Bronchopulmonary Dysplasia

Synonyms: Chronic lung disease (CLD) of prematurity, BPD

Bronchopulmonary Dysplasia (BPD) arises as a consequence of the treatment of pre-term and term infants suffering from primary respiratory disease. It most commonly affects pre-term infants born with hyaline membrane disease - infant respiratory distress syndrome or RDS.

It appears to be due to the effects of positive pressure ventilation and supplemental oxygen on the development of alveoli and pulmonary vasculature. The role of surfactant therapy in causing the condition is less clear. Without surfactant, many babies would not survive to be in a position to develop BPD.
The exact aetiology is uncertain. A combination of the following factors probably plays a role:

• Alveolar barotrauma³/volutrauma and failure of alveologenesis⁴
• Oxygen-free-radical damage
• Activation of inflammatory cascades, with leucocytes releasing a potent mix of inflammatory mediators^5,6
• Infection causing inflammation^7,8
• Suboptimal nutrition and hydration of neonates
• Genetic susceptibility⁹
• Pulmonary vascular dysfunction leading to pulmonary hypertension

Figures for incidence vary depending on criteria used. A recent study found that approximately half of all admissions to a UK neonatal ICU weighing <1250g developed BPD.¹⁰ The incidence has changed over recent years due to policies to offer neonatal intensive care more widely to the most immature infants.¹¹Population-based studies show rates of BPD among surviving infants still hospitalised at 36 weeks after birth range from 13 - 35%.¹²

Infants affected are usually immature and have very low birth weight.

• They respond well to initial surfactant and ventilation, but then have an increase in their oxygen and ventilatory requirements in first 2 weeks of life.
• This dependence on respiratory support tends to worsen from week 2 to 4.
• There is then persistent hypoxia ± difficulty with ventilator weaning.
• Usually they have tachypnoea, tachycardia and signs of respiratory distress such as intercostal recession, grunting and nasal flaring. The infants gain weight poorly and have higher energy requirements than ventilated babies without BPD.

• Poorly responsive infant respiratory distress syndrome
• Pulmonary atelectasis
• Pneumonia
• Air leak syndrome
• Patent ductus arteriosus
• Subglottic stenosis or tracheomalacia
• Cystic fibrosis
• Post-infective bronchiectasis
• Obliterative bronchiolitis

• CXR: Hyperinflation, cyst formation, mobile atelectasis and pulmonary interstitial emphysema. The diagnostic and prognostic usefulness of the CXR in BPD is highly variable.^13,14
• Arterial blood gases show acidosis, hypercapnoea and relative hypoxia (for the inspired 0₂ concentration).
• CT/MRI have been used to give more detailed pictures of the lung, but their routine use isn't widespread.
• Pulmonary histology shows signs of acute lung injury and bronchiolitis with stages of exudation, proliferation and obliterative fibroproliferation.¹⁵

General measures

There is little useful evidence to support most treatments or preventive measures used in BPD, due to the extreme difficulty of conducting useful trials in this area.¹⁶ Emphasis is placed on prevention of the condition by:

• Using early surfactant administration with nasal continuous positive airways pressure rather than positive pressure ventilation where possible.¹⁷
• Careful management of ventilation and weaning.¹⁸
• Avoiding hyperoxia and providing expert nutritional support.
• Giving prophylactic steroids to mothers at risk of premature labour to reduce risk of infant RDS.¹⁹

Pharmacological

• Furosemide and other diuretics are used to treat fluid overload and pulmonary hypertension.
• Bronchodilators (such as albuterol) have a role in reducing airways resistance and sodium cromoglycate purportedly reduces inflammatory aggravation of the condition.
• Methylxanthines such as theophylline and caffeine are used and nitric oxide is given for its pulmonary vasodilator actions, appearing to improve long-term neurodevelopmental outcome.²⁰
• There is no evidence to support the routine use of steroids such as dexamethasone,²¹ as harm probably outweighs benefit,²² but inhaled steroids do seem to ease ventilatory weaning.²³
• As yet there is no convincing evidence to support the use of antioxidants/superoxide dismutase.²⁴
• Inhaled nitric oxide rescue therapy does not appear to be effective and may increase the risk of severe IVH. Later use to prevent BPD also does not appear to be effective.²⁵

• Early: Impaired cognition, cerebral palsy, feeding problems. O₂ desaturation during feeds occurs.
• Late: By adolescence/early adulthood the main changes remaining are airways obstruction, airways hyper-reactivity and hyperinflation. There is evidence of an increased risk of emphysema.²⁶

Fortunately lung function tends to slowly improve throughout childhood, but spirometric and radiological evidence of impaired function/damage usually persists.

• Increased tendency to suffer pulmonary infection, particularly respiratory syncytial virus (RSV). Some clinicians use RSV immunoglobulin or RSV monoclonal antibody injections (palivizumab) in the winter months to prevent this potentially fatal complication in BPD sufferers.^27,28 Recent study suggests that it is cost-effective for the NHS in prophylaxis of RSV infection.²⁹
• Vaccination against influenza should be considered.³⁰

• Periventricular leucomalacia
• Intraventricular haemorrhage
• Ventriculomegaly
• Sepsis
• Retinopathy

• Most sufferers survive infancy, but are prone to growth retardation, infections, airway hyperreactivity/asthma, neurological and cardiac dysfunction.³¹
• The first 2 years are the 'danger' period for airways disease.
• Infants with persistent right ventricular hypertrophy or pulmonary hypertension unresponsive to oxygen supplementation carry a worse prognosis.