Rising ratio of matrix metalloprotenase 9/ tissue inhibitor metalloproteinase 1 in trachoalveoilar fluid: a predictor for development of chronic lung disease in ventilated preterm neonates

Bronchopulmonary dysplasia [BPD] or chronic lung disease [CLD] is a disorder of lung injury and repair originally ascribed to positive pressure mechanical ventilation and oxygen toxicity. Matrix metalloproteinases [MMPs] including MMP9 act in remodeling and destruction of extracelluar lung matrix and basement membranes. Tissue inhibitor metalloproteinase 1 [TIMP1] is the specific tissue inhibitor of MMP9. Imbalance in the level of MMP9 relative to its inhibitor TIMP1 has been implicated in matrix disruption and remodeling with further development of [CLD]. to study the value of rising ratio MMP9/ TIMP1 in serial TAF samples in prediction of CLD in neonates needing mechanical ventilation for a long duration. A prospective study conducted on 48 preterm neonates having respiratory distress syndrome [RDS] recruited from NICU of Kasr El Eini Hospital. They were all receiving mechanical ventilation. Their mean gestational age [GA] was 32.03 +/- 1.07 weeks and mean birth weight [BW] was 1118 +/- 93.38 gm. They were subjected to 3 serial tracheal aspirate fluid collections [TAF] during the routine tracheal lavage. 1st sample was collected during the 1st 24 hours of life, 2nd sample during the period from the 8th to the 11th day postnatal and the 3rd sample during the period from the 12th to the 16th day postnatal. Levels of MMP9 and TIMP1, were measured using ELISA technique. Ratio MMP9/TIMP1 was calculated. Patients who completed the 3 serial samples were subdivided into 2 groups: Group I: including patients who developed CLD and Group II including patients who did not develop CLD. Ratio of MMP9/TIMP1 was compared in the 3 serial samples in both groups. 18 neonates died before they completed the 3 successive samples and were excluded from the final analysis of the study. The results of the present study showed that MMP9/TIMP1 ratio was rising over the 3 successive samples in CLD group. In 1st sample ratio in CLD group was 3.6 +/- 0.92 versus 3.32 +/- 0.8 in no CLD group P Value 0.426 non significant but ratio rises in 2nd samples to reach 5.12 +/- 1.44 in CLD group versus 3.30 +/- 0.82 in no CLD group p value 0.002 highly significant. In the 3rd sample the ratio rises more to be 6.50 +/- 1.79 in CLD group versus 3.09 +/- 0.78 in no CLD group P Value 0.001 very highly significant. A rising ratio MMP9/ TIMP1 in TAF in early life might be of use as a predictor for the development of CLD in ventilated neonates. Supplementation of tissue inhibitor [TIMP1] when available could be an effective strategy in the prophylaxis and treatment of CLD

C-reactive protein as a marker for early onset neonatal sepsis: the good, the better and the best

C-reactive protein [CRP] analysis is a simple, established and widely available test to identify an evidence of plasma acute phase response to infection and tissue injury. Standard CRP assays such as: latex agglutination and quantitative assays lack sensitivity at the early onset of neonatal sepsis. They can detect CRP concentrations. The development of the new high sensitivity immunoassay technique for CRP [HSCRP] has enabled its detection at lower concentrations. In HSCRP immunoassay, anti CRP antibodies react with antigen in the serum to form antigen antibody complex measured turbidimetrically. Evaluation of the diagnostic value of highly sensitivity CRP immunoassay in comparison to standard CRP latex agglutination and quantitative assays in early onset neonatal sepsis. A prospective controlled study including 51 neonates with culture proven bacterial sepsis. Ten healthy neonates served as control group. All neonates were subjected to full clinical examination, and laboratory investigations including: CBC with differential leukocytic count, blood culture and sensitivity. CRP analysis was performed using 3 techniques for each patient: CRP latex agglutination, CRP quantitative assay where values ? 6mg/L were considered abnormal, and HSCRP immunoassay where values ? 2mg/L were considered abnormal. CRP latex agglutination was positive in 8/51 [15.68%] and had sensitivity of 15.68%, specificity 100%, positive predictive value 100%, negative predictive value 18.86% and diagnostic accuracy 29.5%. CRP quantitative assay was positive in 12/51 [23.52%]. At cut of level 6mg/L: sensitivity was 23.5%, specificity 100%, positive predictive value 100%, negative predictive value 20.4% and diagnostic accuracy 36.06%. HSCRP immunoassay was positive in 34/51 [66.66%]. At cut off level 2mg/L: sensitivity was 66.6%, specificity 100%, positive predicative value 100%, negative predictive value 37.03% and diagnostic accuracy 72.13%. CRP analysis using high sensitivity immunoassay is likely to improve the diagnostic accuracy of CRP in detection of early onset neonatal sepsis. It allows detection of CRP at low concentrations. Only 40micro l of serum is needed, and results are available within 15 minutes