Page 85 - Škrgat, Sabina, ed. 2022. Severe Asthma - Basic and Clinical Views. Koper: University of Primorska Press. Severe Asthma Forum, 1
P. 85
tum eosinophils in eosinophilic asthma, mechanism and role of periostin in the patho- 85
have yielded somewhat mixed results, blood physiology of asthma are still unclear. Mouse
eosinophil counts have been useful in the se- models suggest that periostin plays a role in biomarkers in severe asthma
lection of patients for eosinophil-targeting mucus production, eosinophil recruitment,
agents. The exact cut-off value is still debat- and subepithelial fibrosis.
able, but the cut-off used in the clinical tri-
als to define high blood eosinophil counts has In a recent study conducted by Taka-
ranged between 150 and 300 cells/μL. Some hashi et al., it was presented that serum per-
studies showed that patients with eosinophil iostin levels were good predictors of blood eo-
counts above 300 cells/_L have more frequent sinophilia (r = 0.36), which could mean that
exacerbations and acute respiratory events13. periostin levels serve as a biomarker of eosino-
philic airway inflammation21,22.
Markers of Eosinophil Activation
50 ng/L is considered the cut-off in most
The predominant mediators in the eosinophil studies while values above 50 ng/L are con-
granules are cytotoxic cationic proteins, such sidered high periostin levels. The limitation
as eosinophil cationic protein (ECP), and eo- of periostin is that it is also secreted by oste-
sinophil-derived neurotoxin (EDN), major oblasts and the levels can be elevated in some
basic protein (MBP), and reactive oxygen spe- tumours (brain tumours, bony metastasis),
cies (ROS). Some of these mediators can be and growing children23.
measured in blood and used as a guide in bet-
ter asthma clustering, but also as a potential Dipeptidyl Peptidase-4 - DPP4
treatment target. High ECP levels are detect-
ed in the blood and sputum of severe asthma Dipeptidyl peptidase-4 (DPP-4) is expressed
patients (mostly atopic), compared to those in a variety of lung epithelial and endotheli-
with non-severe asthma. ECP is associat- al cells and submucosal glands, however, the
ed with bronchospasm and airway resistance role in the pathophysiology of asthma is un-
and is elevated in asthma exacerbation, and certain. DPP-4 can be found in bronchoalve-
its levels are reduced after therapy induction. olar lavage (BAL) and correlates with airway
It is assumed that ECP can be used as a mark- inflammation in rat models. Studies relat-
er for corticosteroid induction and dosage, but ed to DPP-4 are limited; IL-13 is thought to
this needs to be confirmed. EDN is another stimulate DPP-4 production, and, like peri-
marker of eosinophilic disease and persistent ostin, DPP-4 can be measured in serum and
airflow limitation in severe asthma patients; it can be used as a guide to induce anti-IL-13
can be measured in serum, urine, and other therapy18,24.
body fluids14-16.
Immunoglobulin E
Periostin
An utterly important predominant biomark-
Periostin is an extracellular matrix protein se- er in patients with asthma is allergen specific
creted by bronchial epithelial cells and lung fi- IgE. IgE is a product of B lymphocytes in re-
broblasts in response to Th2 cytokines, IL-13, action to a foreign antigen25. Serum IgE levels
and IL-4. have been shown to correlate with the severi-
ty of asthma. In the case of severe asthma ex-
In addition to its role in cell prolifera- acerbations, total IgE levels rise, after which
tion, invasion and angiogenesis, periostin also they fall, and stable levels are reached within
plays a significant role in the development of 1-1.5 months after the onset of severe exacer-
inflammatory processes, as well as the devel- bations26. Different specific immunoglobulin
opment of the T2 phenotype19,20. The exact E and their interactions may be an impor-
tant causal mechanism in the development
have yielded somewhat mixed results, blood physiology of asthma are still unclear. Mouse
eosinophil counts have been useful in the se- models suggest that periostin plays a role in biomarkers in severe asthma
lection of patients for eosinophil-targeting mucus production, eosinophil recruitment,
agents. The exact cut-off value is still debat- and subepithelial fibrosis.
able, but the cut-off used in the clinical tri-
als to define high blood eosinophil counts has In a recent study conducted by Taka-
ranged between 150 and 300 cells/μL. Some hashi et al., it was presented that serum per-
studies showed that patients with eosinophil iostin levels were good predictors of blood eo-
counts above 300 cells/_L have more frequent sinophilia (r = 0.36), which could mean that
exacerbations and acute respiratory events13. periostin levels serve as a biomarker of eosino-
philic airway inflammation21,22.
Markers of Eosinophil Activation
50 ng/L is considered the cut-off in most
The predominant mediators in the eosinophil studies while values above 50 ng/L are con-
granules are cytotoxic cationic proteins, such sidered high periostin levels. The limitation
as eosinophil cationic protein (ECP), and eo- of periostin is that it is also secreted by oste-
sinophil-derived neurotoxin (EDN), major oblasts and the levels can be elevated in some
basic protein (MBP), and reactive oxygen spe- tumours (brain tumours, bony metastasis),
cies (ROS). Some of these mediators can be and growing children23.
measured in blood and used as a guide in bet-
ter asthma clustering, but also as a potential Dipeptidyl Peptidase-4 - DPP4
treatment target. High ECP levels are detect-
ed in the blood and sputum of severe asthma Dipeptidyl peptidase-4 (DPP-4) is expressed
patients (mostly atopic), compared to those in a variety of lung epithelial and endotheli-
with non-severe asthma. ECP is associat- al cells and submucosal glands, however, the
ed with bronchospasm and airway resistance role in the pathophysiology of asthma is un-
and is elevated in asthma exacerbation, and certain. DPP-4 can be found in bronchoalve-
its levels are reduced after therapy induction. olar lavage (BAL) and correlates with airway
It is assumed that ECP can be used as a mark- inflammation in rat models. Studies relat-
er for corticosteroid induction and dosage, but ed to DPP-4 are limited; IL-13 is thought to
this needs to be confirmed. EDN is another stimulate DPP-4 production, and, like peri-
marker of eosinophilic disease and persistent ostin, DPP-4 can be measured in serum and
airflow limitation in severe asthma patients; it can be used as a guide to induce anti-IL-13
can be measured in serum, urine, and other therapy18,24.
body fluids14-16.
Immunoglobulin E
Periostin
An utterly important predominant biomark-
Periostin is an extracellular matrix protein se- er in patients with asthma is allergen specific
creted by bronchial epithelial cells and lung fi- IgE. IgE is a product of B lymphocytes in re-
broblasts in response to Th2 cytokines, IL-13, action to a foreign antigen25. Serum IgE levels
and IL-4. have been shown to correlate with the severi-
ty of asthma. In the case of severe asthma ex-
In addition to its role in cell prolifera- acerbations, total IgE levels rise, after which
tion, invasion and angiogenesis, periostin also they fall, and stable levels are reached within
plays a significant role in the development of 1-1.5 months after the onset of severe exacer-
inflammatory processes, as well as the devel- bations26. Different specific immunoglobulin
opment of the T2 phenotype19,20. The exact E and their interactions may be an impor-
tant causal mechanism in the development
