Clinical trial NCT05757583: Impact of Metabolic Dysfunction and Mucus Plugging on Asthma Physiology
Official title: Impact of Metabolic Dysfunction and Mucus Plugging on Asthma Physiology
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Asthma
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-03-07
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will recruit up to 80 asthma participants, at least 20 with obesity and MD, 20 with obesity and no MD, 20 with severe asthma and mucus plugs and 20 with severe asthma and no mucus plugs.

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.

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.

Primary outcomes:
measure: Change in EELV (End Expiratory Lung Volume)
timeFrame: At CPET visit.
Secondary outcomes:
measure: Change in RV (Residual Volume) and TLC (Total Lung Capacity)
timeFrame: At CPET Visit
measure: Change in oxygen saturation during exercise
timeFrame: At CPET Visit
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Airway Clinical Research Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: John Fahy, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: