Reduced Pulmonary Function is Associated with Enhanced Inflammation and Tissue Inhibitor of Metalloproteinase 1 Concentration in the Bronchoalveolar Lavage Fluid of Patients with Lung Parenchymal Sarcoidosis

Abstract

Summary:Lung parenchymal disease is associated with reduced pulmonary function in patients with sarcoidosis, however, the underlying pathophysiology of the condition is unclear. The present study was conducted to characterize the association between pulmonary function and bronchoalveolar lavage (BAL) findings in patients with sarcoidosis. Twenty-three patients with lung parenchymal disease (stage 2) and twenty-five patients without lung parenchymal disease (stage 1) underwent pulmonary function tests, including blood gas analysis, spirometry and diffusing capacity for carbon monoxide (DLco) and BAL, to determine the number of inflammatory cells, matrix metalloproteinase (MMP) 9 activity and tissue inhibitor of metalloproteinase (TIMP) 1 concentration in the lower airway. Vital capacity (VC) to its reference value (%VC) and %DLco were significantly reduced in patients with stage 2 disease in comparison with those with stage 1 disease. BAL fluid analysis revealed that the numbers of total inflammatory and CD8 cells, and TIMP-1 concentration were significantly higher in patients with stage 2 disease in comparison with those in patients with stage 1 disease. There were significant correlations between %VC and the numbers of inflammatory cells and TIMP-1 in the BAL fluid. These results suggest that inflammation and enhanced TIMP-1 concentration in the lower airway play critical roles in the impaired pulmonary function in patients with lung parenchymal sarcoidosis. Key words sarcoidosis, lung parenchymal diseaseCorrespondence to: Dr Koga, Asakura Medical Association Hospital, Raiharu 422-1, Asakura 838-0069, Japan. Tel: +81-946-23-0077 Fax: +81-946-23-0076 E-mail: koga.tk@asakura-med.or.jp Abbreviations: BAL, bronchoalveolar lavage; BHL, bilateral hilar lymphadenopathy; DLco, diffusing capacity for carbon monoxide; ECM, extracellular matrix; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase; VC, vital capacity.

Enhanced Exhalation of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Patients with COPD Exacerbation: A Prospective Study

“…In Alzheimer’s disease it is a suggested biomarker of ongoing central nervous system inflammation [4]. In respiratory pathology it has been shown that some metalloproteinases are elevated locally in bronchoalveolar lavage fluid of patients with pneumonia, sarcoidosis or adult respiratory distress syndrome [2,3,4]. Other studies have revealed increased concentrations of MMPs, especially MMP-8 and MMP-9, in the sputum of patients with COPD [5,6].…”

“…They have been implicated in the dissemination of tumors, as matrix metalloproteinase-9 (MMP-9) is capable of releasing the biologically active form of vascular endothelial growth factor, which seems to play a crucial role in the formation of new blood vessels [1,2]. MMP-9 is also involved in the pathogenesis of cardiovascular diseases, taking part in the development and rupture of atherosclerotic plaques, as well as in acute ischemic stroke promoting blood-brain barrier disruption [3]. In Alzheimer’s disease it is a suggested biomarker of ongoing central nervous system inflammation [4].…”

Matrix metalloproteinases-9 and tissue inhibitor of matrix metalloproteinases-1 in sarcoidosis patients

“…In this study, it was also shown that only TIMP-1 correlated significantly with vital capacity of the lung. Capacity of the lung can be infuenced by inflammation (6) and this could be an explanation for significant correlations obtained only between TIMP-1 and inflammatory parameters in our study. However, Piotrowski et al (20) found no significant correlations between neither MMP-9 nor TIMP-1 with lung function parameters.…”

“…In the study of Fireman et al (5), it was shown that TIMP-1 was higher in sarcoidosis than in controls, but with marginal significance. Nevertheless, Shimada et al (6) observed significantly increased concentrations of TIMP-1 in sarcoidosis patients with stage 2 when compared with patients in stage 1. This suggests that more pronounced inflammation occuring in stage 2 may contribute to higher levels of TIMP-1.…”

“…The sources of TIMP-1 have been considered to be lymphocytes (18) and macrophages (19). Previous report (6) revealed that MMP-9 concentration and MMP-9/TIMP-1 ratio were not altered significantly by the stage of disease indicating that TIMP-1 may be more sensitive to inflammation than MMP-9. In this study, it was also shown that only TIMP-1 correlated significantly with vital capacity of the lung.…”