Pathology of new bronchopulmonary dysplasia
Introduction
Bronchopulmonary dysplasia (BPD) is a disease that is now seen primarily in preterm newborns weighing less than 1000 g who are born at 24–26 weeks of gestation. The use of exogenous surfactant, coupled with the advances in critical care management that have led to less volutrauma and oxygen injury, has resulted in the present pattern of injury, which reflects an extremely immature lung with impaired alveolar and capillary growth and development caused by developmental arrest, withsubsequent abnormal reparative processes. Its pathogenesis involves extreme lung immaturity, treatment-induced oxygen and volutrauma injury, and an inflammatory response that elicits lung injury and some degree of disorganized repair. Recent evidence also suggests that prenatal intrauterine infections may predispose the fetal lung to subsequent oxidant and volutrauma injuries.1
To better understand ‘new’ BPD pathology, a review of human lung development focuses and defines the problem of current BPD in low-birthweight infants.2, 3 The stages and accompanying developmental events of lung development are briefly reviewed and illustrated in Table 1. At 24 weeks, the lung is in the canalicular stage of development, whereas at 30 weeks, it is in the saccular stage. The extent of lung development between 24 and 26 weeks' gestation and 30–32 weeks' gestation is substantial (Fig. 1, Fig. 2;comptd;;center;stack;;;;;6;;;;;width> ;comptd;;center;stack;;;;;6;;;;;width> ): alveolar and capillary development are initiated along with interstitial extracellular matrix loss and remodeling. Although alveoli are present in some infants at 32 weeks' gestation, they are not uniformly present until 36 weeks, during the alveolar stage of development (Fig. 3;comptd;;center;stack;;;;;6;;;;;width> ). Thus, premature birth and the initiation of pulmonary gas exchange interrupt normal alveolar and distal vascular development, thereby triggering the production of two of the major features of new BPD.
Section snippets
Evolution of ‘old’ to ‘new’ BPD pathology
The histopathological changes of severe airway injury and alternating sites of overinflation and fibrosis in ‘old’ BPD (for a review see Ref. 4; see also 5, 6) (Table 2), evoked by elevated oxygen and ventilator-induced injury on a relatively immature and surfactant-deficient lung, were in part lost as technologic advances, improved ventilatory strategies and better nursing techniques were utilized, resulting in the survival of smaller and more immature infants.
Thereafter, several articles
Autopsy pathology of very immature, extremely low-birthweight infants with prenatal steroid and/or postnatal surfactant treatments
In the only surfactant-treated series reported, Husain et al. examined autopsy specimens from 14 surfactant-treated infants with BPD, eight non-surfactant-treated BPD patients and 15 age-matched controls who were autopsied from 1988 through 1994.12 The infants were treated with three doses of exogenous surfactant (either Survanta or Exosurf), given by intratracheal aerosolization during the first 24 h. No history of prenatal steroid treatment was given. Gestational ages of the surfactant-treated
Biopsy pathology of BPD in very immature, extremely low-birthweight infants
As O'Brodrovich and Mellins observed in 1985, autopsy findings represent the severe end of the spectrum in BPD.14 The introduction of treatment with exogenous surfactant and the prenatal use of steroids have resulted in a dramatic decrease in the mortality of infants with BPD, resulting in very few autopsies. It is probably safe to say that the majority of autopsies now performed really do represent the sickest of infants so the findings may not be at all representative of the lung's appearance
Acknowledgements
This work was partially supported by National Institutes of Health grant HL52636. Several of the photomicrographs are from cases referred by Drs Don Null, the late Bob deLemos and Galen Schauer, and are gratefully acknowledged. Special thanks are extended to Vicki Winter, Linda Buchanan and the rest of my laboratory staff for their assistance with manuscript preparation.
Practice points
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The lungs of infants born at 24–26 weeks' gestation are in the canalicular phase of lung development; alveolar
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