Increased levels of MMP-9, TIMP-1 and TIMP-2 were also observed in BAL during acute exacerbations of COPD and were negatively correlated with predicted FEV1%, indicating that MMP-9 and TIMPs may be persistent aggravating factors associated with airway remodeling and obstruction, suggesting a pathway connecting frequent exacerbations to lung function decline [108]. This evidence concerns the gene TIMP1 and chronic obstructive pulmonary disease.