Each year, thousands of premature infants battle to breathe. Thanks to life-saving interventions developed in the past couple decades - steroids given to their mothers to stall pre-term labor, mechanical ventilation, air enriched with extra oxygen, and surfactant, a crucial wetting agent that makes breathing less work - most of these newborns survive with enough lung function to grow and go home.
But as the eldest of this new survivor population now embarks into young adulthood, research suggests that the same miraculous interventions that kept them alive in their first weeks of life may haunt them later on. University of Rochester Medical Center researcher Michael O'Reilly, Ph.D., unveils new research probing just how one such intervention - breathing oxygen-enriched air in those first weeks - may warp signaling pathways that rev up the body to fight respiratory infections, like flu.
The article appeared in the May edition of the American Journal of Respiratory Critical Care Medicine.
"The scope of this problem really begins to register when you consider that, as a nation, we spend a total $26.2 billion each year caring for health needs associated with all children born prematurely," said O'Reilly, an associate professor of Pediatrics and Environmental Medicine who works closely with neonatologists. "Many of today's 'survivor kids' once relied on high oxygen as babies, so a piece of that money represents the cost of their continued care. And that's just the financial burden; other sacrifices associated with poorer health just can't be given a price tag."
Broncopulmonary dysplasia, or BPD, is the most common form of chronic lung disease in infants; 5,000 to 10,000 newborns earn this diagnosis each year. Unfortunately, the ventilators that help such babies' immature lungs must deliver air with a higher-than-normal oxygen concentration (hyperoxia), often under greater pressure than tiny lungs are ready for. Together, the extra pressure and oxygen strain alveoli - the small, balloon-like, gas-exchange structures that compose the lung - throwing a wrench in normal lung development.
"Premature babies develop fewer and more simplified alveoli over time," O'Reilly said. "Their lungs are only partially developed at birth, and in the presence of oxygen, maturation can stall."
Rather than becoming small and plentiful as they should, fed by a rich web of tiny, oxygen-carrying capillaries, these under-developed structures remain bloated, fewer in number, and sometimes laced with less vessels. Children with such lungs wheeze, have difficulty running or rising to aerobic challenges, and are at greater risk for asthma; but that's just the start.
It also seems that these changes last a lifetime, said O'Reilly: These children are more easily sidelined by routine infections and respiratory diseases, like flu, and in many cases, need more frequent hospitalization, especially in the preschool years.
To begin to understand why, O'Reilly and colleagues studied two groups of full-term mice - the only distinction being that, for the first four days of life, one set breathed 100-percent oxygen, and the other breathed normal room air. After they had grown to adulthood (eight weeks), both groups were exposed to influenza A virus, and their susceptibility to infection, immune response, and lung structure was analyzed.
"We realized, as we expected, that mice born in pure oxygen had simplified alveoli, making it harder for them to take in oxygen," O'Reilly said. "Imagine that normal lung alveoli look like a cluster of grapes. Compared to that, these mice's lungs looked like bunches of plums, kiwis, even oranges."
The team also found that such mice had a more difficult time fighting off infection. Though both groups lost significant weight while battling the virus, mice born in pure oxygen took four days longer to regain their healthy weight. They also were more likely to die of the infection - 15 of 18 room-air mice lived, compared to nine of 21 beginning life in pure oxygen.
"We looked to the immune response for an explanation, but we found that both groups were producing the expected amount of virus-specific antibodies. Helper T cells were swarming to differentiate and fight infection, expanding at virtually the same levels in both groups," O'Reilly said. "It seemed mysterious; if both groups marshaled the same response, why was one still struggling to fight the virus?"