Bronchopulmonary dysplasia: Associated Disease

Bronchopulmonary dysplasia (BPD) is characterized by inhibition of lung alveolar septation and varying degrees of lung fibrosis and inflammation. It typically occurs in preterm newborns born at 24-26 weeks, with weight <1000g, and that receive mechanical ventilation or prolonged oxygen supplementation.

Associated Cardiovascular Disease

• Pulmonary Hypertension: secondary to abnormal microvascular development and pulmonary vascular remodeling. Pulmonary hypertension occurs in 25-50% of infants with severe BPD and is suspected with evidence of right-sided heart failure (hepatomegaly, congested systemic veins) or hypoxia. The initial diagnostic test is usually transthoracic echocardiography. Brain natriuretic peptide can be used to trend severity. Management includes supplemental oxygen, inhaled nitric oxide, sildenafil, prostacyclin analogs, and endothelin-receptor antagonists, titrating to an SpO₂ 91-95%, avoid <85% and >97%.

• Cor pulmonale secondary to pulmonary hypertension

• Systemic hypertension- usually transient, lasting 1-10 months

• Left ventricular hypertrophy

Associated Respiratory Disease

• Diminished response to hypoxemia: In normal physiology the increased ventilatory response to hypoxia is largely the result of carotid body stimulation by low PaO₂. Compared to preterm infants without BPD, infants with BPD exhibit a diminished ventilatory response to both hypoxia and hyperoxia, suggesting that BPD is associated with decreased carotid body signaling. The extent of the diminished ventilatory response to hypoxia is correlated with BPD severity. Infants with BPD are more prone to apneas, periodic breathing, and respiratory decompensation.

• Airway lesions including broncho/tracheo/laryngomalacia, stenotic lesions of the airway (i.e. subglottic stenosis)- Related to barotrauma, airway manipulation, and/or recurrent infection.

• Reactive airway disease and asthma: Young adults with BPD have decreased FEV1, FVC, and FEF50%. Common respiratory infections can result in increased morbidity and mortality in BPD survivors, possibly due to disrupted immunoregulatory pathways.

Other Associated Conditions

• Sudden infant death syndrome

• Failure to thrive

• Gastroesophageal reflux

• Renal insufficiency

• Nephrocalcinosis and hypercalciuria

• Delayed motor and cognitive function (tends to resolve by 3-8 years of age)

• Retinopathy of prematurity

Updated definition 2020:

Bronchopulmonary dysplasia (BPD) is a chronic lung disease caused by disruption of pulmonary development and lung injury in preterm infants. These patients develop respiratory distress syndrome shortly after birth requiring oxygen supplementation and positive pressure ventilation. Most infants who develop BPD are born between 24-28 weeks gestational age, during the time of the canalicular and saccular stages of lung development. Arrest of development during these stages results in hypoplastic alveolar structures and dysmorphic pulmonary vasculature. Inflammation and oxidative stress post-delivery further interrupt lung growth and repair in these patients. The severity of BPD is determined by the gestational age of the infant, amount of oxygen supplementation, total duration of oxygen supplementation, and positive pressure requirements. Survivors of BPD often develop sequelae diseases including pulmonary hypertension and obstructive lung disease.

Understanding the pathogenesis of BPD explains its association with pulmonary hypertension and obstructive lung disease. During the late canalicular and early saccular stages of lung development, alveolar ducts form, vascularization increases, and epithelial differentiation occurs. Disruption of alveolar septation due to preterm birth results in fewer and larger alveoli, which significantly decreases surface area available for gas exchange. Additionally, increased collagen and elastic tissue formation leads to airflow obstruction and small airway disease. This can manifest clinically as an asthma-like phenotype with low spirometry values and may persist into adulthood. Disruption of pulmonary angiogenesis causes an abnormal distribution of alveolar capillaries and thickening of the smooth muscle layer of arterioles. This increases pulmonary vascular resistance (PVR) causing pulmonary hypertension and elevated right ventricular pressures. Persistent patent ductus arteriosus and intracardiac shunts, which are also common in preterm infants, can further increase PVR and contribute to pulmonary hypertension.