Bronchopulmonary Dysplasia (BPD) is a debilitating disease that affects up to 50% of infants born at less than 30 weeks gestation. The process begins within the first weeks of life as the premature airway sustains progressive scarring with airway and pulmonary vascular smooth muscle hypertrophy. New cases continue to be reported despite advances in surfactant therapy and ventilation techniques. The pathogenesis may involve a previously unexplored aspect of lung immaturity: specifically, inadequate secretion of protons and S-nitrosylated proteins from lamellar bodies associated with low numbers of Type II alveolar cells. We propose to collect tracheal aspirates in 50 intubated infants: 10 term (>37 weeks gestation) and 40 premature infants (26-30 weeks gestation). S-Nitrosothiol and proton content will be measured, testing the hypotheses that 1) premature infants have both decreased levels of airway S-Nitrosoglutathione -and other S-nitrosothiols- and a higher pH than term infants; and 2) those infants who go on to develop BPD have even lower levels of S-nitrosothiols -and higher pH- than those who do not. If this is true, it may lead to novel therapies for the prevention of BPD and thus reduce the toll of this disease on children.
Paget-Brown, A O; Hunt, J F; Gaston, B (2007) Tracheal aspirate pH is alkaline in pre-term human infants. Eur Respir J 30:840-2 |