Impact of Metabolic Dysfunction and Mucus Plugging on Asthma Physiology

The mechanism of poor exercise tolerance in patients with severe asthma is poorly understood. In preliminary data, the investigators have identified increases in air trapping in patients with obese asthma and metabolic dysfunction and patients with asthma and mucus plugs. The investigators have also found air trapping on CT (Computerized Tomography) scans of severe asthma patients with mucus plugs. Therefore, the investigators hypothesize that obese patients with metabolic dysfunction (MD) and severe asthma patients with mucus plugs develop changes in lung function during exercise.

To test this hypothesis, this protocol will plan for cardiopulmonary exercise testing in patients with obesity or severe asthma. The analyses will compare dynamic hyperinflation, expiratory flow limitation, and the RV/TLC ratio (ratio of residual volume to total lung capacity) before and after exercise between obese patients with and without MD and severe asthma patients with and without mucus plugs.

Inclusion criteria

• Male or female ≥ 18 years old at Visit 0
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
• History of physician diagnosed asthma
• Evidence of bronchodilator reversibility (12% improvement in FEV1 after albuterol administration) or positive methacholine challenge PC20 or PD20. Historical evidence is accepted.
• Meets criteria for obesity or severe asthma a. Obesity: BMI≥30 i. Metabolic dysfunction is defined as presence of either:

• IL-6 high: Plasma IL-6 > 3.0 pg/mL 2. Insulin resistance: HOMA-IR > 3 mass units b. Severe asthma: Requires treatment with high dose inhaled corticosteroids plus a second controller, systemic corticosteroid, or biologic therapy.

i. Mucus Plugging is defined as mucus plug score ≥ 4

Exclusion criteria

• Asthma exacerbation or URI within the previous 6 weeks.
• History of smoking

• If <30 years old: Smoked for ≥5 pack-years
• If ≥30: Smoked for ≥10 pack years
• Pregnancy
• Absolute or relative contraindication to exercise testing per ATS criteria
• Any other criteria that place the subject at unnecessary risk according to the judgment of the Principal Investigator and/or attending physician of record.