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Airway hyperresponsiveness reflects corticosteroid-sensitive mast cell involvement across asthma phenotypes

Hvidtfeldt, Morten ; Sverrild, Asger ; Pulga, Alexis ; Frøssing, Laurits ; Silberbrandt, Alexander ; Hostrup, Morten ; Thomassen, Martin ; Sanden, Caroline LU ; Clausson, Carl Magnus LU and Siddhuraj, Premkumar LU , et al. (2023) In Journal of Allergy and Clinical Immunology 152(1). p.4-116
Abstract

Background: Airway hyperresponsiveness is a hallmark of asthma across asthma phenotypes. Airway hyperresponsiveness to mannitol specifically relates to mast cell infiltration of the airways, suggesting inhaled corticosteroids to be effective in reducing the response to mannitol, despite low levels of type 2 inflammation. Objective: We sought to investigate the relationship between airway hyperresponsiveness and infiltrating mast cells, and the response to inhaled corticosteroid treatment. Methods: In 50 corticosteroid-free patients with airway hyperresponsiveness to mannitol, mucosal cryobiopsies were obtained before and after 6 weeks of daily treatment with 1600 μg of budesonide. Patients were stratified according to baseline... (More)

Background: Airway hyperresponsiveness is a hallmark of asthma across asthma phenotypes. Airway hyperresponsiveness to mannitol specifically relates to mast cell infiltration of the airways, suggesting inhaled corticosteroids to be effective in reducing the response to mannitol, despite low levels of type 2 inflammation. Objective: We sought to investigate the relationship between airway hyperresponsiveness and infiltrating mast cells, and the response to inhaled corticosteroid treatment. Methods: In 50 corticosteroid-free patients with airway hyperresponsiveness to mannitol, mucosal cryobiopsies were obtained before and after 6 weeks of daily treatment with 1600 μg of budesonide. Patients were stratified according to baseline fractional exhaled nitric oxide (FENO) with a cutoff of 25 parts per billion. Results: Airway hyperresponsiveness was comparable at baseline and improved equally with treatment in both patients with FENO-high and FENO-low asthma: doubling dose, 3.98 (95% CI, 2.49-6.38; P < .001) and 3.85 (95% CI, 2.51-5.91; P < .001), respectively. However, phenotypes and distribution of mast cells differed between the 2 groups. In patients with FENO-high asthma, airway hyperresponsiveness correlated with the density of chymase-high mast cells infiltrating the epithelial layer (ρ, −0.42; P = .04), and in those with FENO-low asthma, it correlated with the density in the airway smooth muscle (ρ, −0.51; P = .02). The improvement in airway hyperresponsiveness after inhaled corticosteroid treatment correlated with a reduction in mast cells, as well as in airway thymic stromal lymphopoietin and IL-33. Conclusions: Airway hyperresponsiveness to mannitol is related to mast cell infiltration across asthma phenotypes, correlating with epithelial mast cells in patients with FENO-high asthma and with airway smooth muscle mast cells in patients with FENO-low asthma. Treatment with inhaled corticosteroids was effective in reducing airway hyperresponsiveness in both groups.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
airway hyperresponsiveness, Asthma, inhaled corticosteroids, mast cell
in
Journal of Allergy and Clinical Immunology
volume
152
issue
1
pages
4 - 116
publisher
Elsevier
external identifiers
  • pmid:36907566
  • scopus:85151450512
ISSN
0091-6749
DOI
10.1016/j.jaci.2023.03.001
language
English
LU publication?
yes
id
90c47eb0-faea-4788-9e4d-5e3cfd911031
date added to LUP
2023-05-23 15:25:59
date last changed
2024-05-18 01:41:25
@article{90c47eb0-faea-4788-9e4d-5e3cfd911031,
  abstract     = {{<p>Background: Airway hyperresponsiveness is a hallmark of asthma across asthma phenotypes. Airway hyperresponsiveness to mannitol specifically relates to mast cell infiltration of the airways, suggesting inhaled corticosteroids to be effective in reducing the response to mannitol, despite low levels of type 2 inflammation. Objective: We sought to investigate the relationship between airway hyperresponsiveness and infiltrating mast cells, and the response to inhaled corticosteroid treatment. Methods: In 50 corticosteroid-free patients with airway hyperresponsiveness to mannitol, mucosal cryobiopsies were obtained before and after 6 weeks of daily treatment with 1600 μg of budesonide. Patients were stratified according to baseline fractional exhaled nitric oxide (FENO) with a cutoff of 25 parts per billion. Results: Airway hyperresponsiveness was comparable at baseline and improved equally with treatment in both patients with FENO-high and FENO-low asthma: doubling dose, 3.98 (95% CI, 2.49-6.38; P &lt; .001) and 3.85 (95% CI, 2.51-5.91; P &lt; .001), respectively. However, phenotypes and distribution of mast cells differed between the 2 groups. In patients with FENO-high asthma, airway hyperresponsiveness correlated with the density of chymase-high mast cells infiltrating the epithelial layer (ρ, −0.42; P = .04), and in those with FENO-low asthma, it correlated with the density in the airway smooth muscle (ρ, −0.51; P = .02). The improvement in airway hyperresponsiveness after inhaled corticosteroid treatment correlated with a reduction in mast cells, as well as in airway thymic stromal lymphopoietin and IL-33. Conclusions: Airway hyperresponsiveness to mannitol is related to mast cell infiltration across asthma phenotypes, correlating with epithelial mast cells in patients with FENO-high asthma and with airway smooth muscle mast cells in patients with FENO-low asthma. Treatment with inhaled corticosteroids was effective in reducing airway hyperresponsiveness in both groups.</p>}},
  author       = {{Hvidtfeldt, Morten and Sverrild, Asger and Pulga, Alexis and Frøssing, Laurits and Silberbrandt, Alexander and Hostrup, Morten and Thomassen, Martin and Sanden, Caroline and Clausson, Carl Magnus and Siddhuraj, Premkumar and Bornesund, Daisy and Nieto-Fontarigo, Juan Jose and Uller, Lena and Erjefält, Jonas and Porsbjerg, Celeste}},
  issn         = {{0091-6749}},
  keywords     = {{airway hyperresponsiveness; Asthma; inhaled corticosteroids; mast cell}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{4--116}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Allergy and Clinical Immunology}},
  title        = {{Airway hyperresponsiveness reflects corticosteroid-sensitive mast cell involvement across asthma phenotypes}},
  url          = {{http://dx.doi.org/10.1016/j.jaci.2023.03.001}},
  doi          = {{10.1016/j.jaci.2023.03.001}},
  volume       = {{152}},
  year         = {{2023}},
}