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.

Background Asthma is characterized by an aggravated immune response to respiratory viral infections: This phenomenon is a clinically well-recognized driver of acute exacerbations, but how different phenotypes of asthma respond immunologically to virus is unclear. Objectives To describe the association between different phenotypes and severity of asthma and bronchial epithelial immune responses to viral stimulation. Methods In the Immunoreact study, healthy subjects (n=10) and 50 patients with asthma were included; 30 (60%) were atopic, and 34 (68%) were eosinophilic; 15 (25%) had severe asthma. All participants underwent bronchoscopy with collection of bronchial brushings. Bronchial epithelial cells (BECs) were expanded and stimulated with the viral replication mimic poly (I:C) (TLR3 agonist) in vitro. The expression of TLR3-induced pro-inflammatory and anti-viral responses of BECs were analyzed using RT-qPCR and multiplex ELISA and compared across asthma phenotypes and severity of disease. Results Patients with atopic asthma had increased production of IL-4, IFN-β, IL-6, TNF-α, and IL-1β after poly (I:C) stimulation compared to non-atopic patients, whereas patients with eosinophilic asthma and non-eosinophilic asthma did not differ in the response to poly (I:C). Patients with severe asthma displayed a decreased antiviral IFN-β, and increased expression of IL-8, most pronounced in atopic and eosinophilic asthmatics. Interestingly, release of IL-33 and TSLP in response to poly (I:C) was increased in severe eosinophilic asthma, but not in severe atopic asthma. Conclusions The bronchial epithelial immune response to a viral mimic stimulation differs between asthma phenotypes and severities, which may be important to consider when targeting novel asthma treatments.

Background Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of severe adult asthma patients eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life. Methods This was a prospective cohort study that included adult severe asthma patients from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance and hospital admissions. Results In the matched analysis (n=350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p<0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs 20.55% reduction; p=0.023).) There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43). Conclusions In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes, however anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use.