Hans Jürgen Hoffmann

Airway responsiveness to mannitol in asthma is associated with chymase-positive mast cells and eosinophilic airway inflammation

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Asger Sverrild
  • ,
  • Anders Bergqvist
  • ,
  • Katherine J Baines, Denmark
  • Celeste Porsbjerg
  • ,
  • Cecilia K Andersson, Denmark
  • Simon Francis Thomsen
  • ,
  • Hans Jürgen Hoffmann
  • Peter Gibson
  • ,
  • Jonas S Erjefält
  • ,
  • Vibeke Backer

BACKGROUND: Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol.

METHODS: AHR to inhaled mannitol was measured in 23 non-smoking, corticosteroid-free asthmatic individuals and 10 healthy controls. Mast cells and eosinophils were identified in mucosal biopsies from all participants. Mast cells were divided into phenotypes based on the presence of chymase. mRNA expression of mast cell associated genes was measured by real-time PCR.

RESULTS: The proportion of submucosal MCTC was higher in asthmatic individuals with AHR to mannitol compared with asthmatic individuals without AHR (median: 40.3% vs. 18.7%, p=0.03). Increased submucosal MCTC numbers were associated with increased levels of mRNA for TSLP and CPA3 in asthmatics. Reactivity to mannitol correlated significantly with eosinophils in submucosa (r(s): 0.56, p=0.01).

CONCLUSION: AHR to inhaled mannitol is associated with an altered submucosal mast cell profile in asthmatic individuals. This mast cell profile is associated with increased levels of TSLP and CPA3. The degree of AHR to mannitol is correlated with the degree of eosinophilic inflammation in the airway submucosa.

CAPSULE SUMMARY: Airway hyperresponsiveness to mannitol and methacholine is associated with an increased proportion of chymase-positive mast cells in airway submucosa, which in turn correlated to the expression level of TSLP and CPA3. Finally, airway hyperresponsiveness to mannitol, but not methacholine, is related to submucosal eosinophilic inflammation. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalClinical and Experimental Allergy
Pages (from-to)288–297
Publication statusPublished - Feb 2016

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