Background: This initiative aimed to elucidate the clinical relevance of type 2 (T2) inflammation as a driver of asthma, atopic dermatitis, chronic rhinitis, chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic esophagitis. Methods: A steering committee (SC) conducted a non-systematic literature search to inform the design of a Delphi questionnaire including 23 consensus statements, which was circulated to 30 experts including the SC. Experts rated their agreement with each statement on a 9-point Likert scale and provided optional feedback that was used to develop a second Delphi questionnaire. On 22 October 2020, a meeting was held to discuss the conclusions from the questionnaires and explore how this initiative may impact the management of patients with T2 inflammation-driven disease. Post meeting, a consensus statement on the role of T2 inflammation in eosinophilic esophagitis was circulated to the experts. Results: It was agreed that T2 inflammation may be an underlying driver of asthma, atopic dermatitis, chronic rhinitis, CRSwNP and eosinophilic esophagitis, and that the published evidence suggests that these diseases overlap. Some of this overlap may include related multimorbid conditions driven by T2 inflammation. Thus, in patients with multiple T2 inflammation-driven diseases, a cross-speciality approach is warranted to provide effective care. A question guide with input from relevant experts was proposed, to identify comorbidities and facilitate appropriate holistic patient management. Conclusions: These consensus recommendations should be used as a framework to further understand the extent of T2 inflammation-driven multi-organ disease and to improve the holistic management and care of these patients.

Topical probiotic L. lactis treatment in atopic dermatitis - A double-blinded, placebo-controlled pilot studyTo the Editor,Changes in the skin microbiome have been identified as major pathogenetic components in atopic dermatitis (AD). Probiotics have been studied as potential therapeutic agents to maintain normal cutaneous microbiome and prevent colonization with pathogens.1We aimed to compare the efficacy of probiotic Lactococcus lactislysate cream in different concentrations in AD.We conducted a prospective, double-blinded, randomized, placebo-controlled, split-body clinical interventional study. 13 patients were enrolled and randomly assigned to one of four groups with different concentrations of probiotic lysate cream including placebo (Supplement Table S1).Patient’s skin was investigated 3 times, at baseline, after 4 weeks of treatment and after 4 weeks of follow-up. During each visit, the skin was evaluated, and AD severity was characterized with investigator-dependent methods and patient-reported questionnaires. Online Supplement presents detailed information about the study setting and patient characteristics.There were no clear differences between the treatment groups regarding disease severity (EASI, IGA), TEWL or parameters associated with QoL (pruritus and sleep disturbance VAS, DLQI, POEM, ADCT). Mean changes in disease severity (EASI local and total), TEWL and QoL indicators (DLQI and POEM) are shown in Fig. 1.Mean local EASI (eczema site) baseline values were 3.00, 1.47 and 1.05 in the 3%, 10% and 30% probiotic lysate groups respectively, and 4.93 in the placebo group. After 4 weeks of treatment, local EASI values were 3.20, 1.20 and 0.80 in the probiotic lysate groups and 4.53 in the placebo group, with no significant decrease compared to baseline (p=0.76). Total EASI values showed similar results (p=0.31) and there were also no differences between local EASI and total EASI. IGA values were similar (p=0.61) (Table 1).QoL associated parameters did not change significantly during the study and were similar in all patient groups (Supplement Table S2). Mean DLQI was 9.33, 7.00 and 8.00 in the probiotic lysate groups and 10.67 in the placebo group. At 4 weeks the values were comparable, 9.00, 8.00 and 10.33 in the probiotic lysate groups and 7.67 in the placebo group, with no significant differences (p=0.76). POEM and ADCT showed no significant differences (p=0.76 and p=0.72, respectively). Complete study results, clinical data, eosinophil counts, total serum IgEs and specific IgEs to aeroallergens at baseline are presented in the Supplement (Table S3).While enteral probiotics have been studied in detail, the role of topical probiotics in AD remains uncertain. Several studies have investigated the use of probiotics in creams with living or dead bacteria or bacterial lysates with inconsistent results.2,3 Further evidence is needed to determine efficacy, dosing, and specific bacterial strains. Most of the previous studies observed positive effects, which is contrary to our findings.4In addition to ameliorating disease severity, in vitro studies have shown that probiotics suppress cutaneous inflammation and Th2-responses through immunomodulatory mechanisms.5 We did not measure inflammatory parameters in our patients. However, to our knowledge, our study is the first in vivo study in humans investigating Lactococci in the treatment of AD.Most probiotic preparations are considered relatively safe and are classified as commercial food supplements. We did not observe relevant adverse effects and the used probiotic L. lactis lysate cream was well tolerated.Important study limitations were small and heterogenous patient groups, relatively short follow-up time and no long-term evaluation.We observed no clear differences between the treatment groups of probiotic L. lactis lysate cream and placebo. Further research is needed to investigate the role of topical probiotics in AD. It would be interesting to investigate anti-inflammatory effects in larger patient cohorts.6Table 1: Severity of atopic dermatitis and TEWL values, results of follow-up and comparisons

Background: Microbiome-targeted treatments have been investigated in atopic dermatitis (AD). We aimed to investigate the use of probiotic Lactococcus lactis lysate cream in AD. Methods: 13 patients with mild-to-moderate AD were treated with differently concentrated probiotic creams (3%, 10% and 30%) or placebo cream for 4 weeks. Disease severity (EASI, IGA), epidermal barrier function (TEWL) and patient-reported impact (DLQI, POEM, ADCT, pruritus and sleep disturbance VAS) were measured at baseline, 4 and 8 weeks. Comprehensive clinical data and laboratory values (blood eosinophil count, total serum IgE-levels and specific IgEs to aeroallergens) were obtained. Results: Comparison of the treatment groups showed no clear differences regarding AD severity (EASI, p=0.76, CI: 0.65-1.00), epidermal barrier dysfunction (TEWL, p=0.37, CI: 0.19-0.73) or patient-reported impact (DLQI, p=0.76, CI: 0.65-1.00; POEM, p=0.76, CI: 0.35-0.88; ADCT, p=0.72, CI: 0.65-1.00; pruritus VAS 0.67, CI: 0.55-1.00; sleep disturbance VAS, p=1.00, CI: 0.79-1.00) between different probiotic lysate concentrations and placebo. The probiotic lysate cream was well tolerated and there were no significant adverse effects. Limitations were a small and heterogenous patient groups and a relatively short follow-up with no evaluation of long-term effects. Conclusions: Topical probiotic L. lactis lysate cream showed no clear differences between the tratment groups in mild-to-moderate AD. Although topical probiotics have been reported effective in a limited number of studies, more placebo-controlled clinical studies are needed to explore their potential role in the treatment of AD.