Asthma, Rhinitis, Other Respiratory DiseasesNeutrophil-derived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucocorticoids☆
Section snippets
Subjects
Subjects with asthma were divided into severity categories by use of previous criteria.13 Patients with severe asthma were all referred for severe asthma. Despite treatment with oral and high-dose inhaled steroids, with at least 1 other controller, they had symptoms and used urgent health care. Normal control subjects had normal pulmonary function and no history of respiratory illness. The study was approved by the National Jewish Institutional Review Board, and all subjects gave informed
Subject characteristics
Thirty-nine patients with severe asthma, 9 patients with moderate asthma, 13 patients with mild asthma, and 17 normal control subjects underwent bronchoscopy with BAL for evaluation of cell counts, differentials, and MMP-9 levels (Table I). Subgroups were involved in studies of MMP-9 production and activity as described in the individual sections. As reported previously, MMP-9 protein levels were highest in the severe asthmatics (overall, P = .001). Similarly, the group of patients with severe
Discussion
This study suggests that the increased MMP-9 protein in BAL fluid from patients with severe asthma is derived primarily from neutrophils, with minor contribution from monocyte/macrophages or other cells. Although it has been suggested that increases in MMP-9 after allergen challenge might be neutrophil derived, this is the first study to detail the relationship of BAL fluid MMP-9 to neutrophils and disease severity.18, 19 In addition, in severe asthma, a significantly higher amount of the MMP-9
Acknowledgements
We thank Dr Niels Borregaard for the initial supply of NGAL antibody.
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Supported by NIH grants HL-64087, AI-40600, RR-00051 and ALA of Colo-rado, Oklahoma, and Alaska.
The first 2 authors contributed equally to the development of this manuscript.