Another negative trial of methods to prevent BPD

Abstract

As preterm infants survive at earlier gestational ages and lower birth weights, bronchopulmonary dysplasia (BPD) becomes a more prevalent problem. BPD has changed from a disease of primarily airway injury in larger infants to an interference with alveolar and vascular development in the very low birth weight infants. Nevertheless, the causes of the developmental abnormalities continue to include oxidant injury and ventilator-mediated injury. Different ventilator strategies to decrease the incidence of BPD have shown benefit in some trials but not in others, and the overall advantages to high-frequency oscillation or newer styles of patient-controlled ventilation have not been compelling. Any mechanical ventilation of the very preterm lung is undesirable. The other major player in the pathophysiology of BPD is thought to be oxidant injury and its resultant inflammation. Trials with antioxidants such as selenium, vitamin E, and CuZn-superoxide dismutase have not been beneficial, although vitamin A did decrease BPD in a large trial. N- acetylcysteine is itself a free-radical scavenger and is a precursor for glutathione. Ahola et al asked if a 6-day infusion of N-acetylcysteine begun shortly after birth would decrease death or BPD in a large randomized trial. No benefit or harm was detected for the primary outcome or multiple secondary outcomes. The pathophysiology of BPD is complex and multifactorial, with injury pathways that are likely to be redundant. A single intervention may have little benefit. This depressing reality is reminiscent of the inability to change the outcome of sepsis with a number of molecular interventions directed at the inflammatory cascade.Page 713 As preterm infants survive at earlier gestational ages and lower birth weights, bronchopulmonary dysplasia (BPD) becomes a more prevalent problem. BPD has changed from a disease of primarily airway injury in larger infants to an interference with alveolar and vascular development in the very low birth weight infants. Nevertheless, the causes of the developmental abnormalities continue to include oxidant injury and ventilator-mediated injury. Different ventilator strategies to decrease the incidence of BPD have shown benefit in some trials but not in others, and the overall advantages to high-frequency oscillation or newer styles of patient-controlled ventilation have not been compelling. Any mechanical ventilation of the very preterm lung is undesirable. The other major player in the pathophysiology of BPD is thought to be oxidant injury and its resultant inflammation. Trials with antioxidants such as selenium, vitamin E, and CuZn-superoxide dismutase have not been beneficial, although vitamin A did decrease BPD in a large trial. N- acetylcysteine is itself a free-radical scavenger and is a precursor for glutathione. Ahola et al asked if a 6-day infusion of N-acetylcysteine begun shortly after birth would decrease death or BPD in a large randomized trial. No benefit or harm was detected for the primary outcome or multiple secondary outcomes. The pathophysiology of BPD is complex and multifactorial, with injury pathways that are likely to be redundant. A single intervention may have little benefit. This depressing reality is reminiscent of the inability to change the outcome of sepsis with a number of molecular interventions directed at the inflammatory cascade. Page 713