Bronchopulmonary Dysplasia: An Update on Experimental Therapeutics

Abstract

Bronchopulmonary dysplasia (BPD) is a chronic inflammatory lung disease that affects thousands of newborns and infants every year. Although it is accepted that BPD results from lung damage and inflammation triggered by mechanical ventilation and hyperoxia, the causes and molecular events leading to lung damage and arrested development remain unknown. While recent advances in neonatal care have improved the survival of very low-weight infants, the rates of BPD have not improved accordingly. This is mainly due to our limited understanding of the disease’s pathogenesis and the effective therapeutic options available. Current therapeutics for BPD involve ventilation management, steroid treatment, and administration of various agents, such as pulmonary surfactant, caffeine, vitamin A, nitric oxide, and stem cells. However, the efficacy of these agents in preventing and ameliorating BPD symptoms varies depending on the populations studied and the disease stage. As the field moves towards personalised therapeutic approaches, this review summarises clinical and experimental studies conducted in various models, aiming to increase understanding of the cellular and molecular mechanisms by which these agents can prevent or treat BPD. Due to the increasing number of extremely premature infants, it is imperative that we continue to work towards understanding the mechanisms of BPD pathogenesis and generating more effective therapeutic options.

Effects of postnatal hydrocortisone on cytokine profile in extremely preterm infants

“…One serum sample was lost. The remaining 29 babies were included in the study; median gestational age was 26.1 weeks (IQR: 25.1-27.1 weeks) and birthweight was 791 (658-918) g. The early and late phase serum samples were taken at a median of 11 (7)(8)(9)(10)(11)(12)(13)(14) days and 37 (31-42) days after birth, respectively.…”

“…[5][6][7][8][9] The treatment of BPD involves ventilation management and administration of various agents, such as surfactants, steroids, caffeine, nitric oxide, and vitamin A. 10 However, effective management and prevention of BPD remain challenging. 10 Postnatal corticosteroids may restrict inflammation and improve lung function in infants with established BPD.…”

“…10 However, effective management and prevention of BPD remain challenging. 10 Postnatal corticosteroids may restrict inflammation and improve lung function in infants with established BPD. Indeed, until the early 2000s, dexamethasone was used widely for prevention and treatment of BPD.…”

Neurotrophins: Expression of Brain–Lung Axis Development

“…Bronchopulmonary Dysplasia (BPD) is defined as a chronic lung disease affecting the infant born before 32 weeks of gestational age, with radiological evidence of damage to the lung parenchyma, and requiring respiratory support (either invasive or non-invasive) at 36 weeks of post-menstrual age at least for three or more consecutive days to maintain a peripheral arterial oxygen saturation (SpO2) > 90% [ 76 , 77 ]. BPD recognizes many prenatal risk factors, including maternal smoking, chorioamnionitis, intrauterine growth restriction, and postnatal risk factors such as patent ductus arteriosus, parenteral nutrition, sepsis, and mechanical ventilation [ 78 ].…”

Outcomes of postnatal systemic corticosteroids administration in ventilated preterm newborns: a systematic review of randomized controlled trials

“…However, prolonged MV (PMV) is harmful and increases the risk of developing bronchopulmonary dysplasia (BPD) ( 4 , 5 ). BPD is a chronic inflammatory lung disease of premature neonates characterized by impaired lung development ( 4 , 6 ). It has a multifactorial pathogenesis, wherein prolonged oxygen exposure induces a destructive local inflammatory response in the lung alveoli, associated with a simultaneous impaired repair response ( 6 ).…”