Effect of intubation and mechanical ventilation on exhaled nitric oxide in preterm infants with and without bronchopulmonary dysplasia measured at a median postmenstrual age of 49 weeks

Abstract

BackgroundExhaled nitric oxide (eNO) is a marker of established airway inflammation in adults and children, but conflicting results have been reported in preterm infants when postnatal eNO is measured during tidal breathing. This study investigated the extent to which intubation and mechanical ventilation (MV) affect eNO and NO production (V’NO) in preterm infants with and without bronchopulmonary dysplasia (BPD).Patients and methodsA total of 176 very low birth weight (VLBW) infants (birth weight <1500 g), including 74 (42%) with and 102 (58%) without BPD, were examined at a median postmenstrual age of 49 weeks. Of the 176 infants, 84 (48%) did not require MV, 47 (27%) required MV for <7 days and 45 (26%) required MV for ≥7 days. Exhaled NO and tidal breathing parameters were measured in sleeping infants during tidal breathing, respiratory mechanics were assessed by occlusion tests, and arterialized capillary blood gas was analyzed.ResultseNO was significantly correlated with tidal breathing parameters, while V’NO was correlated with growth parameters, including age and body length (p < 0.001 each). Infants who were intubated and received MV for <7 days had significantly lower eNO (p < 0.01) and V’NO (p < 0.01) than non-ventilated infants. In contrast, eNO and V’NO did not differ significantly in non-ventilated infants and those receiving MV for ≥7 days. Multivariate analysis showed that independent on the duration of MV eNO (p = 0.003) and V’NO (p = 0.018) were significantly increased in BPD infants comparable with the effects of intubation and MV on eNO (p = 0.002) and V’NO (p = 0.017).ConclusionsPreterm infants with BPD show only weak postnatal increases in eNO and V’NO, but these changes may be obscured by the distinct influences of breathing pattern and invasive respiratory support. This limits the diagnostic value of postnatal eNO measurements in the follow-up of BPD infants.

An Overview of Fractional Exhaled Nitric Oxide and Children with Asthma

“…The children in the former study had higher levels of 8-isoprostane, a marker of oxidative stress, leading to speculation that noneosinophilic inflammation, such as neutrophilic inflammation, may be present in formerly premature children and lead to lower FeNO levels in children with asthma and history of BPD. Schmalisch et al have shown that former very-low-birth-weight infants undergoing infant lung function testing at an average of 49 weeks postmenstrual age have significantly lower FeNO if they had a history of receiving mechanical ventilation for <7 days compared to not having this history or receiving noninvasive mechanical ventilation [48]. Together, these studies imply that there are changes that may occur in the airway in formerly premature infants with and without history of BPD that may lead to a lower than expected FeNO value.…”

“…Schmalisch et al showed that FeNO levels were negatively correlated with tidal breathing parameters [48]. FeNO decreased with increased expiratory flow, indicating that measuring FeNO in sedated infants exhibiting tidal breathing may not be optimal to achieve a plateau in FeNO signal that is necessary to obtain an accurate value.…”

“…Schmalisch et al suggest that FeNO as clinical monitoring tool in these infants may not be helpful, given that they appear to be significantly influenced by expiratory breathing patterns and invasive ventilation [48]. …”

Tidal breath eNO measurements in a cohort of unsedated hospitalized neonates—A method validation

“…The methodological variability reported of eNO measurements has been pronounced. It includes off‐line or online measurements, adapted for research by counting and removing irregular breaths; hence, not applicable in a daily clinical setting. Measurements of eNO in premature mechanically ventilated neonates have been performed in the tube as well as in spontaneously breathing infants with a nasal prong or a facemask .…”

“…Williams et al found decreasing eNO levels after 3 days of Dexamethasone in premature, chronically ventilated infants; possibly caused by de‐activation of the enhanced iNOS activity described in inflammatory processes . Inducible NOS is up‐regulated by oxidants, and proinflammatory cytokines Exhaled NO varies in children suffering from various lung diseases; supporting its use as a tool in the differential diagnostics …”