TIMP-1 is crucial to the balance of increased MMP-9 activity, and cigarette smoke exposure among smokers without COPD could be implicated in the activation of several pro-inflammatory signally pathways, including oxidative stress, pro-inflammatory cells, and alveolar macrophages, which results in the activation of several proteases, especially MMP-9. This evidence concerns the gene TIMP1 and chronic obstructive pulmonary disease.