Table 1.
Summary of Evidence Surrounding the Role of MMP-9 and -12 in COPD and Emphysema
| Association Between MMPs in Diseased Cohort? | Author (Year) | Cohort | Finding | |
|---|---|---|---|---|
| MMP-9 | + | Beeh et al96 (2003) | n=12 stable COPD, n=15 IPF, n=14 healthy controls | Induced sputum concentration of MMP-9 higher In COPD vs IPF and controls (p<0.05) |
| + | Brajer et al103 (2008) | n=23 COPD, n=23 healthy controls | Increased MMP-9 levels in serum of COPD, compared to control (p=0.0005) | |
| +- | Wells et al101 (2018) | n=1053 SPIROMICS, n=140 COPDGene | Elevated MMP-9 in plasma of 9% SPIROMICS and 29% COPDGene. Independently associated with risk of AECOPD. | |
| +- | Higashimoto et al97 (2005) | n=72 COPD, n=66 control, n=26 asthma | No difference in serum MMP-9 concentration between groups. Serum MMP-9/TIMP-1 molar ratio significantly lower in COPD cohort, compared to control (p<0.0001). | |
| MMP-12 | + | Demedts et al110 (2006) | n=28 stable COPD, n=14 healthy smokers, n=20 never smokers, n=14 former smokers | MMP-12 levels in BAL between 4–10 fold greater in smokers (p=0.0002) |
| + | Hunninghake et al113 (2009) | n=127 eoCOPD, n=378 NETT, n=1487 Lovelace, n=1468 NAS | SNP in the MMP-12 gene associated with reduced risk of COPD development in smokers | |
| +- | Babusyte et al102 (2007) | n=39 COPD patients (of which n=22 smokers, n=17 ex-smokers), n=8 “healthy” smokers, n=11 healthy non-smokers | % of MMP-12+ alveolar macrophages did not differentiate smoking status in COPD cohort. Increased MMP-12 concentration in induced sputum of COPD, compared to healthy cohorts but did not differentiate smoking status in COPD cohort. | |
| + | Wallace et al115 (2008) | n=54 patients undergoing surgical resection for lung carcinoma (see if can differentiate the cohort) | MMP-12 mRNA expression higher in cultured alveolar macrophages isolated from current smokers, compared with former smokers. Negative correlation between MMP-12 expression and DLCO. |
|
| - | Imai et al112(2001) | n=23 patients with emphysema, n=3 ɑ1ATD-associated emphysema, n=8 normal controls, n=3 normal smokers | No upregulation of MMP-12 in type II pneumocytes isolated from emphysema patients, compared to control |
Notes: (+): studies that have displayed an association or significant difference of MMPs in a diseased cohort; (+-): studies that have found both associations/differences as well as negative data; (-): studies that have shown no association/differences between MMPs in their diseased vs control cohorts. COPD: chronic obstructive pulmonary disease; IPF: idiopathic pulmonary fibrosis; SPIROMICS: SubPopulations and InteRmediate Outcome Measures In COPD Study – a cohort of COPD patients; COPDGene: a cohort of COPD patients; eoCOPD: Boston early-onset COPD – a cohort of COPD patients <53 years of age; NETT: National Emphysema Treatment Trial – a cohort of severe COPD patients with evidence of emphysema onset; Lovelace: a cohort of smokers; NAS: Normative Aging Study – a cohort of healthy controls with median age of 41.5 years; ɑ1ATD: alpha-1 antitrypsin deficiency.