Looking ahead: where to next for animal models of bronchopulmonary dysplasia?

Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth, with appreciable morbidity and mortality in a neonatal intensive care setting. Much interest has been shown in the identification of pathogenic pathways that are amenable to pharmacological manipulation (1) to facilitate the development of novel therapeutic and medical management strategies and (2) to identify the basic mechanisms of late lung development, which remains poorly understood. A number of animal models have therefore been developed and continue to be refined with the aim of recapitulating pathological pulmonary hallmarks noted in lungs from neonates with BPD. These animal models rely on several injurious stimuli, such as mechanical ventilation or oxygen toxicity and infection and sterile inflammation, as applied in mice, rats, rabbits, pigs, lambs and nonhuman primates. This review addresses recent developments in modeling BPD in experimental animals and highlights important neglected areas that demand attention. Additionally, recent progress in the quantitative microscopic analysis of pathology tissue is described, together with new in vitro approaches of value for the study of normal and aberrant alveolarization. The need to examine long-term sequelae of damage to the developing neonatal lung is also considered, as is the need to move beyond the study of the lungs alone in experimental animal models of BPD.