Method of identifying and treating premature infants at risk for BPD
Methods for identifying premature infants at risk for developing bronchopulmonary dysplasia and/or most likely to benefit from administration of inhaled nitric oxide for prevention of bronchopulmonary dysplasia (BPD). Methods for treating premature infants identified as at risk and/or likely to benefit are provided. also provided are methods for identifying premature infants that are not at risk for developing bronchopulmonary dysplasia and/or unlikely to benefit from administration of inhaled nitric oxide for prevention of bronchopulmonary dysplasia, and methods for avoiding risks of toxicity and undesirable side effects associated with inhaled nitric oxide therapy comprising administering only non-iNO treatment modalities to these infants.
1. A method for identifying a premature infant that is likely to have a therapeutic response to inhaled nitric oxide comprising:
a) prior to initiation of inhaled nitric oxide therapy, exposing the premature infant to ambient or nitric oxide free air, such that the premature infant inhales the air;
b) obtaining a sample of the air upon exhalation;
c) measuring a concentration of nitric oxide in the exhaled air;
d) determining whether the measured concentration of nitric oxide is less than 1.5 ppb, wherein a concentration of less than about 1.5 ppb indicates that the premature infant is likely to have a reduction in the likelihood of developing bronchopulmonary dysplasia when treated with inhaled nitric oxide; and
e) treating the premature infant with inhaled nitric oxide to reduce the likelihood of development of bronchopulmonary dysplasia when the measured concentration of nitric oxide in the exhaled air is less than about 1.5 ppb, and
wherein the premature infant is less than 30 weeks gestational age.
2. The method of claim 1 , wherein the measured concentration of nitric oxide is 0.5-1.5 ppb.
3. The method of claim 1 , wherein the measured concentration of nitric oxide is 1 ppb or less.
4. The method of claim 2 , wherein the concentration of nitric oxide is measured between birth and the third day after birth.
5. A method for reducing the likelihood of a premature infant at risk for of developing bronchopulmonary dysplasia, the method comprising:
administering a dose of inhaled nitric oxide, wherein the premature infant has a total concentration of nitrate and nitrite in the plasma that is less than about 50 μM, a concentration of nitric oxide in exhaled air that is less than about 1.5 ppb and/or a genetic mutation in a gene encoding nitric oxide synthase that results in decrease endogenous synthesis of nitric oxide,
wherein the premature infant is less than 30 weeks gestational age.
6. The method of claim 5 , comprising decreasing dosages of inhaled nitric oxide.
7. The method of claim 6 , comprising an initial dose of nitric oxide of 20 ppm for 48-96 hours, and subsequent doses of 10, 5 and 2 ppm at weekly intervals thereafter.
8. The method of claim 5 , which is initiated at least five days after birth.
9. The method of claim 8 , which is initiated at 5-14 days after birth.
10. The method of claim 5 , which is provided for 20-30 days.