Airway hyperresponsiveness reflects corticosteroid-sensitive mast cell involvement across asthma phenotypes
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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; Clausson, Carl Magnus; Siddhuraj, Premkumar; Bornesund, Daisy; Nieto-Fontarigo, Juan Jose; Uller, Lena; Erjefält, Jonas; Porsbjerg, Celeste.
In: Journal of Allergy and Clinical Immunology, Vol. 152, No. 1, 2023, p. 107-116.e4.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Airway hyperresponsiveness reflects corticosteroid-sensitive mast cell involvement across asthma phenotypes
AU - Hvidtfeldt, Morten
AU - Sverrild, Asger
AU - Pulga, Alexis
AU - Frøssing, Laurits
AU - Silberbrandt, Alexander
AU - Hostrup, Morten
AU - Thomassen, Martin
AU - Sanden, Caroline
AU - Clausson, Carl Magnus
AU - Siddhuraj, Premkumar
AU - Bornesund, Daisy
AU - Nieto-Fontarigo, Juan Jose
AU - Uller, Lena
AU - Erjefält, Jonas
AU - Porsbjerg, Celeste
N1 - Copyright © 2023. Published by Elsevier Inc.
PY - 2023
Y1 - 2023
N2 - 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 2inflammation.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 mg of budesonide. Patients were stratified according to baseline fractional exhaled nitric oxide (FENO) with a cutoff of 25 partsper 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 cellsdiffered 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 (p, -0.42; P = .04), and in those with FENO-low asthma, it correlated with the density in the airway smooth muscle (p,-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.
AB - 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 2inflammation.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 mg of budesonide. Patients were stratified according to baseline fractional exhaled nitric oxide (FENO) with a cutoff of 25 partsper 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 cellsdiffered 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 (p, -0.42; P = .04), and in those with FENO-low asthma, it correlated with the density in the airway smooth muscle (p,-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.
KW - Faculty of Science
KW - Asthma
KW - Airway hyperresponsiveness
KW - Mast cell
KW - Inhaled corticosteroids
U2 - 10.1016/j.jaci.2023.03.001
DO - 10.1016/j.jaci.2023.03.001
M3 - Journal article
C2 - 36907566
VL - 152
SP - 107-116.e4
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 1
ER -
ID: 338787666