Chest
Volume 122, Issue 5, November 2002, Pages 1553-1559
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Clinical Investigations: Asthma
Matrix Metalloproteinase-9, but not Tissue Inhibitor of Matrix Metalloproteinase-1, Increases in the Sputum from Allergic Asthmatic Patients After Allergen Challenge

https://doi.org/10.1378/chest.122.5.1553Get rights and content

Objective

The aim of the study was to determine whether allergen inhalation modulates the levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in the induced sputum recovered from patients during a late-phase reaction.

Method

Eight allergic asthma patients and five healthy control subjects inhaled a dose of Dermatophagoides pteronyssinus extract corresponding to the provocative concentration of the allergen causing a 20% fall in FEV1 and saline solution. Lung function was carefully monitored for 6 h, and an induced sputum test was performed at 6 h after sham challenge or allergen challenge. The total and differential cell counts were analyzed, and the levels of MMP-9 (by enzyme-linked immunosorbent assay [ELISA] and zymography), TIMP-1 (by ELISA), and albumin (by rocket immunoelectrophoresis) were measured.

Results

The sputum eosinophil counts (p < 0.01) and MMP-9 levels (p < 0.05) increased significantly in atopic asthma patients after undergoing the allergen challenge but did not in the control subjects. By contrast, TIMP-1 and albumin levels were not significantly increased in any group. MMP-9 levels, measured after the allergen challenge in asthmatic patients, were significantly correlated with FEV1 variations after allergen inhalation (r = 0.51; p < 0.05) and with the sputum neutrophil percentage (r = 0.71; p < 0.01).

Conclusion

The levels of MMP-9, but not TIMP-1, increase after inhaled allergen challenge in the sputum of allergic asthmatic patients. This protease increase may lead to a transient imbalance between MMP-9 and TIMP-1 favoring proteolytic extracellular matrix degradation.

Section snippets

Design of the Study

The study consisted of four visits 1 week apart. The first visit consisted of a clinical examination, skin-prick tests, a lung function test, and a methacholine challenge. The second visit was devoted to a sham challenge consisting of the inhalation of isotonic saline solution for 5 min, monitoring of lung function, and an induced sputum test performed 6 h after the inhalation of the saline solution. The third visit was devoted to an allergen challenge to determine the provocative concentration

FEV1 Variations After Allergen Challenge and Clinical Tolerance

In the asthmatic group, FEV1 was significantly reduced when compared to baseline at 5, 15, 30, 60, 300, and 360 min after the allergen inhalation (p < 0.05) [Fig 1]. Six asthmatic patients displayed a late phase, which was defined as a fall in FEV1 of > 15% 6 h after the allergen challenge. None of our patients experienced systemic symptoms such as fever or myalgia.

Sputum Cell Counts and Albumin Levels

Each subject produced adequate sputum on both occasions. When compared to the sputum produced after a sham challenge, the cytology

Discussion

We found that after allergen inhalation, allergic asthmatic patients displayed a significant fall in FEV1, which was accompanied by an eosinophil influx in the airways. Concomitantly, the levels of MMP-9 were higher after allergen challenge than after sham challenge. By contrast, TIMP-1 levels were unaffected by the allergen challenge.

We chose to study patients with mild asthma who had a documented house dust mite allergy in order to investigate a homogeneous group of patients and to use the

ACKNOWLEDGMENT

We thank Jocelyne Sele and Monique Henket for technical assistance.

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    This work was supported by Fonds National de la Recherche Scientifique (FNRS, Brussels, Belgium) grant FRSM 3.4603.98, the CGER-Assurance 1996/1999 grant, and the CHU, Liège, Belgium. Dr. Cataldo is a research fellow of the FNRS. Dr. Noe¨l is a senior research associate of the FNRS.

    These authors should be considered equal contributors to the study.

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