Department of Medicine, National Jewish Health, , Denver, Colorado, USA.
Thorax. 2013 Oct;68(10):929-37. doi: 10.1136/thoraxjnl-2012-202278. Epub 2013 Jun 19.
Acute pulmonary exacerbations accelerate pulmonary decline in cystic fibrosis (CF). There is a critical need for better predictors of treatment response.
To test whether expression of a panel of leucocyte genes directly measured from whole blood predicts reductions in sputum bacterial density.
A previously validated 10-gene peripheral blood mononuclear cell (PBMC) signature was prospectively tested in PBMC and whole blood leucocyte RNA isolated from adult subjects with CF at the beginning and end of treatment for an acute pulmonary exacerbation. Gene expression was simultaneously quantified from PBMCs and whole blood RNA using real-time PCR amplification. Test characteristics including sensitivity, specificity, positive and negative predictive values were calculated and receiver operating characteristic curves determined the best cut-off to diagnose a microbiological response. The findings were then validated in a smaller independent sample.
Whole blood transcript measurements are more accurate than forced expiratory volume in 1 s (FEV(1)) or C reactive protein (CRP) alone in identifying reduction of airway infection. When added to FEV(1), the whole blood gene panel improved diagnostic accuracy from 64% to 82%. The specificity of the test to detect reduced infection was 88% and the positive predictive value for the presence of persistent infection was 86%. The area under the curve for detecting treatment response was 0.81. Six genes were the most significant predictors for identifying reduction in airway bacterial load beyond FEV(1) or CRP alone. The high specificity of the test was replicated in the validation cohort.
The addition of blood leucocyte gene expression to FEV(1) and CRP enhances specificity in predicting reduced pulmonary infection and may bolster the assessment of CF treatment outcomes.
急性肺部恶化会加速囊性纤维化（CF）的肺部衰退。因此，迫切需要更好的治疗反应预测指标。
测试从全血中直接测量的一组白细胞基因表达是否可预测痰细菌密度降低。
前瞻性地在 CF 成人患者急性肺部恶化开始和结束时的外周血单核细胞（PBMC）和全血白细胞 RNA 中测试经过验证的 10 个基因 PBMC 特征。使用实时 PCR 扩增同时定量 PBMC 和全血 RNA 中的基因表达。计算了测试的特征，包括敏感性、特异性、阳性和阴性预测值，并确定了接收者操作特征曲线以诊断微生物学反应的最佳截止值。然后在一个较小的独立样本中验证了这些发现。
全血转录测量比用力呼气量（FEV1）或 C 反应蛋白（CRP）单独更准确地识别气道感染减少。当添加到 FEV1 时，全血基因谱将诊断准确性从 64%提高到 82%。该测试检测到减少感染的特异性为 88%，持续感染存在的阳性预测值为 86%。检测治疗反应的曲线下面积为 0.81。6 个基因是除 FEV1 或 CRP 外，最能预测气道细菌负荷减少的基因。该测试的高特异性在验证队列中得到了复制。
将血液白细胞基因表达添加到 FEV1 和 CRP 中可提高预测肺部感染减少的特异性，并且可能增强 CF 治疗结果的评估。
