Pulmonary inflammation and bronchopulmonary dysplasia

Various risk factors can induce an injurious inflammatory response in the airways and the pulmonary interstitium of preterm infants with bronchopulmonary dysplasia (BPD). Among these factors, it is possible to remember lung immaturity, oxygen toxicity, baro- and volutrauma, initiation and duration of mechanical ventilation, prenatal and nosocomial infections, and increased pulmonary blood flow secondary to a patent ductus arteriosus. In recent times, increased use of antenatal glucocorticosteroids, more gentle ventilation techniques, and early surfactant treatment have definitely minimized the severity of lung injury in more mature infants with respiratory distress syndrome (RDS) and reduced the incidence of severe BPD. However, there is a new category of very immature infants with a 'new' BPD who have minimal signs of RDS but who subsequently develop oxygen dependency. Various postnatal factors such as pulmonary or systemic infections, inappropriate resuscitation, high airway concentrations of inspired oxygen, and mechanical ventilation may amplify the inflammatory reaction and affect normal alveolarization and pulmonary vascular development in preterm infants with 'new' BPD.
This inflammatory response is characterized by an accumulation of neutrophils and macrophages and of proinflammatory mediators that affect the endothelium and alveolar-capillary integrity.
For instance, a neutrophil influx into the airways was observed immediately after initiation of ventilation and was correlated to an increased risk of developing BPD. Moreover, a prolonged survival of neonatal neutrophils owing to an inappropriate suppression of neutrophil apoptosis has been described.
Before neutrophil migration, cellular attachment to endothelial cells is mediated through interaction of adhesion molecules. Increased concentrations of these molecules have been detected in airway secretions of preterm infants with BPD. In addition, airway secretions of infants with BPD have been shown to contain a number of chemotactic factors responsible for the recruitment of neutrophils and macrophages and the chemotactic activity was considerably higher in infants with BPD, if compared with babies who recovered from RDS. Moreover, lipid mediators and proteases may also be responsible for acute lung injury.
Inflammation induced by tissue injury is normally followed by a phase of repair. Lung injury leads to an induction of transforming growth factor-ß (TGF-ß) which limits some of the inflammatory reactions and plays a key role in mediating tissue remodeling. If the reparative processes are exaggerated and not adequately localized, as in presence of increased levels of TGF-ß, fibrosis could occur. In preterm infants with BPD, increased levels of TGF-ß have been detected in the airway secretions.
Up to now, studies investigating inflammatory mediators in BPD have largely been descriptive and the relative importance of individual factors has not been defined yet. Increasing evidence indicates that BPD results, at least in part, from an imbalance between the proinflammatory and anti-inflammatory mechanisms, in favor of proinflammatory mechanisms. In addition, an impaired generation of growth factors crucial for a normal pulmonary development and repair has recently been implicated as a possible feature in the pathogenesis of BPD. Recent advances in molecular biology will provide the necessary tools to elucidate the underlying mechanisms and regulation of the cytokine- and inflammatory network in BPD.

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