The protein, zonulin, has emerged as a popular serological marker to assess the integrity of the intestinal mucosal barrier. However, there is limited information on the utility of serum zonulin to ...indicate gastrointestinal disease and the validity of zonulin detection in widely-used commercial assays. The current study reports differences in zonulin levels across patient groups with gastrointestinal dysfunction compared with healthy individuals, though methodological inconsistencies indicated that actual zonulin protein was not detected by the commercial assays applied. The nature of the assays' detected antigen was investigated using immunoprecipitation followed by mass spectrometric analysis and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by protein staining. Top matches of the assays' detected antigen included haptoglobin and complement C3 for the assay manufactured by CUSABIO (Wuhan, China) and complement C3 for the assay manufactured by Immundiagnostik AG (Bensheim, Germany). These findings confirm that current commercial zonulin assays are not detecting the actual protein as prehaptoglobin-2. Until assay methodology is improved, we advise the greater scientific and medical community to exercise caution in considering the measurement of serum zonulin as a marker of mucosal barrier integrity.
Irritable bowel syndrome (IBS)‐like symptoms are not uncommon in patients with quiescent inflammatory bowel disease (IBD). While gluten‐free diet is applied by patients, there are no reported ...interventional studies. The low‐FODMAP diet, on the other hand, has efficacy similar to that seen in patients with IBS in three unblinded or observational studies of IBD cohorts who had well‐controlled inflammatory disease and in one small randomized cross‐over study. FODMAP intake by patients with IBD is not elevated, and, in one study, fructan intakes were lower in patients with Crohn's disease than in controls. There is no clear relationship between the level of FODMAP intake and intestinal inflammation. The risk of compromising nutritional status with a restrictive diet must be seriously considered especially as under‐nutrition is already common in this patient population. The effects of FODMAPs on the gut microbiota of patients with Crohn's disease mimic that in IBS, with a balance between prebiosis from the addition of FODMAPs and loss of prebiosis from their reduction. As undernutrition is common in IBD, the use of restrictive diets should be supervised by a dietitian. Thus, low‐FODMAP diet is a viable option for IBS‐like symptoms but should be carefully supervised to mitigate risk.
Asthma is a chronic respiratory condition frequently associated with aberrant airway and systemic inflammation. Various inflammatory phenotypes in asthmatic airways have been described that relate to ...clinical phenotypes and impact on responses to conventional and novel asthma therapies. Macrophages are abundant immunocytes in the lung, capable of mounting diverse responses required for homeostasis and defence against pathogens.Here, we summarise the clinical evidence regarding macrophage dysfunction in asthma. We also describe evidence supporting the role of macrophages as therapeutic targets in asthma. We conclude that macrophage dysfunction in asthma is highly prevalent and heterogeneous, and hypothesise that macrophages may play roles in promoting the discrete inflammatory phenotypes of asthma.These clinical findings, along with recent ground-breaking insights into the ontogeny, behavioural complexity and longevity of pulmonary macrophages, support continued research into the role of macrophages as disease modifiers, biomarkers and therapeutic targets in asthma.
History of the low FODMAP diet Gibson, Peter R
Journal of gastroenterology and hepatology,
March 2017, 2017-Mar, 2017-03-00, 20170301, Volume:
32, Issue:
S1
Journal Article
Peer reviewed
Open access
It has long been known that many short‐chain carbohydrates can induce abdominal symptoms that are similar to those in patients with irritable bowel syndrome (IBS). It was hypothesized that ...restricting the intake of all short‐chain carbohydrates that are either slowly absorbed or not digested in the small intestine should be considered together because they all have similar effects on the intestine by distending the lumen. These groups of carbohydrates were called, Fermentable, Oligosaccharides, Disaccharides and Monosaccharides and Polyols (FODMAPs), because of the lack of a known collective term. By reducing their dietary intake, it was also hypothesized that abdominal symptoms in patients with IBS would be alleviated in patients with visceral sensitivity and a low FODMAP diet was subsequently designed. Over the last 12 years, the mechanisms of action, food content of FODMAPs and efficacy of the diet, among other aspects have been intensively studied. In many parts of the world, the low FODMAP diet is now considered a front‐line therapy for IBS.
Six randomized controlled trials comparing low FODMAP diet with placebo approaches have all indicated efficacy in patients with irritable bowel syndrome (IBS). The studies have provided all the food ...(n = 3) or utilized dietitian‐led education (n = 3). They have variably met criticisms regarding issues such as the choice of placebo, the number of patients studied, the success of blinding, and the duration of the interventions, but the results are uniformly positive for the diet. Real‐world experience of the low FODMAP diet has confirmed the findings of the randomized studies, in that about 70% of patients respond. Difficulty in delivering the diet has not been an issue, and the majority of patients find the diet easy to follow when dietitian led. Observational studies have suggested durability of efficacy, even in association with reintroduction of FODMAPs as recommended. Three studies comparing institution of standard dietary guidelines for IBS with the low FODMAP diet have found either similar or improved outcomes with the latter. Low FODMAP diet also has similar efficacy to that of gut‐directed hypnotherapy, another strategy with broad benefit in IBS. There are currently no clinically applicable indices that predict response to the diet. In conclusion, clinical trials and observational studies support the notion that a dietitian‐led low FODMAP diet is ready for primetime and should be considered as a first‐line therapy for patients with IBS where the use of a restrictive diet is appropriate.
Letter: dietitians are more than coaches Gibson, Peter R.
Alimentary pharmacology & therapeutics,
April 2023, 2023-04-00, 20230401, Volume:
57, Issue:
8
Journal Article
Peer reviewed
Open access
LINKED CONTENT
This article is linked to Wang et al papers. To view this article, visit https://doi.org/10.1111/apt.17221
Irritable bowel syndrome (IBS) is a common, symptom-based condition that has negative effects on quality of life and costs health care systems billions of dollars each year. Until recently, ...management of IBS has focused on over-the-counter and prescription medications that reduce symptoms in fewer than one-half of patients. Patients have increasingly sought natural solutions for their IBS symptoms. However, behavioral techniques and dietary modifications can be effective in treatment of IBS. Behavioral interventions include gastrointestinal-focused cognitive behavioral therapy and gut-directed hypnotherapy to modify interactions between the gut and the brain. In this pathway, benign sensations from the gut induce maladaptive cognitive or affective processes that amplify symptom perception. Symptoms occur in response to cognitive and affective factors that trigger fear of symptoms or lack of acceptance of disease, or from stressors in the external environment. Among the many dietary interventions used to treat patients with IBS, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols is the most commonly recommended by health care providers and has the most evidence for efficacy. Patient with IBS who choose to follow a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols should be aware of its 3 phases: restriction, reintroduction, and personalization. Management of IBS should include an integrated care model in which behavioral interventions, dietary modification, and medications are considered as equal partners. This approach offers the greatest likelihood for success in management of patients with IBS.
Mepolizumab has demonstrated favorable safety and efficacy profiles in placebo-controlled trials of 12 months' duration or less; however, long-term data are lacking.
We sought to evaluate the ...long-term safety and efficacy of mepolizumab in patients with severe eosinophilic asthma (SEA).
COLUMBA (Open-label Long Term Extension Safety Study of Mepolizumab in Asthmatic Subjects, NCT01691859) was an open-label extension study in patients with SEA previously enrolled in DREAM (Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma, NCT01000506). Patients received 100 mg of subcutaneous mepolizumab every 4 weeks plus standard of care until a protocol-defined stopping criterion was met. Safety end points included frequency of adverse events (AEs), serious AEs, and AEs of special interest. Efficacy end points included annualized exacerbation rates, changes from baseline in Asthma Control Questionnaire 5 scores, and blood eosinophil counts. Immunogenicity was also assessed.
Overall, 347 patients were enrolled for an average of 3.5 years (maximum, 4.5 years; total exposure, 1201 patient-years). On-treatment AEs were reported in 94% of patients (exposure-adjusted rate, 3688 events/1000 patient-years). The most frequently reported on-treatment AEs were respiratory tract infection, headache, bronchitis, and asthma worsening. Seventy-nine (23%) patients experienced 1 or more on-treatment serious AEs; there were 6 deaths, none of which were assessed as related to mepolizumab. For patients with 156 weeks or greater enrollment, the exacerbation rate was 0.74 events/y (weeks 0–156), a 56% reduction from the off-treatment period between DREAM and COLUMBA. For all patients, at the first postbaseline assessment, the mean Asthma Control Questionnaire 5 score was reduced by 0.47 points, and blood eosinophil counts were reduced by 78%, with similar improvements maintained throughout the study. The immunogenicity profile (8% anti-drug antibodies) was consistent with previous studies.
These data support the long-term safety and efficacy of mepolizumab in patients with SEA.
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