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) obtaining a blood or tissue sample from the premature infant prior to initiation of inhaled nitric oxide therapy;
b) analyzing the blood or tissue sample for presence of a genetic mutation in a gene encoding a nitric oxide synthase that results in decreased endogenous synthesis of nitric oxide;
c) determining whether the genetic mutation is present or absent, wherein presence of the genetic mutation 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
d) treating the premature infant with inhaled nitric oxide to reduce the likelihood of development of bronchopulmonary dysplasia when the genetic mutation is present,
wherein the premature infant is less than 30 weeks gestational age.
2. The method of claim 1 , wherein the genetic mutation is T-786C or G894T in a gene encoding endothelial nitric oxide synthase (eNOS gene).
3. The method of claim 1 , wherein the blood or tissue sample is analyzed using single nucleotide polymorphism analysis or restriction fragment length polymorphism analysis.
4. A method of avoiding risks associated with administration of inhaled nitric oxide to premature infants at risk for developing bronchopulmonary dysplasia comprising:
a) testing the premature infant for one or more of
(i) a plasma total concentration of nitrate and nitrite;
(ii) a concentration of nitric oxide in exhaled ambient or nitric oxide-free air; and
(iii) presence of a genetic mutation in a gene encoding endothelial nitric oxide synthase (eNOS gene) in a blood or tissue sample that results in decrease endogenous synthesis of nitric oxide;
b) determining whether the total concentration of nitrate and nitrite in the plasma is at least about 50 μM, whether the concentration of nitric oxide in the exhaled air is about 2.5 ppb or higher and/or whether no genetic mutation in the eNOS gene that reduces endogenous synthesis of nitric oxide is present;
c) treating the premature infant only with non-inhaled nitric oxide modalities to reduce the likelihood of development of bronchopulmonary dysplasia if the total concentration of nitrate and nitrite in the plasma is at least about 50 μM, the concentration of nitric oxide in the exhaled air is about 2.5 ppb or higher, and/or the genetic mutation is not present; and
d) treating the premature infant with inhaled nitric oxide to reduce the likelihood of development of bronchopulmonary dysplasia when the total concentration of nitrate and nitrite in the plasma is less than about 50 μM, when the measured concentration of nitric oxide in the exhaled air is less than about 1.5 ppb, and/or when the genetic mutation is present,
wherein the premature infant is less than 30 weeks gestational age.
5. The method of claim 4 , wherein the genetic mutation is T-786C or G894T in the eNOS gene.
6. The method of claim 4 , wherein the blood or tissue sample is analyzed using single nucleotide polymorphism analysis or restriction fragment length polymorphism analysis.