Dexamethasone treatment suppresses collagen synthesis in infants with bronchopulmonary dysplasia

Collagen is an essential component of connective tissue and is present in the pulmonary interstitium. Collagen deposition is known to increase in many acquired chronic diseases, including bronchopulmonary dysplasia (BPD). Urinary excretion of hydroxyproline has been used as a specific index of collagen synthesis. Many studies have demonstrated that dexamethasone therapy is associated with respiratory improvement in infants with BDP but the mechanism of this effect is not well understood. We postulated that in infants with BDP who receive dexamethasone, suppression of collagen synthesis may cause respiratory improvement. Therefore, we studied the effect of dexamethasone on respiratory status and urinary excretion of hydroxyproline in 14 ventilator-dependent infants with BDP. Infants received 0.5 mg/kg/day dexamethasone, tapered by half every 3 days to complete a 12 day course. Eleven of the 14 infants were extubated at a mean +/- SD of 8.7 +/- 4.9 days after starting dexamethasone. Mean urinary hydroxyproline/creatinine ratios at 3, 6, 9, and 12 days of dexamethasone therapy were significantly lower than the mean pretreatment value, but after discontinuation rapidly rose toward baseline values. Decreased urinary excretion of hydroxyproline indicates that dexamethasone suppressed collagen synthesis in these infants. We speculate that suppression of collagen synthesis reduced pulmonary inflammation and fibrosis, resulting in respiratory improvement.