Moving bronchopulmonary dysplasia research from the bedside to the bench

Abstract

Although advances in the respiratory management of extremely preterm infants have led to improvements in survival, this progress has not yet extended to a reduction in the incidence of bronchopulmonary dysplasia (BPD). BPD is a complex multifactorial condition that primarily occurs due to disturbances in the regulation of normal pulmonary airspace and vascular development. Preterm birth and exposure to invasive mechanical ventilation also compromises large airway development, leading to significant morbidity and mortality. Although both predisposing and protective genetic and environmental factors have been frequently described in the clinical literature, these findings have had limited impact on the development of effective therapeutic strategies. This gap is likely because the molecular pathways that underlie these observations are yet not fully understood, limiting the ability of researchers to identify novel treatments that can preserve normal lung development and/or enhance cellular repair mechanisms. In this review article, we will outline various well-established clinical observations while identifying key knowledge gaps that need to be filled with carefully designed preclinical experiments. We will address these issues by discussing controversial topics in the pathophysiology, the pathology, and the treatment of BPD, including an evaluation of existing animal models that have been used to answer important questions.