Contributing Factors in the Pathobiology of Airway Remodeling in Obesity

Recruitment & Eligibility

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

Study & Design

Primary Outcome Measures

Name	Time	Method
Airway fibrosis	Visit 2 (14 days)	Obese asthmatics compared to lean asthmatics, obese non-asthmatics and lean non-asthmatics: A univariate linear model will be constructed to measure the effect of leptin or GLP-1 (glucagon-like peptide-1) on airway fibrosis, as measured by the ratio of Masson's trichrome-stained area to non-stained area in the sub-mucosal region of airway biopsy tissue.
Change in airway fibrosis	Visit 2 (14 days), Visit 4 (1 year + 14 days)	Asthmatics undergoing bariatric surgery and non-asthmatics undergoing bariatric surgery: Each patient will serve as its own control in comparing pre- and post-operative airway fibrosis. A univariate linear model will be constructed to measure the effect of bariatric surgery on airway fibrosis, as measured by the ratio of Masson's trichrome-stained area to non-stained area in the sub-mucosal region of airway biopsy tissue.

Secondary Outcome Measures

Name	Time	Method

Recruitment & Eligibility