Discussion
Overall, there was general agreement that diseases associated with type
2 inflammation commonly coexist, although there is a lack of evidence to
determine the extent of overlap in patients with three or more
coexisting diseases. For some conditions, such as asthma with CRSwNP,
there was agreement that coexisting type 2 inflammation-driven diseases
may be associated with more severe disease. For patients with comorbid
atopic dermatitis and asthma, the general perception is that their
asthma will be mild, as demonstrated in the randomised,
placebo-controlled phase 3 SOLO 1 and SOLO 2 studies of dupilumab in
patients with atopic dermatitis.33,49 However, in our
clinical experience, patients with comorbid atopic dermatitis and asthma
often have severe asthma. There is an urgent need for further
understanding about the overall impact of the coexistence of type 2
inflammation-driven diseases on the total symptom burden in the
individual patient. Such an understanding may also help to optimise
patient management.
In this initiative, consensus on how and whether to use
multidisciplinary team conferences to manage patients with coexisting
type 2 inflammation-driven diseases was not reached. Although it was
acknowledged that a holistic approach to identifying type 2
inflammation-driven comorbidities by a single healthcare provider would
be ideal, it was recognised that the increasing specialisation of
medicine would preclude this.
Given the frequent clinical coexistence of type 2 inflammation-driven
diseases such as atopic dermatitis, asthma, chronic rhinitis, CRSwNP and
eosinophilic esophagitis, it was agreed that there is a need for routine
assessment of type 2 inflammation-driven diseases that are not routinely
evaluated within each specialty. To provide an operational approach to
screening patients, a short question guide was proposed for patients to
complete in the waiting room prior to their consultation. The aim of the
question guide is to aid clinicians from different specialties to
recognise comorbidities and enable them to detect, address and refer
appropriately. This may be an important tool to prevent deterioration of
patients’ health and improve their quality of life. Moreover, patient
education may promote further awareness of the importance of addressing
multi-organ disease. Both clinicians and patients need to be aware of
the importance of the coexistence of multi-organ diseases driven by type
2 inflammation. In addition, our initiative highlighted the need for
validated biomarkers of type 2 inflammation that are relevant to atopic
dermatitis.
Atopic dermatitis lesions are primarily Th2 and Th22 skewed, with
variable contributions of the Th1 and Th17 cytokine pathways depending
on the disease subtype, including a particularly high activation of Th17
cytokine pathways in Asian patients compared with other ethnic
populations.50-54 Patients with chronic atopic
dermatitis have a higher proportion of Th1 cells in the skin infiltrate
compared with patients with acute atopic
dermatitis.55,56 It has been shown that patients with
atopic dermatitis have significantly higher rates of autoimmune
comorbidities (including autoimmune diseases of the skin,
gastrointestinal tract and connective tissue) compared with healthy
individuals.57 These associated autoimmune diseases
are likely not driven by type 2 inflammation, but there is a strong
overlap in genetic risk alleles between autoimmune diseases and atopic
dermatitis.58-60
This consensus approach was limited by the relatively low number of
participants, and their geographic concentration (six Nordic countries)
may limit the applicability of our recommendations in less-developed
areas of the world. Additionally, the experts had diverse specialties
and some of them did not necessarily have sufficient clinical experience
with certain type 2 inflammation-driven diseases outside their area of
expertise. The scope of our initiative did not include other type 2
inflammation-driven diseases such as eosinophilic chronic rhinosinusitis
without nasal polyps.61 In addition, the term ‘chronic
rhinitis’ was used in this multidisciplinary modified Delphi consensus
initiative because those who are not experts in otorhinolaryngology are
generally unable to diagnose non-allergic rhinitis subsets or chronic
rhinosinusitis without nasal polyps. However, we recognise that the term
‘chronic rhinitis’ may include some subsets that are not primarily
driven by type 2 inflammation. Finally, although the modified Delphi
process is an accepted methodology, it is based on expert opinion and is
thus open to possible bias, particularly given the relatively low number
of participants.
In conclusion, our initiative achieved a consensus definition of type 2
inflammation; characterised its role as an immunopathological driver of
asthma, atopic dermatitis, chronic rhinitis, CRSwNP and eosinophilic
esophagitis; and reached consensus on the presence of overlap between
these diseases. Further studies to characterise the overlap between the
diseases are warranted. Our conclusions should be used as a framework to
further understand the extent of type 2 inflammation-driven multi-organ
disease and improve the holistic management and care for patients with
type 2 inflammation-driven disease.