Page 58 - Škrgat, Sabina, ed. 2023. Severe Asthma Forum - Monitoring and Treatable Traits in Severe Asthma. Koper: University of Primorska Press. Severe Asthma Forum, 2
P. 58
Eosinophilic inflammation in the airway nophilic, due to results of severe asthma pa-
mucosa that persists despite the use of high tient cohorts.38
severe asthma forum 2: severe asthma - monitoring and treatable traits in severe asthma doses of inhaled corticosteroids or system-
ic corticosteroids is recognized as a separate Neutrophilic inflammation is also a com-
phenotype, severe asthma. It has been shown mon finding among adults who have persis-
that eosinophilic inflammation despite vigor- tent asthma symptoms despite inhaled corti-
ous antiasthma treatment is associated with costeroid treatment and particularly during
remodelling of the airways, impaired lung asthma exacerbations20. Douwes et al. also
function, and near-fatal asthma attacks15. In found that only around 50% of asthma cas-
es was associated with eosinophilic inflam-
addition to the classic allergen-mediated Th2 mation, and that in most other cases asthma
paradigm, innate immune stimuli such as en- was accompanied by an increase in airway
vironmental factors, air pollution, weath- neutrophils and interleukin 8 (IL-8)21. In-
er changes, and viral infections may be ca- creased neutrophils have been reported in
pable of eliciting Th2 responses associated subjects with severe asthma requiring intuba-
with eosinophilia16. Recruitment of eosino- tion and sudden onset fatal asthma, indicat-
ing a role for neutrophils in the most severe
phils into the airway in allergic asthma is me- forms of asthma22,23. The results of the study
diated by the coordinated action of cytokines by Jatakanon et al. indicate that an increase in
and chemokines including IL-5, IL-13, eo- the number of neutrophils is associated with
taxins, and the adhesion molecules P-selectin a greater degree of severity of symptoms24. Li
and vascular cell adhesion molecule-1. IL-5 is et al. reported that a significant proportion of
a critical cytokine for eosinophil generation asthma and wheezing illness in both adults
in the bone marrow, as well as eosinophil re- and children is associated with neutrophilic
cruitment, activation, and survival17. The ef- airway inflammation and that this pattern is
not limited to individuals with severe symp-
fects of IL-13 include induction of goblet cell toms25. Neutrophils in severe asthma were
metaplasia and increased mucus secretion, in- significantly increased compared with those
creased airway hyperreactivity, and, indirect- with mild asthma and healthy controls but
ly, trafficking of eosinophils to the site of tis- not when compared with those with moderate
sue injury via chemotaxis18. Based on that, asthma26. This raises important and interest-
ing questions regarding the mechanisms and
sputum eosinophil count provides an effective consequences of neutrophilic inflammation,
method to identify patients who will benefit as well as presenting a novel and inviting ther-
from biological therapy. Drugs targeting spe- apeutic target. Neutrophilic inflammation is
cific Th2 cytokines, including monoclonal an- most frequently induced by infection or pol-
tibodies against IL-5 and IL-13, have shown a lutant exposure 27
promising effect in the treatment of refractory
eosinophilic asthma19. Steroid usage in severe The possibility of bacterial infections as
a cause of the neutrophilia was evaluated by
asthma could mask the underlying eosino- examining for intracellular bacteria, which
philic inflammation. There are investigations is a validated technique that correlates with
showing that single sputum measures undere- quantitative microbiology in the detection of
stimate the likelihood of asthma classificati- respiratory tract infections. Interestingly, in-
on as eosinophilic phenotype.37 On some oc- tracellular bacteria levels were higher in asth-
casions, like decreasing corticosteroid therapy ma compared with healthy controls, which
or after antibiotic treatment, it is neccessary may indicate increased exposure of the low-
to repeat the induced sputum after few weeks, er airways to bacteria in asthma. This may
to see if the eosinophils demasking will appe-
ar.Asthma in most patients in reality is eosi-
mucosa that persists despite the use of high tient cohorts.38
severe asthma forum 2: severe asthma - monitoring and treatable traits in severe asthma doses of inhaled corticosteroids or system-
ic corticosteroids is recognized as a separate Neutrophilic inflammation is also a com-
phenotype, severe asthma. It has been shown mon finding among adults who have persis-
that eosinophilic inflammation despite vigor- tent asthma symptoms despite inhaled corti-
ous antiasthma treatment is associated with costeroid treatment and particularly during
remodelling of the airways, impaired lung asthma exacerbations20. Douwes et al. also
function, and near-fatal asthma attacks15. In found that only around 50% of asthma cas-
es was associated with eosinophilic inflam-
addition to the classic allergen-mediated Th2 mation, and that in most other cases asthma
paradigm, innate immune stimuli such as en- was accompanied by an increase in airway
vironmental factors, air pollution, weath- neutrophils and interleukin 8 (IL-8)21. In-
er changes, and viral infections may be ca- creased neutrophils have been reported in
pable of eliciting Th2 responses associated subjects with severe asthma requiring intuba-
with eosinophilia16. Recruitment of eosino- tion and sudden onset fatal asthma, indicat-
ing a role for neutrophils in the most severe
phils into the airway in allergic asthma is me- forms of asthma22,23. The results of the study
diated by the coordinated action of cytokines by Jatakanon et al. indicate that an increase in
and chemokines including IL-5, IL-13, eo- the number of neutrophils is associated with
taxins, and the adhesion molecules P-selectin a greater degree of severity of symptoms24. Li
and vascular cell adhesion molecule-1. IL-5 is et al. reported that a significant proportion of
a critical cytokine for eosinophil generation asthma and wheezing illness in both adults
in the bone marrow, as well as eosinophil re- and children is associated with neutrophilic
cruitment, activation, and survival17. The ef- airway inflammation and that this pattern is
not limited to individuals with severe symp-
fects of IL-13 include induction of goblet cell toms25. Neutrophils in severe asthma were
metaplasia and increased mucus secretion, in- significantly increased compared with those
creased airway hyperreactivity, and, indirect- with mild asthma and healthy controls but
ly, trafficking of eosinophils to the site of tis- not when compared with those with moderate
sue injury via chemotaxis18. Based on that, asthma26. This raises important and interest-
ing questions regarding the mechanisms and
sputum eosinophil count provides an effective consequences of neutrophilic inflammation,
method to identify patients who will benefit as well as presenting a novel and inviting ther-
from biological therapy. Drugs targeting spe- apeutic target. Neutrophilic inflammation is
cific Th2 cytokines, including monoclonal an- most frequently induced by infection or pol-
tibodies against IL-5 and IL-13, have shown a lutant exposure 27
promising effect in the treatment of refractory
eosinophilic asthma19. Steroid usage in severe The possibility of bacterial infections as
a cause of the neutrophilia was evaluated by
asthma could mask the underlying eosino- examining for intracellular bacteria, which
philic inflammation. There are investigations is a validated technique that correlates with
showing that single sputum measures undere- quantitative microbiology in the detection of
stimate the likelihood of asthma classificati- respiratory tract infections. Interestingly, in-
on as eosinophilic phenotype.37 On some oc- tracellular bacteria levels were higher in asth-
casions, like decreasing corticosteroid therapy ma compared with healthy controls, which
or after antibiotic treatment, it is neccessary may indicate increased exposure of the low-
to repeat the induced sputum after few weeks, er airways to bacteria in asthma. This may
to see if the eosinophils demasking will appe-
ar.Asthma in most patients in reality is eosi-
