Contributing Factors in the Pathobiology of Airway Remodeling in Obesity

Duke University

Status: Completed

Conditions: Asthma; Bariatric Surgery Candidate; Obesity; Obesity, Morbid

Study type: Observational

Funder types: Other

Identifiers

NCT03115632

Pro00077482

Details and patient eligibility

About

There are two aims for this study. The purpose of this study is to determine the effects of body weight and hormones on airway fibrosis (scarring) and lung function in obese & lean asthma subjects compared to obese & lean non-asthma subjects (Aim 1). And in obese subjects with asthma undergoing bariatric surgery compared to obese non-asthma subjects undergoing bariatric surgery (Aim 2).

Full description

Main Study

Specific Aim 1: Determine the effects of signaling on airway fibrosis and lung function in obese asthma and non-asthma patients. The investigators will:

•Perform assessments to determine if obese, early-onset asthma patients are more susceptible to airway fibrosis and remodeling than lean, early-onset asthma patients and obese and lean, non-asthma patients.◦

Specific Aim 2: Investigate the mechanism by which bariatric surgery slows the progression of airway fibrosis in obese human asthma. The investigators will:

•Perform assessments to determine if airway fibrosis in obese, early-onset asthma and obese non-asthma patients improves following bariatric surgery and weight loss◦

Enrollment: 31 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Obese asthmatic & lean asthmatic

1. Outpatient adults of either sex 18-60 years of age with an initial asthma diagnosis at < 12 years of age, as defined by the NHLBI National Asthma Education and Prevention Program (NAEPP) guidelines.
2. Lean subjects with body mass index (BMI) ≥ 20 kg/m2 and < 30 kg/m2 or obese subjects with BMI ≥ 30 and ≤ 55 kg/m2
3. Physician diagnosis of asthma
4. Forced expiratory volume at one second (FEV1) within acceptable limits (>45% predicted before and >55% predicted after, bronchodilator administration).
5. Negative pregnancy test in women of childbearing potential (confirmed during screening).
6. Relatively healthy subjects able to undergo bronchoscopy without complications.
7. Willing and able to give informed consent and adhere to visit/protocol schedules.
8. Read and write in English.

Obese non-asthmatic & Lean non-asthmatic

1. Outpatient adults of either sex 18-60 years of age.
2. Lean subjects with body mass index (BMI) ≥ 20 kg/m2 and < 30 kg/m2 or obese subjects with BMI ≥ 30 and ≤ 55 kg/m2
3. Negative pregnancy test in women of childbearing potential (confirmed during screening).
4. Normal lung function.
5. No clinical history of atopy.
6. No significant medical or psychological issues.
7. Healthy subjects able to undergo bronchoscopy without complications.
8. Willing and able to give informed consent and adhere to visit/protocol schedules.
9. Read and write in English.

Asthmatic undergoing bariatric surgery

1. Outpatient adults of either sex 18-60 years of age with an initial asthma diagnosis at < 12 years of age, as defined by the NHLBI NAEPP guidelines.
2. Physician diagnosis of asthma
3. FEV1 within acceptable limits (>45% predicted before and >55% predicted after, bronchodilator administration).
4. Morbidly obese subjects undergoing bariatric surgery and receiving care at the Duke Metabolic and Weight Loss Surgery Center.
5. Negative pregnancy test in women of childbearing potential (confirmed during screening).
6. Relatively healthy subjects able to undergo bronchoscopy without complications.
7. Willing and able to give informed consent and adhere to visit/protocol schedules.
8. Read and write in English.

Non-Asthmatic undergoing bariatric surgery

1. Outpatient adults of either sex 18-60 years of age.
2. Morbidly obese subjects undergoing bariatric surgery and receiving care at the Duke Metabolic and Weight Loss Surgery Center.
3. Negative pregnancy test in women of childbearing potential (confirmed during screening).
4. Normal lung function.
5. No clinical history of atopy.
6. No significant medical or psychological issues.
7. Healthy subjects able to undergo bronchoscopy without complications.
8. Willing and able to give informed consent and adhere to visit/protocol schedules.
9. Read and write in English.

Exclusion criteria

1. Children < 18 years of age.
2. Adults ≥ 18 years of age with an initial asthma diagnosis at ≥ 12 years of age, as defined by the NHLBI NAEPP guidelines.
3. Inpatient status.
4. FEV1 is less than 45% predicted before, or less than 55% predicted after, bronchodilator administration.
5. Upper or lower respiratory tract infection within one month of the study.
6. Use of inhaled or systemic corticosteroids within four weeks of study.
7. Use of long-acting beta-2, GLP-1 receptor agonists, or dipeptidyl peptidase-4 (DPP-4) inhibitors within two weeks of study.
8. Smoking history > 5 pack years or any cigarette use within the previous six months.
9. Significant non-asthma pulmonary disease (stable obstructive sleep apnea is not excluded).
10. Positive pregnancy test for women and/or nursing women.
11. An emergency department visit or inpatient admission for a primary respiratory diagnosis or treatment with antibiotics within 60 days of enrollment.
12. Poorly controlled concomitant conditions that pose additional procedure risk as determined by the investigator.
13. All patients on anticoagulants
14. Uncontrolled sleep apnea
15. Use of e-cigarettes or "vape" devices of any kind

Trial design

31 participants in 4 patient groups

Obese asthmatic & lean asthmatic

Description:

men and women with asthma and either obese or lean BMI

Obese non-asthmatic & lean non-asthmatic

Description:

men and women without asthma and either obese or lean BMI

Asthmatic undergoing bariatric surgery

Description:

Obese asthmatic men and women undergoing bariatric surgery

Non-asthmatic undergoing bariatric surgery

Description:

Obese men and women undergoing bariatric surgery