Page 106 - Škrgat, Sabina, ed. 2022. Severe Asthma - Basic and Clinical Views. Koper: University of Primorska Press. Severe Asthma Forum, 1
P. 106
with smoking, air pollution, obesity, very late h ost-environment interactions and mech-
onset (>50 or > 65 years of age), exercise and anisms of disease (RNA Transcriptomics -
severe asthma forum 1: severe asthma - basic and clinical views cold induced asthma, infective asthma exac- study of gene expression and metabolom-
erbations and bronchiectasis1,4. ics - measurement of mediators or metabolic
products). Minimally invasive analytic tools
Pathophysiology have been reported for asthma, using blood,
sputum, or bronchial brushings1. The omics
Non-type 2 inflammation (T2-low) mediat- approach has been helpful in understanding
ed asthma is difficult to define due to lack of the molecular mechanisms of T2-low asthma.
signature biomarkers. It exists in the absence The potential chemosensory and remodeling
of T2-high or eosinophilic inflammation and signatures recently described in asthmatic
includes neutrophilic and paucigranulocytic airways may point to new endotypes relevant
subtypes. Several cell types and cytokines, in- in T2-low patients7-9.
cluding Th1, Th17, IL-6, and IL-17, contrib-
ute to mechanisms of non-T2 asthma5. Beside the inflammation, some structur-
al abnormalities of the airway smooth mus-
In response to industrial pollutants, in- cles and heightened neuronal dysfunction can
fectious agents, tobacco smoke, and other lead to the increased cough reflex sensitivity
nonspecific stimuli, injured airway epithelial connected with the poor asthma control10.
cells release a multitude of factors that initi-
ate innate and adaptive immunity with sub- There is a negative correlation between
sequent release of toll‐like receptors (TLRs). airway cytotoxic T cells (CD8+) and body
TLR2 and TLR4 are innate immune recep- mass index in severe asthma patients. Des-
tors that are inducing the shift toward Th1 reased expression of CD8+ cytotoxic T cell
and Th17 response so the dominant T cells in network in individuals with T2-low asthma11
T2-low asthma are Th1 and Th17 that gen- is strongly related to obesity and systemic in-
erate pro‐inflammatory cytokines as IL‐8, flammation. A primary function of CD8+ T
IFN‐γ, IL‐6, IL‐17A/F, TNF‐α and IL‐1ß. T cells is host defense against viral infection and
helper 17 (Th17) cell-derived cytokines and an impaired immune response to viral infec-
immune factors mediate neutrophilic influx tions could be a mechanism of exacerbations
to the airways. Th17-secreted interleukin-17A in T2-low asthma.
(IL-17A) is an independent risk factor for se-
vere asthma that impacts airway smooth mus- Airway mucus hypersecretion is asso-
cle (ASM) remodeling. Transforming growth ciated with greater asthma severity, reduced
factor-β1 (TGF-β1) correlates with enhanced lung function, increased number of exacerba-
Th17 activity and is essential to Th17 differ- tion and is a predictor of a poorer response to
entiation and IL-17A production. Vice versa, anti-inflammatory treatment with glucocor-
IL-17A enhance activation of TGF-β1 sign- ticoids. Mutations or polymorphisms in the
aling pathways augmenting the immune re- cystic fibrosis transmembrane conductance
sponse6. regulator (CFTR) gene were detected in hy-
persecreting patients with neutrophilic asth-
The application of cluster analysis in ma, bronchiectasis, pansinusitis and recurrent
asthma has gained increasing attention respiratory infections12.
as a departure from traditional hypothe-
sis-based approaches to phenotyping asthma. Depending on the cellularity, T2-low
This analysis is accomplished through “om- asthma can be further classified into neutro-
ics” methods, which refers to a large data- philic and paucigranulocytic but there are no
set derived from a single sample to gain in- strict borders between those groups.
sight into previously unrecognized molecular
onset (>50 or > 65 years of age), exercise and anisms of disease (RNA Transcriptomics -
severe asthma forum 1: severe asthma - basic and clinical views cold induced asthma, infective asthma exac- study of gene expression and metabolom-
erbations and bronchiectasis1,4. ics - measurement of mediators or metabolic
products). Minimally invasive analytic tools
Pathophysiology have been reported for asthma, using blood,
sputum, or bronchial brushings1. The omics
Non-type 2 inflammation (T2-low) mediat- approach has been helpful in understanding
ed asthma is difficult to define due to lack of the molecular mechanisms of T2-low asthma.
signature biomarkers. It exists in the absence The potential chemosensory and remodeling
of T2-high or eosinophilic inflammation and signatures recently described in asthmatic
includes neutrophilic and paucigranulocytic airways may point to new endotypes relevant
subtypes. Several cell types and cytokines, in- in T2-low patients7-9.
cluding Th1, Th17, IL-6, and IL-17, contrib-
ute to mechanisms of non-T2 asthma5. Beside the inflammation, some structur-
al abnormalities of the airway smooth mus-
In response to industrial pollutants, in- cles and heightened neuronal dysfunction can
fectious agents, tobacco smoke, and other lead to the increased cough reflex sensitivity
nonspecific stimuli, injured airway epithelial connected with the poor asthma control10.
cells release a multitude of factors that initi-
ate innate and adaptive immunity with sub- There is a negative correlation between
sequent release of toll‐like receptors (TLRs). airway cytotoxic T cells (CD8+) and body
TLR2 and TLR4 are innate immune recep- mass index in severe asthma patients. Des-
tors that are inducing the shift toward Th1 reased expression of CD8+ cytotoxic T cell
and Th17 response so the dominant T cells in network in individuals with T2-low asthma11
T2-low asthma are Th1 and Th17 that gen- is strongly related to obesity and systemic in-
erate pro‐inflammatory cytokines as IL‐8, flammation. A primary function of CD8+ T
IFN‐γ, IL‐6, IL‐17A/F, TNF‐α and IL‐1ß. T cells is host defense against viral infection and
helper 17 (Th17) cell-derived cytokines and an impaired immune response to viral infec-
immune factors mediate neutrophilic influx tions could be a mechanism of exacerbations
to the airways. Th17-secreted interleukin-17A in T2-low asthma.
(IL-17A) is an independent risk factor for se-
vere asthma that impacts airway smooth mus- Airway mucus hypersecretion is asso-
cle (ASM) remodeling. Transforming growth ciated with greater asthma severity, reduced
factor-β1 (TGF-β1) correlates with enhanced lung function, increased number of exacerba-
Th17 activity and is essential to Th17 differ- tion and is a predictor of a poorer response to
entiation and IL-17A production. Vice versa, anti-inflammatory treatment with glucocor-
IL-17A enhance activation of TGF-β1 sign- ticoids. Mutations or polymorphisms in the
aling pathways augmenting the immune re- cystic fibrosis transmembrane conductance
sponse6. regulator (CFTR) gene were detected in hy-
persecreting patients with neutrophilic asth-
The application of cluster analysis in ma, bronchiectasis, pansinusitis and recurrent
asthma has gained increasing attention respiratory infections12.
as a departure from traditional hypothe-
sis-based approaches to phenotyping asthma. Depending on the cellularity, T2-low
This analysis is accomplished through “om- asthma can be further classified into neutro-
ics” methods, which refers to a large data- philic and paucigranulocytic but there are no
set derived from a single sample to gain in- strict borders between those groups.
sight into previously unrecognized molecular
