Study of Focal Airway Disease in Asthma Using Image Guided Bronchoscopy

Withdrawn

• Conditions: Asthma; Mucus; Plug, Tracheobronchial
• Interventions: Radiation: Multidetector Computed Tomography (MDCT) Scan; Procedure: Virtual Navigation Bronchoscopy (VNB)

• Registration Number: NCT04514913
• Lead Sponsor: University of California, San Francisco

Brief Summary

This is a single center study of 60 subjects including those with asthma and mucus plugging, those with asthma and without mucus plugging, and healthy controls. Screening data will be reviewed to determine participant eligibility. Participants who meet all inclusion criteria will participate in image-guided bronchoscopy ("virtual navigation bronchoscopy" \[VNB\]) to sample airway biospecimens in mucus plugged and control airways.

Detailed Description

This is a single center study of 60 subjects. The investigators will enroll 30 subjects with asthma who demonstrate mucus plugging on a screening CT lung scan, 15 subjects with asthma without mucus plugging, and 15 healthy controls. The healthy controls and subjects with asthma but without mucus plugging with also undergo CT scans to confirm that their lungs aren't obstructed by mucus.

Screening data will be reviewed to determine participant eligibility. Participants who meet all inclusion criteria will participate in image-guided bronchoscopy ("virtual navigation bronchoscopy" \[VNB\]) to sample airway biospecimens in mucus plugged and control airways. Subjects will participate in up to 5 study visits at the Airway Clinical Research Center.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-08-12
• Study First Submitted QC: 2020-08-12
• Study First Posted: 2020-08-17
• Status Verified: 2023-02
• Study Start: 2023-02
• Primary Completion: 2023-02
• Study Completion: 2023-02
• Last Update Submitted: 2023-02-16
• Last Update Posted: 2023-02-21

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Male or female between the ages of 18 and 70 years at Visit 1 and at least 50% whose age is > 40 years (to ensure age balance among groups and anticipating that group 3 subjects will be older).
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
• Able to perform reproducible spirometry according to ATS criteria.

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Exclusion Criteria

• Upper respiratory tract infection (URI) within the previous 6 weeks.
• History of lung disease.
• Smoking of tobacco or other recreational inhalants in last month and/or >10 pack-year smoking history.
• Currently pregnant.
• History of allergic rhinitis.
• Laboratory evidence of atopy (blood eosinophils > 0.4 cells/dL, IgE > 165 IU/mL)
• History of unstable cardiovascular disease.
• BMI > 45
• Currently taking anticoagulants.

Group 2: Asthmatic Subjects without Mucus Plugs

Inclusion Criteria:

• Male or female between the ages of 18 and 70 years at Visit 1 and at least 50% whose age is > 40 years (to ensure age balance among groups and anticipating that group 3 subjects will be older).
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
• Able to perform reproducible spirometry according to ATS criteria.
• Physiological evidence of airflow obstruction (FEV1 bronchodilator reversibility of ≥ 12% or hyperreactivity to methacholine reflected by a methacholine PC20 ≤ 16 mg/mL). Historical methacholine data from previous studies conducted in the past 5 years at the UCSF ACRC will be allowed.
• Clinical history of asthma per patient report or medical record.
• Asthma requiring treatment with inhaled corticosteroids (ICS) for 3 months or greater.

Exclusion Criteria:

• Asthma exacerbation or URI within the previous 6 weeks.
• Currently pregnant.
• Smoking of tobacco or other recreational inhalants in last month and/or >10 pack-year smoking history.
• Other chronic pulmonary disorders, including cystic fibrosis and chronic obstructive pulmonary disease.
• History of unstable cardiovascular disease.
• BMI > 45.
• Currently taking anticoagulants.

Group 3: Asthmatic Subjects with Mucus Plugs

Inclusion:

• Male or female between the ages of 18 and 70 years at Visit 1.
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
• Able to perform reproducible spirometry according to ATS criteria.
• Physiological evidence of airflow obstruction (FEV1 bronchodilator reversibility of ≥ 12% or hyperreactivity to methacholine reflected by a methacholine PC20 ≤ 16 mg/mL). Historical methacholine data from previous studies conducted in the past 5 years at the UCSF ACRC will be allowed.
• Clinical history of asthma per patient report or medical record.
• Asthma requiring treatment with inhaled corticosteroids (ICS) for 3 months or greater.
• A MDCT lung scan indicating a mucus plug accessible by bronchoscopy in at least one airway.

Exclusion Criteria:

• Asthma exacerbation or URI within the previous 6 weeks.
• Currently pregnant.
• Smoking of tobacco or other recreational inhalants in last month and/or >10 pack-year smoking history.
• Other chronic pulmonary disorders, including cystic fibrosis and chronic obstructive pulmonary disease.
• History of unstable cardiovascular disease.
• BMI > 45.
• Currently taking anticoagulants.
• Mucus plugs inaccessible by bronchoscope.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Asthmatics with mucus plugs	Virtual Navigation Bronchoscopy (VNB)	Participants with asthma and evidence by MDCT lung scan showing mucus plugging.
Asthmatics without mucus plugs	Multidetector Computed Tomography (MDCT) Scan	Participants with asthma and no evidence of mucus plugging.
Asthmatics without mucus plugs	Virtual Navigation Bronchoscopy (VNB)	Participants with asthma and no evidence of mucus plugging.
Healthy Controls	Multidetector Computed Tomography (MDCT) Scan	Participants with no history of asthma or other lung diseases.
Healthy Controls	Virtual Navigation Bronchoscopy (VNB)	Participants with no history of asthma or other lung diseases.
Asthmatics with mucus plugs	Multidetector Computed Tomography (MDCT) Scan	Participants with asthma and evidence by MDCT lung scan showing mucus plugging.

Primary Outcome Measures

Name	Time	Method
Difference in eosinophil percentage in broncheoalveolar biospecimens between asthmatic and non-asthmatic airways	6 months	The investigators will examine differences in type-2 inflammatory markers in bronchoalveolar biospecimens. Eosinophils are an indicator of type 2 inflammation in bronchial lavage samples. Indicators of airway inflammation will be compared with healthy control biospecimens and those of non-mucus plugged asthmatics.
Difference in gene expression of genes that mark IL-13 activation between asthmatic and non-asthmatic airways	6 months	Genes such as periostin, CLCA1, and Serpin B2 will be analyzed for expression in epithelial cell brushings.

Trial Locations

Locations (1)

UCSF Airway Clinical Research Center; 🇺🇸 San Francisco, California, United States