Elevated Ratios of Type I/III Collagen in the Lungs of Chronically Ventilated Neonates with Respiratory Distress

Abstract

ABSTRAm. Increased synthesis of type I collagen, leading to increased ratios of type I to type I11 collagen in the lungs, has been observed in the lungs of animals with experimental pulmonary fibrosis. Similar changes in collagen type ratios have been observed in lungs of humans dying of idiopathic pulmonary fibrosis and of adult respiratory distress syndrome. In this study, lung collagen type ratios were examined in infants with acute and chronic lung disease. Tissue from the right lower lobes of neonates was obtained post mortem. Specific collagen types were quantitated by solubilization of lung collagen with CNBr and fractionation of the resulting mixture of peptides by column chromatography and polyacrylamide gel electrophoresis. Ratios of type I/III collagen were calculated for each lung sample using two independent pairs of marker peptides for these determinations. In some cases the ratio of type V to type 111 collagen in these same lung samples was also quantitated. We observed a significant increase in the ratio of type I/III collagen in infants with a premortem diagnosis of chronic lung disease, usually preceded by respiratory distress syndrome. We also observed two infants with large changes in collagen type ratios who might have had pulmonary fibroplasia secondary to intrauterine lung disease. These data suggest that there may be several subsets of infants with respiratory distress syndrome, each having a different prognosis. (Pediatr Res 18:1176-1180, 1984 Abbreviations RDS, respiratory distress syndrome ARDS, adult respiratory distress syndrome CLD, chronic lung disease TPN, total parenteral nutrition prenatal administration of corticosteroids (1). Infants amicted with RDS often require mechanical ventilation with positive pressure and high partial pressures of oxygen to maintain respiratory exchange. Northway and his colleagues (2) described the complications associated with the therapy of RDS, calling the resulting syndrome bronchopulmonary dysplasia. A prominent pahological feature of this syndrome is the presence of thickened alveolar walls containing excess collagen fibers, i.e. interstitial pulmonary fibrosis. Northway et al. (2) recognized the possibility that bronchopulmonary dysplasia might be an iatrogenic disease secondary to oxygen toxicity. At the same time, Nash et al. (3) described pulmonary fibrosis associated with treatment of ARDS with oxygen therapy and mechanical ventilation.Our interest in collagen types in lungs of infants suffering from RDS stems from several observations in our laboratory. In different animal models of experimentally induced acute respiratory disease, we have observed shifts in the types of collagens being synthesized in lungs of affected animals, in conjunction with increased amounts of collagen (4). We have recently shown (5) that lungs from patients with ARDS also contain increased ratios of type I to type 111 collagen as compared with controls. Seyer et al. (6) have previously reported that similar shifts of collagen type ratios occur in lungs from adul...

Ventilation of the Very Immature Lung In Utero Induces Injury and BPD-Like Changes in Lung Structure in Fetal Sheep

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Pattern of collagen types and molecular structure of collagen in acute post-traumatic pulmonary fibrosis.

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Risk factors, predictors and contemporary diagnostics of bronchopulmonary dysplasia

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