M. Di Stefano

Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference

BACKGROUNDnBreath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular.nnnAIMnThe Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases.nnnMETHODSnExperts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group.nnnRESULTS AND CONCLUSIONSnThe final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.

Non-absorbable antibiotics for managing intestinal gas production and gas-related symptoms

Simethicone, activated charcoal and antimicrobial drugs have been used to treat gas‐related symptoms with conflicting results.

Absorbable vs. non‐absorbable antibiotics in the treatment of small intestine bacterial overgrowth in patients with blind‐loop syndrome

Background :u2002Small intestine bacterial overgrowth is associated with the presence of predisposing conditions, acting through different mechanisms. Therefore, the failure to define a standardized therapy may be due to a methodological bias: to treat a condition characterized by different pathophysiological mechanisms with the same pharmacological approach. Non‐absorbable antibiotics could have a lower efficacy than absorbable drugs in patients with blind loops which exclude a portion of the intestine from the transit.

Early Increase of Bone Resorption in Patients with Liver Cirrhosis Secondary to Viral Hepatitis

Bone loss is an established complication of cholestatic liver cirrhosis, while little is known about bone mass and metabolism in noncholestatic liver cirrhosis. The aim of the present study is, therefore, to evaluate bone mass and mineral metabolism in patients with liver cirrhosis secondary to viral hepatitis. Bone mineral density measurement at lumbar and femoral levels and the evaluation of bone and mineral metabolism and gonadal function were performed in 31 patients with liver cirrhosis and 37 healthy volunteers. Lumbar and femoral bone mineral density values were significantly lower in patients than in healthy volunteers. Prevalence and severity of bone loss increased according to the severity of liver disease. All serum indices of bone and mineral metabolism and of gonadal function showed a similar behavior, but a significant increase of bone resorption was present in all Child-Pugh classes. In particular, class A patients showed normal mean bone mineral density values but increased serum levels of the telopeptide of type I collagen. Liver cirrhosis predisposes to bone loss regardless of the presence of cholestasis. The severity of metabolic osteopathy worsens as liver function does. The underlying mechanism is represented by an increased bone resorption.

Visceral hypersensitivity and intolerance symptoms in lactose malabsorption

Abstractu2002 Lactose malabsorption is not always associated with intolerance symptoms. The factors responsible for symptom onset are not yet completely known. As differences in visceral sensitivity may play a role in the pathogenesis of functional symptoms, we evaluated whether an alteration of visceral sensitivity is present in subjects with lactose intolerance. Thirty subjects, recruited regardless of whether they were aware of their capacity to absorb lactose, underwent an evaluation of intestinal hydrogen production capacity by lactulose breath test, followed by an evaluation of lactose absorption by hydrogen breath test after lactose administration and subsequently an evaluation of recto‐sigmoid sensitivity threshold during fasting and after lactulose administration, to ascertain whether fermentation modifies intestinal sensitivity. The role of differences in gastrointestinal transit was excluded by gastric emptying and mouth‐to‐caecum transit time by 13C‐octanoic and lactulose breath tests. Lactulose administration induced a significant reduction of discomfort threshold in subjects with lactose intolerance but not in malabsorbers without intolerance symptoms or in subjects with normal lactose absorption. Perception threshold showed no changes after lactulose administration. Severity of symptoms in intolerant subjects was significantly correlated with the reduction of discomfort thresholds. Visceral hypersensitivity should be considered in the induction of intolerance symptoms in subjects with lactose malabsorption.

Genetic test for lactase non-persistence and hydrogen breath test: Is genotype better than phenotype to diagnose lactose malabsorption?

BACKGROUNDnAdult-type hypolactasia is a widespread condition throughout the world, causing lactose malabsorption. The lactose breath test is a simple tool for diagnosis but the need for prolonged monitoring of hydrogen excretion has led to a genetic test proposal. The aim of this study was to compare the genetic test with the lactose breath test in order to give some insights into the clinical value of genetic testing.nnnMETHODSnThirty-two consecutive functional patients underwent lactose breath test and lactase genetic polymorphism analysis (C/T 13910 and G/A 22018). Intolerance symptoms after lactose load were also monitored.nnnRESULTSnAll patients with positive lactose breath test showed homozygosis for both polymorphisms. Among the nine patients with a negative breath test result, six showed heterozygosis while three showed homozygosis. Intolerance symptoms were present in 16 homozygotic patients but also in one heterozygotic patient. The k value for the agreement between the genetic test and the lactose breath test was 0.74.nnnCONCLUSIONnA positive genetic test for lactase non-persistence indicates whether lactase activity decline may represent a clinical problem for the patient, but does not give information on actual patient symptoms. On the contrary, this information is already available by combining the lactose breath test with intolerance symptom evaluation. Lactose absorption phenotype may be not yet evident until young adult age.

Cytokine genetic profile in Whipple’s disease

Whipple’s disease (WD) is a very rare chronic systemic condition characterised by a Th2/T regulatory (Treg) dysregulated immune response versus Tropheryma whipplei, a bacterium widely diffuse in the environment. To investigate whether this Th2/Treg polarised response has a genetic background, we investigated the Th1, Th2, Th17 and Treg cytokine genetic profile of 133 patients with WD. Thanks to the European Consortium on WD (QLG1-CT-2002-01049), the polymorphism of 13 cytokine genes was analysed in 111 German and 22 Italian patients using the polymerase chain reaction with sequence-specific primers (PCR-SSP) technique. The frequencies of the genotypes, haplotypes and functional phenotypes were compared with those obtained in 201 German and 140 Italian controls. Clinical heterogeneity was also considered. Functionally, WD patients may be considered as low producers of TGF-β1, having an increased frequency of the genotype TGF-β1+869C/C,+915C/C [12.3xa0% vs. 3.81xa0%, odds ratio (OR)u2009=u20094.131, pu2009=u20090.0002] and high secretors of IL-4, carrying the genotype IL-4-590T/T (5.34xa0% vs. 1.17xa0%, ORu2009=u20095.09, pu2009=u20090.0096). No significant association was found between cytokine polymorphism and clinical variability. Analogously to the recent cellular findings of a Th2/Treg polarised response, we showed that the cytokine genetic profile of WD patients is skewed toward a Th2 and Treg response. This was similar in both German and Italian populations. However, the significant deviations versus the controls are poorer than that expected on the basis of these recent cellular findings.

Increased red cell distribution width and coeliac disease

BACKGROUND/AIMSnDespite availability of sensitive screening tests, coeliac disease is still underdiagnosed. To determine which haematochemical abnormalities might be more predictive of this condition, we reviewed the clinical records of our series of adult patients affected by coeliac disease.nnnMETHODSnSix haematochemical parameters (haemoglobin, red cell distribution width, serum levels of iron, albumin, calcium and potassium) were evaluated in 126 consecutive adult untreated coeliac patients diagnosed since 1990.nnnRESULTSnElevated red cell distribution width was the most frequent haematochemical abnormality, being present in 57.9% of our patients (Chi square analysis, p<0.01 versus other laboratory changes).nnnCONCLUSIONnThe increase of red cell distribution width was more common than iron-deficiency anaemia, a well-known indicator of coeliac disease. Elevated red cell distribution width can thus be considered a new predictor of coeliac disease and in the presence of this a search should be made for antiendomysial antibodies.

Patients with headache and functional dyspepsia present meal–induced hypersensitivity of the stomach

Headache is a frequent feature of functional gastrointestinal disorders but there is no data on the responsible pathophysiological mechanism. The aim of this study was to verify whether alteration of post–prandial gastric tone or sensitivity might explain this association. Fourteen patients affected by functional dyspepsia (7 migraine without aura) and 7 healthy volunteers (HV) underwent gastric tone measurement in fasting condition and after the administration of a liquid meal by barostat. Gastric volume (GV) and accommodation were calculated as difference between mean post–prandial and mean fasting volume. Mean postprandial GV increase and fasting perception and discomfort threshold (DTh) were similar among the 3 groups. DTh after meal was lower in dyspeptic headache patients than in HV and dyspeptic without headache patients. Patients with migraine and functional dyspepsia may be characterised by meal-induced hypersensitivity of the stomach.

Serum regenerating islet-derived 3-alpha is a biomarker of mucosal enteropathies.

The clinical presentation of organic and functional intestinal disorders can overlap and clinicians often rely on invasive and time‐consuming procedures to make a final diagnosis. Regenerating islet‐derived 3‐alpha (Reg3α) is detectable in the circulation of patients with intestinal graft‐versus host disease and patients with inflammatory bowel disease (IBD).