Modulation Of Airway Reactivity With Chronic Mechanical Strain

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).

Inclusion criteria

• Children 8-17 yrs olds with severe asthma (N=120) will be recruited from the Pediatric High Risk Asthma Clinic and Pulmonary Clinics at Riley Hospital for Children at Indiana University Health.
• Severe asthma will be defined by the need for medication therapies following steps 4-6 according to the National Institutes of Health's Asthma Care Quick Reference, September 2012 or high dose of inhaled corticosteroids
• On a stable regimen of asthma medications for at least 8 weeks prior to enrollment without systemic corticosteroids for ≥ 4 weeks

Exclusion criteria

• Obese (>95% predicted BMI)
• Congenital heart disease or chronic lung disease
• History of pneumothorax
• Inability to perform pulmonary function testing
• Oxygen saturation <93%
• forced expiratory volume at one second (FEV1) <70% predicted
• Provocative concentration causing a 20% drop in FEV1 from baseline (PC20) ≥16 mg/ml of methacholine.