ABSTRACT
The term bronchopulmonary dysplasia (BPD) was coined by Northway et al. (1) to reflect the involvement of all lung tissue elements. The described features included airway mucosal metaplasia, airway and vascular smooth-muscle hyperplasia, saccular emphysema, and atelectasis. The same group of investigators subsequently emphasized the additional feature of widespread interstitial fibrosis (2). An intriguing feature of BPD, as seen in the current era, has been a reduced frequency of airway injury (3,4). This may simply reflect a change in population characteristics, in that there has been a proportional increase in the representation of very low birth weight infants among those who survive and go on to acquire BPD. Alternatively, there may have been some unattributed change in management that has resulted in a decrease in the degree of airway injury. There are likely to be multiple factors that result in the histological changes seen with the development of BPD, but the three major candidates are pulmonary oxygen toxicity, barotrauma, and cellular immaturity. Unlike injury to the adult lung, in which lung cell proliferation is superimposed on an essentially growth-arrested organ, BPD occurs in an organ that is normally in a state of active cell division. In the most severely affected infants BPD is characterized by a long-term global
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reduction in alveolar number and surface area (5). However, this long-term failure of lung growth is preceded, in the early stages of injury, by reparative pneumonocyte hyperplasia and later, in those who develop fibrosis, patchy areas of fibroblast hyperplasia. These specific cellular hyperplasia are superimposed on an overall pattern of development in which formation of new alveoli is retarded. Whether these changes reflect an altered pattern of secretion of those polypeptide growth factors that control normal lung growth, or the appearance of different factors, is unknown. There is very little direct information available about the role of polypeptide growth factors, either in normal human lung development or in BPD. In part, this has been due to limited availability of human tissue in the early stages of disease development and, until relatively recently, uncertainty over the identity of likely mediators of cell growth. Although the factors that influence cell growth in BPD remain unknown, there has been considerable recent information obtained from several in vitro and in vivo models of growth, repair, and injury that suggest that immaturity, oxygen concentration, and barotrauma, all may influence the expression of growth factors in the developing lung.
