Impact of Metabolic Dysfunction and Mucus Plugging on Asthma Physiology

NCT ID: NCT05757583

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-04-05
• Study Completion Date: 2026-04-30

Brief Summary

This is a single-center study of 80 subjects with asthma including those with obesity and metabolic dysfunction (MD), those with obesity and without metabolic dysfunction, those with severe asthma and mucus plugging and those with severe asthma and without mucus plugging. Screening data will be reviewed to determine participant eligibility. Participants who meet all inclusion criteria will participate in a cardiopulmonary exercise testing (CPET) visit to compare lung function markers and change in oxygen saturation between obese patients with and without MD and severe asthma patients with and without mucus plugging.

Detailed Description

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.

Conditions

Asthma

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Patients with asthma, obesity and metabolic dysfunction

Otherwise healthy asthmatic subjects with:

1. Body Mass Index (BMI) ≥ 30; and

2. Metabolic dysfunction evidenced by at least one of the following:

• high plasma IL-6 (> 3.0 pg/mL)
• insulin resistance (HOMA-IR > 3 mass units)

No interventions assigned to this group

Patients with asthma, obesity and no metabolic dysfunction

Otherwise healthy asthmatic subjects with:

1. Body Mass Index (BMI) ≥ 30; and

2. No evidence of metabolic dysfunction

No interventions assigned to this group

Patients with severe asthma and mucus plugs

Otherwise healthy asthmatic subjects:

1. Requiring treatment with high dose inhaled corticosteroids plus a second controller, systemic corticosteroid, or biologic therapy; and

2. Evidence of mucus plugs as defined by a mucus plug score ≥ 4

No interventions assigned to this group

Patients with severe asthma and no mucus plugs

Otherwise healthy asthmatic subjects:

1. Requiring treatment with high dose inhaled corticosteroids plus a second controller, systemic corticosteroid, or biologic therapy; and

2. No evidence of mucus plugs as defined by a mucus plug score < 4

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. Male or female ≥ 18 years old at Visit 0

2. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

3. History of physician diagnosed asthma

4. Evidence of bronchodilator reversibility (12% improvement in FEV1 after albuterol administration) or positive methacholine challenge PC20 or PD20. Historical evidence is accepted.

5. Meets criteria for obesity or severe asthma a. Obesity: BMI≥30 i. Metabolic dysfunction is defined as presence of either:

1. 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

1. Asthma exacerbation or URI within the previous 6 weeks.

2. History of smoking

1. If <30 years old: Smoked for ≥5 pack-years

2. If ≥30: Smoked for ≥10 pack years

3. Pregnancy

4. Absolute or relative contraindication to exercise testing per ATS criteria

5. Any other criteria that place the subject at unnecessary risk according to the judgment of the Principal Investigator and/or attending physician of record.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Fahy, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

UCSF Airway Clinical Research Center

San Francisco, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jade Vi, BS

Role: CONTACT

jade.vi@ucsf.edu

415-476-1783

John Fahy, MD, MS

Role: CONTACT

john.fahy@ucsf.edu

415-476-9940

Facility Contacts

Jade Vi, BS

Role: primary

jade.vi@ucsf.edu

415-476-1783

John Fahy, MD, MS

Role: backup

john.fahy@ucsf.edu

415-476-9940

Other Identifiers

R01HL164787

Identifier Type: NIH

Identifier Source: secondary_id

View Link

22-37338

Identifier Type: -

Identifier Source: org_study_id