Quantifying Rome symptoms for diagnosis of the irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, diagnosed on symptom-based criteria. Many have reported discrepancies between formal Rome criteria and diagnoses made in clinical practice. The aim of the study was to explore whether a quantitative version of the Rome criteria would better represent a clinical diagnosis of IBS than the current dichotomous criteria for symptom measure. METHODS: As part of a large, case-control study, participants completed a validated bowel disease questionnaire. Rome criteria were analyzed based on 15 individual symptoms. Penalized logistic regression model with stepwise selection was used to identify significant symptoms of IBS which were independently associated with case-control status. KEY RESULTS: In cases with a clinical diagnosis of IBS, 347 (70%) met Rome criteria for IBS. Increasing number of Rome symptoms were found related to the odds of being diagnosed with IBS. Nearly half of the Rome-negative case group experienced infrequent symptoms suggesting milder disease. Five of 15 Rome symptoms were associated with predicting case-control status in the final model, with 96% correctly classified among Rome-positive cases, 76% for Rome-negative cases, and 91% for controls. CONCLUSIONS AND INFERENCES: Irritable bowel syndrome appears to be a spectrum disorder. Quantifying individual symptoms of Rome criteria has greater utility than the current application in representing the degree of IBS affectedness and appears to better reflect a clinical diagnosis of IBS applied by physicians. The use of a quantitative diagnostic Rome "score" may be helpful in clinical practice and research studies to better reflect the degree an individual is affected with IBS.

Effects of Antidepressants on Gastric Function in Patients with Functional Dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a highly prevalent functional bowel disorder. The effects of antidepressant therapy (ADTx) on gastric sensorimotor function in FD patients are poorly understood. AIMS: Determine whether FD and subtypes with abnormalities in gastric function respond differently to ADTx compared to those with normal physiology. METHODS: This multicenter, prospective trial randomized FD patients to 12 weeks of amitriptyline (AMI; 50 mg), escitalopram (ESC; 10 mg), or matching placebo. Demographics, symptoms, psychological distress, gastric emptying, and satiation were measured. Gastric accommodation (GA) using single-photon emission computed tomography imaging was performed in a subset of patients. An intent to treat analysis included all randomized subjects. The effect of treatment on gastric emptying was assessed using ANCOVA. A post hoc appraisal of the data was performed categorizing patients according to the Rome III subgrouping (PDS and EPS). RESULTS: In total, 292 subjects were randomized; mean age=44 yrs. 21% had delayed gastric emptying. Neither antidepressant altered gastric emptying, even in those with baseline delayed gastric emptying. GA increased with ADTx (P=0.02). Neither antidepressant affected the maximal-tolerated volume (MTV) of the nutrient drink test although aggregate symptom scores improved compared to placebo (P=0.04). Patients with the combined EPS-PDS subtype (48%) had a lower MTV on the nutrient drink test compared to the EPS group at baseline (P=0.02). Postprandial bloating improved with both AMI (P=0.03) and ESC (P=0.02). CONCLUSIONS: Amitriptyline (50 mg) improves FD symptoms but does not delay gastric emptying, even in patients with baseline delayed gastric emptying. GA improved with low-dose ADTx; the precise mechanism of action is unknown warranting further study.

Irritable bowel syndrome and the perinatal period: lower birth weight increases the risk.

BACKGROUND: Early life events have been found to be associated with irritable bowel syndrome (IBS) suggesting a role in development of functional disorders. The study aim was to identify potential perinatal risk factors for adult IBS. METHODS: Utilizing a population-based nested case-control design, cases who met modified Rome III criteria for IBS and age- and-gender matched controls were identified using responses from prior mailed surveys to a random sample of Olmsted County residents. Medical records of eligible respondents were reviewed for perinatal events of interest. The association of early life events with subsequent case status was assessed using conditional logistic regression. KEY RESULTS: Of 3 417 respondents, 513 were born in Olmsted County and 108 met criteria for IBS. Due to missing records, 89 pairs were included in the final analyses. Logistic regression revealed only birth weight as a predictor of IBS. Lower birth weight increased the odds for IBS (OR = 1.54 [95% CI = (1.12, 2.08), p = 0.008]). Median birth weight was 3.35 kg (range: 1.96-5.24) and 3.57 kg (range: 2.18-4.59) for cases and controls, respectively. Maternal age, delivery method, and antibiotic exposure were not associated with IBS status but this study was only powered to detect large odds ratios. CONCLUSIONS AND INFERENCES: Lower birth weight was observed as a risk factor for IBS. It is not clear if in utero developmental delays directly lead to IBS or if low birth weight is a prospective marker for subsequent early life problems leading to IBS.

Prevalence and risk factors for dysphagia: a USA community study.

BACKGROUND: Dysphagia is considered an alarm symptom but detailed population-based data on dysphagia are lacking. We aimed to estimate in a representative USA Caucasian population, the prevalence of dysphagia and potential risk factors. METHODS: A modified version of the previously validated Bowel Disease Questionnaire was mailed to a population-based cohort (n = 7640) of Olmsted County, MN. Dysphagia was measured by one validated question 'In the last year, how often have you had difficulty swallowing (a feeling that food sticks in your throat or chest)?' The medical records were reviewed for organic causes of dysphagia. The associations of reported frequency of dysphagia with potential risk factors were assessed using logistic regression models. KEY RESULTS: The sex-specific, age-adjusted (US White 2000) prevalence for dysphagia experienced at least weekly was 3.0% (95% CI: 2.2, 3.7) in females and 3.0% (95% CI: 2.0, 4.0) in males. Those with frequent heartburn (OR = 5.9 [4.0, 8.6]) and acid regurgitation (OR = 10.6 [6.8, 16.6]) were significantly more likely to report frequent dysphagia. Proton pump inhibitor (PPI) use was significantly associated with frequent (3.1, 95% CI 2.2, 4.4) and infrequent dysphagia (1.5, 955 CI 1.3, 1.8). Gastro-esophageal reflux disease (GERD) was the most common diagnosis in those reporting dysphagia on the medical record; other organic explanations were rare and only found in the frequent dysphagia group. CONCLUSIONS & INFERENCES: Frequent dysphagia is not rare in the community (3%), occurs in both women and men across all adult age groups, and is most likely to indicate underlying GERD.

Immunotherapy trial as diagnostic test in evaluating patients with presumed autoimmune gastrointestinal dysmotility.

BACKGROUND: Chronic gastrointestinal dysmotility greatly impacts the quality of life. Treatment options are limited and generally symptomatic. Neural autoimmunity is an under-recognized etiology. We evaluated immunotherapy as an aid to diagnosing autoimmune gastrointestinal dysmotility (AGID). METHODS: Twenty-three subjects evaluated at the Mayo Clinic for suspected AGID (August 2006-February 2014) fulfilled the following criteria: (1) prominent symptoms of gastrointestinal dysmotility with abnormalities on scintigraphy-manometry; (2) serological evidence or personal/family history of autoimmune disease; (3) treated by immunotherapy on a trial basis, 6-12 weeks (intravenous immune globulin, 16; or methylprednisolone, 5; or both, 2). Response was defined subjectively (symptomatic improvement) and objectively (gastrointestinal scintigraphy/manometry studies). KEY RESULTS: Symptoms at presentation: constipation, 18/23; nausea or vomiting, 18/23; weight loss, 17/23; bloating, 13/23; and early satiety, 4/23. Thirteen patients had personal/family history of autoimmunity. Sixteen had neural autoantibodies and 19 had extra-intestinal autonomic testing abnormalities. Cancer was detected in three patients. Preimmunotherapy scintigraphy revealed slowed transit (19/21 evaluated; gastric, 11; small bowel, 12; colonic, 11); manometry studies were abnormal in 7/8. Postimmunotherapy, 17 (74%) had improvement (both symptomatic and scintigraphic, five; symptomatic alone, eight; scintigraphic alone, four). Nine responders re-evaluated had scintigraphic evidence of improvement. The majority of responders who were re-evaluated had improvement in autonomic testing (six of seven) or manometry (two of two). CONCLUSIONS & INFERENCES: This proof of principle study illustrates the importance of considering an autoimmune basis for idiopathic gastrointestinal dysmotility and supports the utility of a diagnostic trial of immunotherapy.

A case-control study of childhood trauma in the development of irritable bowel syndrome.

BACKGROUND: The etiology of irritable bowel syndrome (IBS) is not been fully elucidated, but childhood trauma may disturb the brain-gut axis and therefore be important. Thus, we conducted a family based case-control study of IBS cases and their relatives with the aims to (i) determine the frequency of childhood trauma among IBS cases and controls as well as their relatives, and (ii) assess childhood trauma among IBS cases with affected relatives (familial IBS). METHODS: Outpatients with IBS, matched controls, and their first-degree relatives completed a self-report version of Bremner' Early Trauma Inventory. Percent of cases and controls with a family history were compared and odds ratios were computed using chi-squared test; recurrence risks to relatives were computed using logistic regression and generalized estimating equations. KEY RESULTS: Data were collected from 409 cases, 415 controls, 825 case relatives, and 921 control relatives. IBS cases had a median age of 50 and 83% were women. Of IBS cases, 74% had experienced any general trauma compared to 59% among controls, yielding an odds ratio of 1.56 (95% CI: 1.13-2.15, p < 0.008). There were no statistical differences between IBS relatives and control relatives with regards to lifetime trauma. CONCLUSIONS & INFERENCES: IBS is associated with childhood trauma, and these traumas often occur prior to onset of IBS symptoms. This provides further insight into how traumatic childhood events are associated with development of adult IBS.

Clinical predictors of small intestinal bacterial overgrowth by duodenal aspirate culture.

BACKGROUND: There has been increasing interest in small intestinal bacterial overgrowth (SIBO) after reports of a link with irritable bowel syndrome (IBS), yet our understanding of this entity is limited. AIM: Our aim was to estimate the yield of patients undergoing duodenal aspirate culture, and to identify symptoms and features that predict SIBO. METHODS: A medical chart review of patients who had undergone duodenal aspirate culture at an academic medical centre in 2003 was performed to record clinical characteristics and culture results. The associations between aspirate results and symptoms, medical diagnoses and medication use were assessed using logistic regression. RESULTS: A total of 675 patients had available aspirate results. Mean age of the sample was 53 (s.d. 17) and 443 (66%) were female patients. Overall, 8% of aspirates were positive for SIBO; 2% of IBS patients had SIBO. Older age, steatorrhoea and narcotic use were associated with SIBO (P < 0.05). PPI use was not associated with SIBO, but was associated with bacterial growth not meeting criteria for SIBO (P < 0.05). Inflammatory bowel disease (IBD), small bowel diverticula and pancreatitis were positively associated with an abnormal duodenal aspirate (P < 0.05), but other conditions including IBS were not associated with SIBO. CONCLUSION: Older age, steatorrhoea, narcotic use, IBD, small bowel diverticula and pancreatitis were associated with small intestinal bacterial overgrowth based on abnormal duodenal aspirate culture results. However, no clear associations of true small intestinal bacterial overgrowth with IBS or PPI use were detected, in contrast to recent speculation.

Irritable bowel syndrome aggregates strongly in families: a family-based case-control study.

Irritable bowel syndrome (IBS) runs in families. Prior family studies surveyed patients inquiring about family history without surveying family members. The stigma associated with IBS may lead relatives to not share information with others,resulting in underestimates of familial aggregation of IBS. The aim of the study was to evaluate the accuracy of patient-report of family history of IBS in cases and controls, and to estimate familial aggregation of IBS using both a case-control and a family-study design. Fifty cases and 53 controls completed symptom questionnaires and provided contact information for first-degree relatives. Questionnaires were mailed to relatives. Relatives were considered to have IBS if they met Rome criteria and did not have an alternate GI diagnosis. Cases and controls identified 573 relatives in their families. A total of 202 (51%) of 396 living relatives participated. The kappa statistics between proband- and relative-reported IBS for case- and control-relatives were 0.27 and 0.04. Cases reported 21%of relatives had IBS; relative-reports showed 37%(P = 0.003). Controls reported 4% of relatives had IBS;relative-reports showed 16% (P = 0.013). Regardless of whether the proband or the relative themselves were the information source, case-relatives were three fold as likely to have IBS than control-relatives (P < 0.05).However, overall rates were higher when data collected from relatives were used. Regardless of approach, strong familial aggregation of IBS was observed. Cases and controls underestimated the frequency of IBS in their relatives and agreement between proband- and relative-report of IBS status was extremely poor, thus emphasizing the need for direct data collection from relatives in IBS family studies.

A genetic association study of 5-HTT LPR and GNbeta3 C825T polymorphisms with irritable bowel syndrome.

A pharmacogenetic study suggests the 5-HTT LPR polymorphism predicts response to alosetron, and another study describes a possible association of the GNbeta3 C825T polymorphism with IBS in patients with dyspepsia. We performed a case-control association study to determine whether these polymorphisms are associated with irritable bowel syndrome (IBS). The study aim was to compare allele and genotype frequencies between cases and controls for the 5-HTT LPR and the GNbeta3 C825T polymorphism. Cases were 50 GI outpatients; controls were 53 General Medicine outpatients matched to cases for age, gender and race at a major medical centre. Participants completed a questionnaire and donated blood. DNA was genotyped using polymerase chain reaction based assays. Eighty-two per cent of cases met Rome II criteria for IBS: 12% constipation-, 46% diarrhoea-, and 42% mixed-IBS. Genotype and allele frequencies for both polymorphisms did not differ between cases and controls. However, the allele frequency of the short (S) allele of the 5-HTT LPR polymorphism was greater in those with mixed-IBS compared with controls (68%vs 45%, P < 0.05). This study suggests that the 5-HTT LPR polymorphism may be associated with mixed-IBS, but not IBS overall. No association was observed for the GNbeta3 C825T polymorphism with IBS overall or subtypes.

The effect of new diagnostic criteria for irritable bowel syndrome on community prevalence estimates.

The 'Rome' criteria for irritable bowel syndrome (IBS) have evolved over 15 years with four published versions. The impact of these changes on community prevalence rates is not known. Study aims were to estimate the prevalence of IBS using the four Rome criteria and agreement between Rome II and previous criteria. Questionnaires were mailed to a random sample of Olmsted County, Minnesota residents in 1992. Age- and gender-adjusted prevalence estimates were calculated for Rome II (1999), Rome I (1992), Rome (1990), and Rome (1989) criteria. Per cent agreement and kappa values were calculated to assess agreement. Of 892 eligible subjects, 643 (72%) responded. The age- and gender-adjusted prevalence of IBS was 5.1% [95% confidence interval (CI): 3.1, 7.0], 6.8% (95% CI: 4.7, 8.9), 5.1% (95% CI: 3.2, 7.1) and 27.6% (95% CI: 23.6, 31.5), respectively. In comparison with Rome II criteria, per cent agreement and kappa values were 97.2% and 0.78 (95% CI: 0.69, 0.88), 96.4% and 0.68 (95% CI: 0.55, 0.80), and 79.0% and 0.29 (95% CI: 0.19, 0.40), respectively. Thus, although differences were seen with the older criteria, compared with the Rome I criteria, good agreement was seen and community prevalence estimates were similar with the Rome II criteria.

A comparison of the Rome and Manning criteria for case identification in epidemiological investigations of irritable bowel syndrome.

OBJECTIVE: The aim of this study was to estimate the prevalence of irritable bowel syndrome using different standard definitions (Rome and Manning criteria) and to determine the degree of agreement between these definitions. METHODS: A population-based, cross-sectional survey study was conducted by mailing a valid, reliable questionnaire to an age- and gender-stratified random sample of residents of Olmsted County, MN, aged 30-69 yr. The threshold for a positive diagnosis of irritable bowel was varied from two to four of the six Manning criteria and from two to three of the five defecation disorders in the Rome criteria. Unadjusted as well as age- and gender-adjusted prevalence rates were calculated for each of the five definitions of IBS. Percent agreement and kappa statistics were calculated to assess agreement between the definitions. RESULTS: Questionnaires were returned by 643 of 892 eligible subjects (72% response rate). The age- and gender-adjusted prevalence of IBS varied from 20.4% using a threshold of two symptoms in the Manning criteria to 8.5% using a threshold of three defecation disorders in the Rome criteria. The percent agreement for each comparison of Manning and Rome definitions was always >90%. The kappa values ranged from 0.55 to 0.78, with the best agreement occurring between a threshold of three symptoms of Manning and two defecation disorders in Rome. CONCLUSIONS: The prevalence of IBS varied substantially depending on the specific definition of IBS used. The range of prevalence estimates in Olmsted County was similar to other published figures when IBS definition was accounted for. These findings are useful in interpreting epidemiological and clinical studies of IBS.