Increased airway reactivity in a neonatal mouse model of continuous positive airway pressure.

Continuous positive airway pressure (CPAP) is a primary form of respiratory support used in the intensive care of preterm infants, but its long-term effects on airway (AW) function are unknown. We developed a neonatal mouse model of CPAP treatment to determine whether it modifies later AW reactivity. Unanesthetized spontaneously breathing mice were fitted with a mask to deliver CPAP (6 cmH2O, 3 h/day) for 7 consecutive days starting at postnatal day 1. AW reactivity to methacholine was assessed using the in vitro living lung slice preparation. One week of CPAP increased AW responsiveness to methacholine in male, but not female mice, compared to untreated control animals. The AW hyper-reactivity of male mice persisted for 2 wk (at P21) after CPAP treatment ended. Four days of CPAP, however, did not significantly increase AW reactivity. Females also exhibited AW hyper-reactivity at P21, suggesting a delayed response to early (7 d) CPAP treatment. The effects of 7 d of CPAP on hyper-reactivity to methacholine were unique to smaller AWs whereas larger ones were relatively unaffected. These data may be important to our understanding of the potential long-term consequences of neonatal CPAP therapy used in the intensive care of preterm infants.