Table 1.
Patient Demographics.
Table 2.
Emphysema characteristics.
Figure 1.
BALF MMP and TIMP-1 protein levels and protease activity in controls, smokers and emphysema subjects.
BALF was performed on 72 normal control subjects, 16 smokers, and 101 subjects with moderate to severe emphysema who had refrained from smoking for at least six months. (A) MMP-1, (B) MMP-9, (C) MMP-12 and (D) TIMP-1 protein levels were recorded. p<0.0001 by Kruskal-Wallis one-way analysis of variance by ranks followed by a Dunn’s multiple comparison test. p values shown, comparing both treatments connected by a line. (E) Collagenase and (F) elastase activity were measured in the BALF of 26 normal controls, 9 smokers without emphysema and 60 emphysema subjects. Differences between cohorts was assessed by ANOVA; p<0.05. (G) MMP-1/TIMP-1 BALF ratios and (H) MMP-9/TIMP-1 BALF ratios were determined in the BALF of 82 normal controls, 18 smokers without emphysema and 98 emphysema subjects. Differences between cohorts was assessed by ANOVA; p<0.05.
Figure 2.
MMP and TIMP-1 levels in the plasma of normal smokers and emphysema subjects.
Luminex multiplex assays for MMP-1 (top panel), MMP-9 (center panel) and TIMP-1 (bottom panel) were done on age-matched plasma samples from non-smoking controls, normal smokers and subjects with moderate to severe emphysema. MMP-12 was measured but levels were below the limit of detection.
Figure 3.
Correlation between MMPs and DLCO or FEV1/FVC % predicted.
Linear regression analyses correlated baseline BALF MMP-1, -9, -12 and TIMP-1 lavage levels with change in DLCO or the FEV1/FVC % predicted ratio at 9-month follow up. R2 = coefficient of correlation.
Figure 4.
Correlation between baseline and follow up BALF and plasma MMP/TIMP levels.
Baseline BALF and plasma protein levels for MMP-1, -9 and TIMP-1 were correlated with follow up MMP/TIMP levels that were collected and measured 3 or 6 months following the baseline tests. The coefficient of determination (R2) was calculated for each value at each time point.
Table 3.
Quartiles of MMP protein expression.
Table 4.
Association between quartile of BALF protein expression and clinical parameters.
Table 5.
Association between quartile of plasma protein expression and clinical parameters.
Table 6.
Coefficients of correlation (R2) between elastase and collagenase activity and COPD disease parameters.
Figure 5.
Correlation between BALF MMP/TIMP levels and % change in FEV1.
BALF protein levels for MMP-1, -9 and TIMP-1 were correlated with the % change from baseline in FEV1 at 6, 9 and 18 months of follow up. The coefficient of determination (R2) was calculated for each value at each time point.
Figure 6.
Correlation between plasma MMP/TIMP levels and % change in FEV1.
Plasma protein levels for MMP-1, -9 and TIMP-1 were correlated with the % change from baseline in FEV1 at 6, 9 and 18 months of follow up. The coefficient of determination (R2) was calculated for each value at each time point.
Figure 7.
There is no correlation between BALF and plasma MMPs and TIMP-1 levels. (
A) Correlation between MMP/TIMP BALF and plasma levels. BALF protein levels for MMP-1, -9 and TIMP-1 were correlated with plasma MMP-1, -9 and TIMP-1 levels that were taken at the same time. The coefficient of determination (R2) was calculated for each value at each time point. (B) Correlation between MMP and TIMP-1 BALF levels. BALF MMP-1, -9 and -12 levels were correlated with BALF TIMP-1 levels that were taken at the same time. The coefficient of determination (R2) was calculated for each value at each time point.