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    ABSTRACT: 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. 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. 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. 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. 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. Monitoring sputum eosinophil counts in subjects with severe asthma may allow identifying the subjects with the greatest disease activity.
    Journal of Allergy and Clinical Immunology 12/2006; 118(5):1033-9. DOI:10.1016/j.jaci.2006.08.003 · 11.48 Impact Factor
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    ABSTRACT: Asthma and obesity are frequently associated, and obesity has been considered a factor contributing to both an increase in severity of asthma and to its development. The present document summarizes the proceedings of a symposium held in Montreal, Quebec, on November 2, 2006, under the auspices of the Réseau en santé respiratoire du Fonds de la recherche en santé du Québec in collaboration with the McGill University - Strauss Severe Asthma Program, Université Laval (Quebec City) and Université de Montréal. It includes an overview of the various aspects of the relationships between asthma and obesity with regard to animal models; genetic, hormonal and physiological determinants; influence of comorbidities (eg, sleep apnea syndrome); epidemiology; clinical and psychological features; and management of asthma in the obese population.
    Canadian respiratory journal: journal of the Canadian Thoracic Society 05/2007; 14(4):201-8. · 1.16 Impact Factor
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    ABSTRACT: Glucocorticoids (GCs) are the most common and effective drugs for treating inflammatory airway respiratory diseases. Despite their efficacy, some patients respond poorly to GC treatment. Alterations in the expression of the receptor that mediates GC actions, the glucocorticoid receptor (GR), are one of the potential mechanisms that would explain GC insensitivity. In this review, we present an update on the GR gene and its products, namely GRalphaand GRbeta, as well as their alterations in disease. GRalpha has a widespread distribution and is responsible for the induction and repression of target genes, whereas GRbeta can act as a dominant negative inhibitor of GRalpha-mediated transactivation and transrepression. Very low GRbeta mRNA levels have been detected in a number of cells and tissues, which often contradict GRbeta protein data. Nevertheless, an association between GC insensitivity and increased GRbeta expression has been reported in asthma, nasal polyposis, and ulcerative colitis, and in vitro, certain pro-inflammatory cytokines upregulate GRbeta expression. However, the role of GRbeta in modulating GC sensitivity in vivo has been highly debated and is as yet unclear.
    Current Allergy and Asthma Reports 06/2007; 7(2):93-9. DOI:10.1007/s11882-007-0005-3 · 2.77 Impact Factor
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