Description

• A chronic lung disease (CLD) of premature infants defined as the need for supplemental oxygen for 28 days and a need for supplemental oxygen +/− positive pressure at 36 weeks postmenstrual age (PMA)
• It is categorized as mild, moderate, and severe based on the following at 36 weeks PMA or discharge (whichever comes first).
  • Mild: breathing room air
  • Moderate: need for <30% oxygen
  • Severe: need for >30% oxygen, with or without positive pressure ventilation or continuous positive pressure

Epidemiology

• BPD is the most common CLD in infants.
• Infants with birth weight (BW) <1,250 g account for 97% of all patients with BPD.
• Prevalence based on BW:
  • 501 to 750 g: 42%
  • 751 to 1,000 g: 25%
  • 1,001 to 1,250 g: 11%
  • 1,251 to 1,500 g: 5%

Risk Factors

• Infants with gestational age (GA) <28 weeks and BW <1,000 g
• Invasive ventilation
• Exposure to hyperoxia
• Sepsis (in utero and postnatal (PN); local/systemic)
• Genetic predisposition

General Prevention

• Prevention of premature birth
• Noninvasive ventilation approaches
• Avoidance of hyperoxia
• Decreasing perinatal infections

Pathophysiology

• Multifactorial with gene-environmental interactions
• Antenatal (AN)-chorioamnionitis
• PN-ventilator injury, hyperoxia, and sepsis
• AN and PN factors act on a genetically predisposed immature lung, causing release of multiple molecular mediators of inflammation, resulting in activation of cellular death pathways, followed by resolution or repair.
• Repair of the injured developing lung results in decreased alveolarization and dysregulated pulmonary vasculature, the pathologic hallmarks of BPD.

History

• AN: pregnancy-induced hypertension, preterm/prolonged rupture of membranes, chorioamnionitis, steroids
• Perinatal: resuscitation at birth
• PN: GA, BW, small for GA (SGA), respiratory distress syndrome (RDS), surfactant use, duration of invasive/noninvasive ventilation, supplemental oxygen
• Family: premature birth, asthma

Physical Exam

• Early phase (up to 1 PN week): normal to severe RDS (i.e., tachypnea, dyspnea)
• Evolving phase (>1 PN week to 36 weeks PMA): increasing respiratory distress and FiO₂
• Established phase (>36 weeks PMA): tachypnea, dyspnea, crackles, stridor (subglottic stenosis), wheezing, "BPD spells" (tracheobronchomalacia), evidence of pulmonary hypertension (PHTN), gastroesophageal reflux (GER), poor growth parameters

Differential Diagnosis

• Pneumonia
• Aspiration
• Congenital heart disease
• Wilson-Mikity syndrome
• Interstitial lung disease
  • Surfactant protein deficiency
  • Pulmonary lymphangiectasia

General Measures

Fluids/nutrition

• Early phase: Restricting fluids to ~140 cc/kg/day may decrease BPD.
• Early/evolving/established phase: Aim to achieve 120 to 140 kcal/kg/day.

Medication

• Oxygen supplementation
  • Prevention of hypoxia and as a pulmonary vasodilator
  • Early/evolving phases: Titrate FiO₂ by pulse oximeter 88-92%, generally, >85-<95%.
  • Established phase: generally ~95%, for prevention of PHTN
• Methylxanthines
  • Acts as a respiratory stimulant, increase diaphragmatic contractility, weak bronchodilator and diuretic action
  • Caffeine use has been associated with decreased BPD and improved neurodevelopmental outcomes.
  • Early/evolving phases: caffeine citrate (IV/PO) 20 mg/kg loading dose, 5 mg/kg/24 h maintenance dose
  • Side effects include feeding intolerance, tachycardia.
  • Therapeutic levels of 5 to 25 mg/L
  • Cardiovascular, neurologic, or GI toxicity reported at serum levels >50 mg/L
• Vitamin A
  • Helpful in maintaining epithelial cell integrity of the respiratory tract
  • Early/evolving phases: 5,000 IU IM 3 times per week for 4 weeks
• Steroids
  • Decreases inflammation, pulmonary edema
  • Evolving phase: dexamethasone (IV/PO, 0.5 mg/kg/24 h × 2 days, then 0.25 mg/kg/24 h × 2 days and then 0.15 mg/kg/24 h × 1 day) may be used to assist with extubation attempts after 3 to 4 PN weeks.
  • Established phase: Prednisolone (PO, 2 mg/kg/24 h × 5 days, then 1 mg/kg/24 h × 3 days and then 1 mg/kg/24 h every other day for 3 doses) may be helpful in weaning oxygen.
  • Side effects include hyperglycemia and hypertension in the short term.
• Diuretics
  • Evolving/established phases: furosemide (PO/IV, 1 to 2 mg/kg/24 h or every other day); chlorothiazide (PO/IV, 20 to 40 mg/kg/24 h) alone or with spironolactone (PO, 2 to 4 mg/kg/24 h) for transient improvement of lung function
  • Side effects include electrolyte abnormalities, nephrocalcinosis, and osteopenia of prematurity.
• Bronchodilators
  • Evolving/established phases: Inhaled β-agonists (e.g., albuterol 1.25 to 2.5 mg given via nebulizer or 2 puffs [180 mcg] given via MDI with spacer device, every 3 to 4 hours as needed) are effective treatment for reversible bronchospasm, although safety and efficacy of long-term use has yet to be established.
  • Muscarinic antagonists (e.g., ipratropium bromide 250 to 500 mcg via nebulizer or 18 mcg/puff via MDI with spacer device, every 6 to 8 hours as needed) may be useful adjuncts, especially in patients who are not significantly responsive to albuterol. It may be better tolerated than albuterol in patients with significant tracheomalacia.
  • Cromolyn has been used for its anti-inflammatory effects and has a low side-effect profile. It has no role in prevention of BPD.

Additional Therapies

Ventilator strategy

• Early phase: Avoid intubation; if intubated, give early surfactant (<2 hours of PN life), use short inspiratory times (0.24 to 0.4 second), rapid rates (40 to 60/min), low peak inspiratory pressure (14 to 20 cm H₂O), moderate positive end-expiratory pressure (4 to 6 cm H₂O), and tidal volumes (3 to 6 mL/kg), with blood gas targets pH 7.25 to 7.35, PaO₂ 40 to 60 mm Hg, PaCO₂ 45 to 55 mm Hg; "rescue" high-frequency ventilation; attempt extubation to nasal intermittent positive pressure ventilation (NIPPV) or nasal continuous positive airways pressure (NCPAP) in the first PN week.
• Evolving phase: Use noninvasive ventilation with blood gas targets pH 7.25 to 7.35, PaO₂ 50 to 70 mm Hg, PaCO₂ 50 to 65 mm Hg.
• Established phase: Use noninvasive ventilation with blood gas targets pH 7.35 to 7.45, PaO₂ 60 to 80 mm Hg, PaCO₂ 45 to 60 mm Hg.

Follow-up Recommendations

• Multidisciplinary approach with primary care physician; pediatric pulmonologist; pediatric cardiologist; nutritionist; and speech, respiratory, occupational, and physical therapists as well as social worker is recommended.
• Monitor linear growth and nutritional status.
• Immunization: prophylaxis against RSV (palivizumab monthly during respiratory season) and influenza
• Neurodevelopmental follow-up

Prognosis

• Infants with BPD have high rates of rehospitalization in the 1st year of life (up to 50%).
• Long-term pulmonary sequelae that may persist into adulthood include airway obstruction, airway hyperreactivity, and concern regarding development of chronic obstructive pulmonary disease (COPD) with aging.
• Long-term neurodevelopmental sequelae associated with BPD is not a specific neuropsychological impairment but more of a global deficit.
• Noninvasive ventilation approaches (NIPPV and NCPAP) hold promise in decreasing BPD.

Complications

• Prolonged intubation may lead to subglottic stenosis, tracheobronchomalacia.
• Undiagnosed PHTN may result in a prolonged oxygen requirement or need for ventilation, poor growth, and cor pulmonale.

ICD9

770.7 Chronic respiratory disease arising in the perinatal period

ICD10

P27.1 Bronchopulmonary dysplasia origin in the perinatal period

SNOMED

67569000 bronchopulmonary dysplasia of newborn (disorder)