Relationship of MMP9 and tissue inhibitor of MMP1 (TIMMP1) to functional and ultrasonographic markers in sarcoidosis and idiopathic pulmonary fibrosis
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Pneumon 2006;19(4):357-366
Metalloproteinases and their tissue inhibitors act on the metabolism of collagen in the interstitial tissue matrix and are involved in the pathogenesis of tissue remodeling and fibrosis. The study objective is to investigate the MMP9 and TIMMP1 status in patients with sarcoidosis and idiopathic pulmonary fibrosis (IPF), and their relationship to functional and ultrasonographic markers. Patient and methods: Serum levels of MMP9 and TIMMP1 in 22 sarcoidosis patients, in 10 IPF patients and 12 control subjects were determined (ELISA, Human Biotrak, Amersam). In sarcoidosis patients, disease stage (Ga167 scintigraphy) and left ventricular diastolic function (pulse and tissue Doppler) were further assessed. In IPF patients, systolic pulmonary artery pressure (SPAP) was measured; all patients underwent comprehensive lung function testing. Results: Serum MMP9 and TIMMP1 levels were similar among patients with either pathology; however, they were significantly higher in patients with sarcoidosis (p<0.001, p<0.01), as well as in patients with IPF (p<0.01, p<0.05) compared to controls. Among sarcoidosis patients, there was a significant relationship between MMP9 levels and both FEF25-75 (p<0.05) and disease activity (p<0.01), whereas among IPF patients MMP9 levels were associated with values for DLCO (p<0.05). 41% of sarcoidosis patients showed left ventricular diastolic dysfunction in terms of impaired relaxation and 40% of IPF patients had SPAP >35 mm Hg. No significant relationship between ultrasonographic findings and MMP9 and TIMMP1 levels, and the molar ratio MMP9/TIMMP1 was found. Conclusion: MMP9 levels reflect lung function impairment in sarcoidosis and IPF patients. Nevertheless, they cannot reliably indicate cardiovascular involvement. However, in sarcoidosis they may represent a useful marker of disease activity. Pneumon 2006; 19(4):357-366.
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