Pneumology and Public Health Department, University of Liege, CHU Liege, Belgium.
Pneumology and Public Health Department, University of Liege, CHU Liege, Belgium.
Biochem Pharmacol. 2020 Sep;179:113981. doi: 10.1016/j.bcp.2020.113981. Epub 2020 Apr 17.
Demonstration of bronchial hyperresponsiveness is a key feature in asthma diagnosis. Methacholine challenge has proved to be a highly sensitive test to diagnose asthma in patients with chronic respiratory symptoms and preserved baseline lung function (FEV1 > 70% pred.) but is time consuming and may sometimes reveal unpleasant to the patient. We conducted a retrospective study on 270 patients recruited from the University Asthma Clinic of Liege. We have compared the values of several lung function indices and fractional exhaled nitric oxide (FeNO) in predicting a provocative methacholine concentration ≤16 mg/ml on a discovery cohort of 129 patients (57 already on ICS) and on a validation cohort of 141 patients (66 already on ICS). In the discovery study (n = 129), 85 patients (66%) had a positive methacholine challenge with PC20M ≤ 16 mg/ml. Those patients had lower baseline % predicted FEV1 (92% vs. 100%; p < 0.01), lower FEV1/FVC ratio (79% vs. 82%; p < 0.05), higher RV/TLC ratio (114% vs. 100%; p < 0,0001), lower SGaw (specific conductance) (0.76 vs. 0.95; p < 0,001) and higher FeNO (29 ppb vs. 19 ppb; p < 0,01). When performing ROC curve the RV/TLC ratio provided the greatest AUC (0.74, p < 0.001), sGAW had intermediate AUC of 0.69 (p < 0.001) while FeNO, FEV1 and FEV1/FVC ratio were modestly predictive (AUC of 0.65 (p < 0.05), 0,67 (p < 0.001) and 0,63 (p < 0.001). These results were confirmed in the validation study (n = 141). Based on a logistic regression analysis, significant variables associated with positive methacholine challenge were FeNO and RV/TLC (% Pred). A combined application of FeNO and RV/TLC (% Pred) for predicting the PC20M had a specificity of 85%, a sensitivity of 59% and an AUC of 0.79. In the validation study, three variables (RV/TLC, FeNO and FEV1) were independently associated with positive methacholine challenge and the combination of these three variables yielded a specificity of 77%, a sensitivity of 39% and an AUC of 0.77. The RV/TLC ratio combined to FeNO may be of interest to predict significant methacholine bronchial hyperresponsiveness.
气道高反应性的检测是哮喘诊断的一个重要特征。乙酰甲胆碱激发试验已被证明是一种高度敏感的检测方法,可用于诊断慢性呼吸道症状且基础肺功能(FEV1 > 70%预计值)正常的患者中的哮喘,但该检测方法耗时,且有时可能使患者感到不适。我们对列日大学哮喘诊所招募的 270 名患者进行了回顾性研究。我们比较了几个肺功能指标和呼出气一氧化氮分数(FeNO)在预测 129 名患者(57 名患者已使用 ICS)的激发乙酰甲胆碱浓度≤16mg/ml 的界值和 141 名患者(66 名患者已使用 ICS)的验证队列中的预测价值。在探索性研究(n=129)中,85 名患者(66%)的乙酰甲胆碱激发试验 PC20M ≤ 16mg/ml 为阳性。这些患者的基础预计值 FEV1 较低(92%对 100%;p < 0.01),FEV1/FVC 比值较低(79%对 82%;p < 0.05),RV/TLC 比值较高(114%对 100%;p < 0.0001),SGaw(特异性气道传导率)较低(0.76 对 0.95;p < 0.001),FeNO 较高(29ppb 对 19ppb;p < 0.01)。进行 ROC 曲线分析时,RV/TLC 比值的 AUC 最大(0.74,p < 0.001),sGAW 的 AUC 居中(0.69,p < 0.001),而 FeNO、FEV1 和 FEV1/FVC 比值的预测能力中等(AUC 分别为 0.65(p < 0.05)、0.67(p < 0.001)和 0.63(p < 0.001)。这些结果在验证研究(n=141)中得到了证实。基于逻辑回归分析,与阳性乙酰甲胆碱激发试验相关的显著变量为 FeNO 和 RV/TLC(% Pred)。FeNO 和 RV/TLC(% Pred)联合应用预测 PC20M 的特异性为 85%,敏感性为 59%,AUC 为 0.79。在验证研究中,三个变量(RV/TLC、FeNO 和 FEV1)与阳性乙酰甲胆碱激发试验独立相关,这三个变量的组合特异性为 77%,敏感性为 39%,AUC 为 0.77。RV/TLC 比值与 FeNO 联合使用可能有助于预测显著的乙酰甲胆碱气道高反应性。