Page 116 - Škrgat, Sabina, ed. 2022. Severe Asthma - Basic and Clinical Views. Koper: University of Primorska Press. Severe Asthma Forum, 1
P. 116
Evolving Concepts of Severe Asthma: mechanisms in asthma has advanced, which
Personalized Asthma Management has further contributed to the differentiation
severe asthma forum 1: severe asthma - basic and clinical views of certain phenotypes and endotypes of asth-
Asthma is a complex respiratory disorder ma.13 Two separate pathophysiological path-
characterized by pronounced heterogenei- ways cause eosinophilic inflammation in asth-
ty in disease triggers and individual respons- ma:
es to therapy. It is a heterogeneous disease
with different phenotypic characteristics that 1. In allergic asthma, dendritic cells af-
arise from the complex interrelationship of ter a contact with the allergen as well as
genotypic characteristics and environmen- alarmins IL-25, IL-33 and thymic stro-
tal factors. Therefore, a standard therapeutic mal lymphopoietin (TSLP) from ex-
approach is not as effective as unique patho- posed epithelial cells of the airway mu-
physiological mechanisms underlying a par- cosa, present antigen to Th0-naive CD4
ticular disease subtype which alter the re- + lymphocytes and induce their trans-
sponse to conventional therapy.8-10 formation into activated Th2 cells,
which produce IL-4, IL-5 and IL -13. In
Severe asthma is defined as an asthma this process, B lymphocytes were also ac-
that requires treatment of level 4 or 5 according tivated to produce IgE antibodies, air-
to GINA guidelines (high doses of ICS/LABA way eosinophilia, and hypersecretion of
and/or tiotropium, leukotrienes or theophyl- mucus.13-15
line) in the previous year or treatment with
systemic corticosteroids (CS) 50% of the pre- 2. In nonallergic eosinophilic asthma, air
vious year to prevent the development of “un- pollution, microbes, and glycolipids in-
controlled” disease or it remains uncontrolled duce the release of cytokines from epi-
despite this therapy. The next therapeutic step thelial cells, including alarmins IL-25,
is to consider the indication for biological ther- IL-33 and TSLP, which activate naive
apy, while oral corticosteroids according to the lymphoid cells (ILC2) in an antigen-in-
latest GINA guidelines revision are a backup dependent manner. Activated ILC2 cells
therapeutic option to consider.3,9 produce high amounts of IL-5 and IL-13
causing eosinophilia, mucosal hyperse-
Treating asthma with biological agents cretion and airway hyperreactivity. The
is the first step towards personalized thera- importance of Th2 lymphocytes in this
py. Such approach is made possible by an in- process was highlighted through the cy-
crease in the understanding of the pathophys- tokines IL-4, IL-5 and IL-13 involved in
iological pathways in asthma and paved the eosinophilic inflammation and IgE pro-
way for new asthma treatments based mainly duction, in an asthma phenotype called
on T2-high pathway cytokines and associated T2-asthma (T2-high asthma).15-17
certain phenotypes of severe asthma. There-
fore, with the help of better identification of Th17 cells with cytokines IL-17, IL-8
asthma phenotypes, we can select an effective and growth factor participate in neutrophilic
targeted therapy (biological) that will allow inflammation in non-T2 asthma (T2-low
us to achieve disease control in patients with asthma).14
severe asthma, in whom standard therapy has
not been effective.10-13 Implications of T2-High and T2-Low
Pathway on Asthma Phenotypes
Two Different Pathways Lead
to Eosinophilic Airway Inflammation Several strategies have been proposed for the
in Asthma identification of severe asthma phenotypes,
based on different clinical characteristics or
In the same time as the recognition of pheno-
types of severe asthma, new knowledge about
the pathophysiological and inflammatory
Personalized Asthma Management has further contributed to the differentiation
severe asthma forum 1: severe asthma - basic and clinical views of certain phenotypes and endotypes of asth-
Asthma is a complex respiratory disorder ma.13 Two separate pathophysiological path-
characterized by pronounced heterogenei- ways cause eosinophilic inflammation in asth-
ty in disease triggers and individual respons- ma:
es to therapy. It is a heterogeneous disease
with different phenotypic characteristics that 1. In allergic asthma, dendritic cells af-
arise from the complex interrelationship of ter a contact with the allergen as well as
genotypic characteristics and environmen- alarmins IL-25, IL-33 and thymic stro-
tal factors. Therefore, a standard therapeutic mal lymphopoietin (TSLP) from ex-
approach is not as effective as unique patho- posed epithelial cells of the airway mu-
physiological mechanisms underlying a par- cosa, present antigen to Th0-naive CD4
ticular disease subtype which alter the re- + lymphocytes and induce their trans-
sponse to conventional therapy.8-10 formation into activated Th2 cells,
which produce IL-4, IL-5 and IL -13. In
Severe asthma is defined as an asthma this process, B lymphocytes were also ac-
that requires treatment of level 4 or 5 according tivated to produce IgE antibodies, air-
to GINA guidelines (high doses of ICS/LABA way eosinophilia, and hypersecretion of
and/or tiotropium, leukotrienes or theophyl- mucus.13-15
line) in the previous year or treatment with
systemic corticosteroids (CS) 50% of the pre- 2. In nonallergic eosinophilic asthma, air
vious year to prevent the development of “un- pollution, microbes, and glycolipids in-
controlled” disease or it remains uncontrolled duce the release of cytokines from epi-
despite this therapy. The next therapeutic step thelial cells, including alarmins IL-25,
is to consider the indication for biological ther- IL-33 and TSLP, which activate naive
apy, while oral corticosteroids according to the lymphoid cells (ILC2) in an antigen-in-
latest GINA guidelines revision are a backup dependent manner. Activated ILC2 cells
therapeutic option to consider.3,9 produce high amounts of IL-5 and IL-13
causing eosinophilia, mucosal hyperse-
Treating asthma with biological agents cretion and airway hyperreactivity. The
is the first step towards personalized thera- importance of Th2 lymphocytes in this
py. Such approach is made possible by an in- process was highlighted through the cy-
crease in the understanding of the pathophys- tokines IL-4, IL-5 and IL-13 involved in
iological pathways in asthma and paved the eosinophilic inflammation and IgE pro-
way for new asthma treatments based mainly duction, in an asthma phenotype called
on T2-high pathway cytokines and associated T2-asthma (T2-high asthma).15-17
certain phenotypes of severe asthma. There-
fore, with the help of better identification of Th17 cells with cytokines IL-17, IL-8
asthma phenotypes, we can select an effective and growth factor participate in neutrophilic
targeted therapy (biological) that will allow inflammation in non-T2 asthma (T2-low
us to achieve disease control in patients with asthma).14
severe asthma, in whom standard therapy has
not been effective.10-13 Implications of T2-High and T2-Low
Pathway on Asthma Phenotypes
Two Different Pathways Lead
to Eosinophilic Airway Inflammation Several strategies have been proposed for the
in Asthma identification of severe asthma phenotypes,
based on different clinical characteristics or
In the same time as the recognition of pheno-
types of severe asthma, new knowledge about
the pathophysiological and inflammatory
