Department of Internal Medicine, Boston Medical Center, Boston, MA, USA.
Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Clin Transl Gastroenterol. 2018 Apr 25;9(4):144. doi: 10.1038/s41424-018-0012-9.
Chronic constipation may be categorized as normal transit (NTC), slow transit (STC), or outlet obstruction. Colonic wake response is a relative increase in colonic motility upon awakening. Colonic manometry studies have demonstrated attenuated wake response in STC. We sought to evaluate wake response among healthy (H), NTC, and STC patients using wireless motility capsule (WMC).
A retrospective study of WMC data from a multicenter clinical trial and a tertiary gastroenterology clinic was performed. WMC motility parameters of contraction frequency (Ct) and area under the contraction curve (AUC) were analyzed in 20-min windows 1-h before and after awakening. T-tests compared parameters between H, NTC, and STC. Linear regression analysis was performed to determine if outlet obstruction confounded data. A receiver operating characteristic curve demonstrated optimal Ct cut-offs to define blunted wake response.
A total of 62 H, 53 NTC and 75 STC subjects were analyzed. At 20, 40, and 60 min after awakening, STC subjects had significantly lower mean Ct when compared to H (p < 0.001) and NTC (p < 0.01). Linear regression demonstrated that outlet obstruction was not associated with a decreased wake response (β = 3.94, (CI -3.12-1.00), P = 0.27). Defined at the Ct threshold of 64 at 20-min post-wake, blunted wake response sensitivity was 84% and specificity was 32% for chronic constipation.
Findings of an impaired wake response in subjects with STC and not NTC adds further evidence to neuronal dysfunction as an etiology of STC, and identifies a possible temporal target for pharmacologic intervention.
慢性便秘可分为正常传输型（NTC）、传输缓慢型（STC）或出口梗阻型。结肠唤醒反应是指苏醒后结肠蠕动相对增加。结肠测压研究表明，STC 患者的唤醒反应减弱。我们旨在使用无线动力胶囊（WMC）评估健康（H）、NTC 和 STC 患者的唤醒反应。
对多中心临床试验和三级胃肠病学诊所的 WMC 数据进行回顾性研究。在觉醒前 1 小时和觉醒后 20 分钟的 20 分钟窗口中分析 WMC 运动参数收缩频率（Ct）和收缩曲线下面积（AUC）。采用 t 检验比较 H、NTC 和 STC 之间的参数。进行线性回归分析以确定出口梗阻是否混淆数据。接受者操作特征曲线显示了确定唤醒反应迟钝的最佳 Ct 截断值。
共分析了 62 名 H、53 名 NTC 和 75 名 STC 患者。在觉醒后 20、40 和 60 分钟，与 H（p<0.001）和 NTC（p<0.01）相比，STC 患者的平均 Ct 显著降低。线性回归表明，出口梗阻与唤醒反应降低无关（β=3.94，（CI-3.12-1.00），P=0.27）。在觉醒后 20 分钟时 Ct 阈值定义为 64，唤醒反应迟钝的敏感性为 84%，特异性为 32%，用于慢性便秘。
在 STC 患者而不是 NTC 患者中发现唤醒反应受损，进一步证明神经元功能障碍是 STC 的病因，并确定了潜在的药物干预的时间靶点。
