GSNOR Phenotyping/GSNO Challenge in Severe Asthma

Inclusion Criteria

For subjects with Asthma

• Adult males or females age ≥ 18 and ≤ 50 years at the time of enrollment
• Non-smoker
• Physician diagnosis of asthma for at least one year
• FEV1 bronchodilator reversibility > 12% or methacholine PC20 55% predicted

Healthy Volunteers

• Adult males or females age ≥ 18 and ≤ 50 years at time of enrollment
• Non-smoker
• No history of asthma, chronic obstructive pulmonary disease (COPD), or other chronic lung disease
• No history of severe allergic/atopic disease requiring immunotherapy or immunomodulators

Exclusion Criteria

-> 5 pack year smoking history

• Body mass index (BMI) > 45
• Unable to perform repeatable consistent efforts in pulmonary function testing
• Individuals with prior diagnosis of vocal cord dysfunction or an anatomic anomaly that would increase the risks associated with the bronchoscopy procedure
• Prior diagnosis of cystic fibrosis, COPD, or other additional lung disease that in the investigator's opinion would make participant unsuitable for study participation
• History of premature birth before 35 weeks gestation
• Planning to relocate away from the clinical center (Cleveland, Ohio or central Indiana) area before study completion
• Lack of reliable communications channel (hard-wire phone, cell phone, email for follow-up contacts after bronchoscopy)
• Allergic to anesthetic medication(s) that would prevent participation in the study's bronchoscopy
• Blood pressure parameters outside the normal range of 90-180 mm Hg systolic and 50-100 mm Hg diastolic at time of screening
• Individuals with diabetes mellitus (type 1 or type 2)
• Individuals with renal failure or creatinine > 1.8 mg/dl at time of screening
• Individuals who are pregnant, breastfeeding, or are unwilling to use a medically acceptable method of birth control (as indicated on the Birth Control Methods Reference Card) from the time of consent until the end of the study to avoid pregnancy
• Individuals who report additional chronic diseases requiring medication of the heart, lungs, kidney, liver, brain, etc., or afflicted with any acute or chronic pathology that in the opinion of the screening physician makes them unsuitable for study such as coronary artery disease
• Asthma exacerbation requiring oral corticosteroids within the previous 30 days (can be rescreened)
• More than 3 exacerbations within the past 6 months
• Intubated for asthma within the past 12 months
• Respiratory or other infection requiring systemic antibiotics within the previous 14 days (can be rescreened)
• Current use of a vitamin K antagonist (warfarin) or other anticoagulant (e.g., heparin, clopidogrel, enoxaparin or dalteparin)
• Current use of beta-adrenergic blockers, tricyclic antidepressants, meperidine (or related central nervous system (CNS) agents), or nitrates
• Unable or unwilling to withhold medications prior to certain study procedures (skin test, spirometry, methacholine challenge)
• Inherited or acquired blood coagulation disorder, congenital methemoglobinemia, or a familial hemoglobinopathy that impacts oxygen delivery (e.g., sickle cell)
• Any illness, condition or recent surgeries that may increase the risks associated with the study
• Participation in any investigational drug study other than the Airway pH Study within the 4 week period prior to screening.
• Any acute viral illness, including active COVID-19 infection or acute viral respiratory symptoms; can rescreen 4 weeks after positive test result.