Page 109 - Škrgat, Sabina, ed. 2022. Severe Asthma - Basic and Clinical Views. Koper: University of Primorska Press. Severe Asthma Forum, 1
P. 109
us clearance. Inhalation therapies should Theophylline in vitro promotes apoptosis 109
be prefferentialy administered via humidi- of neutrophils, inhibits neutrophils from gen-
fied inhalation or aerosol inhalation in order erating reactive oxygen species and causes a t2-low asthma
to moisturize the airway, dilute sputum and decline in neutrophil chemotaxis29.
facilitate expectoration21.
Roflumilast, a phosphodiesterase‐4 in-
Pharmacological Treatment hibitor, can cause the reduction of neutrophil
counts and TNF‐α levels and can improve
ICS could be discontinued or reduced in two FEV1 in mild to moderate asthmatics when
thirds of non-eosinophilic asthma patients added to ICS30.
with no worsening of asthma control or ex-
acerbation. Sometimes that reduction can re- Antifungal treatment should be consid-
veal an eosinophilic inflammation and lead to ered in the patients with the persistent pres-
the change in patient classification and treat- ence of Aspergillus in the respiratory tract31,32.
ment22.
Immunoglobulin replacement therapy:
Tezepelumab is an anti-TSLP monoclo- Patients with severe asthma and recurrent res-
nal antibody that binds human TSLP, pre- piratory infections should be screened and (if
vents interaction with its receptor and, con- appropriate) treated for immunoglobulin de-
sequently, inhibits multiple downstream ficiency since that can improve asthma out-
inflammatory pathways. Blocking of this comes33.
pathways can improwe the severe asthma
control in both T2 and non-T2 asthma23. A proposal of algorithm to T2 low asth-
ma approach is shown in the Figure 1.
Long acting bronchodilators (LAMA
and LABA) can be effective in increasing the Investigational Products
time to first exacerbation and improving lung
function and symptoms24. Because of an unmet need for new therapeu-
tic agents in T2-low asthma, there are plenty
Antibiotic treatment can be effective in of investigational products in development for
patients with recurrent infective exacerba- that indication3,34.
tions. Molecular microbiology and mycolo-
gy with extended cultures, including 16s deep CXCR2 antagonists in preliminary stud-
sequencing, may be considered to direct the ies showed significantly reduced sputum and
treatment. blood neutrophilia in patients with severe
neutrophilic asthma and decreased number
Immunoglobulin replacement may im- of mild exacerbations.
prove asthma control in patients with infec-
tive exacerbations and immunoglobulin defi- Etanercept blocks TNF and in a small
ciency25. study demonstrated improvement in AHR,
FEV1, and symptoms. Other investigated
Azithromycin in long-term non-antibi- anti‐TNF‐α compounds showed unacceptable
otic doses of (250 mg daily three times per toxicity, mainly increased risk of infections.
week) can result in decrease of severe asthma
exacerbations frequency, improvement of the Antibody against IL‐17 receptor did not
quality of life and reduced frequency of res- result in any statistically significant benefit
piratory infections with no significant adverse uptill now.
events26.
Anakinra (IL‐1 receptor antagonist) in
Selective antagonists of cysteinyl leukot- healthy volunteers significantly reduced spu-
rienes receptors in vitro can inhibit superox- tum neutrophilia and caused the rise of spu-
ide generation, production of LTB4 and re- tum IL‐1β, IL‐6, and IL‐8 levels.
lease of elastase by activated neutrophils27,28.
Anti‐IL6 blocking might be a poten-
tial therapeutic target in T2-low asthma, but
be prefferentialy administered via humidi- of neutrophils, inhibits neutrophils from gen-
fied inhalation or aerosol inhalation in order erating reactive oxygen species and causes a t2-low asthma
to moisturize the airway, dilute sputum and decline in neutrophil chemotaxis29.
facilitate expectoration21.
Roflumilast, a phosphodiesterase‐4 in-
Pharmacological Treatment hibitor, can cause the reduction of neutrophil
counts and TNF‐α levels and can improve
ICS could be discontinued or reduced in two FEV1 in mild to moderate asthmatics when
thirds of non-eosinophilic asthma patients added to ICS30.
with no worsening of asthma control or ex-
acerbation. Sometimes that reduction can re- Antifungal treatment should be consid-
veal an eosinophilic inflammation and lead to ered in the patients with the persistent pres-
the change in patient classification and treat- ence of Aspergillus in the respiratory tract31,32.
ment22.
Immunoglobulin replacement therapy:
Tezepelumab is an anti-TSLP monoclo- Patients with severe asthma and recurrent res-
nal antibody that binds human TSLP, pre- piratory infections should be screened and (if
vents interaction with its receptor and, con- appropriate) treated for immunoglobulin de-
sequently, inhibits multiple downstream ficiency since that can improve asthma out-
inflammatory pathways. Blocking of this comes33.
pathways can improwe the severe asthma
control in both T2 and non-T2 asthma23. A proposal of algorithm to T2 low asth-
ma approach is shown in the Figure 1.
Long acting bronchodilators (LAMA
and LABA) can be effective in increasing the Investigational Products
time to first exacerbation and improving lung
function and symptoms24. Because of an unmet need for new therapeu-
tic agents in T2-low asthma, there are plenty
Antibiotic treatment can be effective in of investigational products in development for
patients with recurrent infective exacerba- that indication3,34.
tions. Molecular microbiology and mycolo-
gy with extended cultures, including 16s deep CXCR2 antagonists in preliminary stud-
sequencing, may be considered to direct the ies showed significantly reduced sputum and
treatment. blood neutrophilia in patients with severe
neutrophilic asthma and decreased number
Immunoglobulin replacement may im- of mild exacerbations.
prove asthma control in patients with infec-
tive exacerbations and immunoglobulin defi- Etanercept blocks TNF and in a small
ciency25. study demonstrated improvement in AHR,
FEV1, and symptoms. Other investigated
Azithromycin in long-term non-antibi- anti‐TNF‐α compounds showed unacceptable
otic doses of (250 mg daily three times per toxicity, mainly increased risk of infections.
week) can result in decrease of severe asthma
exacerbations frequency, improvement of the Antibody against IL‐17 receptor did not
quality of life and reduced frequency of res- result in any statistically significant benefit
piratory infections with no significant adverse uptill now.
events26.
Anakinra (IL‐1 receptor antagonist) in
Selective antagonists of cysteinyl leukot- healthy volunteers significantly reduced spu-
rienes receptors in vitro can inhibit superox- tum neutrophilia and caused the rise of spu-
ide generation, production of LTB4 and re- tum IL‐1β, IL‐6, and IL‐8 levels.
lease of elastase by activated neutrophils27,28.
Anti‐IL6 blocking might be a poten-
tial therapeutic target in T2-low asthma, but
