| Chapter Ⅰ Clinical characteristics of extraesophageal symptoms in patients with gastroesophageal reflux diseaseBackground:Gastroesophageal reflux disease (GERD) is a common problem caused by the reflux of gastric contents into the esophagus that that can lead to esophageal and extraesophageal manifestations. The typical symptoms of GERD are generally considered to be heartburn and regurgitation. A variety of extraesophageal symptoms are commonly observed in patients with GERD and they are nonspecific. About 50% of patients with extraesophageal symptoms lack typical symptoms of GERD.Some researches indicated the demographic, endoscopic findings, reflux events and esophageal motility characteristics were different in patients with different symptoms of GERD and the conclusions remains controversial.Objectives:To analyze the clinical characteristics of extraesophageal symptoms in patients with gastroesophageal reflux disease and to compare the endoscopic findings, reflux events and esophageal motility characteristics among patients with different GERD symptoms.Methods:We analyzed the medical records of outpatients with GERD enrolled in Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University from May 2011 to March 2014, with or without extraesophageal symptoms of GERD, such as persistent throat clearing, throat foreign body sensation, throat burning, sore throat, hoarseness, chronic cough and asthma. The patients were divided into three groups, group of patents with both typical symptoms and extraesophageal symptoms, group of patients with typical symptoms alone and group of patients with extraesophageal symptoms alone, according to their symptoms in past one month. The demographic characteristics, the results of high-resolution manometry (HRM) and 24-hour pH impedance monitor were compared among three groups.Results:(1) Finally 257 GERD patients were enrolled.158(61.5%) patients had both typical symptoms and extraesophageal symptoms.50(19.4%) patients had typical symptoms alone and 49(19.1%) patients had extraesophageal symptoms alone. The patients with both typical symptoms and extraesophageal symptoms (46.46±11.62 years) and the patients with extraesophageal symptoms alone (48.04±11.90 years) had significantly older age than the patients with typical symptoms alone (42.36±11.93years) (p=0.040 among three groups, p=0.032 and 0.017 between two groups respectively). There was no statistical difference in gender, height, weight, body mass index(BMI), employment status, smoking and alcohol use among three groups(p>0.05). (2) The most common symptom of the esophagus was foreign body sensation in the throat (78.3%) in this study, and the proportion of this symptom in group of patents with both typical symptoms and extraesophageal symptoms and group of patients with extraesophageal symptoms alone had no significant difference (76.6%vs. 83.7%,p=0.293). (3)242 patients provided the results of esophagogastroduodenoscope (EGD). The patients with extraesophageal symptoms alone (36.9%) had significantly more frequency of reflux esophagitis (RE) than the patients with both typical symptoms and extraesophageal symptoms (18.2%) (p=0.003). Compared with the patients with typical symptoms alone (22.9%), the patients with extraesophageal symptoms alone had an increased trend of RE, however, there was no statistical difference (p=0.089). (4)Pathological acid reflux was observed in 48(18.7%) patients in total and there was no significant difference among three groups (18.4%vs.18.0%vs.18.0%,p=0.748). 120(46.7%)patients had positive symptom-reflux association (SRA) and there was no significant difference among three groups (44.3%vs.48.0%vs.53.1%, p=0.550). (5)The patients with both typical symptoms and extraesophageal symptoms (3.05(2.30,3.60) cm) and the patients with extraesophageal symptoms alone (3.20(2.30,3.70) cm) had significantly shorter length of UES than the patients with typical symptoms alone (3.75(3.00,4.30) cm)(p<0.040 among three groups, p<0.001 and 0.001 between two groups respectively).There was no statistical difference in parameters of esophageal motility among three groups(p>0.05).(5) Logistic regression analysis suggested that the patients with both typical symptoms and extraesophageal symptoms had significantly older age and shorter length of UES than the patients with typical symptoms alone(p=0.043,OR=1.032,95%CI(1.001.1.065));p<0.001,OR=0.452,95%CI (0.299,0.684)). The patients with extraesophageal symptoms alone had significantly older age and shorter length of UES than the patients with typical symptoms alone(p=0.033,OR=1.041,95%CI(1.003,1.081)); p=0.003, OR=0.477,95%CI (0.291, 0.783)).Conclusion:(1)GERD patients with older age and shorter length of UES were more likely to exhibit extraesophageal symptoms. It indicated that age and length of UES were related to extraesophageal symptoms in patients of GERD.(2) Foreign body sensation in the throat was the most common extraesophageal symptoms in our study.(3) Reflux events and esophageal motility characteristics had no association with occurrence of typical symptoms in patients with extraesophageal symptoms.Chapter II Influencing factors of response to proton pump inhibitor treatment in GERD patients with extraesophageal symptomsBackground:Proton pump inhibitor (PPI) therapy is the standard therapy of extraesophageal symptoms in GERD patients. However, the efficacy of PPI therapy varies. Multiple visits to doctors and long-term use of medications contribute to high economic burden for patients with extraesophageal symptoms. Few studies have analyzed the influencing factors of response to PPI treatment and the conclusions remains controversial.Objectives:To assess the characteristics of esophageal motility and reflux in patients with extraesophageal symptoms, and to explore the influencing factors of response to PPI therapy.Methods:We analyzed the medical records of outpatients with GERD enrolled in Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University from May 2011 to March 2014, with or without at least one extraesophageal symptom. The patients who had regularly received PPI medicine two times a day, at least 8 weeks were analyzed. The patients were divided into two groups of PPI-responsive group and PPI-resistant group, according to their response to PPI therapy. The demographic characteristics, psychological factors, the results of high-resolution manometry (HRM) and 24-hour pH impedance monitor were compared between two groups. Logistic regression analysis was used to explore the influencing factors of response to PPI therapy.Results:(1)Finally 135 GERD patients with extraesophageal symptoms were enrolled, with 42(31.1%)PPI-responsive patients and 93(68.9%) PPI-resistant patients. The patients who responded to PPI therapy had significantly higher BMI than PPI-resistant patients((23.62±2.94 kg/m2) vs. (22.33±2.86 kg/m2), p=0.018). The ratio of alcohol use was significantly higher in PPI-responsive patients than which in PPI-resistant patients (35.7%vs.18.3%, p=0.027).(2) The PPI-responsive patients had significantly higher score of heartburn than PPI-resistant patients (4.0(0,6.0) vs.0(0,5.5),p=0.011). (3)The PPI-responsive patients had significantly lower score of self-rating anxiety scale (SAS) than PPI-resistant patients (39.00(33.00,45.75) vs.46.00(39.00,54.50), P=0.011). The PPI-responsive patients had significantly lower frequency of anxiety state than PPI-resistant patients(14.3% vs.37.6%,p=0.008).(4)139 patients provided the results of EGD. The ratio of Hp infection was significantly higher than PPI-resistant patients(26.7% vs.8.2%, p=0.024).(5)There was no statistical difference in parameters of esophageal motility between two groups(p>0.05).(6)The patients in PPI-responsive group had significantly more pathological acid reflux than those in PPI-resistant group(30.9% vs.16.1%, p=0.049). The ratio of positive symptom-reflux association (SRA) was significantly higher in PPI-responsive patients than that in PPI-resistant patients (76.2% vs.39.8%,p<0.001).(7) Logistic regression analysis suggested that BMI (p=0.04,OR=1.883,95%CI(l.016,3.490)), heartburn score (p=0.006, OR=1.696, 95%CI(1.159,2.480)), and SRA(p< 0.001,OR=7.225,95%CI(2.572,20.298)) and anxiety state (p=0.006, OR=0.321,95%CI (0.141,0.727))were relevant for PPI therapy prediction. Alcohol use (adjusted p=0.059), Hp infection (adjusted p=0.071)and pathological acid reflux (adjusted p=0.330)were not the independent factors of efficacy of PPI therapy in those patients.Conclusion:(1)The efficacy of PPI therapy in patients with extraesophageal symptoms was as low as 31.1%. (2)Those patients with higher BMI, higher score of heartburn, positive SRA may have better response to PPI therapy. (3) The patients with anxiety state may have poor efficacy of PPI therapy. (4)Alcohol use, Hp infectionand pathological acid reflux were not the independent factors of efficacy of PPI therapy in those patients.(5) Esophageal motility was not related to efficacy of PPI therapy in patients with extraesophageal symptoms... |
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