Basics
Description
- A chronic lung disease (CLD) of premature infants defined as the need for supplemental O2 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: �
- 501-750 g: 42%
- 751-1,000 g: 25%
- 1,001-1,250 g: 11%
- 1,251-1,500 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; 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
- Postnatal (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.
Diagnosis
History
- Family: premature birth, asthma
- 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 O2
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 (PH), gastroesophageal reflux (GER), poor growth parameters
Diagnostic Tests & Interpretation
Labs: Initial Lab Tests
Blood gases: monitoring of acid-base status, hypo/hyperoxia, hypo/hypercapnia �
Labs: Follow-Up Tests & Special Considerations
- Echocardiogram: evidence of PH-tricuspid regurgitant jet, flattening of the interventricular septum, accelerated pulmonary regurgitation velocity, right atrial enlargement, right ventricular hypertrophy and dilation
- Cardiac catheterization in selective infants, to confirm PH
- Pulmonary function testing: Majority have abnormal spirometry with decreased forced expiratory flow at 1 second (FEV1) and decreased small airway expiratory flows (FEF, 25-75%) and impaired diffusion capacity. Majority of studies reveal no decrease in exercise capacity in former premature babies, although response to exercise differs.
Imaging: Initial Approach
Chest radiography: Early- reticular-granular pattern with air bronchograms (RDS); evolving-pulmonary edema, atelectasis; established-hyperinflation, increased interstitial markings, cysts �
Imaging: Follow-Up & Special Considerations
CT scan: persistent findings which include linear densities, subpleural triangular densities, and emphysema �
Diagnostic Procedures/Other
- Bronchoscopy for subglottic stenosis, trachea/bronchomalacia
- Sleep studies for persistent hypoxia and suspected central or obstructive apnea
- pH probe for GER
Differential Diagnosis
- Pneumonia
- Aspiration
- Congenital heart disease
- Wilson-Mikity syndrome
- Interstitial lung disease
- Surfactant protein deficiency
- Pulmonary lymphangiectasia
Treatment
Medication
- O2 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 PH
- Methylxanthines
- Acts as a respiratory stimulant, increases diaphragmatic contractility, weak bronchodilator and diuretic
- 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
- 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, then 0.15 mg/kg/24 h � 1 day) may be used to assist with extubation attempts after 3-4 PN weeks.
- Established phase: Prednisolone (PO, 2 mg/kg/24 h � 5 days, then 1 mg/kg/24 h � 3 days, 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, 1-2 mg/kg/24 h or every other day; chlorothiazide (PO/IV, 20-40 mg/kg/24 h) alone or with spironolactone (PO, 2-4 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 1.25-2.5 mg given via nebulizer or 2 puffs [180 mcg] given via MDI with spacer device, every 3-4 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 250-500 mcg via nebulizer or 18 mcg/puff via MDI with spacer device, every 6-8 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, although not a bronchodilator, is often used for its anti-inflammatory effects and has a low side-effect profile. It has no role in prevention of BPD.
Alert
- Many patients have oral aversion and feeding difficulties; close monitoring of growth and nutrition is recommended.
- Patients <2 years of age are candidates for respiratory syncytial virus immune globulin injections (palivizumab; Synagis), and those older than 6 months of age should be offered influenza immunization.
- Childhood immunizations are based on chronologic age rather than corrected age.
- There are no evidence-based guidelines regarding diuretic use or weaning off of supplemental oxygen therapy in established BPD.
Additional Therapies
- Ventilator strategy
- Early phase: Avoid intubation; if intubated, give early surfactant (<2 hours of PN life), use short inspiratory times (0.24-0.4 second), rapid rates (40-60/min), low peak inspiratory pressure (14-20 cm H2O), moderate positive end-expiratory pressure (4-6 cm H2O), and tidal volumes (3-6 mL/kg), with blood gas targets pH 7.25-7.35, Pao2 40-60 mm Hg, Paco2 45-55 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 7.25-7.35, Pao2 50-70 mm Hg, Paco2 50-65 mm Hg.
- Established phase: Use noninvasive ventilation with blood gas targets pH 7.35-7.45, Pao2 60-80 mm Hg, Paco2 45-60 mm Hg.
General Measures
Fluids/Nutrition
- Early phase: Restricting fluids to ~140 cc/kg/day may decrease BPD.
- Early/evolving/established phase: Aim to achieve 120-140 kcal/kg/day.
Ongoing Care
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 respiratory syncytial virus (palivizumab injections once a month from October to April) and influenza
- Neurodevelopmental follow-up
Prognosis
- Infants with BPD have high rates of rehospitalization in the first 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 pulmonary obstructive 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.
- PH may result in cor pulmonale.
Additional Reading
- Bhandari �A, Bhandari �V. The "new"� bronchopulmonary dysplasia-a clinical review. Clin Pulm Med. 2011;18(3):137-143.
- Bhandari �A, Bhandari �V. State-of-the-art review article. Pitfalls, problems, and progress in bronchopulmonary dysplasia. Pediatrics. 2009;123(6):1562-1573. �[View Abstract]
- Bhandari �A, McGrath-Morrow �S. Long-term pulmonary outcomes of patients with bronchopulmonary dysplasia. Semin Perinatol. 2013;37(2):132-137. �[View Abstract]
- Bhandari �V. Hyperoxia-derived lung damage in preterm infants. Semin Fetal Neonatal Med. 2010;15(4):223-229. �[View Abstract]
- Bhandari �V. The potential of non-invasive ventilation to decrease BPD. Semin Perinatol. 2013;37(2):108-114. �[View Abstract]
Codes
ICD09
- 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)
FAQ
- Q: Can my patient with BPD receive influenza vaccine?
- A: Yes. Influenza vaccination should be considered for babies older than 6 months of age and their contacts.
- Q: The AAP Committee on Infectious Diseases recommends monthly immunoprophylaxis for infants with BPD who are <2 years old and have been on medical therapy for 6 months prior to onset of second respiratory syncytial viral season. What should I do if my patient turns 2 years old, 2 months after the respiratory season started?
- A: Once initiated, immunoprophylaxis should be completed even if the child turns 2 years old before the respiratory season has ended.
- Q: If my patient gets respiratory syncytial virus infection while on immunoprophylaxis (palivizumab; Synagis), should the monthly injections be stopped?
- A: Monthly prophylaxis with palivizumab should be discontinued because of extremely low likelihood of a second RSV hospitalization in the same season based on the revised AAP 2014 policy statement.
- Q: Will my patient with BPD continue to have respiratory problems?
- A: Survivors of BPD are more likely to be rehospitalized with respiratory illnesses in the first 2 years of their life, but the rate of hospitalization decreases after 2 years of age and is rare after 14 years of age. They are more likely to develop asthma, have abnormal pulmonary function tests, and require respiratory medications as compared to their peers. There is also some concern that survivors may develop a COPD phenotype as they age.
- Q: If my patient with BPD has recurrent croup, should I refer the patient to a pediatric pulmonologist for evaluation of asthma?
- A: Survivors of BPD are more likely to develop asthma as compared to peers born full term. However, upper and large airway problems such as subglottic stenosis and tracheomalacia are common in this population. Recurrent croup may result from a narrowing of the upper airway and hence, referral to a pediatric otolaryngologist should be considered to rule out causes such as subglottic stenosis.
- Q: Will my patient with BPD likely to have neurodevelopmental issues as well?
- A: Yes. Children with BPD are more likely to have delayed speech and language development, visual-motor integration impairments, and behavior problems. They may also have low average IQ, memory and learning deficits, and attention problems.