Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD), also referred to as chronic lung disease of prematurity, is a syndrome of lung immaturity, injury, and inflammation that is complicated by a dysregulated repair response, leading to a persistent oxygen dependence and respiratory problems in neonates. Histopathologically, BPD is characterized by an arrest of alveolar development, with relative alveolar simplification and abnormal vasculature that results in a reduction in surface area and decreased efficacy of the gas-exchange units in the lung. First described in the 1960s, the prevention and management of BPD remains an important and dynamic field of pediatric research as the prevalence of premature birth increases. 

Risk Factors

Preterm birth is the primary risk factor for the development of bronchopulmonary dysplasia. Other risk factors include low birth weight, the need for mechanical ventilation, and maternal smoking and hypertension.

(Source: Antenatal Determinants of Bronchopulmonary Dysplasia and Late Respiratory Disease in Preterm Infants. Am J Respir Crit Care Med 2017. Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.)

Assessment and Diagnosis

The assessment of an infant with suspected BPD begins with the patient’s prenatal and neonatal history. The National Institutes of Health (NIH) consensus definition of BPD is the need for supplemental oxygen at 28 days of life. This can be further stratified into severity classifications depending on the infant’s gestational age.

(Source: Reprinted from Definitions and Diagnostic Criteria for Bronchopulmonary Dysplasia. Semin Perinatol 2006, with permission from Elsevier.)

Infants with BPD have markedly variable exams that can include the following:

• tachypnea and retractions

• increased chest-wall diameter

• fine rales from pulmonary edema; wheeze may be heard if the patient has severe BPD and small-airway obstruction from scarring or mucus retention

• coarse (or even relatively clear) lung sounds

• normal cardiac exam but can suggest pulmonary hypertension in patients with significant pulmonary vascular involvement
  
  

Chest imaging is an important part of the initial diagnosis of BPD. The chest radiograph evolves as BPD progresses and generally appears as a diffuse, hazy interstitial pattern, which can represent both pulmonary edema and, later, airway fibrosis. In severe cases, chest hyperinflation and air trapping will be evident. In the presence of comorbid pulmonary hypertension, there may be fullness of the pulmonary vasculature. All patients with suspected BPD and persistent hypoxemia should have a screening echocardiogram to evaluate pulmonary pressures.

Chest radiograph of a 7-month-old infant with a history of extreme prematurity and moderate bronchopulmonary dysplasia. Note the diffuse, ill-defined reticular markings indicative of chronic lung disease of prematurity. Courtesy of Kevin Gipson.

Management

Once BPD is clinically suspected or diagnosed, several therapeutic strategies can be deployed to mitigate further lung damage. Ventilator strategies include the following:

• volume- and pressure-limited modes to prevent volutrauma and barotrauma

• permissive hypercapnia targeting a PaCO₂ of 50-55 mmHg and a pH ≥7.2

• conservative use of supplemental oxygen to minimize lung injury
  
  

Infants with BPD or at risk for BPD should be extubated as soon as clinically feasible, to minimize exposure to supraphysiological distending pressures and volumes and to reduce the likelihood of developing ventilator-associated pneumonia. Many infants start on nasal continuous positive airway pressure (CPAP) at time of delivery as an intubation-sparing modality, or they are quickly extubated to CPAP to minimize time on the ventilator.

Diuretics: BPD is associated with endothelial dysfunction of the pulmonary vasculature, leading to pulmonary edema and impaired pulmonary dynamics. A major pillar of the medical management of BPD is the use of diuretics, commonly the loop diuretic furosemide, the thiazide diuretic chlorothiazide, and the potassium-sparing diuretic spironolactone. These medications can lead to electrolyte derangements, particularly when used on a long-term daily basis, so monitoring is warranted.

Systemic glucocorticoids: Using systemic glucocorticoids for the prevention and treatment of BPD remains a controversial subject given conflicting conclusions from numerous studies. Recent meta-analysis suggests that benefits of early glucocorticoid therapy (e.g., decreased time on mechanical ventilation and possibly risk of BPD in premature infants) may not outweigh potential adverse effects (including concern for gastrointestinal perforation, hypertension, growth failure, and adverse neurodevelopmental outcomes). Inhaled glucocorticoids have not clearly been shown to provide any advantage over systemic glucocorticoids; however, current studies are exploring whether inhaled glucocorticoids are safer because of decreased systemic absorption.

Outcomes for infants with BPD are variable and depend principally on the severity of lung disease and comorbid conditions (e.g., marked prematurity, central nervous system [CNS] injury). In extremely premature infants (gestational age, 22 0/7 to 28 6/7 weeks), respiratory distress syndrome and bronchopulmonary dysplasia are major proximal causes of death within the first 3 months of life.

(Source: Causes and Timing of Death in Extremely Premature Infants from 2000 through 2011. N Engl J Med 2015.)

Nevertheless, most patients with BPD do well. Very few patients have an ongoing oxygen requirement by age 2 years, and most have subjectively normal respiratory health without overt physical limitations. However, longitudinal pulmonary-function testing often demonstrates persistent airflow limitation. Children born prematurely with a history of BPD appear to have an increased prevalence of asthma that is managed with inhaled glucocorticoids and bronchodilators. Patients with a history of severe BPD have an increased incidence of long-term airflow limitation and may benefit from anticholinergic medications such as tiotropium.

(Source: Causes and Timing of Death in Extremely Premature Infants from 2000 through 2011. N Engl J Med 2015.)