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.