During the previous funding period of this project, our laboratory demonstrated that chronic mechanical strain imposed on the airways in vivo using continuous positive airway pressure (CPAP) results in a dramatic reduction in airway reactivity in vivo in mice, ferrets and rabbits1-3. Lungs, airways and airway smooth muscle (ASM) tissues isolated from CPAP-treated animals studied in vitro exhibited lower responsiveness to bronchoconstrictors1-3. We also observed this suppression of airway responsiveness by chronic mechanical strain in a rabbit model of allergic asthma5. These animal studies led to a small clinical trial in which adults with asthma were treated with nocturnal CPAP for 1 week. CPAP caused a significant reduction in airway reactivity in these patients6. This novel approach for treating airway hyper-reactivity is currently being evaluated in a NIH multi-center Phase II clinical trial of adults with mild to moderate asthma (U01 HL108730).