Pulmonary nitric oxide in preterm and term infants with respiratory failure

Abstract

<div lang="en" class="abs"><p class="abs_header">Abstract</p><p>The aim of the study was to evaluate pulmonary endogenous and inhaled nitric oxide (NO) in neonates with severe respiratory failure.</p><p>Infant autopsy documents were reviewed for fulminant early-onset bacterial pneumonia. 12 infants with the onset at < 72 h of age and three control groups were identified. Immunohistochemistry revealed that 11 of the infants with early-onset pneumonia (92%) had no or faint inducible nitric oxide synthase (NOS2) staining in their alveolar macrophages (AM). All control infants, regardless of their postnatal age, had NOS2-positive AM. The marker of NO-toxicity, nitrotyrosine, was low in all specimens. To confirm this finding, airway specimens of 21 newborns requiring mechanical ventilation were examined. Seven of them had fulminant early-onset pneumonia with maternal ascending intra-uterine infection (IUI). The controls had no infection at birth despite IUI or neither infection nor IUI. In early-onset pneumonia, NOS2 and nitrotyrosine immunoreactivity were low at birth and increased during the recovery phase (p < 0.05). Analyses of interleukin-1 and surfactant protein A showed the same pattern of age-dependent change.</p><p>Of the autopsied infants, 12 had received inhaled NO (iNO) before death. Each case was paired with a matched control. Additional five infants without respiratory failure prior to death were also studied. The iNO-treated ones tended to have more intensive NOS2 staining in the bronchiolar epithelium and adjacent tissue than the controls. No differences in other NOS isoforms or nitrotyrosine were detected.</p><p>A novel method for exhaled NO measurements of intubated infants was developed. Six preterm and six term newborns were prospectively recruited for expired and nasal NO measurements. During the first week of life, the preterm infants showed a different pattern of exhaled NO excretion compared to the term infants.</p><p>For the pilot intervention study on very early iNO, the eligible patients had a birth weight < 1500 g and progressive, therapy-resistant respiratory failure before five hours of age. Five infants received iNO, showed immediately improved oxygenation and survived without deleterious side effects.</p><p>Deficient production of NO in small premature infants is associated with severe infection and respiratory failure. Very early iNO therapy may be exceptionally effective in a select group of infants, and did not appear to cause oxidation lung injury.</p></div>