Contributing Factors in the Pathobiology of Airway Remodeling in Obesity

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◦

Inclusion criteria

Obese asthmatic & lean asthmatic

• 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.
• Lean subjects with body mass index (BMI) ≥ 20 kg/m2 and < 30 kg/m2 or obese subjects with BMI ≥ 30 and ≤ 55 kg/m2
• Physician diagnosis of asthma
• Forced expiratory volume at one second (FEV1) within acceptable limits (>45% predicted before and >55% predicted after, bronchodilator administration).
• Negative pregnancy test in women of childbearing potential (confirmed during screening).
• Relatively healthy subjects able to undergo bronchoscopy without complications.
• Willing and able to give informed consent and adhere to visit/protocol schedules.
• Read and write in English.

Obese non-asthmatic & Lean non-asthmatic

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

Asthmatic undergoing bariatric surgery

• 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.
• Physician diagnosis of asthma
• FEV1 within acceptable limits (>45% predicted before and >55% predicted after, bronchodilator administration).
• Morbidly obese subjects undergoing bariatric surgery and receiving care at the Duke Metabolic and Weight Loss Surgery Center.
• Negative pregnancy test in women of childbearing potential (confirmed during screening).
• Relatively healthy subjects able to undergo bronchoscopy without complications.
• Willing and able to give informed consent and adhere to visit/protocol schedules.
• Read and write in English.

Non-Asthmatic undergoing bariatric surgery

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

Exclusion criteria

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