Hans Strid

Results from the 2nd Scientific Workshop of the ECCO (I): Impact of mucosal healing on the course of inflammatory bowel disease

Over the past years, mucosal healing has emerged as a major therapeutic goal in clinical trials in inflammatory bowel diseases. Accumulating evidence indicates that mucosal healing may change the natural course of the disease by decreasing the need for surgery and reducing hospitalization rates in both ulcerative colitis and Crohns disease. Mucosal healing may also prevent the development of long-term disease complications, such as bowel damage in Crohns disease and colorectal cancer in ulcerative colitis. Histologic healing may be the ultimate therapeutic goal in ulcerative colitis, whereas its impact on the course of Crohns disease is unknown. Complete mucosal healing may be required before considering drug withdrawal. Targeting early Crohns disease is more effective than approaches aimed at healing mucosa in longstanding disease. Several questions remain to be answered: should mucosal healing be systematically used in clinical practice? Should we optimize therapies to achieve mucosal healing? What is the degree of intestinal healing that is required to change the disease course? Large prospective studies addressing these issues are needed.

Physical Activity Improves Symptoms in Irritable Bowel Syndrome: A Randomized Controlled Trial

OBJECTIVES:Physical activity has been shown to be effective in the treatment of conditions, such as fibromyalgia and depression. Although these conditions are associated with irritable bowel syndrome (IBS), no study has assessed the effect of physical activity on gastrointestinal (GI) symptoms in IBS. The aim was to study the effect of physical activity on symptoms in IBS.METHODS:We randomized 102 patients to a physical activity group and a control group. Patients of the physical activity group were instructed by a physiotherapist to increase their physical activity, and those of the control group were instructed to maintain their lifestyle. The primary end point was to assess the change in the IBS Severity Scoring System (IBS-SSS).RESULTS:A total of 38 (73.7% women, median age 38.5 (19–65) years) patients in the control group and 37 (75.7% women, median age 36 (18–65) years) patients in the physical activity group completed the study. There was a significant difference in the improvement in the IBS-SSS score between the physical activity group and the control group (−51 (−130 and 49) vs. −5 (−101 and 118), P=0.003). The proportion of patients with increased IBS symptom severity during the study was significantly larger in the control group than in the physical activity group.CONCLUSIONS:Increased physical activity improves GI symptoms in IBS. Physically active patients with IBS will face less symptom deterioration compared with physically inactive patients. Physical activity should be used as a primary treatment modality in IBS.

T-Cell Activation in Patients With Irritable Bowel Syndrome

OBJECTIVES:Irritable bowel syndrome (IBS) has been found to be associated with low-grade immune activation in a subset of patients. We therefore investigated blood and colonic T-cell activity in IBS patients.METHODS:Blood samples were initially obtained from 74 IBS patients and 30 controls. Supplementary blood samples, to confirm data, were taken from another cohort (26 patients and 14 controls). In addition, colonic biopsies were taken from a third cohort (11 patients and 10 controls). Peripheral blood and colonic mononuclear cells were stimulated with anti-CD3/CD28 antibodies. Proliferation, cytokine secretion, and T-cell phenotype were investigated. IBS symptom severity was assessed.RESULTS:IBS patients displayed an activated phenotype with increased frequencies of blood T cells expressing CD69 and integrin β7/HLA-DR. Anti-CD3/CD28-stimulated blood and colonic T cells from IBS patients proliferated less than T cells from controls. IBS patients had an increased polyclonally stimulated T-cell secretion of IL-1β, which also weakly correlated with increased bowel habit dissatisfaction. Furthermore, despite normal frequencies of CD25high T cells in the blood of IBS patients, lower blood CD25high T-cell frequencies were modestly correlated with more bowel habit dissatisfaction and increased total IBS symptom severity.CONCLUSIONS:IBS patients have an increased frequency of activated T cells, demonstrated by the expression of activation markers and reduced proliferation in response to restimulation in vitro. The increased level of T-cell activation is consistent with the hypothesis of low-grade immune activation in IBS and may also be involved in symptom generation in IBS.

Clinical trial: the effects of a fermented milk containing three probiotic bacteria in patients with irritable bowel syndrome – a randomized, double‐blind, controlled study

Background  The effects of probiotic bacteria in IBS remain controversial.

The intra-individual variability of faecal calprotectin: a prospective study in patients with active ulcerative colitis.

BACKGROUND AND AIMS Leukocyte-derived proteins in faeces, especially calprotectin, are increasingly used to assess disease activity in ulcerative colitis. The objectives of the present study were to assess the importance of factors related to the stool sampling procedure. METHODS For 2 days, patients with active ulcerative colitis collected two stool samples at each bowel movement. The time of defecation, consistency and presence of blood were self-recorded in a diary. The variability in the concentrations of calprotectin during the day and between two consecutive days was assessed, as was the stability of calprotectin concentrations in samples stored at room temperature. RESULTS Altogether, 18 patients collected 287 stool samples. The intraclass correlation coefficient in pairs of samples from 132 bowel movements was 0.79 (95% CI 0.48-0.90). The median individual coefficient of variation in samples collected during the same day was 52% (4-178). There was a correlation between the level of calprotectin and the time between bowel movements (r = 0.5; p = 0.013). After 3 days at room temperature the calprotectin concentrations in stool samples were unchanged, but after 7 days a significant (p < 0.01) decrease was found (mean 28%; 95% CI 0.10-0.47). CONCLUSION The present data reveal a great variability in the concentrations of calprotectin in stool samples collected during a single day. Since the levels of calprotectin increased with longer time between the bowel movements, it seems most appropriate to analyse stool from the first bowel movement in the morning. Moreover, storage of stool samples at room temperature for more than 3 days is not advisable.

Patients with Chronic Renal Failure Have Abnormal Small Intestinal Motility and a High Prevalence of Small Intestinal Bacterial Overgrowth

Background/Aims: Gastrointestinal (GI) symptoms are common among patients with chronic renal failure (CRF). The pathogenesis of these symptoms is probably multifactorial. Our aims were to assess gastric and small intestinal motility and the prevalence of small intestinal bacterial overgrowth (SIBO) in order to clarify possible pathophysiological mechanisms behind these symptoms in CRF patients. Methods: Twenty-two patients with CRF, 12 with GI symptoms and 10 without GI symptoms underwent antroduodenojejunal manometry. All patients with GI symptoms had diarrhea and half of them had abdominal pain, nausea and/or early satiety. Symptoms were unexplained by conventional investigations. Interdigestive motility was recorded for 5 h and postprandially for 1 h. Samples for culture from the small intestine were obtained through the manometry catheter. Results were compared with 34 healthy controls. Results: On manometry, 11 CRF patients demonstrated neuropathic-like abnormalities, with no significant difference between the patients with (7/12) and without (4/10) GI symptoms. SIBO was seen in 8 CRF patients (36%), 3 with and 5 without GI symptoms (p = 0.15). Six of eleven (55%) of the CRF patients with neuropathic-like abnormalities had SIBO, compared to 2/11 (18%) in those without abnormalities on conventional analysis (p = 0.07). The propagation velocity of phase III was significantly faster in CRF patients with GI symptoms compared to CRF patients without symptoms and healthy controls (21.4 (16.4–54.7) vs. 8.1 (4.6–9.6) and 10.8 (7.2–21.6) cm/min, p = 0.007 and p = 0.019, respectively). We found a higher proportion of retrograde pressure waves in late phase II in the proximal duodenum in patients with and without GI symptoms, than in healthy controls (29 (17–38) and 16 (14–42) vs. 8 (0–24)%, p < 0.0001 and p = 0.0005, respectively). The number of long clusters during the fasting recording was higher in both patient groups than in controls (9 (5–21) and 11 (7–15) vs. 4 (2–9)/5, p = 0.046 and p = 0.002, respectively). Conclusion: In the small intestine, abnormal motility and bacterial overgrowth are common in patients with chronic renal failure. These alterations correlate poorly with GI symptoms, but disturbed intestinal motility might explain diarrhea in some of these patients.

Delay in gastric emptying in patients with chronic renal failure

Background: Gastrointestinal (GI) symptoms are common in patients with chronic renal failure (CRF). Delayed gastric emptying might be a possible pathophysiological mechanism. The aims of this study were to evaluate gastric emptying in patients with CRF and to correlate the findings with GI symptoms and evaluate the impact of Helicobacter pylori infection in CRF patients on gastric emptying. Methods: Thirty‐nine patients with CRF (17 F, 22 M) were compared with 131 healthy subjects (74 F, 57 M). A standardized breakfast was given with 20 spherical, radiopaque markers (ROMs). The emptying was followed by fluoroscopy after 4, 5 and 6 h. Gastric emptying was assessed by calculating the individual mean percentual gastric retention of markers, 4 to 6 h after the meal. The perceived severity of GI symptoms was assessed with a validated questionnaire. Because of gender differences in gastric emptying, men and women were compared separately and a percentile of 95 was chosen as the upper reference value. H. pylori infection was assessed using a serological method. Results: Delayed gastric emptying was found in 14 out of 39 (36%) of the CRF patients. There was no relationship between delayed gastric emptying and age, GI symptoms, H. pylori infection or underlying renal disease. However, a higher proportion of patients in peritoneal dialysis demonstrated delayed gastric emptying compared with predialytic patients (6 of 9 versus 2 of 13, P = 0.026). Men with CRF had a higher gastric retention compared with healthy men (16.6 (0–63.3)% versus 0 (0–2.1)%, P < 0.0001), and 10 men with CRF had delayed gastric emptying (P < 0.0001). There was no significant difference in mean gastric retention between women with CRF and healthy women (13.3 (0–55.4)% versus 10.8 (0–30.0)%, P = 0.93), but 4 women with CRF had delayed gastric emptying (P = 0.02). Eighteen of the CRF patients had GI symptoms (6 F, 12 M) and 21 were asymptomatic (11 F, 10 M). There was no difference in mean gastric retention in patients with CRF with and without GI symptoms (M: 13.3 (0–55.0)% versus 47.5 (5.0–65.0)%, P = 0.51, F: 16.6 (0–63.3)% versus 13.3 (0–59.2)%, P = 0.96). Gastric emptying in CRF patients with and without H. pylori infection showed no difference. Conclusions: Delayed gastric emptying is common in patients with chronic renal failure, particularly in men. The delay was not associated with the presence of GI symptoms, underlying renal disease or H. pylori infection. However, the dialytic status might have an impact on gastric emptying in patients with CRF.

B‐cell activation in patients with irritable bowel syndrome (IBS)

Abstract  Patients with irritable bowel syndrome (IBS) may have a low grade immune activation. However, little is known about the properties of B cells of IBS patients. We therefore investigated activation level and antigen presenting phenotype of blood B cells of IBS patients. We also examined B‐cell responses to lipopolysaccharide (LPS) and probiotic bacteria. Blood samples were obtained from 74 IBS patients and 30 healthy subjects. Peripheral blood mononuclear cells were isolated and stimulated with LPS or an UV‐light inactivated bacterial cocktail consisting of the probiotic Gram‐positive strains; Lactobacillus paracasei ssp. paracasei 19, Lactobacillus acidophilus La5, Bifidobacterium lactis B612. The phenotype of CD19+ B cells was investigated by flow cytometry before and after 72 h cell culture. Furthermore, IBS symptom severity was assessed. B cells isolated from blood of IBS patients displayed an amplified activation level as demonstrated by increased cell surface expression of IgG, and also the costimulatory molecules CD80 and CD86. Expression of antigen presenting HLA‐DR and costimulatory molecule CD40 on B cells was, however comparable in IBS patients and controls. B cells of IBS patients displayed an impaired ability to increase expression of CD80, but not CD86, in response to both LPS as well as probiotic bacteria stimulations. To conclude, blood B cells of IBS patients have an increased activation level. Bacterial component induced expression of the costimulatory molecule CD80, regarded as important for tolerance induction, is impaired. These data suggest that B‐cell antigen presentation in IBS patients is associated with altered capacity of providing costimulation to T cells.

Why do subjects with irritable bowel syndrome seek health care for their symptoms

Objective. Irritable bowel syndrome (IBS) is common in the population, but not all subjects seek professional health care for their symptoms. The aim of this study was to compare consulters in secondary/tertiary care with those in primary care and non-consulters by using questionnaires to investigate factors of importance for health-care seeking in IBS. Material and methods. The study included 218 subjects with IBS: 70 non-consulters, 53 patients from primary care and 95 from secondary/tertiary care. The subjects completed questionnaires on gastrointestinal (GI) and psychological symptoms, coping resources, health-related quality of life (HRQOL) and reasons for not seeking health care. Results. Consulters (primary and secondary/tertiary care combined) had poorer HRQOL, more severe psychological symptoms, higher levels of GI-specific anxiety and poor coping resources compared with non-consulters, but the GI symptom severity was similar. Mental health and poor social, emotional and physical functioning were independently predictive of being a health-care seeker (r2=0.41). Independent predictors for being a consulter in secondary/tertiary care were a high degree of anxiety, low scores on physical functioning, physical role and food (IBSQOL) (r2=0.65). Several non-consulters reported mild symptoms and ability to control symptoms as reasons for not seeking health care. Having a close relative with similar symptoms reduced the need to seek health care. Thirty-six non-consulters had sought alternative care or advice from friends and/or relatives about their GI symptoms. Conclusions. GI symptom severity alone cannot explain the illness behavior in IBS. HRQOL and psychological symptoms are important for experience of GI symptoms and the health-care seeking pattern in IBS.

Fecal calprotectin one year after ileocaecal resection for Crohn's disease — A comparison with findings at ileocolonoscopy

BACKGROUND AND AIMS Ileocaecal resection for Crohns disease is commonly performed. The severity of endoscopic lesions in the anastomotic area one year postoperatively is considered to reflect the subsequent clinical course. Fecal calprotectin (FC) has been shown to correlate with the findings at ileocolonoscopy in Crohns disease. The objectives of this study were to assess whether the concentration of FC reflects the endoscopic findings one year after ileocaecal resection and to evaluate the variation of FC in individual patients during 6months prior to the ileocolonoscopy. METHODS Thirty patients with Crohns disease and ileocaecal resection performed within one year were included. Stool samples were delivered monthly until an ileocolonoscopy was performed one year postoperatively. RESULTS One year after surgery the median values of FC were not significantly different between the patients in endoscopic remission (n=17) and the patients with an endoscopic recurrence (189 (75-364) vs 227 (120-1066)μg/g; p=0.25). However, most patients with low values were in remission and all patients with high (>600μg/g) calprotectin values had recurrent disease. The variability of the FC concentration was most pronounced in patients with diarrhea. CONCLUSIONS We found no statistical difference in the concentrations of calprotectin between patients in endoscopic remission and patients with a recurrent disease one year after ileocaecal resection for Crohns disease. However, among the minority of patients with low or high values, FC indicated remission and recurrence, respectively. There was significant variation of the fecal calprotectin concentrations over time, which affects the utility of calprotectin in clinical practice.