Asthma diagnosis and treatment
Airway inflammation assessed by invasive and noninvasive means in severe asthma: Eosinophilic and noneosinophilic phenotypes

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Background

Airway inflammation assessed by bronchial biopsies demonstrates distinct eosinophilic and noneosinophilic phenotypes in severe asthma, but their relationship to other biomarkers of disease (induced sputum and nitric oxide [NO]) is not clear.

Objectives

We sought to compare airway inflammation using noninvasive (induced sputum, exhaled NO), and invasive (bronchial biopsies) methods in moderate and severe asthma and to assess whether induced sputum and exhaled NO would allow the identification of eosinophilic and noneosinophilic phenotypes in severe asthma.

Methods

We performed a cross-sectional study of 32 subjects with severe asthma and 35 subjects with moderate asthma, from whom we obtained bronchial biopsies, induced sputum, and exhaled NO measurements.

Results

Among subjects with severe asthma, we identified eosinophilic and noneosinophilic phenotypes using both bronchial biopsies and sputum cell counts. However, the vast majority of subjects with high sputum eosinophil counts did not have high mucosal eosinophil counts. Exhaled NO was increased in the eosinophilic phenotype as judged from bronchial biopsy findings, but not on the basis of induced sputum. Subjects with high sputum eosinophil counts experienced more asthma exacerbations than the subjects with low sputum eosinophil counts. In contrast, we did not find any differences in the clinical characteristics between eosinophilic and noneosinophilic phenotypes that were identified by bronchial biopsies.

Conclusion

The use of sputum cell counts allowed the identification of a subgroup of subjects with severe asthma who were at risk of more frequent asthma exacerbations.

Clinical implications

Monitoring sputum eosinophil counts in subjects with severe asthma may allow identifying the subjects with the greatest disease activity.

Section snippets

Study design

This is a cross-sectional study comparing airway inflammation assessed by induced sputum, exhaled NO, and bronchial biopsies between subjects with moderate asthma and subjects with severe asthma. Induced sputum and exhaled NO were collected on the same day within no more than 3 weeks of the bronchoscopy.

Subjects

Subjects 18 years of age and older with moderate and severe asthma were enrolled over a 2-year period in 2 specialized respiratory clinics: the Montreal Chest Institute of McGill University

Results

Thirty-five subjects with severe asthma and 32 subjects with mild to moderate asthma were enrolled. Their clinical characteristics are summarized in Table I. As expected, subjects with severe asthma had a lower FEV1, a higher number of asthma exacerbations in the year preceding the study, and more asthma symptoms in spite of a higher dose of inhaled steroids or systemic steroids than the subjects with mild to moderate asthma (Table I).

Discussion

As previously described,12 we found that subjects with severe asthma had eosinophilic and noneosinophilic phenotypes. These phenotypes were identified using both bronchial biopsies and sputum cell counts. However, most (9 out of 13) subjects with high sputum eosinophil counts did not have high mucosal eosinophil counts. Exhaled NO was increased in the eosinophilic phenotype identified from bronchial biopsy findings, but not on the basis of induced sputum. Subjects with high sputum eosinophil

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    • Cited by (0)

    Supported by the Richard and Edith Strauss Canada Foundation and GlaxoSmithKline Canada. Dr Lemière is a scholar of the Canadian Institutes of Health Research.

    Disclosure of potential conflict of interest: P. Ernst has been a consultant to Altana, AstraZeneca, GlaxoSmithKline, Merck, and Novartis, has received a research grant from GlaxoSmithKline, and has been a speaker for AstraZeneca, GlaxoSmithKline, Merck, and Novartis. The rest of the authors have declared that they have no conflict of interest.

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    Copyright © 2006 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.