Using Experimental Models to Identify Pathogenic Pathways and Putative Disease Management Targets in Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is a common and serious complication of preterm birth. Limited pharmacological and other medical interventions are currently available for the management of severely affected, very preterm infants. BPD can be modelled in preclinical studies using experimental animals, and experimental animal models have been extremely valuable in the development of hallmark clinical management strategies for BPD, including pulmonary surfactant replacement and single-course antenatal corticosteroids. A gradual move away from large animal models of BPD in favor of term-born rodents has facilitated the identification of a multitude of new mechanisms of normal and stunted lung development, but this has also potentially limited the utility of experimental animal models for the identification of pathogenic pathways and putative disease management targets in BPD. Indeed, more recent pharmacological interventions for the management of BPD that have been validated in randomized controlled trials have relied very little on preclinical data generated in experimental animal models. While rodent-based models of BPD have tremendous advantages in terms of the availability of genetic tools, they also have considerable drawbacks, including limited utility for studying breathing mechanics, gas exchange, and pulmonary hemodynamics; and they have a less relevant clinical context where lung prematurity and a background of infection are now rarely present in the pathophysiology under study. There is a pressing need to refine existing models to better recapitulate pathological processes at play in affected infants, in order to better evaluate new candidate pharmacological and other interventions for the management of BPD.