Sputum matrix metalloproteinase-8 and-9 and tissue inhibitor of metalloproteinase-1 in bronchiectasis: Clinical correlates and prognostic implications

Background and objective: The triplet of airway infection, inflammation and bronchial wall destruction associated with excessive matrix metalloproteinases (MMP) release and imbalance of tissue inhibitor metalloproteinase-1 (TIMP-1) is implicated in bronchiectasis. We sought to determine the associations between sputum MMP (MMP-8, MMP-9) and TIMP-1 and the severity of bronchiectasis; the utility of MMP in predicting risks of future bronchiectasis exacerbations (BE); and the changes in MMP levels during BE. Methods: We recruited 102 patients with stable bronchiectasis and 22 healthy subjects. For bronchiectasis patients, baseline measurements consisted of sputum inflammation and MMP measurements, bacterial culture, spirometry and chest high-resolution computed tomography (HRCT). Bronchiectasis patients were followed up for 1 year to determine the frequency of BE. Changes in MMP levels during BE were assessed in 36 bronchiectasis patients. Results: Sputum MMP-8, MMP-9 and MMP-9/TIMP-1 ratio in bronchiectasis patients were significantly increased compared with healthy subjects. MMP-8 and MMP-9 levels, but not TIMP-1, were positively correlated with clinical measures, including HRCT scores, spirometry and Bronchiectasis Severity Index. Seventy-nine bronchiectasis patients were included in survival analyses of BE. Lower levels of baseline MMP-9 were associated with reduced risks of and a longer time to the first BE during follow-up. MMP-8 and MMP-9, but not TIMP-1 or MMP-9/TIMP-1 ratio, were significantly heightened during BE. Conclusions: Sputum MMP might be useful biomarkers for the assessment of bronchiectasis severity and the prediction of future risks of BE. Our results provide the rationales for the future clinical application of MMP inhibitors.