turely. This chapter reviews the current understanding of the pathophysiology of chronic lung disease in premature infants and discusses the current interventions used to manage the disease. The term bronchopulmonary dysplasia (BPD) is commonly used interchangeably with chronic lung disease ofprematurity. The term BPD was first used by Northway et al.’ in 1967 to describe clinical, radiologic, and pathologic findings in premature infants who were exposed to high concentrations of oxygen and prolonged mechanical ventilation. Advances in neonatal care, such as use of antenatal steroids, surfactant replacement therapy, gentler ventilation techniques, and optimal nutritional support, have resulted in both an increased survival of extremely premature infants and an increased incidence of BPD.z,J However,the clinical presentation of the “new BPD” is milder than that described originally by Northway et al. Many infants with this new form have mild to moderate initial respiratory distress and receive ventilation with low pressures and oxygen concentration. Subsequently, some of these infants develop progressive deterioration in lung function and ultimately develop BPD. The original definition of BPD described by Northway et al. has changed over time in parallel with the changes in the epidemiology and clinical presentation of the disease. Bancalari et al.” modified the definition of BPD to include respiratory failure early in the neonatal period requiring assisted ventilation for a minimum of 3 days, radiographic abnormalities, and continuing respiratory symptoms and oxygen dependence at 28 days’ postnatal age. With improvements in survival rates of infants at even lower gestational ages, many infants who met these criteria were clinically asymptomatic by the time of discharge from the hospital. Therefore Sheehan et al.? proposed a change in definition from oxygendependence at 28 days’ postnatal age to oxygen dependence at 36 weeks’ postmenstrual age. A severity-based definition now has been proposed.” For the purposes of this review, BPD is defined as follows: 1. Supplemental oxygen requirement at 36 weeks’ postmenstrual age, 2. Persistent abnormalities on chest radiograph, and 3. Clinical signs of respiratory compromise persisting after age 28 days. Epidemiology The incidence of BPD varies significantly among neonatal intensive care units (NICUs)? and based on the definition used. Most cases occur in infants with birth weights <1500 g or who are born at gestational age :S;28 weeks. Approximately 30% to 40% of infants born weighing <1000 g develop BPD.8 Pathophysiology The pathogenesis ofBPD is multifactorial but can be attributed to a combination of three major factors: 1. Lung immaturity, leading to abnormal development of the lung, 2. Injury from inflammatory mediators caused by a variety of inciting factors, and 3. Inadequate repair response due to abnormal development of repair mechanisms. Lung development is a highly structured and sequential process. Alveoli undergo septation, which allows the alveoli to bud out or branch from existing alveoli. Interruption ofthis process leads to arrested alveolarization. In infants with BPD, airways have the same total volume but fewer total alveoli, resulting in larger airspaces. Multiple mediators can disrupt alveolarization, including glucocorticoids, mechanical ventilation, extreme hypoxia or hyperoxia, poor nutrition, and high levels of various cytokines.? Numerous factors induce an inflammatory response in the airways and pulmonary interstitium of preterm infants with BPD.10 This inflammatory response is characterized by the accumulation of neutrophils, macrophages, and proinflammatory mediators. Oxygen toxicity and barotrauma/ volutrauma from mechanical ventilation are associated with inflammation. In addition, volutrauma and atelectrauma cause abnormal stretch of the alveolar capillaries, leading to leakage of intravascular blood and protein. Leakage of these proteins causes mechanical obstruction, attracts other inflammatory cells, and inactivates surfactant, leading to further lung injury. Regardless ofthe initial insult, the final common pathway is release of inflammatory cytokines and chemokines that results in more inflammatory cell recruitment and fibrosis. The antioxidant and antiprotease enzymes in premature infants are immature and cannot easily reverse any damage that has incurred. Other factors that contribute to the development of BPD include the presence of a patent ductus arteriosus, antenatal and postnatal infections, and relative surfactant deficiency. Figure 2A-I outlines the factors that influence antenatal and postnatal lung development in premature infants. Other Pulmonary Complications Associated with BPD (Table 2A-I) Subglottic stenosis is a common complication in infants who require intubation, particularly if they have undergone prolonged or multiple intubations. Use of inappropriately large endotracheal tubes also contributes to the prevalence of subglottic stenosis. Common symptoms are stridor, hoarseness, cyanosis, and apnea. Tracheal or bronchial granulomas may occur and may be related to aggressive suctioning techniques and/or extended endotracheal intubation. Acquired tracheobronchomalacia, or central airway collapse, is an extremely common complication in infants with BPD. It is due to barotrauma .