Defining Clinically Relevant Phenotypes of PPI Non-Responders

描述（由申请人提供）：30%至50%的诊断为胃食管反流病（GERD）的患者对质子泵抑制剂（PPI）的症状控制不满意。这组患者; PPI无应答者（PPI-NR），追求进一步的诊断程序和干预措施，产量较低。这种方法是有问题的，因为在至少50%的接受动态反流测试的PPI-NR中，症状与病理性反流无关，因此它不能改善结局，甚至不能告诉我们为什么患者对PPI没有反应。由于对PPI应答者的定义缺乏一致意见，并且缺乏解释持续症状产生异质性的模型，因此限制了针对这一人群的新型治疗方法的开发。我们的目标是验证PPI-NR模型，该模型可解释病理性反流以上和以外的因素，减少对低产量动态反流监测的需求，并为新型治疗的开发提供信息。研究1将提供一个方程，其中试验前临床和问卷数据足以估计来自动态反流监测的4种反流表型中每一种的概率。研究2将产生一个类似的方程，该方程将预测一个人在有指征时撤回PPI治疗的能力。 公共卫生相关性：胃食管反流病（GERD）是一种越来越常见的医学疾病，影响至少10%的美国成年人口。尽管质子泵抑制剂（PPI）非常有效，但高达30-50%的患者对其反应不满意，并继续出现难治性症状。该提案旨在确定持续症状的原因，并确定系统诊断方案是否能更好地定义PPI无应答者的治疗策略。

DESCRIPTION (provided by applicant): Thirty to 50 percent of patients diagnosed with gastroesophageal reflux disease (GERD) are not satisfied with symptom control derived from proton pump inhibitors (PPI). This group of patients; PPI non-responders (PPI- NR), pursue further diagnostic procedures and interventions with low yield. This approach is problematic because symptoms are not related to pathologic reflux in at least 50% of PPI-NRs referred for ambulatory reflux testing and therefore it does not lead to improved outcomes or even inform us as to why a patient did not respond to PPI. The development of novel therapies for this group is limited by lack of agreement on the definition of a PPI responder and the lack of a model that accounts for the heterogeneity of continued symptom generation. Our goal is to validate a PPI-NR model that accounts for factors above and beyond pathologic reflux, reducing the need for low-yield ambulatory reflux monitoring and informing the development of novel treatments. Study 1 will provide an equation in which pre-test clinical and questionnaire data sufficiently enables probability estimation for each of 4 reflux phenotypes, derived from ambulatory reflux monitoring. Study 2 will yield a similar equation which will predict one's ability to withdraw PPI therapy when indicated. PUBLIC HEALTH RELEVANCE: Gastroesophageal reflux disease (GERD) is an increasingly common medical condition affecting at least ten percent of the adult US population. Despite the fact that proton pump inhibitors (PPI) are extremely effective, up to 30-50% of patients are unsatisfied with their response and continue to have refractory symptoms. This proposal seeks to identify the reason for continued symptoms and to determine whether a systematic diagnostic protocol will better define treatment strategies for PPI non-responders.