在8至26岁期间，早产与血浆CC16水平降低（-1.15 ng/ml [95%CI -1.22, -1.08], P<0.0001）、ppFEV1/FVC降低（-1.9% [-3.1, -0.8], P=0.001）以及哮喘风险升高（OR 1.83 [1.28, 2.62], P=0.001）相关。CC16水平偏低与成年期ppFEV1/FVC下降（P<0.0001）和哮喘风险增加（P=0.007）相关。多变量中介分析表明，CC16分别介导了早产对成年期ppFEV1/FVC和哮喘影响的16%和9%。
结论：低CC16水平是早产对青年成年期肺功能缺损和哮喘影响的潜在中介因素。未来研究应探讨CC16能否作为早产个体的预测性生物标志物及潜在治疗靶点。
Nipasiri, Voraphani; Susanna, Klevebro;Abstrast
BACKGROUND: Club cell secretory protein (CC16) is a pneumoprotein that has anti-inflammatory and antimicrobial properties and whose levels are reduced in preterm infants.
OBJECTIVE: To investigate the role of circulating CC16 in the association of preterm birth (<37 weeks) with lung function and asthma from childhood into young adult life in longitudinal and mediation analyses.
METHODS: Using the BAMSE birth cohort (n=2557 participants, 10631 longitudinal observations), we assessed plasma CC16 (ages 8, 24 years), spirometry (ages 8, 16, 24, 26), and asthma (ages 8, 12, 16, 24, 26). Longitudinal associations between preterm birth, CC16, percent predicted FEV(1)/FVC (ppFEV(1)/FVC), and asthma were examined in longitudinal multivariable mixed models. CC16 (ages 8-24) was tested as a mediator for the relations of preterm birth to pre- and post-bronchodilator ppFEV(1)/FVC and asthma in adulthood (ages 24-26).
RESULTS: Preterm birth was associated with reduced plasma CC16 (-1.15 ng/ml [95%CI -1.22, -1.08], P<0.0001), lower ppFEV(1)/FVC (-1.9% [-3.1, -0.8], P=0.001), and higher risk for asthma (1.83 [1.28, 2.62], P=0.001) across ages 8-26. CC16 deficits were related to decreased ppFEV(1)/FVC (P<0.0001) and increased risk for asthma (P=0.007) in adulthood. Multivariable mediation analyses suggested that CC16 mediated 16% and 9% of the effects of preterm birth on ppFEV(1)/FVC and asthma in adult life, respectively.
CONCLUSION: Low CC16 is a potential mediator of the effects of prematurity on lung function deficits and asthma in young adulthood. Future studies should address whether CC16 can be used as a predictive biomarker and, possibly, therapeutic target in individuals born preterm.
背景：克拉拉细胞分泌蛋白（CC16）是一种具有抗炎和抗菌特性的肺特异性蛋白，其在早产儿体内水平降低。
目的：通过纵向和中介分析，探讨循环CC16在早产（<37周）与从儿童期至青年成年期肺功能及哮喘关联中的作用。
方法：利用BAMSE出生队列（n=2557名参与者，10631次纵向观察），我们评估了血浆CC16（8岁、24岁）、肺量测定（8岁、16岁、24岁、26岁）和哮喘（8岁、12岁、16岁、24岁、26岁）数据。采用纵向多变量混合模型检验早产、CC16、预计值百分比FEV1/FVC（ppFEV1/FVC）及哮喘之间的纵向关联。并检验了CC16（8-24岁）作为早产与成年期（24-26岁）支气管扩张剂使用前后ppFEV1/FVC及哮喘关系的中介因素。
结果： 在8至26岁期间，早产与血浆CC16水平降低（-1.15 ng/ml [95%CI -1.22, -1.08], P<0.0001）、ppFEV1/FVC降低（-1.9% [-3.1, -0.8], P=0.001）以及哮喘风险升高（OR 1.83 [1.28, 2.62], P=0.001）相关。CC16水平偏低与成年期ppFEV1/FVC下降（P<0.0001）和哮喘风险增加（P=0.007）相关。多变量中介分析表明，CC16分别介导了早产对成年期ppFEV1/FVC和哮喘影响的16%和9%。
结论：低CC16水平是早产对青年成年期肺功能缺损和哮喘影响的潜在中介因素。未来研究应探讨CC16能否作为早产个体的预测性生物标志物及潜在治疗靶点。
（中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校）
（J Allergy Clin Immunol 2025 Sep 19;(0) DOI:10.1016/j.jaci.2025.09.004 IF: 10.228）
The role of CC16 in the associations of preterm birth with lung function and asthma in adult life.Nipasiri, Voraphani; Susanna, Klevebro;Abstrast
BACKGROUND: Club cell secretory protein (CC16) is a pneumoprotein that has anti-inflammatory and antimicrobial properties and whose levels are reduced in preterm infants.
OBJECTIVE: To investigate the role of circulating CC16 in the association of preterm birth (<37 weeks) with lung function and asthma from childhood into young adult life in longitudinal and mediation analyses.
METHODS: Using the BAMSE birth cohort (n=2557 participants, 10631 longitudinal observations), we assessed plasma CC16 (ages 8, 24 years), spirometry (ages 8, 16, 24, 26), and asthma (ages 8, 12, 16, 24, 26). Longitudinal associations between preterm birth, CC16, percent predicted FEV(1)/FVC (ppFEV(1)/FVC), and asthma were examined in longitudinal multivariable mixed models. CC16 (ages 8-24) was tested as a mediator for the relations of preterm birth to pre- and post-bronchodilator ppFEV(1)/FVC and asthma in adulthood (ages 24-26).
RESULTS: Preterm birth was associated with reduced plasma CC16 (-1.15 ng/ml [95%CI -1.22, -1.08], P<0.0001), lower ppFEV(1)/FVC (-1.9% [-3.1, -0.8], P=0.001), and higher risk for asthma (1.83 [1.28, 2.62], P=0.001) across ages 8-26. CC16 deficits were related to decreased ppFEV(1)/FVC (P<0.0001) and increased risk for asthma (P=0.007) in adulthood. Multivariable mediation analyses suggested that CC16 mediated 16% and 9% of the effects of preterm birth on ppFEV(1)/FVC and asthma in adult life, respectively.
CONCLUSION: Low CC16 is a potential mediator of the effects of prematurity on lung function deficits and asthma in young adulthood. Future studies should address whether CC16 can be used as a predictive biomarker and, possibly, therapeutic target in individuals born preterm.
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