BPD most commonly occurs in the smallest, sickest infants, those weighing less than 1.5 kg.
Bronchopulmonary dysplasia (BPD) and chronic lung disease (CLD) are often used interchangeably to describe chronic lung disorders that develop in infancy. BPD can develop from any disorder that produces an acute lung injury or requires treatment using positive-pressure ventilation.1 CLD defines a heterogeneous group of respiratory diseases experienced from infancy that evolves into acute and then chronic respiratory disorders.1 BPD is a CLD that evolves after premature birth and RDS (respiratory distress syndrome). RDS develops due to a lack of surfactant. BPD develops from the aggressive interventions used to manage serious neonatal respiratory disorders. The absence of RDS at birth does not eliminate the risk of developing BPD or CLD.1 New treatment options have prompted an evolution for defining BPD.
The incidence of BPD is difficult to quantify due to changing epidemiology and inconsistent definitions.2 Recent advances in medical management, including respiratory care, have helped to make BPD a rare disorder in infants weighing more than 1.2 kg. The incidence of BPD in infants weighing less than 1 kg remains approximately 30%.1 Most premature infants do not experience RDS, but often require prolonged mechanical ventilation for apnea or poor respiratory effort, still putting them at risk for developing BPD. Data from the US National Institute of Child Health and Human Development Neonatal Research Network2 indicate that, in 1996, the incidence of RDS in infants with birth weights of 750 g to 1 kg (26 weeks gestational age) was 63%. Approximately 42% of the survivors suffered symptoms related to BPD. The 37% who did not develop RDS appear to have had clinically mature lungs. These figures, however, may be misleading.
Old and New BPD
Northway first described BPD in premature infants with RDS in 1967.1,4-7 In 1971, Bancalari et al6 proposed three basic criteria to define BPD: a supplemental oxygen requirement 28 days after birth, persistent abnormalities in the chest radiograph, and tachypnea in the presence of rales or retractions. This is now considered the old definition of BPD. Old BPD was characterized by airway injury with airway epithelial metaplasia, increased smooth-muscle mass and fibrosis, nonuniform inflation of the lungs with a combination of emphysema and fibrosis, marked reduction in alveolar development, and inflammation.7,8 Oxygen supplementation for more than 28 days was often used for the diagnosis of BPD or chronic lung disease.1,6,7
Medical and technological advances, along with the changing characteristics of the disorder, created a need to refine the definition of BPD. It is now defined as a supplemental oxygen requirement at a postmenstrual age of 36 weeks.1,6 New BPD is associated with a persistent oxygen requirement, tachypnea, wheezing, and other signs of airway narrowing.7 The characteristics of new BPD include less severe airway injury, less inflammation, less parenchymal fibrosis, more uniform lung inflation, and a marked reduction in alveolar development.7
The risk of developing BPD is directly related to the infants birth weight and gestational age, the severity of the initial lung disease, the duration of mechanical ventilation, and whether high concentrations of inspired oxygen were used during the initial weeks of life.1,5
Preterm infants most likely to develop BPD are born during the canalicular phase of lung development.8 This phase occurs at approximately 17 to 26 weeks gestation,7,9 when alveolar and distal vascular development commence.8 Lowbirth-weight infants usually experience RDS due to prematurity.
Prevention and Management
The effort to prevent RDS and BPD begins before birth through improved prenatal care, which prevents thousands of premature births. Treatment of premature infants relies on a network of high-tech neonatal intensive care units (NICUs), and there appear to be vast differences in BPD incidence among NICUs.5 Centers that emphasize ventilation using low airway pressures, permit permissive hypercapnia, and avoid intubation or promote early extubation have fewer cases of BPD.5 In the Holden NICU in Mott Childrens Hospital at the University of Michigan, Ann Arbor, RTs are encouraged and expected to be actively involved in ventilator management. Physicians and nurses frequently rely on the knowledge and specialized skills of the RTs. The evolving definition of BPD and increased survival of children with this disorder are often attributed to the widespread use of antenatal steroids (beginning in the 1970s), the more recent use of surfactant-replacement therapy, vast improvements in ventilator technology, better nutritional interventions, and oxygen monitoring.1
One factor contributing to the survival of premature infants is the antenatal administration of corticosteroids.5 An analysis by Crowley3 found that antenatal cortico-steroids decreased the incidence of RDS by 50%, with little effect on the incidence of BPD. The apparent failure of antenatal corticosteroids to decrease the incidence of BPD may be explained by the increasing survival rates of the infants most at risk.2 Postnatal administration of corticosteroids has been shown to decrease inflammation, increase surfactant synthesis, enhance beta-adrenergic activity, increase production of antioxidants, stabilize cell membranes, and inhibit prostaglandin and leukotriene synthesis.10 Increased dynamic compliance and decreased pulmonary resistance are common after corticosteroid administration.10 Further, the postnatal use of corticosteroids appears to lessen the severity of BPD in ventilator-dependent premature infants, but does not significantly affect mortality or length of stay.10-13
New Research continues to focus on reducing ventilator-induced lung injury (VILI) to prevent BPD. The premature lung is at higher risk for developing alveolar structural damage, pulmonary edema, inflammation, and fibrosis from VILI.1,9 Evidence is mounting against the inflammatory process and the edema associated with lung injury as factors leading to abnormal alveolization and pulmonary vascular development.8,9 There are four mechanisms of VILI: barotrauma (high pressure), volutrauma (large volume), atelectotrauma (alveolar collapse and re-expansion), and biotrauma (increased inflammation).9 It is important to understand the mechanisms of lung injury associated with mechanical ventilation in order to prevent it. For example, although airway pressures are routinely monitored, transpulmonary pressures are not routinely monitored in patients at risk for VILI or BPD. It is also known that ventilation-induced lung edema occurs due to lung overinflation.9 Nasal continuous positive airway pressure (CPAP) is increasingly being used as an alternative to conventional mechanical ventilation. Early initiation of nasal CPAP has been shown to reduce the need for conventional mechanical ventilation, artificial surfactant, and supplemental oxygen.14 Nasal CPAP is also being used in combination with surfactant prophylaxis as an effective (and potentially less damaging) support mode capable of reducing the need for long-term mechanical ventilation.15 The usefulness of nasal CPAP in treating premature infants of less than 28 weeks gestation has not been proven.15 High-frequency oscillatory ventilation (HFOV) is another option for treating neonatal respiratory disorders. Studies16 to determine the benefits of HFOV have, however, been inconclusive.16 Further, the elective use of HFOV appears to decrease the incidence of BPD or CLD, but may increase the risk of intraventricular hemorrhage and periventricular leukomalacia.16,17 A review18 of several studies found that HFOV had little effect on the mortality of infants at 28 days of age or approximate term-equivalent age. Laboratory investigations16,17 suggest that the benefit of HFOV (optimization of volume) could be replicated with low tidal volume and high positive end-expiratory pressure using conventional modes of ventilation.
Other treatments and potential treatments for BPD include permissive hypercapnia, nitric oxide therapy, liquid ventilation, and aerosolized diuretics. It is believed that permissive hypercapnia may decrease volutrauma, decrease the duration of positive-pressure ventilation, reduce alveolar ventilation, and increase oxygen unloading in tissues.20 A meta-analysis by Woodgate and Davies19 of two trials involving 269 infants showed no evidence, however, that permissive hypercapnia reduced the incidence of chronic lung disease or death at 36 weeks after birth. There also appeared to be no decrease in the incidence of intraventricular hemorrhage or periventricular leukomalacia.19 Therefore, there appears to be little or no benefit associated with permissive hypercapnia in newborn infants.19 More clinical trials are needed.19
Nitric oxide therapy is used to reduce hypoxia in term infants, and appears to be associated with a small reduction in the severity of BPD or chronic lung disease.20 Its effectiveness in premature infants, however, requires further research.
Liquid ventilation continues to be researched aggressively and its potential remains promising.21 Another treatment option being researched is the use of aerosolized diuretics. Current research is promising, demonstrating improved lung mechanics, but more double-blind randomized trials are recommended.22
Thanks to advances in mechanical ventilation, surfactant therapy, and antenatal glucocorticoid administration, the number of infants who develop BPD has been significantly reduced. Nonetheless, the incidence of BPD in infants weighing less than 1.5 kg is increasing due to their increased survival. As technology continues to improve, more premature infants will survive without developing BPD or chronic lung disorder. BPD incidence will decrease because management of conventional mechanical ventilation will be designed to prevent VILI. It is important to conduct a benefit and risk comparison before considering any treatment option.
Megan Rauch, RRT, and Heather Borges, RRT, are respiratory care practitioners, Holden Neonatal Intensive Care Unit, Mott Childrens Hospital, University of Michigan Medical Center, Ann Arbor.
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