Increased Lung Volume as Controller Therapy for Asthma

The effect of 10 versus 0 cmH2O CPAP on airways responsiveness to inhaled methacholine will be studied using an adaptive "3+3" phase I/II study design.

Dose Titration Phase (phase I):

The efficacy of 8 hours of CPAP on airway responsiveness will be tested in three subjects.

Efficacy will be defined as a 25% improvement in the impedance response to methacholine in all three subjects. If this occurs in all subjects, shorter durations of CPAP will be studied (4 hours then one hour).

Conversely, if "dose escalation" is required, 3 nights, then 7 nights of CPAP will be studied.

Randomized-controlled study phase (phase II):

Participants will be randomized to CPAP 10 or Sham 0. The duration of CPAP will be determined in the dose titration phase. The effect on response to inhaled methacholine, lung function and asthma control will be determined in patients with asthma and a BMI ≥ 30 kg/m2, and also in healthy controls without asthma

Inclusion criteria

for people with asthma:

• Physician diagnosis of asthma
• PC20 to methacholine < 16 mg/ml
• IgE < 100 IU/ml
• Ages 18-65 years
• BMI >=30 kg/m2

Inclusion criteria

for controls:

• No physician diagnosis of asthma
• PC20 to methacholine > 16 mg/ml
• IgE < 100 IU/ml
• Ages 18-65 years
• BMI >=30 kg/m2

Exclusion criteria

• FEV1 < 60 % predicted
• Other significant disease that in the opinion of the investigator would interfere with study.
• Inability to perform required testing.
• Smoking within last 6 months.
• ≥ 20 pack year smoking history
• Inability to provide informed consent
• Pregnancy
• Known obstructive sleep apnea/ high likelihood of obstructive sleep apnea
• Asthma exacerbation in the prior 6 weeks
• Stoke or heart attack in the prior 3 months
• Known aortic aneurysm
• Renal failure
• A known severe heart, vascular, liver, renal, or hematological disease
• Active allergic rhinitis
• Recent eye surgery (within the last month)