贝母枳术方治疗胃食管反流性咳嗽的回顾性队列研究

Treatment of Gastroesophageal Reflux Cough with Beimu ZhizhuPrescription:A Retrospective Cohort Study

【目的】回顾性分析297例胃食管反流性咳嗽(gastroesophageal reflux cough,GERC)患者临床资料,探讨贝母枳术方(枳术丸加味)治疗GERC的临床疗效和安全性。【方法】采用回顾性队列研究,共计纳入2021年7月至2023年7月就诊于中国中医科学院望京医院门诊的297例胃气上逆型GERC患者,根据是否应用贝母枳术方分为暴露组136例和非暴露组161例,暴露组应用贝母枳术方治疗,非暴露组应用质子泵抑制剂(艾司奥美拉唑镁肠溶片)治疗,并经1∶1倾向性评分匹配(PSM)得到119对病例,观察匹配后2组患者治疗前后唾液胃蛋白酶水平的变化情况,比较匹配后2组患者治疗2周、8周后的咳嗽缓解总有效率和反流相关症状缓解率(包括反酸、烧心、嗳气、胃胀缓解率),并记录不良反应发生情况。【结果】(1)症状缓解率方面,匹配后,暴露组治疗2周后的咳嗽缓解总有效率及反酸、烧心、嗳气、胃胀等反流相关症状缓解率分别为84.87%(101/119)、80.77%(84/104)、82.61%(76/92)、82.5%(66/80)、84.42%(65/77),非暴露组分别为73.95%(88/119)、72.90%(78/107)、70.41%(69/98)、65.38%(51/78)、64.38%(47/73),组间比较,暴露组除反酸缓解率外的其他症状缓解率均明显优于非暴露组(P<0.05或P<0.01);暴露组治疗8周后的咳嗽缓解总有效率及反酸、烧心、嗳气、胃胀等反流相关症状缓解率分别为94.74%(36/38)、91.67%(33/36)、91.43%(32/35)、93.75%(30/32)、94.12%(32/34),非暴露组分别为77.78%(35/45)、74.42%(32/43)、71.43%(30/42)、68.42%(26/38)、66.67%(24/36),组间比较,暴露组的各项症状缓解率均明显优于非暴露组(P<0.05或P<0.01)。(2)唾液胃蛋白酶水平方面,匹配后,暴露组治疗2周后的唾液胃蛋白酶水平较治疗前明显下降(P<0.01),非暴露组的唾液胃蛋白酶水平未见明显下降(P>0.05),暴露组对唾液胃蛋白酶水平的下降作用明显优于非暴露组,组间治疗2周后及治疗前后差值比较,差异均有统计学意义(P<0.05或P<0.01)。(3)安全性方面,非暴露组有4例(2.48%)患者出现不适反应,暴露组未出现相关不良反应,2组不良反应发生率比较,差异无统计学意义(χ^(2)=1.180,P=0.178)。【结论】贝母枳术方可有效缓解胃气上逆型GERC患者的咳嗽及反酸、烧心、嗳气、胃胀等反流相关症状,降低唾液胃蛋白酶水平,且具有较高的安全性。

Objective To explore the clinical efficacy and safety of Beimu Zhizhu Prescription(derived from the modification of Zhizhu Pills)in the treatment of GERC by retrospectively analyzing the clinical data of 297 patients with gastroesophageal reflux cough(GERC).Methods A retrospective cohort study was conducted in a total of 297 patients with GERC of rebellious stomach qi type who were admitted to the Outpatient Department of Wangjing Hospital of China Academy of Chinese Medical Sciences from July 2021 to July 2023.The patients were divided into an exposure group(136 cases)and a non-exposure group(161 cases)according to the medication of Beimu Zhizhu Prescription or not.The exposure group was treated with Beimu Zhizhu Decoction,and the non-exposure group was treated with proton pump inhibitor of Esomeprazole Magnesium Enteric-coated Tablets.A total of 119 pairs of cases were obtained after propensity score matching(PSM)at the ratio of 1 to 1.The changes of salivary pepsin level before and after treatment in the two groups were observed.After two weeks and eight weeks of treatment,the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching and gastric distension were compared between the two groups,and the incidence of adverse reactions was recorded.Results(1)After two weeks of treatment,the comparison of symptom remission rate after PSM showed that the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching and gastric distension in the exposure group were 84.87%(101/119),80.77%(84/104),82.61%(76/92),82.5%(66/80),84.42%(65/77),respectively,and those in the non-exposure group were 73.95%(88/119),72.90%(78/107),70.41%(69/98),65.38%(51/78),64.38%(47/73),respectively.The intergroup comparison showed that the remission rates for all of the symptoms except for acid reflux in the exposure group was significantly superior to that in the non-exposure group(P<0.05 or P<0.01).After eight weeks of treatment,the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching,and gastric distension in the exposure group were 94.74%(36/38),91.67%(33/36),91.43%(32/35),93.75%(30/32),94.12%(32/34),respectively,and those in the non-exposure group were 77.78%(35/45),74.42%(32/43),71.43%(30/42),68.42%(26/38),66.67%(24/36),respectively.The intergroup comparison showed that the remission rate of all of the symptoms in the exposure group was significantly superior to that in the non-exposure group(P<0.05 or P<0.01).(2)After two weeks of treatment,the comparison of salivary pepsin level after PSM showed that the salivary pepsin level of the exposure group was significantly lower than that before treatment(P<0.01),while that of the non-exposure group was not significantly decreased(P>0.05).The decrease of salivary pepsin level in the exposure group was significantly superior to that in the non-exposure group.Statistically significant differences were presented in the post-treatment salivary pepsin level after two weeks of treatment and in the pre-and post-treatment difference of salivary pepsin level between the two groups(P<0.05 or P<0.01).(3)There were four cases(2.48%)of adverse reactions in the non-exposure group,while no related adverse reactions occurred in the exposure group.There was no significant difference in the incidence of adverse reactions between the two groups(χ^(2)=1.180,P=0.178).Conclusion Beimu Zhizhu Decoction can effectively relieve cough and reflux-related symptoms of acid reflux,heartburn,belching,and gastric distension in patients with GERC of rebellious stomach qi type,reduce the level of salivary pepsin,and has high safety.