Matrix Metalloproteinase-9 Increases in the Sputum from Allergic Occupational Asthma Patients after Specific Inhalation Challenge

Abstract

BACKGROUND: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a role in the pathogenesis of asthma. MMP-9 increases in the sputum of asthmatic patients after bronchial challenge with common allergens. We sought to assess whether a high-molecular-weight occupational allergen was able to induce changes in MMP-9 as well as in other MMPs and TIMPs in subjects with occupational asthma. METHODS: Ten patients underwent specific inhalation challenge (SIC) on 2 consecutive days. We monitored changes in lung function by measuring FEV(1) for 7 h. Induced sputum test was performed at 6 h after sham and flour challenge. The total and differential cell counts were analyzed. Levels of MMPs (specifically MMP-2, MMP-7, MMP-9 and MMP-13) were measured using Fluorokine® MultiAnalyte Profiling kits and a Luminex® Bioanalyzer, while levels of TIMP-1 and TIMP-2 were measured by ELISA. RESULTS: Flour challenge increased the percentage of eosinophils in sputum samples. Asthmatic reactions induced by flour were associated with a significant increase in the sputum level of MMP-9 (p = 0.05), but not in the levels of MMP-2, MMP-7, MMP-13, TIMP-1 and TIMP-2. Sputum levels of MMP-9 measured after flour challenge were nearly significantly correlated (r = 0.67; p = 0.06) with the maximal fall in FEV(1) observed during the asthmatic reaction, but they did not correlate with the number of neutrophils (r = 0.18; p = 0.7) and eosinophils (r = 0.55; p = 0.2). CONCLUSIONS: This study showed that MMP-9 increases in sputum samples from sensitized occupational asthma patients after SIC with flour.