Rectal 5-ASA should be considered a first-line therapy for patients with mild to moderately active distal UC. The optimal total daily dose and dose frequency of 5-ASA remain to be determined. Future research should define differences in efficacy among patient subgroups defined by proximal disease margin and disease activity. There is a strong need for consensus standardization of outcome measurements for clinical trials in ulcerative colitis.

A probiotic formulation of Enterococcus faecium R0026 and Bacillus subtilis R0179 has been evaluated in previous clinical trials. However, B. subtilis R0179 has not been evaluated as a single probiotic strain or in combination with other strains at doses higher than 0.1×109 cfu. To establish oral dose-response tolerance and gastrointestinal (GI) viability of B. subtilis R0179, a randomised, double-blind, placebo-controlled trial in healthy adults (n=81; 18-50 years old) was conducted. Participants received B. subtilis R0179 at 0.1, 1.0 or 10×109 cfu/capsule/day or placebo for four weeks. General wellness was assessed using a daily questionnaire evaluating GI, cephalic, ear-nose-throat, behavioural, emetic, and epidermal symptoms. GI symptoms were further evaluated using a weekly gastrointestinal symptom rating scale (GSRS). GI transit viability of B. subtilis R0179 was assessed by plating and microbiota analysis by 16S rRNA at baseline, week 4 of the intervention and washout. General wellness and GI function were not affected by oral consumption of B. subtilis R0179 at any dose. Daily questionnaire syndrome scores were not different from baseline and did not exceed a clinically significant score of 1. GSRS syndrome scores were not different from baseline and ranged from 1.1±0.1 to 1.9±0.2. Faecal viable counts of B. subtilis R0179 demonstrated a dose response: the placebo group (1.1±0.1 log10 cfu/g) differed from 0.1×109 (4.6±0.1 log10 cfu/g), 1×109 (5.6±0.1 log10 cfu/g) and 10×109 (6.4±0.1 log10 cfu/g) (P<0.0001). No significant changes in phyla were observed, but sequence reads binned to multiple operational taxonomic units matching closest to Ruminococci increased during probiotic supplementation. B. subtilis R0179 survives passage through the human GI tract and is well tolerated by healthy adults at intakes from 0.1 to 10×109 cfu/day. The trial has been registered at www.clinicaltrials.gov under NCT01802151.

The limited data available suggest that rectal 5-ASA is effective and safe for maintenance of remission of mild to moderately active distal UC. Well designed randomized trials are needed to establish the optimal dosing regimen for rectal 5-ASA, to compare rectal 5-ASA with rectal corticosteroids and to identify subgroups of patients who are more or less responsive to specific rectal 5-ASA regimens. The combination of oral and rectal 5-ASA appears to be more effective than either oral or rectal monotherapy for induction of remission. The efficacy of combination therapy for maintenance of remission has not been assessed and could be evaluated in future trials.

BackgroundThe beneficial effect of corticosteroids and anti-interleukin (IL)-5 on exacerbations of airway disease becomes apparent at blood eosinophil counts above 0.15 × 109/L, well within the normal range. One potential explanation is that the upper limit of the normal range is artificially high because studies have included patients with allergic disease and eosinophilic inflammation. We have assessed the normal range for blood eosinophil counts in volunteers with no self-reported history of allergic disease and compared this with the findings from a more traditional control population.MethodsWe recruited 78 volunteers (15 male) with a mean age of 38.8 years. Volunteers with a self-reported history of asthma, allergic rhinitis and/or eczema were excluded. The differential cell count was carried out using sysmex XN analyser and serum IgE measured using automated enzyme immunoassay by Phadia Immunocap equipment. Result were compared with an unscreened population (n = 120) used to calculate our local normal ranges.ResultsOne outlier value of 0.79 × 109/L, (>5 SD above the mean) was excluded from further analysis. In the remainder the mean blood eosinophil count was 0.15 × 109/L with an upper limit of normal range of 0.27 × 109/L. Volunteers with no self-reported history of allergic disease but an IgE >120 iu/L and/or positive specific IgE to house dust mites or grass were not statistically different. The mean blood eosinophil count in the laboratory population was 0.19 × 109/L (p 0.018 vs our population) and the upper limit of normal range 0.42 × 109/L.ConclusionsThe upper limit of the normal range for blood eosinophil count is lower in a population who have no clinical history of allergic disease.