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Caffeine prevents airway hyperreactivity in a neonatal mouse model of continuous positive airway pressure
Panvathu Rungsiyaphornratana1, Catherine A Mayer1, Shannon McAllister1
1Department of Pediatrics, Division of Neonatology, UH Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OH, USA.
Insights
Neonatal caffeine administration prevents long-term airway hyperreactivity and lung damage caused by continuous positive airway pressure (CPAP) in preterm infants. This finding suggests caffeine therapy can mitigate CPAP
Area of Science:
- Neonatal respiratory support and lung development
- Pharmacological interventions in neonatal care
Background:
- Continuous positive airway pressure (CPAP) is vital for preterm infants but may cause long-term airway hyperreactivity (AHR).
- Caffeine is commonly given to preterm neonates and is linked to reduced bronchopulmonary dysplasia (BPD) rates.
Purpose of the Study:
- To investigate if caffeine administration during neonatal CPAP can prevent long-term AHR in a mouse model.
- To assess the impact of caffeine on CPAP-induced lung remodeling.
Main Methods:
- Neonatal mice received CPAP (6 cmH2O) for 3 hours daily for the first 7 postnatal days.
- Mice were injected with caffeine (10 mg/kg/day) or saline (control) before each CPAP session.
- Airway hyperreactivity and lung remodeling parameters were evaluated 2 weeks post-treatment.
Main Results:
- CPAP induced long-term AHR, increased airway αSM-actin, thickened airway epithelium and alveolar walls, and reduced alveolar counts.
- Co-administration of caffeine with CPAP completely prevented these adverse effects.
- Caffeine administration protected against CPAP-induced lung remodeling.
Conclusions:
- Early caffeine administration effectively protects against the long-term adverse effects of CPAP on AHR and lung development.
- Caffeine directly impacts lung and airway development, improving long-term respiratory function after neonatal CPAP.
- Caffeine therapy can mitigate CPAP-associated wheezing disorders in former preterm infants.
Background:
Continuous positive airway pressure (CPAP) is a primary non-invasive respiratory support modality for preterm infants. While there are benefits to CPAP, evidence suggests it may contribute to long-term wheezing and airway hyperreactivity (AHR) in preterm infants. Most preterm neonates also receive caffeine in addition to CPAP, which is associated with decreased rates of BPD. In a mouse model, we investigated whether caffeine administration during neonatal CPAP prevents long-term AHR.
Methods:
Neonatal mice were fitted with a custom-made mask and received CPAP (6 cmH20) for 3 h/day for the first 7 postnatal days. Mice also received a subcutaneous injection of caffeine (10 mg/kg/day) or saline (control mice) immediately prior to each CPAP session. Two weeks after treatment, mice were assessed for AHR and parameters of lung remodeling.
Results:
CPAP resulted in long-term AHR (vs control mice), which was associated with increased airway αSM-actin expression, epithelial and alveolar septal wall thickening, and decreased radial alveolar counts. Co-administration of caffeine prevented CPAP effects.
Conclusion:
Early caffeine administration protected against the long-term effects of CPAP on AHR and lung remodeling. These data demonstrate that neonatal caffeine benefits long-term respiratory function after CPAP administration by a direct effect on lung and airway development.
Impact:
Neonatal CPAP may have long-term adverse consequences to the immature lung. This study demonstrates that caffeine attenuates the adverse effects of CPAP on lung development and airway remodeling. The results enhance our understanding of the complex effects that caffeine can have on lung development. CPAP may be a contributor to wheezing disorders of former preterm infants, but can be prevented by caffeine therapy. This study raises the clinical significance of CPAP effects on lung development and how caffeine could be optimized to help mitigate its adverse consequences.
