Effect of proton pump inhibitort on salivary pepsin concentration in patients with laryngopharyngeal reflux
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摘要: 目的 探讨质子泵抑制剂(PPI)治疗对咽喉反流(LPR)患者唾液胃蛋白酶浓度的影响。方法 以2019年8月—2020年12月西安交通大学第二附属医院收治的以咽部异物感、咽干、痰多等非特异性症状为主诉的152例疑似LPR初诊患者为研究对象，应用反流症状指数量表(RSI)与反流体征指数量表(RFS)评分将所有患者分为LPR(+)组与LPR(-)组、RSI(+)组与RSI(-)组、RFS(+)组与RFS(-)组。对LPR(+)组患者给予PPI(泮托拉唑钠肠溶片)治疗1个月后再次评估。所有患者在初诊及治疗后复诊时均收集唾液样本，用酶联免疫吸附法(ELISA法)测定唾液胃蛋白酶浓度，比较治疗前后RSI、RFS评分和唾液胃蛋白酶浓度差异。结果 LPR(+)组唾液胃蛋白酶浓度中值显著高于LPR(-)组(73.01 ng/mL vs 25.66 ng/mL，P < 0.01)，RFS(+)组唾液胃蛋白酶浓度中值亦显著高于RFS(-)组(78.00 ng/mL vs 35.79 ng/mL，P < 0.01)。LPR(+)患者PPI治疗1个月后的RSI(11.00 vs 7.00，P < 0.05)和RFS(9.00 vs 7.00，P < 0.01)量表评分中位数显著降低，唾液胃蛋白酶浓度中值亦显著下降(53.60 ng/mL vs 46.49 ng/mL，P < 0.05)，且咽部异物感及烧心、胸痛、胃痛等症状及假声带沟、红斑或充血、声带水肿、后连合增生及喉内黏稠黏液附着等体征评分在治疗后亦显著下降(P < 0.05)。结论 LPR患者应用PPI治疗1个月后部分症状及体征评分和唾液胃蛋白酶浓度均显著下降，提示胃蛋白酶在LPR发病过程中发挥重要作用，且胃蛋白酶可能与咽部异物感及声带水肿等症状体征密切相关。Abstract: Objective To investigate the effect of proton pump inhibitor(PPI) treatment on salivary pepsin concentration in laryngopharyngeal reflux(LPR).Methods 152 patients with suspected LPR complaining non-specific symptoms such as foreign body sensation, dry throat, phlegm and other non-specific symptoms were enrolled, in the Second Affiliated Hospital of Xi'an Jiaotong University from August 2019 to December 2020. According to the scores of reflux symptom index(RSI) and reflux finding score(RFS), all the patients were divided into LPR (+) group and LPR (-) group, RSI (+) group and RSI (-) group, RFS (+) group and RFS (-) group. Patients in the LPR (+) group were reassessed after 1 month of PPI treatment. Saliva samples were collected from all the patients at initial diagnosis and follow-up diagnosis after treatment. The salivary pepsin concentration was determined by enzyme linked immunosorbent assay (ELISA). The differences of RSI, RFS scores and salivary pepsin concentrations before and after treatment were compared.Results The median concentration of salivary pepsin in LPR (+) group was significantly higher than that in LPR (-) group, and (73.01 ng/mL vs 25.66 ng/mL, P < 0.01), the median concentration of salivary pepsin in RFS (+) group were significantly higher than that in RFS (-) group(78.00 ng/mL vs 35.79 ng/mL, P < 0.01) Furthermore, the median scores of RSI (11.00 vs 7.00, P < 0.05) and RFS (9.00 vs 7.00, P < 0.01) of LPR (+) patients notably decreased after PPI treatment for 1 month, and the salivary pepsin median concentration was memorably lower than that before treatment(53.60 ng/mL vs 46.49 ng/mL, P < 0.05). Meanwhile, the scores of symptoms such as pharyngeal paraesthesia, heartburn, chest pain, stomachache, and the scores of signs such as false vocal fold, erythema or congestion, vocal fold edema, posterior commissure hypertrophy and thick endolaryngeal mucus were conspicuously lower after treatment than those before treatment(P < 0.05).Conclusion After 1 month of PPI treatment, the scores of partial symptoms and signs, and the salivary pepsin concentrations of LPR patients decreased significantly, suggesting that pepsin plays an important role in the pathogenesis of LPR, and pepsin may be closely related to the symptoms and signs such as pharyngeal paraesthesia and vocal fold edema.
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表 1 LPR(+)组与LPR(-)组患者唾液胃蛋白酶浓度比较
M(P25，P75) 组别 例数 唾液胃蛋白酶浓度中位数/(ng·mL-1) Z P LPR(+)组 112 73.01(34.18，110.73) -4.919 < 0.001 LPR(-)组 40 25.66(17.42，51.64) RSI(+)组 46 48.15(31.12，90.53) -0.255 0.799 RSI(-)组 106 55.24(25.16，89.38) RFS(+)组 90 78.00(34.79，115.10) -4.148 < 0.001 RFS(-)组 62 35.79(19.68，61.14) 
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表 2 LPR患者应用PPI治疗前后RSI、RFS量表评分及唾液胃蛋白酶浓度变化
M(P25，P75) 指标 治疗前 治疗后 Z值 P值 RSI总分 11.00(6.00，15.00) 7.00(3.00，14.00) -2.109 0.035 声嘶或发声障碍 0.00(0.00，2.00) 0.50(0.00，2.25) -0.241 0.809 持续清嗓 2.00(1.00，3.00) 1.00(0.00，3.00) -1.491 0.136 痰过多或鼻涕倒流 1.00(0.00，3.00) 1.00(0.00，2.00) -0.529 0.597 吞咽食物、水或药片不利 0.00(0.00，1.00) 0.00(0.00，1.00) -0.062 0.951 饭后或躺下后咳嗽 0.00(0.00，1.00) 0.00(0.00，1.00) -0.360 0.719 呼吸不畅或反复窒息发作 0.00(0.00，1.00) 0.00(0.00，1.00) -0.874 0.382 烦人的咳嗽 0.00(0.00，1.00) 0.00(0.00，1.00) -1.195 0.232 咽部异物感 3.00(1.00，4.00) 1.00(0.75，3.00) -3.884 < 0.001 烧心、胸痛、胃痛 1.00(0.00，2.00) 0.00(0.00，1.00) -2.223 0.026 RFS总分 9.00(8.25，11.00) 7.00(5.00，9.00) -5.402 < 0.001 假声带沟 2.00(2.00，2.00) 2.00(2.00，2.00) -2.646 0.008 喉室消失 0.00(0.00，2.00) 0.00(0.00，2.00) -0.947 0.344 红斑或充血 2.00(2.00，2.00) 2.00(1.00，2.00) -2.457 0.014 声带水肿 1.00(1.00，1.00) 1.00(0.00，1.00) -4.315 < 0.001 弥漫性喉水肿 1.00(1.00，1.00) 1.00(1.00，1.00) -1.263 0.207 后连合增生 1.00(1.00，1.00) 1.00(1.00，1.00) -2.714 0.007 肉芽肿 0.00(0.00，0.00) 0.00(0.00，0.00) -1.512 0.131 喉内黏稠黏液附着 2.00(2.00，2.00) 0.00(0.00，2.00) -5.385 < 0.001 唾液胃蛋白酶浓度/(ng·mL-1) 53.60(28.13，86.06) 46.49(21.85，65.00) -2.444 0.015
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