Researchers identify process that causes chronic neonatal lung disease
Pediatric researchers at UT Southwestern Medical Center have identified a key component of the pathogenesis of bronchopulmonary dysplasia (BPD), a devastating and sometimes fatal lung disease that affects premature infants. Their findings clarify what prompts the inflammatory response that results in BPD, which previously had been unclear.
The study determined how the NLRP3 inflammasome activates the protein Interleukin 1 beta, which in turn triggers inflammation and development of BPD.
In an animal model of BPD, researchers also tested two FDA-approved drugs that either block the effect of or decrease the production of Interleukin 1 beta and found that these treatments allowed more normal lung development.
Bronchopulmonary dysplasia, a common chronic lung disease in premature infants, develops as a result of the ventilation and oxygen necessary for these infants to survive. Infants born before 30 weeks gestation have immature lungs that lack surfactant, a substance comprised of phospholipids and proteins that is needed for lungs to properly function. This causes premature infants to develop respiratory distress syndrome, requiring the aid of mechanical ventilation. The infants’ exposure to elevated oxygen levels during ventilation activates the process of inflammation that leads to BPD.
‘The same ventilation that ultimately saves their lives, damages their lungs,’ said Dr. Rashmin Savani, Professor and Chief of Neonatal-Perinatal Medicine. ‘Our findings suggest that if we target premature infants born at less than 28 weeks gestation from three to 10 days after birth with this therapy, we might be able to drastically reduce or even eliminate the development of BPD.’ Dr. Savani also holds the William Buchanan Chair in Pediatrics.
Next steps include testing the therapeutic intervention strategies outlined in this study in larger animal models, potentially followed by a Phase 1 clinical trial.
UT Southwestern Medical Center http://tinyurl.com/j2yjrtz
