Paper Title
Pulmonary and Systemic Mmps and Timps Levels in Stable Chronic Obstructive Pulmonary Disease

Abstract
Authors contribution: All authors participated in the research and article preparation. Particular contribution of each author is as follows: Conception / initiation of the study: M Petrek and V Kolek; Analysis of MMPs/TIMPs protein levels and interpretation: Z Navratilova, Alvar Agusti; Statistical analyses: Z Navratilova, M Petrek; Patients and control subjects recruitment, characterisation: J Zatloukal, V Kolek; Drafting of the MS: all authors, finalisation and editing: M Petrek and Z Navratilova and Alvar Agusti. Study coordination and management: M Petrek. Conflict-of-interest: No financial or other potential conflicts of interest exist for any author that participated in the research and article preparation. Abstract-Background: Matrix MetalloProteinase (MMP) 9 and Tissue Inhibitor of MetalloProteinase (TIMP) 1 have been implicated in Chronic Obstructive Pulmonary Disease (COPD). However, there is the limited information on usefulness of any MMPs/TIMPs as possible indicator(s) of exacerbation (ECOPD) risk in COPD. Our aim was, therefore, to investigate whether the above mentioned and other members of MMPs/TIMPs family may be related to the presence of ECOPD within the first year after blood/BAL sampling. Methods: Multiplex xMAP technology was used to measure serum concentrations of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9 and TIMP1, TIMP2, TIMP3 and TIMP4 in 39 patients with stable COPD. In addition, bronchoalveolar lavage (BAL) was obtained from a subgroup of 21 COPD patients. Patients were subdivided according to the presence of ECOPD within the first year after blood/BAL sampling. Results: Serum concentration of TIMP2 was elevated in COPD patients with ECOPD within the first follow-up year compared to those without ECOPD in this period (p0.02). Serum MMPs and their inhibitors TIMP1, TIMP3 and TIMP4 did not differ among COPD patients stratified according to presence of ECOPD within the first follow-up year (p0.05). There were no differences in BAL concentrations of measured MMPs/TIMPs in the two patients group (p0.05). Conclusion: The elevated serum levels of TIMP2 deserve further investigation focused on the stable patients who suffer frequent episodes of exacerbation (ECOPD). Key Words- bronchoalveolar cells, COPD, ECOPD, exacerbation.