Page 117 - Škrgat, Sabina, ed. 2022. Severe Asthma - Basic and Clinical Views. Koper: University of Primorska Press. Severe Asthma Forum, 1
P. 117
relation to the types of cellular airway in- patients for targeted type 2 asthma treatment. 117
filtration. Although the stratification of asth- Blood eosinophils due to its high predictive
ma phenotypes by blood eosinophils is rela- value of ≥300/µL is used as an initial bio- eosinophilic and allergic asthma phenotype and therapeutic possibilities
tively easy, it does not allow a deeper/more marker to predict treatment responses target-
detailed identification of clinical phenotypes. ing IL-4, IL-5, and IL-13.15,23
Therefore, cluster analysis is used to identify
groups of patients with asthma who share spe- Consistent with its central role in the de-
cific clinical characteristics, e.g., cluster anal- velopment of allergic asthma, serum value
ysis using clinical characteristics of patients of IgE is a good biomarker of an atopic sta-
such as asthma onset age, lung function value, tus. Serum IgE levels are positively correlated
bronchodilator reversibility and demograph- with the severity of asthma in adults and chil-
ics. The Severe Asthma Research Program dren. Serum total IgE is used to predict re-
(SARP) identified five clinical groups of asth- sponses to anti-IgE therapy, but is not useful
ma in adults, in which four groups showed eo- for monitoring responses.15,24
sinophilia of varying degrees.18
The role of periostin and FENO in tai-
In order to identify severe asthma phe- loring the biologic therapy targeting type 2
notypes, ADEPT study19 was conducted asthma is less clear. Periostin is an extracellu-
and identified four clusters of asthma, which lar matrix protein secreted from IL-4 and IL-
were also present in the UBIOPRED study.20 13-induced airway epithelial cells, but has not
Three of these four asthma clusters were asso- been shown to be a good biomarker in routine
ciated with eosinophilia. use. Changes in FENO after dupilumab ther-
apy (anti IL-13/IL-4) correlate well with im-
In the evolution of knowledge of clinical provement in FEV1.25-27
phenotypes, Saly Wenzel and her co-workers
have made a definition as follows: early-on- Allergic and Eosinophilic Asthma
set allergic, late-onset eosinophilic and exer- Phenotype
cise-induced phenotype, all identified by bio-
markers of Th2 asthma; and three phenotypes The decision to choose biological therapy is
of non-Th2 asthma, obesity- related, neutro- preceded by a process of asthma phenotyping
philic and asthma in smokers. No biomarkers based on the identification of clinical charac-
of non-Th2 asthma have been identified so far teristics and driving mechanisms of inflam-
as a basis for new biologics and markers of a mation. Biomarkers help us in the rational
positive response to that treatment.21,15 This is choice of biological and predict a positive re-
due to the lack of knowledge of the non-T2- sponse of patients to the selected treatment:
High (T2-Low) immune response associat-
ed with the activation of Th1 and/or Th17 1. The “Early-onset allergic asthma” phe-
cells and IL-17, IL-8 cytokines and the mech- notype usually begins before the age of
anisms underlying the recruitment and main- 12. Triggers are allergens and other al-
tenance of neutrophilic inflammation.22 lergic diseases, and/or a positive fam-
ily history is associated too. Specific
Biological Agents Targeting Airway biomarkers are elevated total IgE, spe-
Inflammation in Asthma: cific IgE and cytokines of T2 inflamma-
The Rational Choice tion.9,10,13, 21
Biomarkers can warn of the severity of the dis- 2. In the “Late-onset persistent eosinophil-
ease and predict the response to a particular ic asthma” phenotype, symptoms begin
treatment. Some of the biomarkers, alone or in adulthood, often are associated with
in combination, will be useful in identifying chronic sinusitis and nasal polyposis. Bi-
omarkers of this phenotype are elevat-
ed eosinophils of peripheral blood and
filtration. Although the stratification of asth- Blood eosinophils due to its high predictive
ma phenotypes by blood eosinophils is rela- value of ≥300/µL is used as an initial bio- eosinophilic and allergic asthma phenotype and therapeutic possibilities
tively easy, it does not allow a deeper/more marker to predict treatment responses target-
detailed identification of clinical phenotypes. ing IL-4, IL-5, and IL-13.15,23
Therefore, cluster analysis is used to identify
groups of patients with asthma who share spe- Consistent with its central role in the de-
cific clinical characteristics, e.g., cluster anal- velopment of allergic asthma, serum value
ysis using clinical characteristics of patients of IgE is a good biomarker of an atopic sta-
such as asthma onset age, lung function value, tus. Serum IgE levels are positively correlated
bronchodilator reversibility and demograph- with the severity of asthma in adults and chil-
ics. The Severe Asthma Research Program dren. Serum total IgE is used to predict re-
(SARP) identified five clinical groups of asth- sponses to anti-IgE therapy, but is not useful
ma in adults, in which four groups showed eo- for monitoring responses.15,24
sinophilia of varying degrees.18
The role of periostin and FENO in tai-
In order to identify severe asthma phe- loring the biologic therapy targeting type 2
notypes, ADEPT study19 was conducted asthma is less clear. Periostin is an extracellu-
and identified four clusters of asthma, which lar matrix protein secreted from IL-4 and IL-
were also present in the UBIOPRED study.20 13-induced airway epithelial cells, but has not
Three of these four asthma clusters were asso- been shown to be a good biomarker in routine
ciated with eosinophilia. use. Changes in FENO after dupilumab ther-
apy (anti IL-13/IL-4) correlate well with im-
In the evolution of knowledge of clinical provement in FEV1.25-27
phenotypes, Saly Wenzel and her co-workers
have made a definition as follows: early-on- Allergic and Eosinophilic Asthma
set allergic, late-onset eosinophilic and exer- Phenotype
cise-induced phenotype, all identified by bio-
markers of Th2 asthma; and three phenotypes The decision to choose biological therapy is
of non-Th2 asthma, obesity- related, neutro- preceded by a process of asthma phenotyping
philic and asthma in smokers. No biomarkers based on the identification of clinical charac-
of non-Th2 asthma have been identified so far teristics and driving mechanisms of inflam-
as a basis for new biologics and markers of a mation. Biomarkers help us in the rational
positive response to that treatment.21,15 This is choice of biological and predict a positive re-
due to the lack of knowledge of the non-T2- sponse of patients to the selected treatment:
High (T2-Low) immune response associat-
ed with the activation of Th1 and/or Th17 1. The “Early-onset allergic asthma” phe-
cells and IL-17, IL-8 cytokines and the mech- notype usually begins before the age of
anisms underlying the recruitment and main- 12. Triggers are allergens and other al-
tenance of neutrophilic inflammation.22 lergic diseases, and/or a positive fam-
ily history is associated too. Specific
Biological Agents Targeting Airway biomarkers are elevated total IgE, spe-
Inflammation in Asthma: cific IgE and cytokines of T2 inflamma-
The Rational Choice tion.9,10,13, 21
Biomarkers can warn of the severity of the dis- 2. In the “Late-onset persistent eosinophil-
ease and predict the response to a particular ic asthma” phenotype, symptoms begin
treatment. Some of the biomarkers, alone or in adulthood, often are associated with
in combination, will be useful in identifying chronic sinusitis and nasal polyposis. Bi-
omarkers of this phenotype are elevat-
ed eosinophils of peripheral blood and
