Alterations of exhaled nitric oxide in pre-term infants with chronic lung disease

Abstract

Animal models suggest that reduced nitric oxide (NO) synthase activity results in lower values of exhaled NO (eNO) present at birth in those individuals who are going to develop chronic lung disease of infancy (CLDI).Online tidal eNO was measured in 39 unsedated pre-term infants with CLDI (mean gestational age (GA) 27.3 weeks) in comparison with 23 healthy pre-term (31.6 weeks) and 127 term infants (39.9 weeks) at 44 weeks post-conceptional age, thus after the main inflammatory response. NO output (NO output (V9NO)5eNO6flow) was calculated to account for tidal-flow-related changes. Sex, maternal atopic disease and environmental factors (smoking, caffeine) were controlled for.The mean eNO was not different (14.9 ppb in all groups) but V9NO was lower in CLDI compared with healthy term infants (0.52 versus 0.63 nL?s ). Values for healthy pre-term infants were between these two groups (0.58 nL?s -1 ). Within all pre-term infants (n562), V9NO was reduced in infants with low GA, high clinical risk index for babies scores and longer duration of oxygen therapy but not associated with post-natal factors, such as ventilation or corticosteroid treatment. After accounting for flow, the lower nitric oxide output in premature infants with chronic lung disease of infancy is consistent with the hypothesis of nitric oxide metabolism being involved in chronic lung disease of infancy.KEYWORDS: Chronic lung disease, infants, lung function, nitric oxide, prematurity R ecent evidence supports the hypothesis that chronic lung disease of infancy (CLDI) is the result of arrested or disturbed alveolar and vascular development [1]. The insult leading to this disturbed lung development may occur due to intra-uterine and postnatal infections, prematurity with surfactant deficiency or as a consequence of ventilation, hyperoxia (oxidative stress) or other factors. An inflammatory response with a peak at the age of ,10 days followed by a progressive decline [2] has been observed in this condition; however, little is known about the ongoing effects of these mechanisms after the acute phase during the first month of life.Various inflammatory processes, with a dominance of neutrophilic inflammation and oxidative stress, are involved in the pathogenesis of CLDI. Premature infants exhibit an immature response to oxidative stress [3], immature interleukin-10-mediated inflammatory responses [4,5], persistence of neutrophilic inflammation and an imbalance of a 1 -protease inhibitor activity [6]. Nitric oxide (NO) metabolism plays a crucial role in many of these inflammatory processes. Exhaled NO (eNO) is altered during both oxidative stress [7] and neutrophilic inflammation [8]. There is also increasing evidence that NO is involved in lung development and growth, as well as in angiogenesis [9,10]. Recently, it has been demonstrated that premature baboons, in which CLDI subsequently develops, show pre-existing alterations of NO metabolism at birth [11]. These animals have decreased levels of constitutive forms of NO synthase (endothelial nitr...

Relation of exhaled nitric oxide levels to development of bronchopulmonary dysplasia

“…In older infants16 and children17 18 who had had BPD, similar or lower eNO levels compared with controls have been reported. The children, however, were of school age18 or studied between 4 and 25 months17 and the infants examined at 44 weeks PMA,16 when the authors state they felt the main inflammatory process was over.…”

Exhaled nitric oxide in childhood asthma: a review

“…Mieskonen et al [137], however, did not find any differences in FE NO between controls and school-age children with CLD. Studies in younger children revealed values to be equal to or higher in patients with CLD compared with controls, although NO output seemed lower in preterm infants with CLD [38,138,165].…”

Smoke exposure, airway symptoms and exhaled nitric oxide in infants: the Generation R study

“…Compared with healthy infants, lower FeNO levels have been found in infants with virus-associated acute, wheezing bronchitis [5] and in infants with upper respiratory symptoms (URS), such as rhinorrhoea [6]. Several preand post-natal factors have been shown to influence the levels of FeNO in infants, such as tobacco smoke exposure [7][8][9], coffee consumption during pregnancy [8], maternal atopic disease [8,10], birth weight [11], gestational age [11,12], sex [8] and infections [13]. However, the influence of risk factors for respiratory morbidity on FeNO in infancy is not clear.…”