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Airway hyperresponsiveness to inhaled mannitol identifies a cluster of non-eosinophilic asthma patients with high symptom burden

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@article{45a4cd14659649309ed03d77756ddfac,
title = "Airway hyperresponsiveness to inhaled mannitol identifies a cluster of non-eosinophilic asthma patients with high symptom burden",
abstract = "BACKGROUND: Patients with asthma are heterogeneous in clinical presentation and in response to treatment. Despite this, tools to guide treatment are limited and include mainly measures of eosinophilic inflammation and symptoms. Airway hyperresponsiveness (AHR) to mannitol is present in patients across inflammatory phenotypes and improve with inhaled corticosteroids.OBJECTIVE: To investigate whether measuring AHR to mannitol in addition to eosinophilic inflammation and symptoms adds information to the phenotypic characterization of patients with asthma.METHODS: A total of 317 patients with asthma from 6 different cohorts were included in the analysis. All patients had measures of AHR to mannitol, blood eosinophils, and Asthma Control Questionnaire 5 available. A cluster analysis using Ward minimum variance method was performed. The distribution of fraction of exhaled nitric oxide, immunoglobulin E, lung function, induced sputum inflammatory cell count, age of onset, and severity of disease was compared between clusters.RESULTS: Four clusters were identified. Three of the clusters had proportionate levels of AHR, eosinophilic inflammation, and symptoms, but 1 cluster presented with low levels of eosinophilic inflammation and a significant symptom burden. Half of the subjects in this cluster presented with AHR to inhaled mannitol. Lung function, fraction of exhaled nitric oxide, body mass index, and immunoglobulin E were normal.CONCLUSIONS: Information on AHR to mannitol in addition to blood eosinophils and symptoms identifies a subgroup of asthma patients with symptomatic, noneosinophilic disease. Airway hyperresponsiveness to mannitol may provide a treatable trait in a subgroup of patients with noneosinophilic asthma.",
keywords = "Airway hyperresponsiveness, Asthma, Cluster analysis, Eosinophilic inflammation, Inhaled mannitol, Phenotype",
author = "Asger Sverrild and Andreasen, {Anne H} and Westergaard, {Christian G} and {von B{\"u}low}, Anna and Udesen, {Pernille B} and Thomsen, {Simon F} and Allin, {Kristine H} and Vibeke Backer and Celeste Porsbjerg",
note = "Copyright {\textcopyright} 2021. Published by Elsevier Inc.",
year = "2021",
month = nov,
doi = "10.1016/j.jaip.2021.07.021",
language = "English",
volume = "9",
pages = "4029--4036.e2",
journal = "Journal of Allergy and Clinical Immunology: In Practice",
issn = "2213-2198",
publisher = "Elsevier",
number = "11",

}

RIS

TY - JOUR

T1 - Airway hyperresponsiveness to inhaled mannitol identifies a cluster of non-eosinophilic asthma patients with high symptom burden

AU - Sverrild, Asger

AU - Andreasen, Anne H

AU - Westergaard, Christian G

AU - von Bülow, Anna

AU - Udesen, Pernille B

AU - Thomsen, Simon F

AU - Allin, Kristine H

AU - Backer, Vibeke

AU - Porsbjerg, Celeste

N1 - Copyright © 2021. Published by Elsevier Inc.

PY - 2021/11

Y1 - 2021/11

N2 - BACKGROUND: Patients with asthma are heterogeneous in clinical presentation and in response to treatment. Despite this, tools to guide treatment are limited and include mainly measures of eosinophilic inflammation and symptoms. Airway hyperresponsiveness (AHR) to mannitol is present in patients across inflammatory phenotypes and improve with inhaled corticosteroids.OBJECTIVE: To investigate whether measuring AHR to mannitol in addition to eosinophilic inflammation and symptoms adds information to the phenotypic characterization of patients with asthma.METHODS: A total of 317 patients with asthma from 6 different cohorts were included in the analysis. All patients had measures of AHR to mannitol, blood eosinophils, and Asthma Control Questionnaire 5 available. A cluster analysis using Ward minimum variance method was performed. The distribution of fraction of exhaled nitric oxide, immunoglobulin E, lung function, induced sputum inflammatory cell count, age of onset, and severity of disease was compared between clusters.RESULTS: Four clusters were identified. Three of the clusters had proportionate levels of AHR, eosinophilic inflammation, and symptoms, but 1 cluster presented with low levels of eosinophilic inflammation and a significant symptom burden. Half of the subjects in this cluster presented with AHR to inhaled mannitol. Lung function, fraction of exhaled nitric oxide, body mass index, and immunoglobulin E were normal.CONCLUSIONS: Information on AHR to mannitol in addition to blood eosinophils and symptoms identifies a subgroup of asthma patients with symptomatic, noneosinophilic disease. Airway hyperresponsiveness to mannitol may provide a treatable trait in a subgroup of patients with noneosinophilic asthma.

AB - BACKGROUND: Patients with asthma are heterogeneous in clinical presentation and in response to treatment. Despite this, tools to guide treatment are limited and include mainly measures of eosinophilic inflammation and symptoms. Airway hyperresponsiveness (AHR) to mannitol is present in patients across inflammatory phenotypes and improve with inhaled corticosteroids.OBJECTIVE: To investigate whether measuring AHR to mannitol in addition to eosinophilic inflammation and symptoms adds information to the phenotypic characterization of patients with asthma.METHODS: A total of 317 patients with asthma from 6 different cohorts were included in the analysis. All patients had measures of AHR to mannitol, blood eosinophils, and Asthma Control Questionnaire 5 available. A cluster analysis using Ward minimum variance method was performed. The distribution of fraction of exhaled nitric oxide, immunoglobulin E, lung function, induced sputum inflammatory cell count, age of onset, and severity of disease was compared between clusters.RESULTS: Four clusters were identified. Three of the clusters had proportionate levels of AHR, eosinophilic inflammation, and symptoms, but 1 cluster presented with low levels of eosinophilic inflammation and a significant symptom burden. Half of the subjects in this cluster presented with AHR to inhaled mannitol. Lung function, fraction of exhaled nitric oxide, body mass index, and immunoglobulin E were normal.CONCLUSIONS: Information on AHR to mannitol in addition to blood eosinophils and symptoms identifies a subgroup of asthma patients with symptomatic, noneosinophilic disease. Airway hyperresponsiveness to mannitol may provide a treatable trait in a subgroup of patients with noneosinophilic asthma.

KW - Airway hyperresponsiveness

KW - Asthma

KW - Cluster analysis

KW - Eosinophilic inflammation

KW - Inhaled mannitol

KW - Phenotype

UR - http://www.scopus.com/inward/record.url?scp=85114680431&partnerID=8YFLogxK

U2 - 10.1016/j.jaip.2021.07.021

DO - 10.1016/j.jaip.2021.07.021

M3 - Journal article

C2 - 34332175

VL - 9

SP - 4029-4036.e2

JO - Journal of Allergy and Clinical Immunology: In Practice

JF - Journal of Allergy and Clinical Immunology: In Practice

SN - 2213-2198

IS - 11

ER -

ID: 66949961