Page 84 - Škrgat, Sabina, ed. 2022. Severe Asthma - Basic and Clinical Views. Koper: University of Primorska Press. Severe Asthma Forum, 1
P. 84
of quiescent state of asthma, involvement of There is no perfect biomarker, and unlike for
upper respiratory airways and/or nasal pol- some other disorders, biomarkers for asth-
severe asthma forum 1: severe asthma - basic and clinical views yps etc. The topic concerning asthma phe- ma are less precise, and still not completely
notypes is very important as personalized, known. Generally, based on these markers,
individually tailored treatment adjusted to asthma can be divided into two groups, T2-
the understanding of underlying phenotype high asthma, and T2-low (or non-T2) asth-
mechanisms yields much better results in ma11,10.
asthma patients4,5.
Continuous improvement of asthma phe-
Asthma phenotype description dates notypes and their identification has led to an
from the mid-20th century, with Rackeman’s individualized, targeted approach in asthma
idea from 1947 about extrinsic and intrinsic therapy, especially in severe cases. Biomarkers
asthma, emphasizing the triggering role of al- are the key to understanding and recognizing
lergens in asthma6. After the enthusiasm for phenotypes, and accordingly the key to thera-
inhaled corticosteroid treatment in asthma in py and treatment assessment.
the’80s of the previous century, and the intro-
duction of LABAs (long acting beta agonists) Type 2 high-inflammation asthma is
in asthma treatment in the ‘90s7, with much characterized by eosinophilic airway inflam-
better achievements in asthma control, the mation, while type 2 low-inflammation asth-
first decade of the new millennium brought a ma includes neutrophilic and paucigranulo-
rise in the asthma heterogeneity awareness8. cytic asthma. A larger proportion of cases of
severe asthma are type 2-high asthma17,18.
However, observable characteristics are
not enough, because of many overlapping A high level of type 2 cytokines is charac-
symptoms of the disease, so the common un- teristic of T2-high asthma, and those areIL-5,
derlying pathophysiological mechanism in IL-4, IL-13, IL-25, IL-33, and thymic stro-
asthma is important. Due to these facts, a new mal lymphopoietin (TSLP). Biomarkers of
term was developed - asthma endotypes9. type 2 inflammation have proven valuable for
endotyping in asthma17,18.
Biomarkers are specific measurable dis-
ease characteristics. These are quantifiable Biomarker: Type 2 Inflammation
factors distinguishing between physiological
and pathological processes and could be used Blood Eosinophils
as a pathway for therapy selection and ther-
apeutic response monitoring10. The mecha- Eosinophils are specialized leukocytes pro-
nisms leading to the disease are complex and it duced in the bone marrow, primarily found in
is still a challenge to choose suitable biomark- tissues and in the respiratory system, airway
ers to adequately stratify patients, which be- mucosa, and airways, which promote inflam-
came especially important with the introduc- mation by releasing an abundance of inflam-
tion of biologicals in asthma treatment11. The matory mediators. These mediators, together
key point is biomarkers for the endotypic (and with those released from T2 cells, cause eosin-
phenotypic) criteria. The right combination ophilic inflammation, bronchoconstriction,
of various biomarkers in different phenotypes and airway remodelling. Blood eosinophil
is under investigation hoping to help research- counts are a potential surrogate biomarker
ers and clinicians in better disease evaluation for eosinophilic inflammation in asthma and
since the individual approach and personal- are relatively easy to obtain. However, their
ized medicine are imperative11,12. Today, de- levels depend on the time of sampling (high-
fining a severe asthma phenotype is a pro- est at midnight, lowest at midday), time since
cess based on a b iomarker-driven approach10. eating, exercise, and therapy (corticosteroids
reduce eosinophilia)13. Although studies of
blood eosinophil count, as predictors of high
upper respiratory airways and/or nasal pol- some other disorders, biomarkers for asth-
severe asthma forum 1: severe asthma - basic and clinical views yps etc. The topic concerning asthma phe- ma are less precise, and still not completely
notypes is very important as personalized, known. Generally, based on these markers,
individually tailored treatment adjusted to asthma can be divided into two groups, T2-
the understanding of underlying phenotype high asthma, and T2-low (or non-T2) asth-
mechanisms yields much better results in ma11,10.
asthma patients4,5.
Continuous improvement of asthma phe-
Asthma phenotype description dates notypes and their identification has led to an
from the mid-20th century, with Rackeman’s individualized, targeted approach in asthma
idea from 1947 about extrinsic and intrinsic therapy, especially in severe cases. Biomarkers
asthma, emphasizing the triggering role of al- are the key to understanding and recognizing
lergens in asthma6. After the enthusiasm for phenotypes, and accordingly the key to thera-
inhaled corticosteroid treatment in asthma in py and treatment assessment.
the’80s of the previous century, and the intro-
duction of LABAs (long acting beta agonists) Type 2 high-inflammation asthma is
in asthma treatment in the ‘90s7, with much characterized by eosinophilic airway inflam-
better achievements in asthma control, the mation, while type 2 low-inflammation asth-
first decade of the new millennium brought a ma includes neutrophilic and paucigranulo-
rise in the asthma heterogeneity awareness8. cytic asthma. A larger proportion of cases of
severe asthma are type 2-high asthma17,18.
However, observable characteristics are
not enough, because of many overlapping A high level of type 2 cytokines is charac-
symptoms of the disease, so the common un- teristic of T2-high asthma, and those areIL-5,
derlying pathophysiological mechanism in IL-4, IL-13, IL-25, IL-33, and thymic stro-
asthma is important. Due to these facts, a new mal lymphopoietin (TSLP). Biomarkers of
term was developed - asthma endotypes9. type 2 inflammation have proven valuable for
endotyping in asthma17,18.
Biomarkers are specific measurable dis-
ease characteristics. These are quantifiable Biomarker: Type 2 Inflammation
factors distinguishing between physiological
and pathological processes and could be used Blood Eosinophils
as a pathway for therapy selection and ther-
apeutic response monitoring10. The mecha- Eosinophils are specialized leukocytes pro-
nisms leading to the disease are complex and it duced in the bone marrow, primarily found in
is still a challenge to choose suitable biomark- tissues and in the respiratory system, airway
ers to adequately stratify patients, which be- mucosa, and airways, which promote inflam-
came especially important with the introduc- mation by releasing an abundance of inflam-
tion of biologicals in asthma treatment11. The matory mediators. These mediators, together
key point is biomarkers for the endotypic (and with those released from T2 cells, cause eosin-
phenotypic) criteria. The right combination ophilic inflammation, bronchoconstriction,
of various biomarkers in different phenotypes and airway remodelling. Blood eosinophil
is under investigation hoping to help research- counts are a potential surrogate biomarker
ers and clinicians in better disease evaluation for eosinophilic inflammation in asthma and
since the individual approach and personal- are relatively easy to obtain. However, their
ized medicine are imperative11,12. Today, de- levels depend on the time of sampling (high-
fining a severe asthma phenotype is a pro- est at midnight, lowest at midday), time since
cess based on a b iomarker-driven approach10. eating, exercise, and therapy (corticosteroids
reduce eosinophilia)13. Although studies of
blood eosinophil count, as predictors of high
