Markers of extracellular matrix metabolism in pediatric patients with acute lung injury
Intensive Care Units, Pediatric
Introduction: The nature of the fibroproliferative response in pediatric patients with acute lung injury (ALI) and its rote in outcome has not been evaluated. Therefore we are investigating the relationship between markers of extracellular matrix (ECM) metabolism and clinical outcome in the pediatric population in a pilot study. Patients and Methods: Children ≥ 1 year old who met criteria for ALI (Pa02/FiO2 <300, bilateral infiltrates on chest radiograph and noncardiogenic pulmonary edema) with need for mechanical ventilation (MV) were enrolled in an IRB-approved protocol. Serum samples were obtained at regular intervals when the child was on MV. Levels of antigens derived from the interstitium [procollagen type I C- terminal pepttde (PICP) and procollagen type III N-terminal peptide (PIIINP)] or basement membrane [laminin (P1) and type IV collagen (CIV)] were measured by specific immunoasttys. Lung tissue was evaluated by electron microscopy (EM). Oxygenation Index (OI) and alveolar-arterial oxygen gradient (A-a) were recorded for each day of the study. Data were analyzed with Student t-test and Pearson coefficient. Results: Four patients have been enrolled to date. The average age was 9 yrs. (range 1-16); three patients died (D) and one survived (S). The mean peak value for PICP (770 ng/ml) in D trended higher than in S (355 ng/ml), (p=.12). For PIIINP, P1 and CIV the mean peak values were (D listed first); 85 ng/ml and 17 ng/ml, 634 ng/ml and 449 ng/ml, and 800 ng/ml and 515 ng/ml; these differences were not statistically significant. In three patients, OI and A-a varied directly with PIIINP (0.72 and 0.72). Lung tissue was available in two patients (D). EM revealed marked fibroproliferative consolidation with loss of the epithelium, the endothelium and destruction of the basement membranes. Fibrillar collagen bundles were seen in direct contact with red Mood cells. Hyperactive fibroblasts were prominent. Conclusions: The results suggest that serum levels of antigens derived from the intcrstitium and basement membrane in the lung can be used as markers for changes in the pulmonary ECM. Abnormal deposition of collagen type III may contribute to mortality by impairing oxygenation. Further correlation of ECM markers in serum to changes in the pulmonary ECM is needed to confirm these preliminary findings.