BackgroundCaffeine is a nonspecific adenosine receptor antagonist used in premature neonates to treat apnea of prematurity. While its use may reduce the incidence of bronchopulmonary dysplasia (BPD), the precise mechanisms remain unknown. Evidence of increased adenosine levels are noted in chronic lung diseases including tracheal aspirates of infants with BPD. Utilizing a well characterized newborn mouse model of alveolar hypoplasia, we hypothesized that hyperoxia-induced alveolar inflammation and hypoplasia is associated with alterations in the adenosine signaling pathway.MethodsNewborn murine pups were exposed to a 14-day period of hyperoxia and daily caffeine administration followed by a 14-day recovery period in room air. Lungs were collected at both time points for bronchoalveolar fluid (BAL) analysis as well as histopathology and mRNA and protein expression.ResultsCaffeine treatment increased inflammation and worsened alveolar hypoplasia in hyperoxia exposed newborn mice. These changes were associated with decreased alveolar type II cell numbers, increased cell apoptosis, and decreased expression of A2A receptors. Following discontinuation of caffeine and hyperoxia, lung histology returned to baseline levels comparable to hyperoxia exposure alone.ConclusionResults of this study suggest a potentially adverse role of caffeine on alveolar development in a murine model of hyperoxia-induced alveolar hypoplasia.

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26838 more pregnancies with 2 survivors. Furthermore, there were 4649 fewer cases of NDI. On one-way sensitivity analyses, if the probability of NDI after SFLP for pregnancies affected by stage I TTTS was above 0.078, then EM was the cost-effective strategy (Figure). MCA demonstrated that SFLP was cost-effective in 98.1% of runs. CONCLUSION: With base-case estimates, SFLP is a more cost-effective strategy than EM for the treatment of Stage I TTTS. However, given the limited data informing base-case estimates, further determination of outcome probabilities is needed to determine with high confidence which strategy is more cost-effective.