Department of Respiratory Medicine, Academic Medical Centre and University of Amsterdam, Amsterdam, The Netherlands.
Respir Res. 2011 Jan 18;12(1):11. doi: 10.1186/1465-9921-12-11.
Eosinophilic airway inflammation has successfully been used to tailor anti-inflammatory therapy in chronic obstructive pulmonary disease (COPD). Airway hyperresponsiveness (AHR) by indirect challenges is associated with airway inflammation. We hypothesized that AHR to inhaled mannitol captures eosinophilia in induced sputum in COPD.
Twenty-eight patients (age 58 ± 7.8 yr, packyears 40 ± 15.5, post-bronchodilator FEV1 77 ± 14.0%predicted, no inhaled steroids ≥4 wks) with mild-moderate COPD (GOLD I-II) completed two randomized visits with hypertonic saline-induced sputum and mannitol challenge (including sputum collection). AHR to mannitol was expressed as response-dose-ratio (RDR) and related to cell counts, ECP, MPO and IL-8 levels in sputum.
There was a positive correlation between RDR to mannitol and eosinophil numbers (r = 0.47, p = 0.03) and level of IL-8 (r = 0.46, p = 0.04) in hypertonic saline-induced sputum. Furthermore, significant correlations were found between RDR and eosinophil numbers (r = 0.71, p = 0.001), level of ECP (r = 0.72, p = 0.001), IL-8 (r = 0.57, p = 0.015) and MPO (r = 0.64, p = 0.007) in sputum collected after mannitol challenge. ROC-curves showed 60% sensitivity and 100% specificity of RDR for >2.5% eosinophils in mannitol-induced sputum.
In mild-moderate COPD mannitol hyperresponsiveness is associated with biomarkers of airway inflammation. The high specificity of mannitol challenge suggests that the test is particularly suitable to exclude eosinophilic airways inflammation, which may facilitate individualized treatment in COPD.
Netherlands Trial Register (NTR): NTR1283.
嗜酸性气道炎症已成功用于调整慢性阻塞性肺疾病（COPD）的抗炎治疗。间接挑战引起的气道高反应性（AHR）与气道炎症有关。我们假设吸入甘露醇引起的 AHR 可捕获 COPD 诱导痰中的嗜酸性粒细胞。
28 名年龄 58±7.8 岁、吸烟指数 40±15.5、支气管扩张剂后 FEV1 占预计值的 77±14.0%、4 周内未吸入皮质类固醇的轻度至中度 COPD（GOLD I-II）患者完成了两次随机访问，分别进行高渗盐水诱导痰和甘露醇挑战（包括痰收集）。甘露醇的 AHR 用反应剂量比（RDR）表示，并与痰中细胞计数、ECP、MPO 和 IL-8 水平相关。
甘露醇的 RDR 与嗜酸性粒细胞数（r = 0.47，p = 0.03）和高渗盐水诱导痰中 IL-8 水平（r = 0.46，p = 0.04）呈正相关。此外，RDR 与嗜酸性粒细胞数（r = 0.71，p = 0.001）、ECP 水平（r = 0.72，p = 0.001）、IL-8 水平（r = 0.57，p = 0.015）和 MPO 水平（r = 0.64，p = 0.007）在甘露醇挑战后收集的痰中也存在显著相关性。ROC 曲线显示，RDR 对甘露醇诱导痰中 >2.5%嗜酸性粒细胞的灵敏度为 60%，特异性为 100%。
在轻度至中度 COPD 中，甘露醇的高反应性与气道炎症的生物标志物有关。甘露醇挑战的高特异性表明该测试特别适合排除嗜酸性气道炎症，这可能有助于 COPD 的个体化治疗。
荷兰试验注册处（NTR）：NTR1283。
