Long-term outcomes of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD), defined as the need for supplemental oxygen for at least 28 days after birth, is a chronic respiratory disease that develops in premature infants exposed to mechanical ventilation and oxygen supplementation. Symptoms of this disease may persist even in adult age, suggesting that lung injuries early in life may have lifelong consequences. However, natural history and possible outcomes of BDP into adulthood are still largely unknown. What is now considered the "old" BPD was originally described in slightly preterm newborns with the respiratory distress syndrome (RDS), who had been exposed to aggressive mechanical ventilation and high concentrations of inspired oxygen. Diffuse airway damage, smooth-muscle hypertrophy, neutrophilic inflammation, and parenchymal fibrosis reflected extensive disruption of relatively immature lung structures. However, despite the introduction of measures to prevent and treat RDS, the overall prevalence of BPD has not changed because, with the improved survival rate among preterm infants, a "new" form of BPD interpreted as a developmental disorder has been described. Infants at risk for this condition often have only mild respiratory distress syndrome at birth, but even minimal exposure to injurious factors may affect the normal processes of pulmonary microvascular growth and alveolarization. However, most of the information on long-term lung function in survivors of BPD refers to the era before surfactant treatment was available or to patients who had severe pulmonary disease as neonates, thus reflecting the outcomes of the old form of BPD. Moreover, because these patients are surviving, the characterization of the long-term pulmonary outcome after premature birth remains primarily clinical, since it is not possible to gather data on pathological findings from tissue examination. Several studies have reported increased rates of wheezing, chronic coughing, asthmalike symptoms and the use of inhaled asthma medication among preschool and school-age children who were born prematurely, especially those who experienced BPD, than among persons born at term. Analysis of forced expiratory flows shows substantial airflow limitation during the first 3 years of life, probably reflecting the coupled effects of an unresolved lung injury plus the developmental interferences related to prematurity itself, at a time when the infants are growing rapidly. The degree of airflow limitation in the first years of life also seems to predict later pulmonary function, suggesting an irreversible early airway-remodelling process. Spirometric values are consistently lower in survivors of BPD at any age than in controls born at term, indicating substantial airway obstruction and alveolar hyperinflation. Some investigators have expressed concern that survivors of BPD may be susceptible to COPD in later life. In fact, there may be an overlap in the clinical and physiological characteristics of the two conditions, but longer follow-up will be needed before BPD can be included in the well-established diagnosis of COPD. At present, there are few indications for the treatment of persistent BPD in childhood and adulthood. Corticosteroid therapy is still controversial, due to the risk of serious short-term adverse events and of neurodevelopmental impairment. The use of inhaled bronchodilators, including ß2-agonists and anticholinergic agents, can improve short-term lung function, but whether they can prevent exacerbations and improve the quality of life remains to be demonstrated. However, when inhaled drugs are used, metered-dose inhalers, with a spacer and mask, seem to have several advantages over nebulizers. In conclusion, BPD may potentially be associated to some important long-term outcomes, such as COPD. Because many BPD survivors are now approaching adulthood, more cases of this novel chronic pulmonary disease, which begins in neonatal life, are expected in the next years. Tools should be developed for phenotype specific diagnosis and management of chronic lung disease.

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