Biomarkers of Type 2 and Non-type 2 Inflammation in Asthma Axacerbations

Introduction: In adult-onset asthma, two major endotypes have been proposed: T2 with eosinophilia
and non-T2 characterised by neutrophils and interleukin (IL)-17. The objective of the study was to examine the endotype marker profile in patients with severe asthma who were hospitalized for exacerbations,
with a focus on differentiating between viral and non-viral triggers.
Material and methods: Forty-nine patients with asthma, admitted for exacerbations, and 51 healthy
controls (HCs) were recruited. We further categorized the exacerbated asthma patients into two groups:
non-viral infected (n = 38) and viral infected (n = 11) groups. Blood was drawn and a nasopharyngeal
swab taken at the time of admission and eosinophil numbers, eosinophil cationic protein (ECP), immunoglobulin E (IgE), tryptase and viral infection were determined. Additionally, levels of IL-17, IL-33 and
IL-31 were assessed.
Results: The majority of patients had adult onset asthma (age of diagnosis, 42.8 ±16.1) with a duration of 7.7 ±10.8 years, 24.5% being atopic. Patients had higher levels of eosinophils, ECP and
IgE than healthy controls (eosinophils, p = 0.003; ECP and IgE, p = 0.0001). Immunohistochemistry confirmed eosinophils as a source of ECP. Tryptase (p = 0.0001), IL-17 (p = 0.0005), IL-31
(p = 0.0001) and IL-33 (p = 0.0002) were also higher in patients than controls. ECP correlated with tryptase
(r = 0.08, p = 0.62). IL-17 showed the best correlation with other mediators, including ECP (r = 0.35,
p = 0.24), tryptase (r = 0.69, p = 0.0001), IgE (r = 0.50, p = 0.0001), IL-33 (r = 0.95, p = 0.0001) and IL-31
(r = 0.89, p = 0.0001). IgE, IL-17, and IL-31 had a high AUC when differentiating those with severe and
non-severe asthma. The group with exacerbated viral infection showed elevated levels of serum IL-17
and IL-31 compared to the non-infected group.
Conclusions: Patients with asthmatic exacerbations were found to have higher levels of both T2
and non-T2 inflammatory markers than healthy controls. In the study, levels of IgE, IL-17, and IL-31
differentiated between patients with severe and non-severe asthma. The last two cytokines were also able
to distinguish between exacerbated asthma caused by viral infection and exacerbated asthma caused
by non-viral infection.