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呼出气体冷凝物中的生物标志物可表明儿童囊性纤维化的存在及严重程度。

Biomarkers in exhaled breath condensate indicate presence and severity of cystic fibrosis in children.

作者信息

Robroeks Charlotte M H H T, Rosias Philippe P R, van Vliet Dillys, Jöbsis Quirijn, Yntema Jan-Bart L, Brackel Hein J L, Damoiseaux Jan G M C, den Hartog Gertjan M, Wodzig Will K W H, Dompeling Edward

机构信息

Department of Paediatric Pulmonology, University Hospital Maastricht, Maastricht, The Netherlands.

出版信息

Pediatr Allergy Immunol. 2008 Nov;19(7):652-9. doi: 10.1111/j.1399-3038.2007.00693.x. Epub 2008 Feb 27.

Abstract

Chronic airway inflammation is present in cystic fibrosis (CF). Non-invasive inflammometry may be useful in disease management. The aim of the present cross-sectional study was to investigate: (i) the ability of fractional exhaled nitric oxide and inflammatory markers (IM) [exhaled breath condensate (EBC) acidity, nitrite, nitrate, hydrogen peroxide (H(2)O(2)), 8-isoprostane, Th1/Th2 cytokines] to indicate (exacerbations of) CF; and (ii) the ability of these non-invasive IM to indicate CF disease severity. In 98 children (48 CF/50 controls), exhaled nitric oxide was measured using the NIOX, and condensate was collected using a glass condenser. In CF interferon (IFN-gamma) and nitrite concentrations were significantly higher, whereas exhaled nitric oxide levels were significantly lower compared with controls (3.3 +/- 0.3 pg/ml, 2.2 +/- 0.2 microM, 10.0 +/- 1.2 p.p.b. vs. 2.6 +/- 0.2 pg/ml, 1.4 +/- 0.1 microM, 15.4 +/- 1.4 p.p.b. respectively). Using multivariate logistic regression models, the presence of CF was best indicated by 8-isoprostane, nitrite and IFN-gamma [sensitivity 78%, specificity 83%; area under receiver operating characteristic curve (AUC) 0.906, p < 0.001]. An exacerbation of CF was best indicated by 8-isoprostane and nitrite (sensitivity 40%, specificity 97%, AUC curve 0.838, p = 0.009). Most indicative biomarkers of CF severity were exhaled nitric oxide, and condensate acidity (sensitivity 96%, specificity 67%; AUC curve 0.751, p = 0.008). In this cross-sectional study, the combination of different exhaled IM could indicate (exacerbations of) CF, and severity of the disease in children. Longitudinal data are necessary to further confirm the role of these markers for the management of CF in children.

摘要

囊性纤维化(CF)患者存在慢性气道炎症。非侵入性炎症测定法可能对疾病管理有用。本横断面研究的目的是调查:(i)呼出一氧化氮分数和炎症标志物(IM)[呼出气冷凝物(EBC)酸度、亚硝酸盐、硝酸盐、过氧化氢(H₂O₂)、8-异前列腺素、Th1/Th2细胞因子]指示CF(病情加重)的能力;以及(ii)这些非侵入性IM指示CF疾病严重程度的能力。在98名儿童(48名CF患者/50名对照)中,使用NIOX测量呼出一氧化氮,并使用玻璃冷凝器收集冷凝物。与对照组相比,CF患者的干扰素(IFN-γ)和亚硝酸盐浓度显著更高,而呼出一氧化氮水平显著更低(分别为3.3±0.3 pg/ml、2.2±0.2 μM、10.0±1.2 p.p.b. 对比2.6±0.2 pg/ml、1.4±0.1 μM、15.4±1.4 p.p.b.)。使用多变量逻辑回归模型,8-异前列腺素、亚硝酸盐和IFN-γ对CF的存在指示效果最佳[敏感性78%,特异性83%;受试者操作特征曲线下面积(AUC)0.906,p<0.001]。8-异前列腺素和亚硝酸盐对CF病情加重的指示效果最佳(敏感性40%,特异性97%,AUC曲线0.838,p = 0.009)。CF严重程度的最具指示性的生物标志物是呼出一氧化氮和冷凝物酸度(敏感性96%,特异性67%;AUC曲线0.751,p = 0.008)。在本横断面研究中,不同呼出IM的组合可指示儿童CF(病情加重)及疾病严重程度。需要纵向数据来进一步证实这些标志物在儿童CF管理中的作用。

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