Cytochrome P450 Epoxygenase Pathway Regulation of Macrophage Function

Exclusion Criteria

• •1. Current pregnancy or lactation, as medications used during the bronchoscopy can be excreted in the breast milk of lactating mothers
• •2. Current smoker or significant second-hand smoke exposure (defined by urine cotinine \>200 ng/mL at screening)
• •3. Post-bronchodilator FEV1 \< 70% of predicted
• •4. For asthmatics, any indication of moderate or severe asthma such as:
• •* Physician-directed emergency treatment for an asthma exacerbation within the preceding 12 months
• •* Any use of systemic steroid therapy during the last year or continuous use of inhaled steroids over a period of 1 month or longer during the past 6 months
• •* Regular use of cromolyn (except for prophylaxis of exercise induced bronchospasm) or any use of leukotriene inhibitors (Montelukast or Zafirlukast) within the past month
• •* Symptoms including:
• •* Night-time symptoms of cough or wheeze greater than 1x/week
• •* Exacerbations of asthma more than 2x/week
• •* Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness)
• •5. Bleeding disorders or regular use of aspirin or other non-steroidal anti-inflammatory drugs (which inhibit platelet function) or other drugs that prolong bleeding time such as warfarin, heparin or derivatives, or clopidogrel and related ADP inhibitors
• •6. Sickle cell disease or GP6 deficiency
• •7. Facial deformity or major facial surgery
• •8. Asthma exacerbation or respiratory infection 4 weeks prior to study visit
• •9. Allergy or history of adverse reactions to lidocaine, midazolam, or fentanyl
• •10. Vital signs (temperature, blood pressure, pulse rate) that are outside of the established CRU limits
• •11. Body weight \<50 kg (\<110 lbs)
• •12. The following abnormal clinical laboratory values (obtained during Visit 1 assessment):
• •* Platelet count \<100,000 per L
• •* White blood cells count \<3000 per L
• •* Absolute neutrophil count \<1000 per L
• •* Hematocrit \<35% for both female and male
• •* PT/INR and PTT based on reference laboratory established reference ranges
• •* Serum creatinine \>1.4 mg/dL
• •13. Any condition that, in the investigator's opinion, places the participant at undue risk for complications associated with required study procedures.
• •14. Use of the medication colchicine (commonly used to treat gout attacks) in the past 2 weeks.
• •Volunteers meeting any of the below temporary exclusions may enroll in the study, but may not
• •undergo the bronchoscopy procedure within the time frames specified for each below temporary exclusion. If any of the following conditions are met, the bronchoscopy will be rescheduled such that none of these temporary exclusions apply:
• •Temp. EXCL 1. An asthma exacerbation requiring increased asthma medications for more than 1 day (and other than exercise-induced asthma) within 1 month of bronchoscopy
• •Temp. EXCL 2. Viral upper respiratory tract infection or any acute infection requiring antibiotics within 4 weeks of bronchoscopy
• •Temp. EXCL 3. Use of anti-inflammatory medications (including over-the-counter preparations) during the 48 hours prior to the bronchoscopy and aspirin during the 14 days prior to bronchoscopy.
• •Temp. EXCL 4. Any food or fluids for 8 hours prior to the bronchoscopy