Project 2 Airway Potential Hydrogen (pH) in Asthma

Inclusion Criteria: Subjects with Severe Asthma 1. Asthma diagnosis established during at least 3 months of evaluation and care by an asthma specialist (pulmonologist or allergist). 2. Adult male or female age ≥ 18 and ≤ 50 years at the time of enrollment 3. Forced expiratory volume in 1 second (FEV1) bronchodilator reversibility \> 12% or methacholine FEV1 by 20% of baseline (PC20) \< 16 mg/ml (historical methacholine data from previous NIH trial including Severe Asthma Research Program (SARP) or Asthma Network (AsthmaNet) will be allowed). 4. If FEV1 is \<50% predicted, precluding methacholine challenge testing, investigator acceptance of the diagnosis of asthma is acceptable 5. Treatment with high-dose inhaled corticosteroids (\> 880 mcg fluticasone or highest marketed equivalent/day) along with a second controller or systemic corticosteroids for at least 3 months prior to enrollment and for at least 6 of the last 12 months. 6. Lack of asthma control despite this treatment evidenced by any one of the following: 1. Asthma Control Questionnaire (ACQ) \> 1.5 or Asthma Control Test (ACT) \< 20 2. \>2 bursts of systemic corticosteroids (3 days or more) in the previous 12 months 3. \>1 hospitalization or ICU stay for acute asthma in the previous 12 months 4. Mild to moderate obstructive lung disease with 45%\< FEV1 \< 80% predicted (with low FEV1/FVC) prior to bronchodilator 7. Post bronchodilator FEV1 \< 55% predicted on the day of study procedures including the Inhaled glycine buffer challenge test and bronchoscopy. (These events may be rescheduled in the event participants meet all inclusion criteria at the time of screening) Healthy Volunteers 1. Adult males or females age ≥ 18 and ≤ 50 years at time of enrollment 2. Non-smokers 3. No history of asthma, chronic obstructive pulmonary disease (COPD), or other chronic lung disease 4. No history of severe allergic/atopic disease requiring immunotherapy or immunomodulators Subjects with Cystic Fibrosis 1. Adult male or female age ≥ 18 and ≤ 50 at time of enrollment 2. Confirmed diagnosis of CF as evidenced by 1 or more clinical features consistent with the CF phenotype and 1 or more of the following laboratory criteria: 1. Sweat chloride equal to or greater than 60 m/Eq/L by quantitative pilocarpine iontophoresis test (Sweat Test) 2. Two well-characterized disease causing mutations in the Cystic fibrosis transmembrane conductance regulator (CFTR) gene. 3. Weight \> 50 kg at screening visit 4. Mild obstructive lung disease defined as post bronchodilator baseline FEV1 \> 70% predicted for age, height and gender 5. Clinically stable with no significant changes in health status within 4 weeks, including FEV1 within 10% of baseline, at the time of screening (may be rescreened) Exclusion Criteria: General (applying to all participants) 1. \> 5 pack year smoking history 2. Body mass index (BMI) greater than 45 3. Unable to perform repeatable consistent efforts in pulmonary function testing 4. Individuals with prior diagnosis of vocal cord dysfunction or an anatomic anomaly that would increase the risks associated with the bronchoscopy procedure 5. Prior diagnosis of any chronic lung disease that in the investigator's opinion would make them unsuitable for study participation 6. History of premature birth before 35 weeks gestation 7. Planning to relocate away from the clinical center (Cleveland, Ohio) area before study completion 8. Lack of reliable communications channel (hard-wire phone, cell phone, email for follow-up contacts after bronchoscopy) 9. Allergic to anesthetic medication(s) that would prevent participation in the study's bronchoscopy 10. Blood pressure parameters outside the normal range of 90-180 mm Hg systolic and 50-100 mm Hg diastolic at time of screening 11. Individuals with diabetes mellitus (type 1 or type 2) (subjects with CF who have CF related diabetes may be enrolled) 12. Individuals with renal failure or creatinine \> 1.8 mg/dl at time of screening 13. 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 14. 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 15. Respiratory or other infection requiring systemic antibiotics within the previous 14 days (can be rescreened) 16. Current use of a vitamin K antagonist (warfarin) or other anticoagulant (e.g., heparin, clopidogrel, enoxaparin or dalteparin) 17. Current use of beta-adrenergic blockers, tricyclic antidepressants, meperidine (or related central nervous system (CNS) agents), or nitrates 18. Inherited or acquired blood coagulation disorder, congenital methemoglobinemia, or a familial hemoglobinopathy that impacts oxygen delivery (e.g., sickle cell) 19. Any illness, condition or recent surgeries that may increase the risks associated with the study 20. Participation in an investigational drug study within the 4 week period prior to screening (Visit 1) Severe Asthma specific exclusion criteria 1. Asthma exacerbation within 4 weeks prior to screening (Visit 1) (may be rescreened) 2. Initiation of new chronic treatment or change in dose of chronic treatment for asthma within 2 months of screening 3. Intubation for asthma within the past 12 months 4. More than 3 exacerbations within the past 6 months Cystic fibrosis specific exclusion criteria 1. Positive sputum culture for Burkholderia cepacia complex organism within the previous 12 months 2. Active treatment for non-tuberculous mycobacterium 3. International Normalized Ratio (INR) \> 1.2 at time of screening 4. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 times the upper limit of normal at screening, history of biliary cirrhosis or portal hypertension 5. Treatment with Kalydeco (ivacaftor) within 12 weeks of screening 6. History of pulmonary hypertension 7. Severe malnutrition 8. Pulse oximetry \< 92% at screening or chronic use of supplemental oxygen 9. Currently listed for lung or other organ transplantation 10. Pneumothorax within 2 years 11. Hemoptysis other than trace during the past 12 months or history of life threatening hemoptysis ever 12. Initiation of any new chronic treatment with 4 weeks of screening (can be rescreened)