603 - Early Caffeine Administration Prevents Long-term Airway Hyperreactivity in a Mouse Model of Neonatal CPAP

Poster Number: 603
Publication Number: 603.1441

Background: Continuous positive airway pressure (CPAP) is the primary non-invasive mode of respiratory support for preterm infants. However, emerging evidence suggests CPAP could be an underlying contributor to the unintended pathophysiology of wheezing and associated airway hyperreactivity (AHR) in former preterm infants. As most preterm neonates also receive caffeine therapy and given its therapeutic benefits, we investigated whether caffeine offers protection against CPAP-induced AHR.

Objective: Using a mouse model, examine whether early caffeine administration prevents long-term increase in airway reactivity following neonatal CPAP.

Design/Methods: Neonatal male mice received CPAP (6 cm H20) for 3 hours/day using a custom-designed face mask for the first 7 postnatal (P) days. Control (Ctrl) mice experienced the same conditions as experimental animals only without CPAP. Mice also received a daily subcutaneous injection of caffeine (+Caff, 10 mg/kg/day) or equivolume saline (+sal) daily prior to each CPAP session. Two weeks after CPAP and caffeine administration (at P21), mice were sacrificed and airway reactivity to increasing doses of methacholine (0.25µM-8µM) was measured using the precision cut lung slice method. Lung sections were stained and imaged for α-smooth muscle actin proliferation (DAPI staining).

Results: CPAP caused a long-term increase in airway reactivity (vs Ctrl+sal mice, Fig. 1) which was associated with increased airway smooth muscle proliferation. Caffeine administration during CPAP prevented AHR and showed preliminary evidence of decreased airway smooth muscle proliferation.

Conclusion(s): Early caffeine treatment protects against the long-term adverse consequences that CPAP has on airway hyperreactivity possibly via an effect involving airway remodeling. These data may have implications for caffeine administration as a therapy for preventing later wheezing disorders in former preterm infants who had received prior CPAP.