Pain-relief drug may prevent lung problems, blindness in premature infants

October 19, 2002

Irvine, Calif. -- A popular pain-relief drug may prevent lung and eye disorders common in premature infants, a UC Irvine College of Medicine study has found.

The study indicates that the drugs, Cox-2 inhibitors that go by the trade name Celebrex, may improve on current treatments to preserve the growth of tiny lungs and eyes in premature babies. The study will be presented at the annual meeting of the American Academy of Pediatrics in Boston.

Dr. Houchang Modanlou, professor of pediatrics at UCI and a premature birth specialist at UCI Medical Center, and his colleagues at Long Beach Memorial Medical Center found in rabbits that Cox-2 inhibitors promoted elevated levels of crucial growth-inducing chemicals that help lungs and tissues grow. These increases occurred despite the fact that, at the same time, the newborns were given oxygen to assist breathing. Oxygen typically decreases levels of these important chemicals.

Typically, premature infants do not have fully developed lungs. Bronchopulmonary dysplasia, a complication arising from this lack of development, is a chronic inflammation of the airways and the lung tissue of premature newborns. About 5,000 to 10,000 new cases of this disease are reported each year, according to the National Heart, Lung and Blood Institute. Retinopathy of prematurity is another common complication of premature birth that has ties to excess oxygen. It is marked by excessive branching and growth of blood vessels in the infant eye.

"Premature infants are exposed to high concentrations of oxygen to assist their underdeveloped lungs with breathing," Modanlou said. "Unfortunately, oxygen also contributes to the development of retinopathy of prematurity and bronchopulmonary dysplasia, two common diseases among premature infants. Cox-2 inhibitors seem to preserve the growth factors that are shut down by too much oxygen and may prevent these diseases if effective in humans."

Modanlou and his colleagues found in experiments conducted at Long Beach Memorial that while oxygen decreased growth factors called VEGFs three- to five-fold and lowered VEGF's receptors in the lung by three- to four-fold, the Cox-2 inhibitors along with the oxygen actually increased the number of VEGF receptors.

The painkiller also maintained levels of two key chemical variants of the VEGF molecule. Receptors for VEGF are necessary for the molecule to stimulate the growth of blood vessels in lung tissues and encourage growth.

The drug dexamethasone, currently used in premature infants to stave off the negative effects of oxygen, decreased the number of receptors. Dexamethasone is a steroid-based drug that has some success in preventing diseases common in premature births but has been associated with a number of side effects, including delayed brain and body development and increased risks of cerebral palsy.

"This study indicates that Celebrex may be a more suitable alternative than dexamethasone in preventing the growth-suppressing effects of oxygen," Modanlou said. "We will still need to see how this can be effective in humans, but we may be able to preserve the growth factors necessary for healthy development without the side effects seen in current treatments."

Modanlou and his colleagues are continuing to search for other methods that may help preserve the growth of premature infants and at ways to reduce the complications of premature birth.

Modanlou's colleagues in the study include Drs. Francis Tambunting and Arwin Valecia of UCI, and Kay Beharry and Dr. Aamir Akmal of Long Beach Memorial.
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