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Eosinophils in the bronchial mucosa in relation to methacholine dose-response curves in atopic asthma

Publication Date
  • Adult
  • Asthma/Immunology/*Pathology/*Physiopathology
  • Biopsy
  • Bronchi/*Pathology/Physiopathology
  • Bronchial Hyperreactivity/Chemically Induced/Physiopathology
  • Bronchoconstrictor Agents/Pharmacology
  • Dose-Response Relationship
  • Drug
  • Eosinophils/Drug Effects/Pathology/*Physiology
  • Female
  • Forced Expiratory Volume
  • Humans
  • Immunohistochemistry
  • Male
  • Methacholine Chloride/*Pharmacology
  • Middle Aged
  • Mucous Membrane/Drug Effects/Pathology/Physiopathology
  • Regression Analysis
  • Research Support
  • Non-U.S. Gov'T
  • Chemistry


abstractAsthma is characterized by both local infiltration of eosinophils in the bronchial mucosa and bronchial hyperreactivity (BHR). A detailed characterization of BHR implies analysis of a histamine or methacholine dose-response curve yielding not only the dose at 20% fall of baseline forced expiratory volume in 1 s (FEV1), but also a plateau (P) representing the maximal narrowing response in terms of percent change in FEV1 and reactivity as the steepest slope at 50% of P (%FEV1/doubling dose). In the baseline condition, the specific airway conductance (sGaw) may be considered closely related to airway lumen diameter. In 20 nonsmoking asthmatic patients, methacholine dose-response curves were obtained, and a sigmoid model fit yielded the BHR indexes. Immunohistochemistry with the monoclonal antibodies (EG1 and EG2) was used to recognize the total number of eosinophils and activated eosinophils, respectively. The number of activated eosinophils was significantly correlated to both P (r = 0.62; P < 0.05) and sGaw (r = -0.52; P < 0.05), whereas weaker and nonsignificant correlations were found for dose at 20% fall of baseline FEV1 and the total number of eosinophils. We conclude that the number of activated eosinophils can be considered a marker of the inflammation-induced decrease of airway lumen diameter as represented by the plateau index and sGaw.text

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