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Coeliac disease is an immune-mediated disease caused by ingestion of gluten in genetically susceptible individuals. Coeliac disease has been thought to affect mainly people of European origin but subsequently many studies revealed that it affects people living in North America, Oceania, South America, Asia as well as Africa. The global pooled seroprevalence and prevalence of biopsy-confirmed coeliac disease are 1.4% and 0.7% respectively. The pooled incidence rates in women and men are 17.4 (95% CI: 13.7-21.1) and 7.8 (95% CI: 6.3-9.2) per 100 000 person-years respectively. The systematic reviews, based on many population-based data, suggest that both the prevalence and the incidence of coeliac disease has increased over past three decades, which may be attributable not only to an increase in the detection rate (improvement in diagnostic tests, simplification of diagnostic criteria and increase in awareness about the disease) but also because of modernisation and globalisation related changes in the dietary practices including increase in the use of convenience food and dietary gluten. In addition to genetic factors, while there are many environmental risk factors, including age at the first introduction of gluten, breastfeeding, caesarean section, exposure to antibiotics and gut microbiome; the amount of gluten ingestion during early part of life, however, has been shown to increase the risk of coeliac disease, and this is relevant from the point of view of primary prevention. In this review, we have reviewed and summarised the literature, up till year 2021, related to the global and continent-wise epidemiology and risk factors associated with coeliac disease., (© 2022 John Wiley & Sons Ltd.)

Background: Coeliac disease is an immune-mediated intestinal disease characterised by lifelong intolerance to dietary gluten in genetically predisposed individuals. Microbial factors including infections or bacterial microbiota have long been suspected to be involved in the aetiology, but the scientific literature on the topic is scattered and heterogeneous., Aims: To review human observational studies on microbes and coeliac disease METHODS: We identified 135 publications judged relevant. Most studies were cross-sectional, and prone to reverse causation and other biases. Only a few were prospective. Cohort studies and longitudinal studies that have sampled biological specimens before disease onset are emphasised in the review., Results: Infections during early childhood were associated with an increased risk of subsequent coeliac disease in nine studies , whereas maternal infections during pregnancy did not show a clear association. For the most frequently studied microbial factors, some evidence for an association was found, including Helicobacter pylori (four out of 16 studies), adenovirus (two out of nine studies) and enterovirus (two out of six studies). Rotavirus infections have been associated with disease development, and rotavirus vaccination may reduce the risk. Among the many studies of gut microbiota, most were cross-sectional and, therefore, potentially influenced by reverse causation. Only two smaller prospective case-control studies with sampling before disease onset were identified; they reported inconsistent findings regarding the faecal microbiome., Conclusions: Several microbes are potentially linked to coeliac disease. As microbial factors are amenable to interventions, larger prospective studies are still warranted., (© 2020 John Wiley & Sons Ltd.)

The incidence of type 1 diabetes (T1D) is increasing annually, in addition to other childhood-onset autoimmune diseases. This review is inspired by recent strides in research defining the pathophysiology of autoimmunity in celiac disease, a disease that has significant genetic overlap with T1D. Population genetic studies have demonstrated an increased proportion of newly diagnosed young children with T1D also have a higher genetic risk of celiac disease, suggesting that shared environmental risk factors are driving the incidence of both diseases. The small intestine barrier forms a tightly regulated interface of the immune system with the outside world and largely controls the mucosal immune response to non-self-antigens, dictating the balance between tolerance and immune response. Zonulin is the only known physiological modulator of the intercellular tight junctions, important in antigen trafficking, and therefore, is a key player in regulation of the mucosal immune response. While usually tightly controlled, when the zonulin pathway is dysregulated by changes in microbiome composition and function, antigen trafficking control is lost, leading to loss of mucosal tolerance in genetically susceptible individuals. The tenant of this hypothesis is that loss of tolerance would not occur if the zonulin-dependent intestinal barrier function is restored, thereby preventing the influence of environmental triggers in individuals genetically susceptible to autoimmunity. This review outlines the current research and a structured hypothesis on how a dysregulated small intestinal epithelial barrier, a "leaky gut," may be important in the pathogenesis of autoimmunity in certain individuals at risk of both T1D and celiac disease., (© 2020 John Wiley & Sons Ltd.)

Unlabelled: Coeliac disease is triggered by an interplay of environmental and genetic factors and is one of the most prevalent autoimmune diseases in children, occurring in about 1% of Europeans. Over the last few decades, there has been a growing interest in the role of the perinatal environment in coeliac disease and this review discusses the growing body of literature on coeliac disease and perinatal risk factors., Conclusion: There is still only circumstantial evidence that the perinatal environment influences coeliac disease development. Large-scale cohort studies and emerging scientific concepts, such as epigenetics, may help us establish the role of these environmental factors., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE > 85 kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: New evidence emerged on early feeding practices and the risk of coeliac disease., Aim: To systematically update evidence on these practices to find out whether there is a need to revise current recommendations., Methods: MEDLINE, EMBASE and the Cochrane Library were searched from July 2012 (end of last search) to February 2015 for studies of any design that assessed the effect of gluten consumption and breastfeeding on the development of coeliac disease and/or coeliac disease-related autoimmunity., Results: We identified 21 publications, including two, new, large, randomised controlled trials performed in high-risk infants. Exclusive or any breastfeeding, as well as breastfeeding at the time of gluten introduction, did not reduce the risk of developing coeliac disease during childhood. For infants at high risk of developing coeliac disease, gluten introduction at 4 months of age in very small amounts, or at 6 or 12 months of age, resulted in similar rates of coeliac disease diagnosis in early childhood. Later gluten introduction was associated with later development of coeliac specific autoimmunity and coeliac disease during childhood, but not total risk reduction. Observational studies indicate that consumption of a higher amount of gluten at weaning may increase the risk for coeliac disease development., Conclusions: Infant feeding practices (breastfeeding, time of gluten introduction) have no effect on the risk of developing coeliac disease during childhood (at least at specific timeframes evaluated in the included studies), necessitating an update of current European recommendations., (© 2015 John Wiley & Sons Ltd.)

Aim: To evaluate whether coeliac disease (CD) can be diagnosed by measuring autoantibodies without small-intestinal mucosal biopsies in children with type 1 diabetes., Methods: Case finding of CD was undertaken in 181 consecutive IgA-competent children with type 1 diabetes using transglutaminase 2 (TG2) and endomysial IgA antibody (EMA) tests in serum and the rapid point of care test in fingertip whole-blood sample. Endoscopy with intestinal biopsies was recommended for patients with high TG2-IgA titres (>96 U) and in children with lower positive tests if either the EMA test or the rapid point of care test was additionally positive. The duodenal mucosal biopsies were graded according to the Marsh classification., Results: The TG2-IgA test had a 15.5% and the EMA test a 6.0% seropositivity. All seven biopsied high-titre TG2-IgA-positive children were symptom free and found to have CD (Marsh 3 type lesion). These patients were also positive for EMA and in the rapid point of care test. Lower titre TG2-IgA-positive children had histological Marsh 1 to 3a lesions., Conclusions: None of the type 1 diabetes children with high TG2-IgA titres would have needed endoscopy with duodenal biopsies to reach a CD diagnosis. Lower TG2-IgA-positive patients need to be biopsied., (©2012 The Author(s)/Acta Paediatrica ©2012 Foundation Acta Paediatrica.)

Background: PREVENTCD, Prevent Coeliac Disease, is an international project investigating the hypothesis of possible induction of tolerance to gluten in genetically predisposed children through introducing small quantities of gluten during the period of breastfeeding., Aim: To summarise current knowledge on the possible relationship between early feeding practices and the risk of coeliac disease (CD)., Methods: The Cochrane Library, MEDLINE, and EMBASE databases were searched in May 2011, and the search was updated in January 2012, and again in July 2012., Results: Breastfeeding (BF) and CD: some studies show a protective effect of BF, while others show no effect. No studies have shown a long-term preventive effect. BF at the time of gluten introduction and CD: Results from a meta-analysis of five observational case-control studies suggest that BF at gluten introduction is associated with a lower risk of CD compared with formula feeding. It is unclear whether BF provides a permanent protection or only delays the onset of CD. Timing of gluten introduction: The data suggest that both early (≤4 months) and late (≥7 months) introduction of gluten may increase the risk of CD. Amount of gluten at weaning (and later) and CD: One incident case-referent study documented that the introduction of gluten in large amounts compared with small or medium amounts increased the risk of CD., Conclusions: In the absence of clear evidence, in order to decrease the risk of later coeliac disease, it is reasonable to avoid both early (<4 months) and late (≥7 months) introduction of gluten, and to introduce gluten while the infant is still being breastfed. Future studies may clarify the remaining uncertainties., (© 2012 Blackwell Publishing Ltd.)

Background: Little is known about perinatal risk factors and coeliac disease., Aim: To investigate the relationship between perinatal risk factors and subsequent coeliac disease among offspring., Methods: Record linked abstracts of birth registrations, maternity, in-patient and day case records in a defined population of southern England., Results: Using univariate analysis, coeliac disease in the child was associated with maternal coeliac disease (odds ratio = 20.6; 95% CI = 5.04-84.0; based on two cases in both mother and child) and with social class, year of birth, maternal smoking and parity. Multivariate analysis confirmed an increased risk of coeliac disease of 3.79 (95% CI = 1.85-7.79) for classes IV and V compared with I and II, an increased risk of 1.92 (1.06-3.49) for births during 1975-1979 compared with 1970-1974 and an increased risk of 1.80 (1.05-3.09) for 'subsequent' compared with 'first' births. Smoking during pregnancy was no longer associated with coeliac disease. Because numbers were small, maternal coeliac disease was excluded from the multivariate analysis., Conclusions: This study shows increased risks of coeliac disease for manual social classes, births during the late 1970s and 'subsequent' births. Overall, perinatal risk factors seem to have a limited role in the aetiology of coeliac disease in children and young adults.

Background: A prevalence of 1.2% of coeliac disease (CD) in patients with chronic hepatitis C was recently reported, suggesting a possible epidemiological link between these two diseases. However, other studies have not found this relationship., Aim: To conduct a French multicentre prospective study to assess the prevalence of CD in hepatitis C virus (HCV)-infected patients., Methods: Between June 2003 and November 2005, 624 consecutive HCV-positive out-patients were tested for antiendomysial IgA antibodies (AEA), antigliadin IgA and IgG antibodies (AGA). Patients with positive AEA or IgA AGA and positive IgG AGA in a context of a high suspicion of CD were asked to undergo gastroscopy with duodenal biopsies., Results: Isolated IgA AEA, IgA AGA and IgG AGA were 0.16%, 5.7% and 4.4%, respectively. Gastroscopy was required for 39 patients, 31 were performed (eight refusals), but only 25 duodenal biopsies were performed as six patients had cirrhosis. CD was never detected., Conclusions: The prevalence of CD in HCV-positive patients was 0% (95% confidence interval: 0-0.59%), but there is a low prevalence of CD in the whole French population.

Aim: To report a series of 17 children affected by eosinophilic oesophagitis. Six of them also received a diagnosis of coeliac disease., Methods: Seventeen children with history of dyspeptic symptoms were investigated., Results: Six patients (M/F:2/4; mean age +/- s.d.: 5.6 +/- 1.3 years, range: 4-7 years; Group A) affected by eosinophilic oesophagitis also received a diagnosis of coeliac disease. The other 11 children (M/F:10/1, mean age +/- s.d.:7.5 +/- 2.3 years, range: 4-10 years, Group B) were affected solely by eosinophilic oesophagitis. All children underwent a change in dietary regimen. Group A received a gluten-free diet. Group B attempted dietary restriction based on the allergy testing results. After 6 months follow-up, all patients in Group A showed a complete disappearance of symptoms and three of them, who underwent upper gastrointestinal endoscopy, showed histologic remission. Patients from Group B had moderate clinical improvement and in seven of them (64%) a repeated upper gastrointestinal endoscopy showed a statistically significant reduction in eosinophilic infiltration., Conclusions: This is the first reported group of patients with an association between coeliac disease and eosinophilic oesophagitis. To date, it is not possible to exclude that in a subgroup of children with coeliac disease the oesophageal eosinophilic infiltration could be caused by coeliac disease itself.

This study will discuss our current understanding of celiac disease (CD), thyroid disorders, and atlanto-axial instability, three important areas of medical management in individuals with Down syndrome (DS). In this study, we highlight our current knowledge, as well as what we need to study in order to gather the necessary data to refine the empirically based screening protocols which are now in place.

Background: In coeliac disease, wheat, barley and rye are traditionally excluded in the gluten-free diet. However, few studies have examined the small intestinal immune response to barley and rye., Aim: To investigate the immunogenicity of barley and rye prolamins (hordein and secalin respectively) in comparison with wheat gliadin., Methods: Duodenal biopsies from 22 coeliac patients and 23 disease controls were cultured for 4 h with gliadin, hordein or secalin and compared with culture medium alone. Proinflammatory cytokines, interferon-gamma and interleukin-2, were quantified by TaqMan polymerase chain reaction and enzyme-linked immunosorbent assay., Results: Hordein caused the greatest increase in interferon-gamma mRNA in coeliac patients (median: 3.3-fold) in comparison with control subjects (median: 0.28-fold, P < 0.085). Secalin and gliadin induced similar levels of interferon-gamma mRNA with median fold-changes of 3.4 and 2.8, respectively, in coeliac patients in comparison with 1.6- and 1.1-fold increases in control subjects (P < 0.294 and P < 0.105, respectively). The median fold-changes for interleukin-2 mRNA did not differ between coeliac patients and controls. Cytokine protein was not upregulated., Conclusion: The findings of this study provide evidence that barley and rye cause immune activation in the mucosa of coeliac patients and support the practice that barley and rye should be excluded from the gluten-free diet.

Aim: To study the relationship between socio-economic factors and coeliac disease., Methods: This study was part of a prospective cohort study of 16 286 children born from 1 October 1997-1 October 1999 (the ABIS study; All Babies in Southeast Sweden). Eight paediatric departments recorded all children with coeliac disease in southeast Sweden. Coeliac disease was confirmed through biopsy. Socio-economic characteristics (maternal employment, civil status, whether parents were born in Sweden, parental education, place of living before pregnancy and during pregnancy, crowded living), infant sex, previous siblings, parental age and maternal alcohol consumption during pregnancy were analysed using logistic regression. All data, except for those related to diagnosis of coeliac disease, were obtained through a questionnaire distributed at birth., Results: Coeliac disease in the offspring was less common among mothers who had worked < 3 mo during pregnancy (odds ratio, OR = 0.29; 95% CI: 0.09-0.94; p = 0.039). This risk decrease remained after adjustment for confounders (adjusted OR = 0.28; 95% CI: 0.09-0.92; p = 0.035). No other socio-economic factor was related to coeliac disease., Conclusion: This study indicates that most socio-economic factors are probably of little importance to the development of coeliac disease.

Background: The assessment of exocrine pancreatic insufficiency is part of the routine work-up of patients with persistent diarrhoea or suspected steatorrhoea. Direct and indirect tests for the diagnosis of exocrine pancreatic insufficiency have their drawbacks. Measurement of faecal elastase 1 by enzyme-linked immunoabsorbent assay is a simple, non-invasive, robust test for exocrine pancreatic insufficiency., Methods: We performed a prospective comparison of the para-aminobenzoic acid test and faecal elastase 1 test in 45 patients being investigated for diarrhoea or suspected steatorrhoea. Details of clinical suspicion, imaging and response to treatment were recorded., Results: Exocrine pancreatic function was normal in 20 patients with normal para-aminobenzoic acid and faecal elastase 1 levels. Eight patients had exocrine pancreatic insufficiency with low para-aminobenzoic acid and faecal elastase 1 levels, which improved with enzyme supplementation. In 14 of the 15 patients with low or borderline low para-aminobenzoic acid and normal faecal elastase 1 levels, a non-pancreatic cause was found; one patient had a false positive para-aminobenzoic acid test. Two had normal para-aminobenzoic acid but low faecal elastase 1 levels. One improved with pancreatic supplementation, and imaging revealed chronic pancreatitis. The other had a false positive faecal elastase 1 test related to profuse diarrhoea., Conclusions: Faecal elastase 1 estimation is a simple, non-invasive, robust test of exocrine pancreatic insufficiency, performed on an out-patient stool sample. Its diagnostic performance is superior to that of the para-aminobenzoic acid test in investigating patients with diarrhoea or suspected steatorrhoea.

Unlabelled: The aims of this study were to estimate the prevalence of coeliac disease (CD) in Czech children with insulin dependent diabetes mellitus (IDDM), and to determine the contribution of HLA-DQA1 and DQB1 to CD susceptibility among diabetic children. We screened 345 children with IDDM (186 boys and 159 girls, aged 0 to 18 y) for coeliac disease using the IgA endomysial antibodies (EMA) test. In all EMA-positive children, small bowel biopsy was performed to confirm CD. To determine the role of the HLA-DQA1*05-DQB1*0201 (DQ2) and the DQA1*03-DQB1*0302 (DQ8) molecules in CD susceptibility among diabetic children, the HLA-DQA1-DQB1 was genotyped in all EMA-positive, and in 186 of EMA-negative diabetic patients. EMA positivity was found in 15/345 (4.3%) diabetic children. The diagnosis of CD was established in 14/345 (4.1%) children based on a bioptic finding of villous atrophy, while the remaining EMA-positive patient had a normal bioptic finding, being diagnosed as a potential CD. The HLA DQA1*05-DQB1*0201 (DQ2) molecule conferred a significant risk of CD among diabetic children (odds ratio = 4.1, CI 95% 1.1-15), being found more frequently in diabetic children with CD (80%) than in diabetic children without CD (49%)., Conclusion: The high prevalence of CD (4.1%) found in Czech children with IDDM emphasizes the need for their regular screening. We suggest that this CD screening protocol may be individualized according to the DQA1*05-DQB1*0201 positivity.

Most children with cystic fibrosis (CF) show persisting steatorrhoea even when treated with pancreatic enzyme. As a low duodenal pH could be responsible for this persisting fat loss, we evaluated the effects of a proton-pump inhibitor (lansoprazole) on both steatorrhoea and growth parameters in 15 CF patients, aged 3.1-22.6 y. Acid steatocrit, anthropometry and dual-energy X-ray absorptiometry were used to evaluate steatorrhoea and the nutritional status before, during and 3 months after stopping lansoprazole treatment (15 mg/d for 3 months). Mean +/- SD acid steatocrit values decreased from 37.1 +/- 8.8% to 28.5 +/- 10.6% (p = 0.02). Significant mean Z-score improvements were found for weight (+0.14; p = 0.02), height (+0.15; p = 0.03), subscapular (+0.61; p = 0.003), supra-iliac (+0.8; p = 0.002) and the sum of the four measured skinfolds (+0.61; p = 0.002). Z-scores deteriorated again after stopping lansoprazole. Fat mass and bone mineral content increased significantly on lansoprazole (p = 0.008 and p = 0.005, respectively). We conclude that lansoprazole as adjuvant therapy significantly improves both steatorrhoea and the nutritional status in CF children who maintain steatorrhoea while on pancreatic enzymes.

Background: Choosing the optimum pancreatic enzyme replacement therapy for patients with exocrine insufficiency remains a problem. An enteric coated enzyme microsphere pancreatic enzyme preparation (Pancrease) has been marketed with several levels of lipase activity, implying that there is a dose-response relationship between dose and effectiveness such that the high potency form appears to be the most cost effective., Methods: In a randomized, single-blind, cross-over study, we evaluated the effectiveness of a commercial enzyme preparation with different amounts of lipase per dosage unit in adults with exocrine pancreatic insufficiency. Patients received a diet comprising 100 g fat each day for 6 days. With each meal (three per day) they received two capsules of either Pancrease MT4 (8000 unit lipase), Pancrease MT10 (20,000 units lipase), Pancrease MT16 (32,000 units lipase) or placebo. A 72-h quantitative faecal collection was carried out for the last 3 days of the 6-day period., Results: There was a reduction in faecal fat excretion with each of the preparations compared to placebo. The difference failed to reach significance with the 8000 units lipase preparation (P > 0.05) but was significant (P = 0.02) with the 20,000 units lipase and the 32,000 units lipase preparations (faecal fat excretion: placebo = 42.1 +/- 29 g, lipase 8000 = 22.1 +/- 7.3 g, lipase 20,000 = 10.2 +/- 4.5 g and lipase 32,000 = 15.8 +/- 12.5 g, P < for 20,000 units and 32,000 units lipase compared to placebo)., Conclusion: A dose-response relationship between the amount of lipase administered with each meal and a reduction in faecal fat was not evident. The most potent preparation did not provide additional benefits compared to the less expensive lower potency dosage form.

Malabsorption of fat is an important gastrointestinal cause of malnutrition and growth retardation in childhood. The gold standard for the evaluation of fat malabsorption is the faecal fat balance method. The acid steatocrit method has recently been introduced as a simple method to evaluate faecal fat. The present study was aimed at evaluating the acid steatocrit in clinical practice. Faecal fat excretion and acid steatocrit results were determined in 42 children, half with and half without fat malabsorption. Acid steatocrit results correlated significantly with both faecal fat excretion (p < 0.01) and faecal fat concentration (p < 0.001). Sensitivity and specificity of the acid steatocrit for the diagnosis of malabsorption were 90% and 100%, respectively. We consider the acid steatocrit method useful for the screening and monitoring of patients with steatorrhoea.

A substantial minority of patients with coeliac disease (estimated at anything between 7 and 30%) fail to respond to treatment with a gluten-free diet. Non-responsiveness may be primary, that is when the patient fails to respond to treatment following initial diagnosis, or secondary, when a patient who has previously had a documented response to gluten exclusion becomes non-responsive to therapy. The commonest cause of non-responsiveness is continued gluten ingestion, either voluntary or inadvertent. Other causes to be considered include intolerances to dietary constituents other than gluten (e.g. milk, soya), pancreatic insufficiency, enteropathy-associated T-cell lymphoma and ulcerative jejunitis. There is some evidence that ulcerative jejunitis is, in fact, a manifestation of lymphoma. The most important steps in the management of the non-responsive coeliac patient are (a) to determine whether the patient is indeed coeliac, (b) to exclude lymphoma and (c) to establish the cause of the non-responsiveness. In those coeliac patients with no demonstrable cause for non-responsiveness, a variety of therapeutic stratagems (mostly based on small, uncontrolled studies) have been described; these include elimination diets, dietary supplementation with zinc and copper, and pharmacological therapy in the form of steroids, azathioprine and cyclosporin. In a minority of non-responsive patients, the clinical course is characterized by a rapid decline, and total parenteral nutrition is required. None of the therapies described above has been subjected to rigorous controlled studies. The precise mechanisms of non-responsiveness in coeliac patients need to be unravelled before rational therapeutic approaches can be established.

The effect on steatorrhoea of a pH-sensitive enteric-coated pancreatic preparation (Eurobiol 25,000) was compared with a conventional pancreatic enzyme preparation (Eurobiol) in six adult patients with exocrine pancreatic insufficiency. In addition, the fate of orally ingested pancreatic enzymes in the upper digestive tract was evaluated by measuring gastric and duodenal pH, amount of enzymes in the stomach, duodenal enzyme output, and fat absorption at the angle of Treitz for the 4 hours following a standard meal. When compared with placebo, Eurobiol and Eurobiol 25,000 reduced daily faecal fat excretion by 24% (not significant) and 43% (P less than 0.05), respectively. With the conventional preparation, enzyme output and fat absorption at the duodeno-jejunal flexure were significantly improved (P less than 0.05). Marked inter-individual differences in duodenal enzyme recovery (lipase 3% to 80%; chymotrypsin 26% to 100%) and, consequently, in the reduction of steatorrhoea (0% to 67%) were observed, with the gastric emptying rate emerging as a key determinant factor. With the enteric-coated preparation, enzyme output and fat absorption at the duodenojejunal flexure were not significantly improved. Discrepancy between the marked reduction of faecal fat excretion and the low duodenal enzyme recovery could indicate that enzyme delivery from microtablets occurs further down in the small bowel. Efficacy of enteric-coated preparations could be enhanced by adding unprotected enzymes, especially in patients with rapid gastric emptying.

Enteric-coated microspheres of pancreatin were compared with non-enteric-coated pancreatin combined with cimetidine taken 40 min before meals in the treatment of patients with cystic fibrosis. Fourteen adults with steatorrhoea due to cystic fibrosis were investigated in an open, randomized crossover study, over two consecutive 28-day treatment periods. Lipase intake was adjusted to each patient's previous requirements and was the same during both months; they were instructed to continue with their normal diet. Patients collected faeces for 72 h at the end of each month and completed diary cards daily throughout. Bowel actions were less frequent on enteric-coated microspheres of pancreatin than on non-enteric-coated pancreatin/cimetidine (1.7 vs. 2.4/day; P less than 0.001) and stool character was improved (P less than 0.001). Mean daily faecal weight was similar on enteric-coated microspheres of pancreatin to that on the combination (254 g vs. 291 g; N.S.), whereas daily faecal fat excretion tended to be less on enteric-coated microspheres of pancreatin (21 g vs. 27 g; N.S.), and percentage fat absorption tended to be greater (81% vs. 73%; N.S.). Mean body weight increased by 0.3 kg on enteric-coated microspheres of pancreatin and fell by 0.1 kg on the combination (N.S.). These data indicate that enteric-coated microspheres of pancreatin are at least as effective as non-enteric-coated pancreatin with cimetidine in the treatment of steatorrhoea in cystic fibrosis.