Clinical Application Of Hydrogen Breath Test In Irritable Bowel Syndrome

BackgroundAs the most common type of functional gastrointestinal disorders (FGIDs), irritable bowel syndrome (IBS) is widely engaged and diagnosed in gastroenterology clinic, with the frequency varied from 10%-20%, it has become one of the chief complaint among young and middle-aged patients. Though firstly found over 150 years ago, IBS still face lots of challenge and confusion on its pathogenesis, physiopathologic mechanism, differential diagnosis and standard treatment.Current researches have showed that neurohumoral mechanism, psychological factors, alteration of intestinal flora, genetic abnormality, gastrointestinal(GI) dismotility, visceral hypersensitivity and disorder of the mucosal immune system may contribute to the happening and development of IBS separately or collectively, which account for the noteworthy heterogeneity of IBS. Whereby, intestinal bacterial overgrowth, especially small intestinal bacterial overgrowth (SIBO) has been the research focus involving gastrointestinal disorders in the recent years, much attention is attracted about how SIBO works to trigger or aggravate IBS. What’s more, discovering, recognizing and diagnosing motility disorders of IBS timely as well as effectively is much helpful for treatment in clinical practice.Hydrogen breath test (HBT) is a newly occurred testing method in recent years, which is mainly used on diagnosing lactose intolerance or evaluating SIBO, gastrointestinal motility dysfunction, insufficient secretion of gastric acid and pancreatic exocrine function. Low cost, less damage, easy operation and better tolerance makes HBT widely applicated in clinical practice. However, clinical experience of HBT application is still limited, few researches focus on estimating different sub-types of IBS by HBT.ObjectiveInvestigating the frequency of SIBO in different subtypes of IBS. To explore variance of orocecal transit time (OCTT) in different subtypes of IBS and its possible influence factors.Methods1. Subjects, Inclusion and Exclusion criteriaAccording to daily Gastroenterology outpatients in Guangdong General Hospital, we enrolled 93 diarrhea-predominant IBS (IBS-D) patients (average age is 40.9±14.9y,50 males and 43 females),36 constipation-predominant IBS (IBS-C) patients (average age is 46.3±15.9y,18 males and 18 females),33 functional dyspepsia (FD) patients (average age is 40.33±14.2y,15 males and 18 females) and 30 healthy volunteers (average age is 39.8±14.6y,12 males and 18 females) from 1st June 2015 to 1st October 2015, all the basic information (age, sex, height, weight) of every subject was recorded completely. Any patients or volunteers who took antibiotics, proton pump inhibitors (PPIs), H2-receptor antagonists, probiotics, prokinetics, laxatives, anesthetics during the last 4 weeks, accepted LHBT in the recent 2 weeks or had various chronic diseases like diabetes mellitus, thyroid disorder, connective tissue disease, any other gut organic disorders, GI operation experience were ruled out from our research. The study protocol was approved by the Ethics Review Committee of Guangdong General Hospital. Informed consent was waived by the board.2. Testing MethodsAll the subjects accepted LHBT and GHBT for detecting OCTT and SIBO frequency.13C breath test of Helicobacter pylori (Hp) infection, anxious/depressive scores and body mass index (BMI) measurement were finished at the same period. SPSS 19.0 statistical software was used to compare the SIBO incidence of each group, explore the consistency or dissimilarity between GHBT and LHBT on evaluating SIBO, and compare average OCTT (OCTT) of each group as well as analyzing the relation between OCTT and SIBO, Hp infection, anxiety/depression, BMI. Since the Rome Consensus Conference published in 2009 suggests that GHBT is superior to LHBT with a better sensitivity and specificity on diagnosing SIBO, this research GHBT for evaluating SIBO as well as detecting OCTT with LHBT.Pre-examination:fasting for over 12 hours; stop smoking for at least 1 day; no coffee, milk, soybean milk, tea, jam, vegetable, fruit or gum during the last night before examination; brush teeth and defecate that day in the morning; gargle with 20ml 1% chlorhexidine or distilled water and make sure subjects have a smooth breathe as usual.During examination:keep a state of rest(subjects can read newspaper or listen music to release tension, anxiety if needed); take a deep breath and hold on for about 5 s before blowing smoothly and evenly into the acceptor device of hydrogen breath test, blow for 4 continuous times before drink glucose or lactulose solution, take the average value(unit:ppm(parts per million)) as basal level of H2; GHBT:50g glucose +distilled water=250ml solution, drink up within 1 minute, then blow every 15 minutes and record results, totaled 8 times; LHBT:the next day after GHBT, 10g lactulose + distilled water=150ml solution, drink up within 1 minute, then blow every 15 minutes and record results, totaled 12 times.Result interpretation:Based on Methodology and indications of H2-breath testing in gastrointestinal diseases:the Rome Consensus Conference published in 2009, A peak of H2 values>12 ppm above the basal value after 50 g of glucose ingestion is considered having SIBO. The time interval between ingestion of lactulose and rise in breath H2 concentration^10 ppm in two consecutive readings above the basal value is measure of OCTT. 3. Statistical ProcessingThe statistical analysis was performed using IBM SPSS Statistics 19.0. Differences among groups in proportion of test positives were evaluated by chi-square test, McNemar test, Fisher exact test; differences among mean value were evaluated by independent-samples t test, test for Equal variances and One-Way ANOVA (SNK, LSD and Bonferroni method). Values of P< 0.05 were considered to be significant.Results1. Basic InformationThe average age, percentage of males, Hp infection rate in IBS-D group, IBS-C group, FD group and healthy control group were 40.9±14.9y,46.3±15.9y, 40.3±14.2y,39.8±14.6y,53.8%,50.0%,45.5%,40.0% and 12.9%,19.4%,24.2%, 6.7%, respectively. There was no difference on age distribution (F=1.81, p=0.168>0.05) and sex ratio (x2=1.72, p=0.432>0.05) among all groups, which showed a good balance of population statistics data among groups, no difference of Hp infection has been found among all groups (x 2=4.77, p=0.189>0.05).2. Compariosn of SIBO Positive Rate in Different GroupsThe frequency of SIBO was 32.6%,19.4%,24.2%,6.7% respectively in IBS-D group, IBS-C group, FD group and healthy control who accept GHBT, contrastive analysis showed an obvious difference of SIBO ratio between IBS-D group and healthy control (x 2=7.68, p=0.013＜0.05).3. Comparison of OCTT in Groups and Possible Influence FactorsStatistical differences was found among groups on OCTT, SIBO rate, mental and psychological disorder (anxiety/depression) frequency and average BMI. The OCTT of IBS-D group, IBS-C group, FD group and healthy control was 86.2± 35.3min,143.3±36.0min,112.9±35.1min and 105.0±31.3min respectively, OCTT in IBS-D group was obviously faster than that in IBS-C group (t=-4.56, p<0.01), FD group (t=-2.83, p=0.006<0.05) and healthy control (t=-2.54, p=0.014<0.05), OCTT in IBS-C group was much slower than that in FD group (t=2.98, p=0.004<0.05) and healthy control (t=2.08, p=0.047<0.05). The Hp infection in IBS-D group, IBS-C group, FD group and healthy control was 12.9%,19.4%,24.2%,10.0%. SIBO ratio in IBS-D group, IBS-C group, FD group and healthy control was 32.6%,19.4%, 24.2%,6.7%. Anxiety/depression rate was 25.8%,19.4%,27.3%,3.3% in IBS-D group, IBS-C group, FD group and healthy control, average BMI in IBS-D group, IBS-C group FD group and healthy control was 22.6±3.8kg/m2,21.4±3.2 kg/m2, 22.2±3.7 kg/m2,20.2±2.0kg/m2, separately. Comparative analysis revealed that anxiety/depression rate (x 2=7.07, p=0.008<0.05), average BMI (t=3.70, p=0.002<0.01) and SIBO frequency (x2=7.72, p=0.005<0.01) in IBS-D group was statistically higher than those in healthy control.anxiety/depression rate in FD group was obviously higher than the control group (x 2=5.54, p=0.019<0.05). There was no difference on Hp infection among all groups.Based on the result of GHBT, all group was further divided into SIBO positive subgroup, SIBO negative subgroup, psychological abnormal subgroup, healthy subgroup, Hp positive subgroup and Hp negative subgroup, comparative analysis revealed that SIBO positive subgroup had an apparently faster OCTT than SIBO negative subgroup, while no difference had been found between psychological abnormal subgroup and healthy subgroup in IBS-D group. In FD group, Hp positive subgroup had an apparently faster OCTT than Hp negative subgroup, no difference was found neither between SIBO positive subgroup and SIBO negative subgroup, nor between psychological abnormal subgroup and healthy subgroup. In IBS-C group, psychological abnormal subgroup had an apparently faster OCTT than the healthy subgroup. Correlation analysis hinted that negative correlation had been found between OCTT and BMI in the IBS-D group(r=-0.405, p=0.008<0.01), but the dependency was weak.Obvious correlation between OCTT and BMI was not found among other groups.Conclusions1. IBS-D and FD group has a higher SIBO frequency, and no difference of SIBO rate has been found between IBS-C group and healthy control.2. IBS-D patients usually has an apparently faster OCTT, while the OCTT of IBS-C patients is much slower.3. A certain relationship has been found between the pathogenesis of IBS/FD and anxiety/depression, SIBO, there is apparent correlation between SIBO, abnormal increase of BMI and abnormality of motility in IBS-D patients.4. Evaluating anxiety/depression, SIBO among IBS or FD patients may offer useful guidance when applying anti-anxiety and depression drugs or prokinetic agents in clinical practice.