Table 2.
Plasma MMP Levels Are Associated with Mortality in Pediatric ARDS
| Biomarker | Survivors (n = 193) (ng/ml) [Median (IQR)] | Nonsurvivors (n = 42) (ng/ml) [Median (IQR)] | P Value | Adjusted OR (95% CI) | Adjusted P Value |
|---|---|---|---|---|---|
| MMP-1 | 1,092.4 (662.5–2,324.3) | 1,665.5 (618.6–2,798.0) | 0.215 | 1.2 (0.6–2.8) | 0.688 |
| MMP-2 | 486.1 (358.5–727.7) | 517.9 (405.6–649.3) | 0.704 | 1.2 (0.2–6.3) | 0.856 |
| MMP-3 | 3.3 (1.9–7.8) | 4.8 (3.0–14.0) | 0.044 | 2.3 (1.0–5.5) | 0.048 |
| MMP-7 | 420.4 (173.0–1,039.8) | 461.2 (185.3–1,472.2) | 0.224 | 1.0 (0.5–2.0) | 0.967 |
| MMP-8 | 29.6 (13.0–57.7) | 31.3 (9.0–89.0) | 0.877 | 1.1 (0.5–2.4) | 0.780 |
| MMP-9 | 116.0 (64–248) | 89.0 (46–186) | 0.123 | 1.0 (0.3–3.2) | 0.972 |
| aMMP-9 | 242.3 (126.9–510.2) | 135.1 (76.9–274.5) | 0.007 | 0.8 (0.3–1.7) | 0.493 |
| TIMP-1 | 274.5 (138–487) | 475.5 (335–996) | <0.001 | 4.5 (1.3–15.7) | 0.019 |
| TIMP-2 | 78.4 (60.9–98.1) | 81.1 (70.4–97.1) | 0.369 | 2.3 (0.2–26.4) | 0.495 |
| MMP-9/TIMP-1 | 0.49 (0.17–1.11) | 0.14 (0.07–0.54) | <0.001 | 0.5 (0.2–1.1) | 0.101 |
| aMMP-9/TIMP-1 | 0.98 (0.34–2.27) | 0.26 (0.11–0.74) | <0.001 | 0.5 (0.2–0.9) | 0.044 |
Definition of abbreviations: aMMP = active MMP; ARDS = acute respiratory distress syndrome; CI = confidence interval; IQR = interquartile range; MMP = matrix metalloproteinase; OR = odds ratio; TIMP = tissue inhibitor of metalloproteinase.
Of 235 patients, n = 170 patients have all nine MMPs, n = 38 patients have just MMP-3/-9/TIMP1, n = 27 patients have just MMP-1/-2/-7/-8/-9a/TIMP2. Therefore, n = 208 for MMP-3, MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio; n = 197 for MMP-1, MMP-2, MMP-7, MMP-8, aMMP-9, and TIMP-2; and n = 170 for aMMP-9/TIMP-1. Univariate significance was tested using the Wilcoxon rank sum test. Adjustment for multiple comparisons using the Benjamini-Hochberg procedure confirmed significantly different distributions of aMMP-9, TIMP-1, MMP-9/TIMP-1, and aMMP-9/TIMP-1 but not MMP-3 among survivors versus nonsurvivors. Adjusted associations were measured using logistic regression for the outcome of hospital survival with the predictor of log10-transformed plasma biomarker and confounding variables of PaO2/FiO2 ratio and cancer/hematopoietic cellular transplantation status. Mortality OR with 95% CIs and P values are reported. Bold P values indicate statistical significance with an a priori set threshold of P < 0.05.