Club cell secretory protein and lung function in children with cystic fibrosis.

Club cell secretory protein and lung function in children with cystic fibrosis.
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囊性纤维化儿童的俱乐部细胞分泌蛋白和肺功能。

DOI:
10.1016/j.jcf.2022.03.007
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发表时间:
2022-09
影响因子:
5.2
通讯作者:
Guerra, Stefano
Guerra, Stefano
中科院分区:
医学2区
文献类型:
--
作者:
Zhai, Jing;Emond, Mary J.;Spangenberg, Amber;Stern, Debra A.;Vasquez, Monica M.;Blue, Elizabeth E.;Buckingham, Kati J.;Sherrill, Duane L.;Halonen, Marilyn;Gibson, Ronald L.;Rosenfeld, Margaret;Sagel, Scott D.;Bamshad, Michael J.;Morgan, Wayne J.;Guerra, Stefano

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俱乐部细胞分泌蛋白 (CC16) 在肺部疾病中发挥抗炎功能。我们试图确定囊性纤维化 (CF) 儿童中血清 CC16 缺陷和控制血清 CC16 的遗传变异与肺功能的关系。我们使用了 CF 儿童的纵向数据(EPIC 研究),在入组前没有铜绿假单胞菌阳性培养物。对青春期 FEV1 水平最低和最高的参与者(分别为 LLF 和 HLF 组;每组 N=130)之间的 CC16 循环水平和炎症评分(由 CRP、SAA、钙卫蛋白、G-CSF 生成)进行比较。使用混合模型测试了 SCGB1A1、EHF-APIP 基因座中的单核苷酸变异 (SNV) 与循环 CC16 以及 FEV1 下降和 FEV1/FVC % 预测水平在 7-16 岁之间的关联。与 HLF 组相比,LLF 组的 CC16 水平较低(几何平均值:分别为 8.2 与 6.5 ng/ml;p=0.0002),而标准化炎症评分水平较高(-0.21 vs 0.21,p=0.0007)。最低 CC16 和最高炎症三分位数的参与者发生 LLF 的几率最高(与最高 CC16 和最低炎症三分位数的参与者相比,p<0.0001)。在与循环 CC16 相关的 7 个 SNV 中,最高的 SNV rs3741240 与 FEV1/FVC 下降以及 FEV1 略有下降相关(分别为 p=0.003 和 0.025;N=611 名参与者,20,801 项肺功能观察)。血清 CC16 缺乏与 CF 肺病的严重程度密切相关,并且其影响与全身炎症相加。 rs3741240A 等位基因与低循环 CC16 相关,并且可能与 CF 中肺功能加速下降有关。
Club cell secretory protein (CC16) exerts anti-inflammatory functions in lung disease. We sought to determine the relation of serum CC16 deficits and genetic variants that control serum CC16 to lung function among children with cystic fibrosis (CF). We used longitudinal data from CF children (EPIC Study) with no positive cultures for Pseudomonas aeruginosa prior to enrollment. Circulating levels of CC16 and an inflammatory score (generated from CRP, SAA, calprotectin, G-CSF) were compared between participants with the lowest and highest FEV1 levels in adolescence (LLF and HLF groups, respectively; N=130-per-group). Single nucleotide variants (SNVs) in the SCGB1A1, EHF-APIP loci were tested for association with circulating CC16 and with decline of FEV1 and FEV1/FVC % predicted levels between ages 7–16 using mixed models. Compared with the HLF group, the LLF group had lower levels of CC16 (geometric means: 8.2 vs 6.5 ng/ml, respectively; p=0.0002) and higher levels of the normalized inflammatory score (−0.21 vs 0.21, p=0.0007). Participants in the lowest CC16 and highest inflammation tertile had the highest odds for having LLF (p<0.0001 for comparison with participants in the highest CC16 and lowest inflammation tertile). Among seven SNVs associated with circulating CC16, the top SNV rs3741240 was associated with decline of FEV1/FVC and, marginally, FEV1 (p=0.003 and 0.025, respectively; N=611 participants, 20,801 lung function observations). Serum CC16 deficits are strongly associated with severity of CF lung disease and their effects are additive with systemic inflammation. The rs3741240A allele is associated with low circulating CC16 and, possibly, accelerated lung function decline in CF.
3-95 岁年龄范围的多种族肺活量测定参考值:2012 年全球肺功能方程。
DOI: 10.1183/09031936.00080312
发表时间: 2012-12
期刊: The European respiratory journal
影响因子: --
作者:
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DOI: 10.1016/j.jcf.2018.12.005
发表时间: 2020-01
期刊: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
影响因子: --
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DOI: 10.3892/mmr.2018.9216
发表时间: 2018-08
影响因子: 3.4
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DOI: 10.1186/1465-9921-11-140
发表时间: 2010-10-08
影响因子: 5.8
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