The restrictions on research imposed for the COVID-19 pandemic prevented us from launching study recruitment and visits. At this stage our funding is not sufficient to allow us to enroll sufficient numbers of patients so we will close the study.

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.

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.

Group 1: Healthy Controls

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.

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.

Participants with asthma who present with or without mucus plugs, as well as healthy controls, all between the ages of 18 and 70.

There is no plan to make IPD available to other researchers.