Contributing Factors in the Pathobiology of Airway Remodeling in Obesity

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).

Study Overview

• Status: Completed
• Conditions: Obesity; Asthma; Obesity, Morbid; Bariatric Surgery Candidate

Detailed 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◦

• Study Type: Observational
• Enrollment (Actual): 31

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Asthma Allergy and Airway Center
    • Durham, North Carolina, United States, 27704
      • Duke Metabolic and Weight Loss Surgery Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Subjects will be recruited from the clinics of the Duke Asthma, Allergy and Airway Center, the Duke Metabolic and Weight Loss Surgery Center, the Duke Raleigh Weight Loss Surgery Center, and the Duke Diet and Fitness Center. Healthy controls without lung disease will be recruited from the surrounding area.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Obese asthmatic & lean asthmatic; men and women with asthma and either obese or lean BMI
Obese non-asthmatic & lean non-asthmatic; men and women without asthma and either obese or lean BMI
Asthmatic undergoing bariatric surgery; Obese asthmatic men and women undergoing bariatric surgery
Non-asthmatic undergoing bariatric surgery; Obese men and women undergoing bariatric surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airway fibrosis	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.	Visit 2 (14 days)
Change in airway fibrosis	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.	Visit 2 (14 days), Visit 4 (1 year + 14 days)

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Loretta Que, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2018
• Primary Completion (Actual): June 27, 2023
• Study Completion (Actual): June 27, 2023

Study Registration Dates

• First Submitted: April 4, 2017
• First Submitted That Met QC Criteria: April 11, 2017
• First Posted (Actual): April 14, 2017

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Pathological Conditions, Anatomical; Obesity; Obesity, Morbid; Airway Remodeling
• Other Study ID Numbers: Pro00077482

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No