Clinical Characteristics Of PPI Poor Efficacy Of Non-erosive Reflux Disease, Of Visceral Hypersensitivity Mechanisms And Treatment

Abstract Ⅰ Investigation of Clinical Features with Non-Erosive Reflux Disease Failed to Response to PPI TherayBACKGROUND Gastroesophageal reflux disease(GERD) is a common chronic upper gastrointestinal disease including non-erosive reflux disease(NERD), reflux esophagitis and Barrett’s esophagus. The reasons about why some patients with NERD failed to responcse to PPI therapy are still unknown.OBJECTIVES To evaluate the clinical features including demographics, symptom spectrum, quality of life, and psychological status in patients with NERD failed to response to PPI therapy.SUBJECTS&METHODS We prospectively enrolled175patients with acid reflux, regurgitation, heartburn or chest pain for at least6months without esophageal erosion and ulcer, systematic disease. All patients were asked to complete NERD questionnaires, including reflux symptoms, extra-esophageal and overlapping symptoms, quality of life questionnaire, and questionnaires of psychological status.RESULTS (1)175patients (72M/103F, mean age47.79±11.78yrs) were investigated. The proportion of NERD failed to response to PPI therapy were38.29%.(2) Patients with NERD failed to response to PPI therapy were significantly younger (45.26±12.13vs49.36±11.33, P<0.05), more likely to lose weight (P<0.05).(3) Compared to patients with NERD well response to PPI therapy, the course disease was shorter (47.46±62.54months vs69.59±86.82months,P<0.05) while the reflux symptom score was higher (12.14±4.89vs10.22±4.18,p<0.05) and more likely to suffer the retrosternal pain(P <0.05).(4) Patients with NERD failed to response to PPI therapy had lower prevalence rate of cough (10.61%vs35.19%, P<0.05). The percentages of other extra-esophageal symptoms and overlapping symptoms of the two groups were not significantly different.(5) Quality of life in failed to response to PPI group were lower, while the prevalence of abnormal psychological status was obviously higher (52.24%vs25.96%, P<0.05).CONCLUSIONS Patients with NERD failed to response to PPI therapy were younger, and had a higher prevalence of abnormal psychological status and poorer quality of life, which suggested that the abnormal psychological status may play an important role in NERD failed to response to PPI therapy. Abstract II Investigation Esophageal Hypersensitivity and Related Factors in Patients with NERD Failed to Response to PPI TherapyBACKGROUND Patients with NERD failed to response to PPI therapy tend to have normal esophageal acid exposure and abnormal psychological status. It is assumed that esophageal visceral hypersensitivity plays an important role in physiological mechanism of this group of NERD.OBJECTIVES To evaluate the features of visceral hypersensitivity and related factors including abnormal ANS function and psychological status in patients with NERD failed to response to PPI therapy.SUBJECTS&METHODS104patents with NERD had esophageal24h pH monitoring test (24h-pH),89patients performed esophageal manometry (EM),30patients with NERD failed to response to PPI therapy had autonomie nerve system test (ANS) and acid perfusion test (APT). APT includes three periods of esophageal perfusion, first was perfused saline (NS) for3min, then0.1N HCl for10min and NS for another10min. The acid hypersensitivity parameters were T-lag (time to symptom perception after acid perfusion), I (sensory intensity rating,0-10), APSS (acid perfusion symptom score), Td (time of symptom disappearing during NS stage). ANS was assessed by the standardized measurement of cardiovascular reflexes. Parasympathetic function was evaluated by the heart rate variation during deep breathing and the immediate heart rate response to standing. Sympathetic function was assessed by the fall in systolic blood pressure in response to standing.RESULTS (1) Positive rate of24h-pH monitoring test was less in NERD failed to response to PPI group(10.53%vs33.33%, P<0.05).(2) There was no statistical difference in EM between the two groups.(3) There was no significant difference in T-Lag, I and APSS (P>0.05) between the two groups, but Td was obviously prolonged in patients of NERD failed to response to PPI (P<0.05).(4) The immediate heart rate response to standing was more abnormal with NERD failed to PPI than with HS.CONCLUSIONS There may exist different mechanisms of esophageal hypersensitivity between patients with NERD failed to response to PPI therapy and response well to PPI therapy. The two groups of NERD both existed abnormal ANS function especially the abnormal vagal nerve function. Esophageal visceral hypersensitivity and abnormal ANS function might play important roles in the pathophysiological mechanisms of NRED failed to response to PPI therapy. Abstract III Evaluation for Efficacy of Citalopram on Non-Erosive Reflux Disease failed to response to PPI therapyBACKGROUNDS Some patients with non-erosive reflux disease (NERD) failed to response well to PPI therapy and often had abnormal psychological status, low quality of life. Clinically, antidepressants-selective serotonin reuptake inhibitors (SSRIs) appear to be useful for some patients with FGIDs for improving the symptom and quality of life. Citalopram is one of SSRIs, it can significantly decrease chemical and mechanical sensitivity in healthy volunteers with hypersensitivity to oesophageal stimulation.OBJECTIVE To evaluate the efficacy of citalopram on NERD failed to response to PPI therapy and identify the therapeutic effect of citalopram in order to find a new effective way to these NERD patients.METHODS17patients (7M/10F, mean40.29±9.19yrs), all failed to response to PPI therapy, reflux symptom scores decreased<50%and presented positive in APT. Psychological status (Hamilton anxiety and depression scale; Zung self-assessment anxiety and depression scale), the quality of life (SF-36), APT and ANS were re-evaluated after the treatment of citalopram (10mg qn, Day1-7,20mg qn Day8-42) for six weeks. The patients were allowed to take Hydrotalcite2#on demand.RESULTS (1) Citalopram significantly reduced the reflux symptom scores from12.76±5.25to5.00±2.76(P<0.05).(2) Citalopram significantly improved the psychological status, Hamilton Anxiety&Depression scores were reduced from18.17±5.61to6.76±3.25,20.71±4.27to7.88±2.98(P<0.05) respectively; Self-assessment Anxiety&Depression scores were decreased from48.1±10.3to30.7±2.4,52.0±15.2to30.3±8.2(P<0.05)respectively.(3) The GERD-Health Related Quality of Life score was reduced from14.88±6.10to5.35±4.69(P<0.05).(4) Eight domains of SF-36were significantly improved (P<0.05).(5) There were no differences in T-Lag, but Td was obviously shorten (P<0.05). I and APSS between patients were significantly decreased (P<0.05).(6) There were not any improvements of ANS after the therapy.CONCLUSIONS Citalopram significantly improved the reflux symptoms, psychological status and the quality of life and also significantly lowered esophageal hypersensitivity of the NERD who failed to PPI therapy.