Introduction
Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease caused by a combination of prenatal and postnatal factors that leads to the disruption of lung development and abnormal repair, this is a condition that is commonly seen in premature infants1 .With technological improvements in technology, the survival rate of very early preterm infants has increased significantly compared with previous years, and the incidence of severe BPD has decreased, However, the prevalence of BPD has not decreased2 .The overall prevalence of BPD is 45%3. A previous study found that more than 70% of infants with a birth weight of less than 1000 grams went on to develop BPD4.In a recent cohort study of the prevalence and risk factors for BPD in very low gestational age infants( ≤28 weeks),the mean gestational age (GA) and birth weight (BW) of the cohort was 25. 3 ± 1. 4weeks and 724 ±14g, respectively, with a moderate to severe BPD of 67%5.The pathology of classical BPD is dominated by severe airway compromise, such as severe epithelial damage, smooth muscle hyperplasia in the airway, and fibrosis6. As medical treatments have advanced, the pathology of BPD has changed; new BPD is characterized by simplification of the alveolar structure, abnormal vascular development ,and impaired lymphatic function, as the main pathological features7,8. The prevention of prematurity, the systematic use of non-aggressive ventilator measures, the avoidance of supra-physiological oxygen exposure, and the administration of diuretics, caffeine and vitamin A have all been shown to lead to a significant reduction in the risk of BPD development9,However, we have yet to develop a method that can completely prevent and treat BPD10.A growing number of clinical studies have shown that caffeine not only prevents apnea, but also reduces the incidence of BPD11-14.Therefore, caffeine is receiving increasing attention with regards to the prevention of BPD.
Caffeine, also known as 1, 3 and 7 methylxanthine, can act as an antagonist of adenosine receptors, an inhibitor of phosphodiesterase and an activator of ryanodine receptors. At physiological concentrations, caffeine acts primarily as an inhibitor of the adenosine receptor. However, with increasing plasma concentrations, caffeine may also inhibit other receptors, such as the gamma-aminobutyric acid receptor and cholinergic receptors 15. Caffeine has been used for the treatment of apnea in preterm infants since the 1970s. The recommended dose for use in neonates is 20 mg/kg (loading)with a 5-10 mg/(kg-d) maintenance dose given after 24 h16 . Furthermore, clinical studies have found that early caffeine treatment, and high-dose caffeine treatment, exerts a protective against BPD in the prevention and treatment of apnea in preterm infants17,18.Early caffeine treatment is also known to reduce neurological sequelae, such as cerebral palsy and hearing impairment19.
In this article, we review the clinical value of caffeine in the treatment of BPD and its potential mechanisms of action. Our aim was to provide a new theoretical basis for the clinical treatment of BPD.
Multiple Benefits of Caffeine for the Treatment of BPD