Study flowchart.

<p>Study flowchart.</p

Adjuvant treatment with the bacterial lysate (OM-85) improves management of atopic dermatitis: A randomized study

<div><p>Background</p><p>Environmental factors play a major role on atopic dermatitis (AD) which shows a constant rise in prevalence in western countries over the last decades. The Hygiene Hypothesis suggesting an inverse relationship between incidence of infections and the increase in atopic diseases in these countries, is one of the working hypothesis proposed to explain this trend.</p><p>Objective</p><p>This study tested the efficacy and safety of oral administration of the bacterial lysate OM-85 (Broncho-Vaxom^®, Broncho-Munal^®, Ommunal^®, Paxoral^®, Vaxoral^®), in the treatment of established AD in children.</p><p>Methods</p><p>Children aged 6 months to 7 years, with confirmed AD diagnosis, were randomized in a double-blind, placebo-controlled trial to receive, in addition to conventional treatment with emollients and topical corticosteroids, 3.5mg of the bacterial extract OM-85 or placebo daily for 9 months. The primary end-point was the difference between groups in the occurrence of new flares (NF) during the study period, evaluated by Hazard Ratio (HR) derived from conditional Cox proportional hazard regression models accounting for repeated events.</p><p>Results</p><p>Among the 179 randomized children, 170 were analysed, 88 in the OM-85 and 82 in the placebo group. As expected most children in both treatment groups experienced at least 1 NF during the study period (75 (85%) patients in the OM-85 group and 72 (88%) in the placebo group). Patients treated with OM-85 as adjuvant therapy had significantly fewer and delayed NFs (HR of repeated flares = 0.80; 95% confidence interval (CI): 0.67–0.96), also when potential confounding factors, as family history of atopy and corticosteroids use, were taken into account (HR = 0.82; 95% CI: 0.69–0.98). No major side effect was reported, with comparable and good tolerability for OM-85 and placebo.</p><p>Conclusions</p><p>Results show an adjuvant therapeutic effect of a well standardized bacterial lysate OM-85 on established AD.</p></div

Repeated events (NF) description according to per-protocol analysis: Number of patients experiencing an event (NF), average time to event (in days) in treatment groups.

<p>HRs consider both a multiple-events model, and the time to the first event only.</p

Repeated events (NF) description: Number of patients experiencing an event (NF), average time to event (in days) in treatment groups.

<p>HRs estimates are reported, considering both, a multiple-events model, and the time to the first event only.</p

SCORAD evolution over time (median, q1 and q3) by group and visit: Visit 1 (baseline), visit 2 (1 month), visit3 (3 moths), visit 4 (6 months) and visit 5 (9 month).

<p>q1 = first quartile (25° percentile); q3 = third quartile (75° percentile). ^ p for non parametric analysis of variance (ANOVA) for repeated measures, adjusting for age and sex. * p for visit 4 = 0.02. ** p for visit 5 = 0.08.</p

New flare definition.

<p>New flare definition.</p

<i>S</i>. <i>aureus</i> was identified only in AD children and correlated with high IgE levels.

<p>(A) Ratios of average counts for bacterial species and their respective phyla found in the inflamed zones and control-matched zones of atopic dermatitis (AD) patients and their non-AD counterparts, respectively. (B) Colony-forming units (CFU/ml) of <i>S</i>. <i>aureus</i> from sampled zones in AD and non-AD subjects. Mann-Whitney, mean values with SEM are shown, p**<0.01. The black square denotes a patient with undetermined IgE values. (C) AD subjects were sorted in relation to the amounts of IgE antibodies (kU/l) measured in their blood. (B, C) Total IgE over 1000kU/l is shown in red, between 100 and 1000 kU/l in blue and below 100 kU/l in green. (D) Enterotoxins were identified in <i>S</i>. <i>aureus</i> clones from AD subjects (P02-P39) by DNA array.</p

List of antibodies used.

<p>List of antibodies used.</p

IL-4-producing peripheral T CD4⁺ cells against Der p allergens are increased in AD children compared to IFN-γ- producing T CD4⁺ cells.

<p>(A) IFN-γ and IL-4 ELISPot assays (spot forming units/10⁶ T cells) were performed on peripheral blood from non-AD (N = 14) and AD (N = 15) children in response to crude extracts of Der p. (B) Ratio of IL-4 <i>vs</i> IFN-γ CD4⁺ T cell spots relative to titers of total or Der p1 specific IgE antibodies (kU/ml) in AD patients. Mann-Whitney, mean values with SEM are shown, p*<0.05, p**<0.01.</p

The <i>S</i>. <i>aureus</i> and <i>S</i>. <i>epidermidis</i> secretomes exert opposite effects on the Treg suppressive function.

<p>CFSE-labeled conventional CD4⁺ T cells (Tconv) were cultured in the presence of beads pre-loaded with anti-CD2, -CD3 and -CD28 antibodies and CD4⁺CD25⁺CD127^dim/- T cells (Treg cells expressing Foxp3) pretreated for 24 hours with medium only (NT), or the secretomes of <i>S</i>. <i>aureus</i> (S.a) or <i>S</i>. <i>epidermidis</i> (S.e) at Tconv to Treg ratios of 1:1 (A) and 2:1 (B). Proliferation was assessed by flow cytometry after 5 days and the percentage of suppression was calculated as (1—proliferation of Tconv with Treg / proliferation of Tconv without Treg) X100. Paired t-test, p*<0.05, p**<0.01, N = 5.</p