No participants were enrolled in protocol A due to COVID-related restrictions and funding issues.

This is a single-center study that will evaluate the safety and tolerability of removal of mucus plugs by bronchoscopy in patients with asthma. This protocol will also plan for the analysis of the features of the mucus plugs removed.

The investigators' research shows that a large subgroup of asthma patients have mucus plugs, and quantification of these plugs using a bronchopulmonary segment-based scoring system reveals a strong negative correlation between the CT (Computed Tomography) mucus plug score and FEV1 (Forced Expiratory Volume at 1 second). The FOCUS study is a single-center study that has the overarching goal to explore the biology of airway mucus plugs in asthma.

Through the FOCUS study, the investigators will initially explore the safety and tolerability of bronchoscopic removal of airway mucus plugs in patients with asthma and mucus plugs. They will then evaluate potential improvements in lung function outcomes in a dose-dependent manner (i.e., by removing mucus plugs from one lung vs both lungs). A secondary objective of the FOCUS study is to perform detailed cellular and molecular analyses of mucus and epithelial cells from airways impacted with mucus. With these biospecimens, the investigators intend to extend their preliminary findings that mucus plugged airways are characterized by intense type 2 inflammation, determine the mechanisms of epithelial and immune cell reprogramming, as well as how cellular reprogramming affects the promotion and persistence of type 2 airway inflammation.

Protocol A:

Inclusion Criteria:

• Males or females between the ages 18 to 70 at the time of visit 1.
• Clinical history of asthma per patient report or medical record.
• Pre-bronchodilator FEV1 < 80% predicted and ≥ 35% predicted
• CT mucus plug score > 5.
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

Exclusion Criteria:

• Smoking of tobacco or other recreational inhalants in the last month and/or >10 pack-year smoking history.
• History of other pulmonary disorders including cystic fibrosis and COPD (Chronic Obstructive Pulmonary Disease).
• History of unstable cardiovascular disease.
• BMI > 45
• Current use of anticoagulant medications.
• Upper Respiratory Infection (URI) within the previous 6 weeks
• Currently pregnant and/or unwillingness to practice medically acceptable birth control or complete abstinence during the study
• History of COVID-19 (coronavirus disease) in the past 6 months.

Protocol B:

Inclusion Criteria:

• Males or females between the ages 18 to 80 at the time of visit 1.
• Undergoing clinically indicated bronchoscopy for removal of mucus plugs.
• Clinical history of airway disease (including asthma, COPD and bronchiectasis) per patient report or medical record.
• Written informed consent obtained from subject.

Exclusion Criteria:

• Upper Respiratory Infection (URI) in the past 30 days.
• History of COVID-19 in the past 30 days.
• Currently pregnant during the study.