The contribution of experimental models to our understanding of the pathogenesis and treatment of bronchopulmonary dysplasia.

The extensive data from animal models of BPD and specific aspects of lung injury have helped to expand and refine the concept of pathogenesis introduced by Northway et al. Given the complexity and heterogeneity of the human illness, it is unreasonable to presume that any single model or research group could elucidate all of the features and interactions of this complex disease. Therefore, we have combined data from animal homologues of BPD with that available on specific injury mechanisms to construct a more comprehensive model of pathogenesis (Fig. 5). Of particular interest is the recent data suggesting that the accelerated maturation of the prematurely born infant is associated with specific defects in gene expression that might increase vulnerability to lung injury. Additional animal research is needed both to further refine this model of pathogenesis and to develop the basis for a more rationale approach to the prevention and treatment of BPD. Based on the research progress to date, we feel the priorities for the future should at the least include continued definition of the biochemical and molecular mechanisms underlying various types of lung injuries; evaluation of those mechanisms (and the consequences of their interruption) in a developmentally relevant setting; and further elaboration of the currently available BPD models to include factors (such as ante- and postpartum infections) that have not previously been part of these animal model systems. This approach, we feel, will complement human studies and ultimately lead to the prevention and better clinical management of this major health care problem.