Changes in collagen turnover in early acute respiratory distress syndrome

Pulmonary fibrosis is a well-recognized feature of acute respiratory distre ss syndrome (ARDS). Using immunoassays of bronchoalveolar ravage (BAL), flu id we investigated the synthesis of type I procollagen (PICP) and type I/II collagen degradation products (COL2-3/4C(short) neoepitope) in patients wi th ARDS, acute lung injury (ALI), subjects with risk factors for ARDS (At R isk), and healthy/ventilated control subjects. PICP was measured by ELISA a s a marker of type I procollagen synthesis. COL2-3/4C(short) neoepitope was measured by an inhibition ELISA as a marker of collagenase degradation of type I/II collagen. BAL was performed initially within 48 h of ventilation (Day 1) and then subsequently on Day 4. Dilution of epithelial lining fluid (ELF) was corrected for by plasma urea comparison. increased PICP levels w ere observed in the ELF from ARDS and ALI subjects on Day 1 compared with s ubjects At Risk (median values, 124.9 and 95.0 ng/ml versus 38.0 ng/ml, res pectively, p < 0.0005). By contrast, the levels of COL2-3/4C(short) neoepit ope were significantly reduced in the subjects with ARDS versus the At Risk subjects (13.22 ng/ml versus 32.33 ng/ml, p < 0.0005). This translated int o a greatly increased PICP:COL2-3/4C(short) ratio in the subjects with ARDS (p < 0.0001). There was a significant decline in the PICP level in the sub jects with ARDS between Days 1 and 4 (n = 15, p < 0.05). Linear regression analysis showed a significant association between PICP and lung injury scor e in the subjects with ARDS (p = 0.01). Our data suggests an early shift in balance between type I collagen synthesis and degradation by collagenase. The resultant increase in type I collagen would favor matrix deposition and the development of pulmonary fibrosis in the lungs of subjects with ARDS.