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