Electrical Potential Difference Across the Nasal Epithelium Is Reduced in Premature Infants With Chronic Lung Disease but Is Not Associated With Lower Airway Inflammation

Abstract

Airway liquid content and insufficient absorptive airway ion transport at birth are potentially important factors in the development and severity of neonatal respiratory disease. The role of deficient absorptive airway ion transport in the development of chronic lung disease of prematurity is unknown. Additionally, lung inflammatory mediators modulate airway ion transport. Their effect on preterm lung ion transport and absorptive capacity is not established. We performed serial nasal potential difference studies and broncho-alveolar lavage in preterm infants born less than 30 wk postmenstrual age over the first four postnatal weeks. Our study aims were to: 1) compare nasal potential difference between preterm infants developing chronic lung disease and babies of similar gestation who do not; and 2) examine for an association between airway inflammation and ion transport parameters. We found that potential difference across the nasal epithelium increased with gestation, remained low and unchanged in infants developing chronic lung disease over the first four postnatal weeks, was significantly lower at four weeks in chronic lung disease infants, and was not associated with lower airway inflammation at any time point. We conclude that infants with chronic lung disease postnatally have a persistently reduced absorptive airway ion transport capacity. (Pediatr Res 61: 77-82, 2007) T he incidence of chronic lung disease of prematurity (CLD) in very preterm infants has not changed significantly over the last decade despite the routine administration of antenatal steroids and postnatal exogenous surfactant (1,2).A greater residual airway liquid content resulting from incompletely developed absorptive airway ion transport processes at birth is a potentially important factor in the pathogenesis and severity of the neonatal respiratory distress syndrome (RDS) (3-5). Compared with preterm babies without neonatal lung disease, those with RDS have an increased lung liquid content (6,7).Lung inflammation is present in preterm infants with RDS (8,9). Those who develop CLD experience a persistent and greater lung inflammatory response (10,11).Recent studies have demonstrated that inflammatory mediators influence airway ion transport processes (12-16). However, in vitro studies have given conflicting results with respect to the effect of cytokines on airway ion transport processes. Interleukin (IL)-4 and interferon-␥ inhibit the amiloride sensitive epithelial sodium channel (ENaC) (12,13) in polarized cultured human bronchial epithelial cells whereas tumor necrosis factor (TNF)-␣ was not found to modulate ion transport (13). In vivo experiments have demonstrated a TNF-␣ (14), IL-1␤ (15) and TGF-␣ (16) mediated increase in lung liquid absorption. These studies were conducted with single cytokines in models of mature lung epithelium. There are no data on the impact of cytokines on the airway ion transport processes of the human newborn lung in vivo.The aim of this study was to examine in vivo the association between cytoki...

Pulmonary Fluid Balance in the Human Newborn Infant

“…In the nasal epithelium of the preterm newborn infant, amiloride-sensitive N-PD, a correlate for ENaC activity, has been shown to correlate with gestational age [50] . Preterm infants have significantly lower amiloride-sensitive N-PD than term infants [51,52] , suggesting impaired airway epithelial ion transport and inability to clear the lung of perinatal fluid.…”

“…In TTN, there is a lower amiloride-sensitive N-PD than in healthy newborn infants [2] . N-PD measurements have also been performed on preterm infants with and without BPD, showing that at 29 days of age infants with BPD have significantly lower N-PD than those without BPD [50] . Accordingly, BPD may be associated with a prolonged impairment of airway ion transport.…”

Expression and activity of epithelial sodium channel in hyperoxia‐induced bronchopulmonary dysplasia in neonatal rats

“…reported that infants at high risk of developing BPD had lower amiloride‐sensitive nasal potential difference (ASNPD) values in the immediate postnatal period; 13 Gaillard et al . reported that at 29 days of age infants with BPD had significantly lower nasal potential difference (N‐PD) than those without BPD 12 . The above researchers chose nasal epithelial cells as substitute for alveolar epithelial cells, so the conflicting results with ours may be due to different study methods and cell types.…”

“…and Thome et al . indicated that pathogenesis of BPD may be related to Na + transport disorders 12,13 . Therefore, we adopted a classic hyperoxia‐induced BPD model in neonatal rats and examined the dynamic changes in ENaC expression levels.…”

I have taken my umbrella, so of course it does not rain: Figure 1

“…One can assume that this will not have the same patterns of inflammation as COPD in smokers. There has been much speculation that the survivors of premature birth and bronchopulmonary dysplasia may be at risk for COPD, but such evidence as exists is that they do not have airway inflammation 11. Thus, treatment strategies trialled in patients with ‘smoking COPD’ may be inappropriate in other forms of persistent airflow obstruction.…”