Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan.
J Breath Res. 2020 Feb 25;14(2):026007. doi: 10.1088/1752-7163/ab71a4.
Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory lung disease. It is important to identify patients who would respond to anti-inflammatory treatment. This prospective study aims to determine how inflammatory biomarkers could be used to predict the potential effect of inhaled corticosteroids (ICS) in terms of symptoms and lung function. We evaluated the levels of blood eosinophils, exhaled nitric oxide fraction at a flow rate of 50 ml s (FeNO), alveolar nitric oxide concentration (Calv), immunoglobulin E and atopy in 43 patients with symptomatic COPD and correlated these expression levels with the changes in the COPD Assessment Test (CAT) and lung function by 12 weeks of add-on therapy with ciclesonide 400 μg d on bronchodilators. The mean changes in the CAT score and FEV were -1.4 points and +90 ml, respectively, with significant variation in the levels of change. The area under the receiver's operating characteristic curve (AUC) for FeNO in predicting improvements in both the CAT score and FEV was 0.92. The AUC for Calv and blood eosinophils was 0.82 and 0.65. Two cutoffs were chosen, one corresponding to a high value of FeNO associated with certainty for response inclusion (FeNO = 35 ppb; sensitivity = 0.67, specificity = 0.94; positive predictive value = 0.80) and the other with certainty for response exclusion (FeNO = 20 ppb; sensitivity = 1.00, specificity = 0.58, negative predictive value = 1.00). Baseline FeNO values were significantly correlated with changes in FEV and CAT (all p < 0.0001). FeNO could be a valuable biomarker for identifying individuals who respond to steroid therapy among patients with symptomatic COPD in terms of symptoms and airflow limitation. The study was prospectively registered with the University Hospital Medical Information Network (UMIN) in Japan (protocol ID 000010711).
慢性阻塞性肺疾病（COPD）是一种异质性炎症性肺部疾病。识别对抗炎治疗有反应的患者非常重要。本前瞻性研究旨在确定炎症生物标志物如何用于预测吸入性皮质类固醇（ICS）在症状和肺功能方面的潜在疗效。我们评估了 43 例有症状的 COPD 患者的血液嗜酸性粒细胞水平、流速为 50 ml s 时的呼气一氧化氮分数（FeNO）、肺泡一氧化氮浓度（Calv）、免疫球蛋白 E 和特应性，并将这些表达水平与 12 周布地奈德 400 μg d 添加治疗后 COPD 评估测试（CAT）和肺功能的变化相关联。CAT 评分和 FEV 的平均变化分别为-1.4 分和+90 ml，变化水平存在显著差异。FeNO 预测 CAT 评分和 FEV 改善的受试者工作特征曲线（ROC）下面积（AUC）为 0.92。Calv 和血液嗜酸性粒细胞的 AUC 分别为 0.82 和 0.65。选择了两个截止值，一个对应于与纳入反应确定性相关的 FeNO 高值（FeNO = 35 ppb；敏感性= 0.67，特异性= 0.94；阳性预测值= 0.80），另一个对应于排除反应的确定性（FeNO = 20 ppb；敏感性= 1.00，特异性= 0.58，阴性预测值= 1.00）。FEV 和 CAT 的变化与基线 FeNO 值显著相关（均 p < 0.0001）。FeNO 可能是一种有价值的生物标志物，可用于识别症状性 COPD 患者中对类固醇治疗有反应的个体，以改善症状和气流受限。该研究在日本大学医院医疗信息网络（UMIN）进行了前瞻性注册（方案 ID 000010711）。
