"Chronic lung disease is a major source of morbidity in these infants. Neonatologists have been trying to figure out how to prevent it for years," said Philip Ballard, MD, PhD, lead study author and professor of pediatrics at UCSF.
According to Ballard, the advantage of inhaled nitric oxide for infants born close to term and suffering from the lung disease known as pulmonary hypertension has been known for some time, but the effect in premature infants or preemies had not been clearly determined.
Nitric oxide, which is a gaseous compound normally produced by the body, is produced in inadequate amounts by premature infants. Recent clinical studies done elsewhere have found positive effects of inhaled nitric oxide in very premature infants, whereas some animal research has suggested that inhaled nitric oxide in preemies might hinder the production of pulmonary surfactant, a substance vital to normal lung development and functioning.
However, the new study findings, reported in the August 2007 issue of "Pediatrics," found no adverse affects of inhaled nitric oxide on surfactant production or function, said Ballard.
"Inhaled nitric oxide is a promising therapy, but we've been concerned about safety. We found no adverse effects of inhaled nitric oxide and perhaps a beneficial effect in terms of surfactant function," Ballard said.
The controlled, randomized clinical trial of nitric oxide was headed by Roberta Ballard, MD, UCSF professor emeritus of neonatology. The trial included 582 very premature infants who were enrolled between 2000 and 2005 in the study at 7 to 21 days old at 21 hospitals around the country.
Laboratory studies were performed in 83 of these infants to study whether inhaled nitric oxide had a negative effect on pulmonary surfactant, a lipid-protein mixture that coats the lungs and greatly reduces surface tension.
Surfactant essentially allows the lungs to inflate easily after exhalation, eliminating the work of breathing. Very premature infants produce insufficient amounts of surfactant, so any therapy that inhibited the work of surfactant would be harmful.
In the study, half the infants were treated with nitric oxide and half received a placebo. Fluid from their lungs was then collected and examined for surfactant levels and properties. The results showed that "there were no significant differences" between the two groups in surfactant amount and that inhaled nitric oxide may have a positive effect on surfactant function.
"This is very good news in terms of the safety profile for this promising new therapy. Inhaled nitric oxide is going to be safer than the corticosteroid and more effective than both therapies," Ballard said.