Background/aims Inhaled NO (iNO) has been tested for prevention of bronchopulmonary dysplasia in premature infants, however the role of cGMP is not known. We hypothesised that levels of NO metabolites (NOx) and cGMP in urine, as a non-invasive source for biospecimen collection, would reflect the dose of iNO and relate to pulmonary outcome.
Methods Studies were performed on 125 infants <29 weeks gestation who required mechanical ventilation at 7–14 days and received 24 days of iNO at 20–2 ppm. A control group of 19 infants did not receive iNO.
Results In NO-treated infants there was a significant dose-dependent increase of both urinary NOx and cGMP per creatinine (maximal 3.1- and 2-fold, respectively, at 10–20 ppm iNO) compared to off iNO. The ratio of cGMP to NOx, which may reflect efficiency of NO signalling via guanylate cyclase, was lower (mean 38%) at all doses of iNO compared to off NO. NOx and cGMP concentrations at both 2 ppm and off iNO were inversely related to severity of lung disease (Respiratory Severity Score) during the first month, and the NOx levels were lower in infants who died or developed BPD at term. NOx was higher in Caucasian compared to other infants at all iNO doses.
Conclusions Urinary NOx and cGMP are biomarkers of endogenous NO production and lung uptake of iNO, and levels at some doses reflect the severity of lung disease in infants. These results support a role of the NO-cGMP pathway in lung development and repair from injury.