Bronchopulmonary Dysplasia (BPD)

BPD has a multifactorial etiology. The lungs of preterm infants are more vulnerable to the inflammatory changes that result from mechanical ventilation. The development of normal lung architecture is interrupted; fewer and larger alveoli develop, and the interstitium is thickened. Also, the pulmonary vasculature develops abnormally, with fewer and/or abnormally distributed alveolar capillaries; pulmonary resistance may be increased and pulmonary hypertension can develop (1).

Significant risk factors include:

• Prolonged mechanical ventilation

• High concentrations of inspired oxygen

• Infection (eg, chorioamnionitis or sepsis)

• Degree of prematurity

Additional risk factors include:

• Pulmonary interstitial emphysema

• High peak inspiratory pressures

• Large end-tidal volumes

• Repeated alveolar collapse

• Increased airway resistance

• Increased pulmonary artery pressures

• Male sex

• Intrauterine growth restriction

• Genetic susceptibility

• Maternal tobacco smoking

Symptoms and signs of bronchopulmonary dysplasia include respiratory distress, hypoxia or oxygen requirement, and, in older infants and toddlers, coughing, wheezing, reactive airway disease, and poor growth.

• Established diagnostic criteria, based on oxygen use or respiratory support needs

• Characteristic findings on chest imaging

BPD typically is suspected when a ventilated infant is unable to wean from oxygen therapy, mechanical ventilation (invasive or noninvasive), or both. Infants typically develop worsening hypoxemia, hypercapnia, and increasing oxygen requirements. Additionally, when an infant cannot be weaned within the expected time, possible underlying disorders, including patent ductus arteriosus and nursery-acquired pneumonia, should be considered.

For diagnosis of BPD, infants born at > 32 weeks gestation are to have required at least 28 days of > 21% oxygen, and infants born at < 32 weeks gestation have to have continued need for respiratory support at ≥ 36 weeks postmenstrual age (1, 2). Other diagnostic criteria exist as well, as do grading systems for BPD severity (see table Criteria for Diagnosis and Grade of Bronchopulmonary Dysplasia in Infants < 32 Weeks Gestational Age) (3).

Chest radiograph initially shows diffuse haziness due to accumulation of exudative fluid; appearance then becomes multicystic or spongelike, with alternating areas of emphysema, pulmonary scarring, and atelectasis. Alveolar epithelium may slough, and macrophages, neutrophils, and inflammatory mediators may be found in the tracheal aspirate.

Bronchopulmonary Dysplasia (Radiograph)

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The infant in this image has a history of prematurity and bronchopulmonary dysplasia. The frontal chest radiograph shows coarse reticular pulmonary opacities and hyperinflation in both lungs.

© Springer Science+Business Media

Evidence-based practices for preventing BPD include (1–4):

• Use of antenatal glucocorticoids as indicated

• Early noninvasive ventilatory strategies (eg, delivery room continuous positive airway pressure [CPAP], or noninvasive or nasal intermittent positive pressure ventilation [NIPPV] in infants 28 to 32 weeks gestational age) versus intubation

• Early selective surfactant administration, preferably by less-invasive methods versus intubation

• Prophylactic use of methylxanthines (caffeine)Prophylactic use of methylxanthines (caffeine)

• Selective use of systemic corticosteroids

• Volume-targeted versus pressure-limited ventilation

• Permissive hypercarbia to minimize ventilator pressures and volumes

• Avoidance of excessive fluid intake or administration

Early use of systemic corticosteroids (< 7 days of age) does decrease likelihood of death and BPD but is associated with intestinal perforations and cerebral palsy and thus not recommended (5). Later initiation of corticosteroids (> 7 days of life) may result in reduction of death and BPD at 36 weeks postmenstrual age without long-term neurologic detriment, but an optimal dosing regimen is not established. The available evidence does not support the use of inhaled corticosteroids in the prevention of BPD.

Many other therapies, including inhaled nitric oxide and vitamin A supplementation, are not as well supported by evidence (Many other therapies, including inhaled nitric oxide and vitamin A supplementation, are not as well supported by evidence (1, 2).

• Nutritional optimization

• Fluid restriction

• Diuretics

• Oxygen supplementation as needed

• Respiratory syncytial virus (RSV) prophylaxis and influenza vaccine

• Diagnosis and treatment of pulmonary hypertension

Treatment of evolving or established BPD is supportive and includes nutritional supplementation, fluid restriction, diuretics, and perhaps inhaled bronchodilators and, as a last resort, inhaled glucocorticoids (1). Respiratory infections must be diagnosed early and treated aggressively. Weaning from mechanical ventilation and supplemental oxygen should be accomplished as early as possible.

Enteral nutrition, preferably with human milk, should provide adequate energy (150 calories/kg/day) and protein (3.5 to 4 g/kg/day); caloric requirements are increased because of the increased work of breathing and to aid lung healing and growth.

Because pulmonary congestion and edema may develop, daily fluid intake is often restricted to120 to 140 mL/kg/day. Diuretic therapy transiently improves pulmonary mechanics but not long-term clinical outcome (1). Thiazide or loop diuretics can be used for short-term benefit in patients who do not respond adequately to or cannot tolerate fluid restriction. Oral chlorothiazide with or without oral spironolactone is often tried first. Furosemide may be used for short periods, but prolonged use causes hypercalciuria with resultant osteoporosis, fractures, and renal calculi. If long-term diuretic use is required, ). Thiazide or loop diuretics can be used for short-term benefit in patients who do not respond adequately to or cannot tolerate fluid restriction. Oral chlorothiazide with or without oral spironolactone is often tried first. Furosemide may be used for short periods, but prolonged use causes hypercalciuria with resultant osteoporosis, fractures, and renal calculi. If long-term diuretic use is required,chlorothiazide is preferred because it has fewer adverse effects. Hydration and serum electrolytes should be monitored closely during diuretic therapy.

Inhaled bronchodilators (eg, albuterol) do not appear to improve long-term outcome and are not used routinely. However, they may be helpful for acute episodes of bronchoconstriction (Inhaled bronchodilators (eg, albuterol) do not appear to improve long-term outcome and are not used routinely. However, they may be helpful for acute episodes of bronchoconstriction (1).

Evidence does not support the use of inhaled corticosteroids to prevent BPD when given early, but they may help treat symptoms when given later (2). Although systemic corticosteroids may result in clinical improvement in BPD by decreasing inflammation, concerns about adverse neurodevelopmental outcomes resulting from repeated and/or prolonged courses of dexamethasone for BPD (). Although systemic corticosteroids may result in clinical improvement in BPD by decreasing inflammation, concerns about adverse neurodevelopmental outcomes resulting from repeated and/or prolonged courses of dexamethasone for BPD (3) led to the reaffirmed American Academy of Pediatrics' 2014 policy statement discouraging the routine use of dexamethasone for BPD () led to the reaffirmed American Academy of Pediatrics' 2014 policy statement discouraging the routine use of dexamethasone for BPD (4). More recent studies of hydrocortisone and inhaled budesonide in BPD found no long-term significant adverse neurodevelopmental outcomes (). More recent studies of hydrocortisone and inhaled budesonide in BPD found no long-term significant adverse neurodevelopmental outcomes (5); however, because other possible adverse effects (eg, hypertension, cardiomyopathy, worsening of retinopathy of prematurity) are a concern, systemic and inhaled corticosteroids are used only in cases where there is thought to be no other alternative.

Weeks or months of additional ventilator support, supplemental oxygen, or both may be required for advanced BPD. Ventilator pressures or volumes and fraction of inspired oxygen (FIO2) should be reduced as rapidly as tolerated, but the infant should not be allowed to become hypoxemic. The degree of lung inflation (tidal volume measured in mL/kg) has a higher risk of causing or worsening BPD than does the degree of airway pressure as an absolute number in cm of H2O (6). Arterial oxygenation should be continuously monitored with a pulse oximeter and maintained at ≥ 89% saturation. Respiratory acidosis may occur during ventilator weaning, and treatment and is acceptable as long as the pH remains > 7.25 and the infant does not develop severe respiratory distress.

Two monoclonal antibodies used for RSV prophylaxis in infants and young children are available in the United States. Nirsevimab is preferred but may not be available to some infants (Two monoclonal antibodies used for RSV prophylaxis in infants and young children are available in the United States. Nirsevimab is preferred but may not be available to some infants (7, 8); if it is not available, eligible high-risk infants and children should receive palivizumab (see also ); if it is not available, eligible high-risk infants and children should receive palivizumab (see alsoPrevention of RSV for indications).

Infants > 6 months also should be vaccinated against influenza.

Pulmonary hypertension should be identified and treated as appropriate.

Mortality rates of BPD vary by severity, from approximately 1 to 2% in cohort studies of outpatients to 16% in studies of infants with life-threatening disease (1–3).

Infants with BPD are at increased risk of developing asthma later in life as well as lower respiratory tract infections (particularly pneumonia or bronchiolitis) and may develop respiratory decompensation if pulmonary infection occurs (4, 5). The threshold for hospitalization should be low if signs of respiratory distress develop.

In addition to chronic lung disease and other pulmonary complications, infants with BPD have an increased risk of growth failure, cerebral palsy, and intellectual disability (6).