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      Elevation of sputum matrix metalloproteinase-9 persists up to 6 months after smoking cessation: a research study

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          Abstract

          Background

          Smoking cessation is the best possible way to prevent the progression of smoking related airway diseases. However, the effect and time scale of smoking cessation on airway inflammation/remodelling are largely unknown. This prospective study evaluated the effects of smoking cessation on induced sputum (IS) neutrophils, matrix metalloproteinases (MMP-7, -8, -9) and tissue inhibitor of metalloproteinase-1 (TIMP-1).

          Methods

          A total of 61 subjects participated in the study; 17 stopped smoking for 3 months and 9 for 6 months. The proportion of IS neutrophils and the levels of MMPs and TIMP-1 by ELISA were determined at baseline and at 3 and 6 months after cessation.

          Results

          In the smokers, baseline IS neutrophils, MMPs and TIMP-1 were significantly higher compared to non-smokers. Levels of MMP-7, -8 and TIMP-1 decreased nearly to those of non-smokers but the levels of MMP-9 increased significantly from the baseline of the same subjects at 3 months after cessation (p = 0.009) with no significant decline at 6 months after cessation.

          Conclusions

          Sputum MMP-9 remained elevated after 6 months of smoking cessation, which may contribute to ongoing lung damage typical of COPD.

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          Most cited references31

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          Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.

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            Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study.

            To determine whether a program incorporating smoking intervention and use of an inhaled bronchodilator can slow the rate of decline in forced expiratory volume in 1 second (FEV1) in smokers aged 35 to 60 years who have mild obstructive pulmonary disease. Randomized clinical trial. Participants randomized with equal probability to one of the following groups: (1) smoking intervention plus bronchodilator, (2) smoking intervention plus placebo, or (3) no intervention. Ten clinical centers in the United States and Canada. A total of 5887 male and female smokers, aged 35 to 60 years, with spirometric signs of early chronic obstructive pulmonary disease. Smoking intervention: intensive 12-session smoking cessation program combining behavior modification and use of nicotine gum, with continuing 5-year maintenance program to minimize relapse. Bronchodilator: ipratropium bromide prescribed three times daily (two puffs per time) from a metered-dose inhaler. Rate of change and cumulative change in FEV1 over a 5-year period. Participants in the two smoking intervention groups showed significantly smaller declines in FEV1 than did those in the control group. Most of this difference occurred during the first year following entry into the study and was attributable to smoking cessation, with those who achieved sustained smoking cessation experiencing the largest benefit. The small noncumulative benefit associated with use of the active bronchodilator vanished after the bronchodilator was discontinued at the end of the study. An aggressive smoking intervention program significantly reduces the age-related decline in FEV1 in middle-aged smokers with mild airways obstruction. Use of an inhaled anticholinergic bronchodilator results in a relatively small improvement in FEV1 that appears to be reversed after the drug is discontinued. Use of the bronchodilator did not influence the long-term decline of FEV1.
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              Mediators of chronic obstructive pulmonary disease.

              Chronic obstructive pulmonary disease (COPD) is a major and increasing global health problem that is now a leading cause of death. COPD is associated with a chronic inflammatory response, predominantly in small airways and lung parenchyma, which is characterized by increased numbers of macrophages, neutrophils, and T lymphocytes. The inflammatory mediators involved in COPD have not been clearly defined, in contrast to asthma, but it is now apparent that many lipid mediators, inflammatory peptides, reactive oxygen and nitrogen species, chemokines, cytokines, and growth factors are involved in orchestrating the complex inflammatory process that results in small airway fibrosis and alveolar destruction. Many proteases are also involved in the inflammatory process and are responsible for the destruction of elastin fibers in the lung parenchyma, which is the hallmark of emphysema. The identification of inflammatory mediators and understanding their interactions is important for the development of anti-inflammatory treatments for this important disease.
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                Author and article information

                Journal
                BMC Pulm Med
                BMC Pulmonary Medicine
                BioMed Central
                1471-2466
                2010
                14 March 2010
                : 10
                : 13
                Affiliations
                [1 ]Department of Medicine, Division of Pulmonary Medicine, University of Helsinki, Helsinki, Finland
                [2 ]Finnish Institute of Occupational Health, Helsinki, Finland
                [3 ]University of Helsinki, Helsinki, Finland
                [4 ]Department of Medicine, Division of Infection, Inflammation and Repair, Southampton General Hospital, Southampton, UK
                Article
                1471-2466-10-13
                10.1186/1471-2466-10-13
                2841651
                20226090
                c23ded0c-6c1b-4e83-a665-898e7b2622bd
                Copyright ©2010 Louhelainen et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 October 2009
                : 14 March 2010
                Categories
                Research article

                Respiratory medicine
                Respiratory medicine

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