重症哮喘患者气道中的骨膜蛋白能否区分T2内型哮喘？
2018/11/14
摘要
背景：重症哮喘具有临床及生物学上具有异质性，并且通常难以控制。特别是，2型（T2）免疫内型哮喘越来越受到关注，因为其对新型生物治疗敏感，并且可以改变这些患者的生活质量。本研究的目的是分析重症哮喘患者气道中骨膜蛋白浓度，评估其在T2内型中的作用。
方法：我们招募了40名患有严重哮喘的患者（T2内型：n = 25;非T2内型：n = 15），21名轻度至中度哮喘患者和15名健康对照受试者。所有入组的受试者均接受呼出气冷凝物（EBC）和痰液收集，外周血嗜酸性粒细胞计数，呼出气一氧化氮及血清IgE测量。通过EBC酶联免疫吸附测定试剂盒和诱导痰（IS）上清液评估骨膜蛋白。
结果：与轻度至中度哮喘患者及健康对照组相比，重症哮喘患者组呼出气冷凝物（0.75±0.46 vs 0.70±0.19 vs 0.11±0.05 ng / mL，P <.05和P <.01）和诱导痰(0.55 ± 0.23 vs 0.31 ± 0.13 vs 0.16 ± 0.120 ng/mL, P < .05 和P < .01)较高的骨膜蛋白水平。我们进一步发现T2基因型中两种样本中骨膜蛋白水平与非T2内型相比有所增加（呼出气冷凝物：0.88±0.46 vs 0.52±0.46 ng / mL; 诱导痰：0.69±0.19 vs 0.39±0.16 ng / mL; P < .05）并且呼出气冷凝物中的骨膜蛋白水平与痰液骨膜蛋白之间具有相关性。
结论：我们发现骨膜蛋白在气道中具有可测性，并且重症哮喘患者中有所增加，尤其是T2内型的患者。与血清骨膜素不同，血清骨膜素可能源自肺外其他组织，气道骨膜素可为重症嗜酸性粒细胞型哮喘标志物，可能有助于分型对生物制剂反应良好的患者。
Looking for Airways Periostin in Severe Asthma: Could It Be Useful for Clustering Type 2 Endotype?
Carpagnano GE, Scioscia G
Abstract
BACKGROUND: Severe asthma is heterogeneous clinically and biologically and is often difficult to control. In particular, the type 2 (T2) immunity endotype of severe asthma is gaining increasing interest because it is susceptible to newly developed biologic treatments that can transform the quality of life of these patients. The aim of this study was to analyze periostin concentrations in the airways of patients with severe asthma, evaluating its role in clustering the T2 endotype.
METHODS: We enrolled 40 consecutive patients with severe asthma (T2 endotype: n = 25; non-T2 endotype: n = 15), 21 patients with mild to moderate asthma, and 15 healthy control subjects. All subjects enrolled underwent exhaled breath condensate (EBC) and sputum collection, eosinophil count in blood, fractional exhaled nitric oxide, and IgE measurement. Periostin was assessed by an enzyme-linked immunosorbent assay kit on EBC and induced sputum (IS) supernatant.
RESULTS: We were able to detect higher periostin levels in the EBC (0.75 ± 0.46 vs 0.70 ± 0.19 vs 0.11 ± 0.05 ng/mL, P < .05 and P < .01) and in IS (0.55 ± 0.23 vs 0.31 ± 0.13 vs 0.16 ± 0.120 ng/mL, P < .05 and P < .01) of patients with severe asthma compared with patients with mild to moderate asthma and healthy control subjects, respectively. We further found an increase of periostin levels in both samples in T2 endotype compared with non-T2 endotype (EBC: 0.88 ± 0.46 vs 0.52 ± 0.46 ng/mL; IS: 0.69 ± 0.19 vs 0.39 ± 0.16 ng/mL; P < .05) and a correlation between periostin levels in EBC and sputum.
CONCLUSIONS: We found that periostin is measurable in the airways and increased in patients with severe asthma, especially in those from the T2 endotype. Unlike serum periostin, which may be derived from several sources outside the lung, airways periostin is a useful marker of severe eosinophilic asthma and may help to phenotype patients that will respond to the biologic agents.
背景：重症哮喘具有临床及生物学上具有异质性，并且通常难以控制。特别是，2型（T2）免疫内型哮喘越来越受到关注，因为其对新型生物治疗敏感，并且可以改变这些患者的生活质量。本研究的目的是分析重症哮喘患者气道中骨膜蛋白浓度，评估其在T2内型中的作用。
方法：我们招募了40名患有严重哮喘的患者（T2内型：n = 25;非T2内型：n = 15），21名轻度至中度哮喘患者和15名健康对照受试者。所有入组的受试者均接受呼出气冷凝物（EBC）和痰液收集，外周血嗜酸性粒细胞计数，呼出气一氧化氮及血清IgE测量。通过EBC酶联免疫吸附测定试剂盒和诱导痰（IS）上清液评估骨膜蛋白。
结果：与轻度至中度哮喘患者及健康对照组相比，重症哮喘患者组呼出气冷凝物（0.75±0.46 vs 0.70±0.19 vs 0.11±0.05 ng / mL，P <.05和P <.01）和诱导痰(0.55 ± 0.23 vs 0.31 ± 0.13 vs 0.16 ± 0.120 ng/mL, P < .05 和P < .01)较高的骨膜蛋白水平。我们进一步发现T2基因型中两种样本中骨膜蛋白水平与非T2内型相比有所增加（呼出气冷凝物：0.88±0.46 vs 0.52±0.46 ng / mL; 诱导痰：0.69±0.19 vs 0.39±0.16 ng / mL; P < .05）并且呼出气冷凝物中的骨膜蛋白水平与痰液骨膜蛋白之间具有相关性。
结论：我们发现骨膜蛋白在气道中具有可测性，并且重症哮喘患者中有所增加，尤其是T2内型的患者。与血清骨膜素不同，血清骨膜素可能源自肺外其他组织，气道骨膜素可为重症嗜酸性粒细胞型哮喘标志物，可能有助于分型对生物制剂反应良好的患者。
（中日友好医院呼吸与危重症医学科 张鑫 摘译 林江涛 审校）
（Chest. 2018 Oct 8）
（Chest. 2018 Oct 8）
Looking for Airways Periostin in Severe Asthma: Could It Be Useful for Clustering Type 2 Endotype?
Carpagnano GE, Scioscia G
Abstract
BACKGROUND: Severe asthma is heterogeneous clinically and biologically and is often difficult to control. In particular, the type 2 (T2) immunity endotype of severe asthma is gaining increasing interest because it is susceptible to newly developed biologic treatments that can transform the quality of life of these patients. The aim of this study was to analyze periostin concentrations in the airways of patients with severe asthma, evaluating its role in clustering the T2 endotype.
METHODS: We enrolled 40 consecutive patients with severe asthma (T2 endotype: n = 25; non-T2 endotype: n = 15), 21 patients with mild to moderate asthma, and 15 healthy control subjects. All subjects enrolled underwent exhaled breath condensate (EBC) and sputum collection, eosinophil count in blood, fractional exhaled nitric oxide, and IgE measurement. Periostin was assessed by an enzyme-linked immunosorbent assay kit on EBC and induced sputum (IS) supernatant.
RESULTS: We were able to detect higher periostin levels in the EBC (0.75 ± 0.46 vs 0.70 ± 0.19 vs 0.11 ± 0.05 ng/mL, P < .05 and P < .01) and in IS (0.55 ± 0.23 vs 0.31 ± 0.13 vs 0.16 ± 0.120 ng/mL, P < .05 and P < .01) of patients with severe asthma compared with patients with mild to moderate asthma and healthy control subjects, respectively. We further found an increase of periostin levels in both samples in T2 endotype compared with non-T2 endotype (EBC: 0.88 ± 0.46 vs 0.52 ± 0.46 ng/mL; IS: 0.69 ± 0.19 vs 0.39 ± 0.16 ng/mL; P < .05) and a correlation between periostin levels in EBC and sputum.
CONCLUSIONS: We found that periostin is measurable in the airways and increased in patients with severe asthma, especially in those from the T2 endotype. Unlike serum periostin, which may be derived from several sources outside the lung, airways periostin is a useful marker of severe eosinophilic asthma and may help to phenotype patients that will respond to the biologic agents.
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一项试验性随机对照试验，比较基于短信收发和网络哮喘行动计划与书面行动计划对哮喘恶化的影响
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血清sST2水平可预测哮喘的重度急性发作
