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severe asthma forum 1: severe asthma - basic and clinical views Figure 3. Mechanisms of non-T2 (T2-low) asthma. PMN, polymorphonuclear cell; Th, T helper cells.
Adapted from Corren, 2019.
asthma and are associated with more severe be inefficacious in these patients but may ex-
disease (targeting CRTH2)5,7,11,13. acerbate the underlying inflammatory state
through increased Th1 recruitment. High
Non-T2 (T2-low) asthma is typified by Th17 is marked by increased levels of IL-
the absence of markers of T2-high disease. 17A, IL-17F, and IL-22 and IL-17F frequent
It is generally characterized by neutrophilic exacerbator endotype has been recently de-
(sputum neutrophils > 40–60%) or pauci- scribed. Additionally, IL-6 has been recent-
granulocytic (i.e., normal sputum levels of ly shown to cause systemic inflammation in a
both eosinophils and neutrophils) inflam- subgroup of asthma patients with obesity and
mation and a lack of response to corticos- severe disease5,7,11,13.
teroid therapy. Mechanisms underlying re-
cruitment and maintenance of neutrophilic Currently, due to the availability of ther-
airway inflammation are yet unknown: the apies targeted toward T2 cytokines, the ap-
role of the neutrophil itself is in debate. It has proach is to divide patients into those with
been linked with the Th1 and/or Th17 cells, T2-high and non-T2 (T2-low) asthma.
cytokines IL-17A, IL-17F, IL-22, IFN-γ, There continue to be critical unanswered
TNF-α, IL-1β, IL-6, IL-8, and NLRP3 in- questions in severe asthma, mainly since our
flammasome. It is also possible that some understanding of the inflammatory microen-
non-T2 endotype are labelled as such only vironment in the lower airway and the con-
because steroid therapy has masked the T2 tributions to the clinical expression of the
signature (Figure 3)5,7,11,13. disease remains incomplete. Recent advanc-
es have provided further insight into molecu-
High Th1 is marked by the produc- lar mechanisms underlying steroid resistance,
tion of IFN-γ. Elevated IFN-γ was associ- tissue remodelling, and disease exacerba-
ated with high airway resistance, increased tions. The accurate translation of discoveries
inflammatory infiltrates, and corticosteroid from these studies will require careful c linical
refractoriness. Corticosteroids may not only
Adapted from Corren, 2019.
asthma and are associated with more severe be inefficacious in these patients but may ex-
disease (targeting CRTH2)5,7,11,13. acerbate the underlying inflammatory state
through increased Th1 recruitment. High
Non-T2 (T2-low) asthma is typified by Th17 is marked by increased levels of IL-
the absence of markers of T2-high disease. 17A, IL-17F, and IL-22 and IL-17F frequent
It is generally characterized by neutrophilic exacerbator endotype has been recently de-
(sputum neutrophils > 40–60%) or pauci- scribed. Additionally, IL-6 has been recent-
granulocytic (i.e., normal sputum levels of ly shown to cause systemic inflammation in a
both eosinophils and neutrophils) inflam- subgroup of asthma patients with obesity and
mation and a lack of response to corticos- severe disease5,7,11,13.
teroid therapy. Mechanisms underlying re-
cruitment and maintenance of neutrophilic Currently, due to the availability of ther-
airway inflammation are yet unknown: the apies targeted toward T2 cytokines, the ap-
role of the neutrophil itself is in debate. It has proach is to divide patients into those with
been linked with the Th1 and/or Th17 cells, T2-high and non-T2 (T2-low) asthma.
cytokines IL-17A, IL-17F, IL-22, IFN-γ, There continue to be critical unanswered
TNF-α, IL-1β, IL-6, IL-8, and NLRP3 in- questions in severe asthma, mainly since our
flammasome. It is also possible that some understanding of the inflammatory microen-
non-T2 endotype are labelled as such only vironment in the lower airway and the con-
because steroid therapy has masked the T2 tributions to the clinical expression of the
signature (Figure 3)5,7,11,13. disease remains incomplete. Recent advanc-
es have provided further insight into molecu-
High Th1 is marked by the produc- lar mechanisms underlying steroid resistance,
tion of IFN-γ. Elevated IFN-γ was associ- tissue remodelling, and disease exacerba-
ated with high airway resistance, increased tions. The accurate translation of discoveries
inflammatory infiltrates, and corticosteroid from these studies will require careful c linical
refractoriness. Corticosteroids may not only
