INTRODUCTION

A type 2 immune response is triggered by the activation of T helper 2 (Th2) cells and/or innate lymphoid type 2 cells (ILC2), leading to the expression of type 2 inflammatory cytokines such as interleukin (IL)-4, IL-5 and IL-13,1,2 as well as IL-31 in the skin (Figure 1A).3 Type 2 inflammation can be characterised by the elevation of biomarkers such as immunoglobulin E (IgE), blood and/or tissue eosinophils, and elevated fractional exhaled nitric oxide (FeNO).1,2,4
Type 2 inflammation has been identified as a key driver of the pathogenesis of various diseases such as allergic asthma,5,6 non-allergic eosinophilic asthma,7 atopic dermatitis,6,8chronic rhinitis,6,9 chronic rhinosinusitis with nasal polyps (CRSwNP)6,10 and eosinophilic esophagitis,11-13 and as an important pathogenic cofactor in chronic urticaria, food allergy and conjunctivitis (Figure 1B–E).14,15 Although co-occurrence of these diseases in individual patients has been reported, the heterogeneity of epidemiological studies makes it difficult to draw valid conclusions about the extent of multi-organ disease driven by type 2 inflammation.16-28
Inhibition of IL-1329-32 and IL-4 receptor (R)33-35 is effective for the treatment of asthma, atopic dermatitis and CRSwNP. Inhibition of IL-4R,34IL-536 and IL-5R37 is effective for the treatment of patients with asthma, but IL-5 inhibition lacked efficacy in a short study of mepolizumab in patients with atopic dermatitis.38 Inhibition of IL-1339, IL-4R40, IL-541 and IgE42 is effective for the treatment of eosinophilic esophagitis.
IL-31 is a potent pruritogenic cytokine that is involved in type 2 inflammation and may be a potential novel target for the treatment of pruritus in patients with atopic dermatitis.43 In addition, thymic stromal lymphopoietin, an epithelial-cell-derived cytokine that has a major role in type 2 inflammation, is being investigated as a target for the treatment of type 2 inflammation-driven diseases.44
In patients with asthma, biomarkers such as FeNO and blood eosinophils are predictive biomarkers of response to corticosteroids and biologic agents targeting type 2 inflammation.45 The discovery of this association has led to a paradigm shift in the treatment of severe asthma. Many biomarkers have been identified that assist with characterising the subtypes of CRSwNP, such as eosinophil count and bitter/sweet taste receptors, but biomarkers linked to the intrinsic biomolecular mechanism of the disease are needed.46Biomarkers of treatment response for eosinophilic esophagitis, such as microRNAs, are currently being investigated.47 The future discovery of biomarkers in type 2 inflammation-driven diseases has the potential to enable accurate phenotyping, tailored management and a deeper understanding of the variation of immunological drivers behind the diseases.
There is a need to discuss the extent to which type 2 inflammation is the underlying cause of multi-organ disease, as this may have important implications for patient management and prognosis. To address this need, Sanofi Genzyme invited a group of experts representing different relevant specialties (allergy; clinical immunology; dermatology; ear, nose, and throat [ENT]; internal medicine; paediatrics; respiratory) from the Nordic region (Denmark, Estonia, Finland, Iceland, Norway, Sweden), based on their expertise related to the treatment of patients with type 2 inflammatory diseases in their respective fields, to gather for a consensus meeting using a modified Delphi process. The consensus meeting aimed to identify, in the clinical points of view of the experts, which diseases are predominantly driven by type 2 inflammation, assess the extent of multi-organ disease, evaluate whether the diseases can be considered to belong to the same spectrum of type 2 inflammation-driven multi-morbidities rather than being distinct primary diseases and comorbidities, and outline the impact on the holistic management of patients presenting with diseases related to type 2 inflammation.