Bronchopulmonary dysplasia, or BPD, is a respiratory disorder of neonates, often occurring in babies having gestational ages below 26 weeks, underweight preemies (<1kg), or babies with unique etiological, pathological and clinical characteristics. According to the definition of NIH, babies are diagnosed with BPD if they were born before the expected due date (EDD) and still require supplemental oxygen after the EDD. Babies with BPD are graded as mild, moderate or severe based on their degrees of dependence on oxygen.

Babies suffering from BPD have symptoms such as alveolar and microvascular dysplasia, smaller alveolus, fewer alveolar septa, and alveolar wall fibrosis. Other features include shortness of breath and wheezing breath sounds. They may often have complications such as severe pulmonary hypertension (PH), patent ductus arteriosus (PDA), intraventricular haemorrhage (IVH), and interstitial fibrosis. Moreover, BPD may also delay the development of brains and nervous systems. Because of the immature lung, BPD patients are easily subject to bacterial infections. Such repetitive and frequent infections of lungs could deteriorate the course of the disease.

Sources: Meridigen Biotech. Co., Ltd.

BPD is a chronic pulmonary inflammatory disease caused by multiple factors. Possible causes include infections and inflammations of the uterus during pregnancy or before delivery. For examples, chorioamnionitis causes the inflammation factors in the amniotic fluid enter into the fetus, leading to inflammation on and damage in fetal lung. It may also be the case that the external respiratory support, such as mechanical ventilation or oxygen supplement, causes dysplasia, or obstructs the development of alveoli because of alveolar dysplasia.

Breathing supports like mechanical ventilation are required for preemies to have normal breaths because of their incomplete development of lung. However, research has indicated that the longer the use of mechanical ventilation is, the higher the incidence rate of BPD. It is because the excessive pressures during mechanical ventilation may directly damage the trachea and alveolar epithelial cells. Such damages destroy the integrity of lung and cause the fusion between pulmonary alveoli and emphysema, which aggravates the damage in a lung. The overexpansion of premature lung may rupture the microvascular endothelial, epithelial cells, and microvascular basement membranes, causing serious mechanical damage. Besides, mechanical ventilation may induce severe pulmonary inflammation and release of inflammatory factors that could lead to additional impairments of lungs. Therefore, mechanical ventilation is considered as one of the important causes of BPD.

Recent research has found that infections of the lung, either during pregnancy or after the birth, can induce a release of a large amount of inflammatory mediators causing inflammation, damage, abnormal development of lung and alveoli, and possibly leading to BPD. Patent ductus arteriosus (PDA) is also a risk factor of BPD. Preemies with PDA would likely have pulmonary congestion and edema. These would gradually lead to a damage-induced proliferation of pulmonary blood vessels, pulmonary hypertension, increased right ventricular afterload and increased inflammation of lungs. In addition, other risk factors include small for gestational age (SGA) and insufficient intake of nutrients.

Overall, the incidence of PBD is on the basis of underdeveloped lungs of preemies. It started with a primary lung injury, such as infant respiratory distress syndrome (RDS), infectious pneumonia and aspiration pneumonitis. Subsequently, it is followed by further impairments of lungs due to hyperoxia, air pressure, or infections. That is a development of secondary pulmonary inflammation. Finally, BPD forms with the mediation of hyperoxia, free radicals, and inflammatory mediators. The whole pathogenic process is a complicated process involving interactions of multiple risk factors.

Sources: Meridigen Biotech. Co., Ltd.

Statistics have shown at least 20,000 new-borns per annum are diagnosed with BPD. Vermont Oxford Network’s report has indicated the incidence rate of BPD is 29% and 26% in 2003 and 2007 respectively. Generally, the lower the gestational age is, the higher the incidence rate would be. However, the statistical incidence rate may vary because the diagnostic criteria adopted by hospitals may be different. Currently, no accurate incidence rate of BPD in Taiwan has been investigated. While we may derive the incidence rate by reckoning the following. Around 10% of new-borns in Taiwan (200,000 babies per annum), which is around 20,000 new-borns, were preemies, and 10% of them were very low birth weight (VLBW) infants (less than 1500 gram). Whereby, we can estimate that around 2,000 infants are incidental to BPD. Therefore, the incidence rate of BPD in Taiwan may be at least 500 - 1,000 people per annum. The rate clearly fits the definition of the prevalence of rare diseases. Importantly, BPD should be recognized the urgent need.

Currently, BPD is mainly treated by various types of respiratory supporting, providing good cares and sufficient nutrients, and treatment to prevent complications. Sometimes, patients may require supplemental surfactants, glucocorticoids, bronchodilator, caffeine, and diuretics. However, these treatments have their limits and side effects that are still controversial. For examples, literature has indicated that glucocorticoids may increase the chance of neurodevelopmental disorders, increasing the risk of cerebral palsy. Caffeine, on the other hand, has to be cautiously used in infants to avoid side effects, such as nausea, vomiting, and arrhythmia. It is not recommended to use diuretics for a long time since they have side effects including hypovolemia, hypokalaemia, and hyponatremia. Therefore, there is an unmet need for a much safer and more effective drug launched for the BPD treatment.