PEEP as Rescue Therapy for Asthmatics With Elevated BMI

This study will investigate whether PEEP can prevent and/or reverse bronchoconstriction in asthmatics with a BMI > 30 kg/m2.

People with late-onset non-allergic asthma that develops in the setting of obesity do not respond well to conventional asthma medications, likely because all treatments for asthma have been developed to treat early-onset allergic disease in lean patients. There is a critical need to understand the pathophysiology of airway disease in late-onset, non-allergic obese asthmatics, in order to develop therapies to target this disease.

Airway hyperresponsiveness (AHR) is a defining characteristic in asthma. Lung function tests in individuals with late onset asthma in the setting of obesity are suggestive of distal airway closure rather than airway narrowing as a cause of hyperresponsiveness; these individuals tend to have more collapsible lung peripheries than obese individuals who do not develop asthma. If late onset asthma in obesity is related to a tendency of airways to close, it should respond to therapies designed to keep airways open, such as Positive End-Expiratory Pressure (PEEP).

The purpose of this study is to investigate the efficacy of PEEP on prevention and reversal of bronchoconstriction in obese people with asthma. This will be achieved by investigating the efficacy of PEEP therapy on preventing and reversing bronchoconstriction in response to the inhalation of methacholine, while measuring changes in respiratory impedance using the forced oscillation method.

Participants will initially perform a conventional methacholine challenge test.

Participants will return for 2 visits in which methacholine will be administered concurrently with varying levels of PEEP (using PEEP to prevent bronchoconstriction) while measuring changes in respiratory impedance using the forced oscillation method.

Participants will return for another 2 visits in which PEEP will be administered subsequent to methacholine challenge (using PEEP to reverse bronchoconstriction) while measuring changes in respiratory impedance using the forced oscillation method.

These studies will be completed over 5 visits.

Inclusion criteria

• PC20 to methacholine < 16 mg/ml
• Asthma diagnosis when ≥ 18 years of age
• Serum Immunoglobulin E < 100 IU/ml
• Ages ≥ 18 years
• BMI ≥ 30 kg/m2

Exclusion criteria

• Asthma exacerbation (defined as a hospitalization, ED visit, urgent care visit for asthma or new corticosteroids for asthma) in prior 6 weeks.
• Forced Expiratory Volume in 1 second < 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