The study was redesigned to be conducted in an outpatient setting.

The purpose of this study is to determine the beneficial effect of n-acetylcysteine (NAC), an inhaled medication that breaks down mucus, on lung function. NAC is a medication approved by the US Food and Drug Administration (FDA) for the treatment of chronic diseases of the respiratory system, including asthma. With CT lung imaging, the investigators seek to identify a subgroup of patients with asthma with a 'mucus' profile. This is a single-arm study which means all participants will receive the same treatment.

N-acetylcystine (NAC) is a mucolytic medication, meaning that it breaks apart mucus. Investigators know that mucus is a factor in severe asthma attacks. However, mucus may be a factor in chronic severe asthma as well. This role has been hard to prove because of difficulty in showing that mucus occludes the lumen in chronic severe disease. Using a novel approach of scoring mucus occlusion, investigators have used CT imaging to uncover that a majority of people with severe asthma have at least one lung segment with a mucus plug and 27% have more than four lung segments with mucus plugs.

Historically, studies of mucolytics, like NAC, have not shown benefit in other obstructive lung diseases, like COPD. However, utilizing CT mucus scores as a biomarker, investigators believe that mucolytic treatment may prove useful for those with significant mucus impaction.

This is a single-arm study of participants with asthma who also have evidence of mucus in their lungs as determined by CT imaging. Investigators hypothesize that by treating asthmatics, chosen based on the presence of mucus in the airways, with a mucolytic like NAC, will result in an improvement of lung function.

Inclusion Criteria:

1. Male or female between the ages of 18 and 80 years of age at Visit 1
2. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
3. Able to perform reproducible spirometry according to ATS criteria
4. Physiological evidence of airflow obstruction (FEV1 bronchodilator reversibility of ≥ 12% or hyperreactivity to methacholine reflected by a methacholine PC20 ≤ 16 mg/mL)
5. Clinical history of asthma per patient report or medical record
6. Pre-bronchodilator FEV1 > 35% predicted
7. Post-bronchodilator FEV1 > 40% but < 90% predicted
8. Asthma requiring treatment with inhaled corticosteroids (ICS) for 3 months or greater
9. CT mucus score > 3

Exclusion Criteria:

1. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
2. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
3. Smoking of tobacco or other recreational inhalants in last year and/or >10 pack-year smoking history
4. Current participation in an investigational drug trial
5. Other chronic pulmonary disorders, including (but not limited to) cystic fibrosis, chronic obstructive pulmonary disease, chronic bronchitis, vocal cord dysfunction (that is the sole cause of respiratory symptoms and at the PI's discretion), severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways
6. Unwillingness to follow study procedures
7. History of allergy or intolerance to study drug
8. Any other criteria that places the subject at unnecessary risk according to the judgment of the Principal Investigator

3 months

Adverse events will be monitored by the Clinical PIs (Drs. Fahy, Woodruff and Lazarus) in real-time. Safety and tolerability data will be summarized quarterly. Adverse events will be tabulated and will include the number of patients for whom the event occurred, the rate of occurrence, and the severity and relationship to study drug. All AEs will be reviewed quarterly.