Cytochrome P450 Epoxygenase Pathway Regulation of Macrophage Function

NCT02743468 | Completed

• 2 other identifiers: 16009616-E-0096
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Respiratory diseases affect more than 1 billion people worldwide. They are a growing public health concern. The lungs are constantly exposed to environmental factors such as dust, fumes, microbes, and pollutants. But much is still not known about how these pollutants lead to respiratory illnesses. Researchers want to collect samples from lungs and blood to see how genetics and environmental pollutants affect cellular responses or functioning. Objectives: To study how cytochrome P450 epoxygenase pathway enzymes affect macrophage function in the lungs and inflammatory responses. Eligibility: Adults ages 18 65 who can have a bronchoscopy. Design: All study visits will take place at the NIEHS Clinical Research Unit in Research Triangle Park, NC. At study visit 1, participants will be screened with medical history and physical exam. They will have blood and urine tests. They will take tests that measure their lung function. They will answer questionnaires. Before the visit, they will be given a list of medicines they cannot take. They also must not have caffeine on the day of their visit. The visit will last about 3 hours. At study visit 2, participants will give blood samples. They will undergo bronchoscopy. For this, they will get an intravenous line in a vein to get sedatives. Their airways will be numbed. Cells will be collected from their lungs. They will fast for 8 hours before the visit. They must have someone else drive them home from the visit. The visit will last about 3-4 hours. Participants will get a follow-up phone call about 1 day after study visit 2.

Conditions

Polymorphism; Lung Inflammation

Keywords

Bronchoscopy; Pollutants; Human Pulmonary Cells; Macrophage Function; Soluble Epoxide Hydrolase; Natural History

Outcome Measures

Primary Outcomes (1)

• The primary outcome measure will evaluate macrophage phagocytosis of fluorescein isothiocyanate (FITC)-labeled beads and bacteria (Streptococcus pneumoniae) in an ex vivo assay, comparing alveolar macrophages from groups of individuals with and ...

  The primary outcome measure will evaluate macrophage phagocytosis of fluorescein isothiocyanate (FITC)-labeled beads and bacteria (Streptococcus pneumoniae) in an ex vivo assay, comparing alveolar macrophages from groups of individuals with and without EPHX2 and CYP2J2 polymorphisms of interest.

  Cross-sectional

Study Arms (1)

Healthy Volunteers

Healthy Volunteers

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers

You may qualify if:

• Age 18 to 65 years, inclusive (males and females)
• Able to travel to the NIEHS CRU for required study visits
• Able to present a valid government-issued form of identification for entry to the NIEHS campus
• Able to fast for 8 hours prior to the visit where bronchoscopy occurs
• Has a responsible party who is willing and able to attend Visit 2 and drive the participant away from the CRU after completion of Visit 2, if the participant elects to undergo conscious sedation
• Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates:
• Wild type with respect to EPHX2 K55R, EPHX2 R287Q, and CYP2J2\*7; or
• Homozygous for EPHX2 K55R (wild type for the other SNPs); or
• Homozygous for EPHX2 R287Q (wild type for the other SNPs); or
• Homozygous for CYP2J2\*7 (wild type for the other SNPs)

You may not qualify if:

• Current pregnancy or lactation, as medications used during the bronchoscopy can be excreted in the breast milk of lactating mothers
• Current smoker or significant second-hand smoke exposure (defined by urine cotinine \>200 ng/mL at screening)
• Post-bronchodilator FEV1 \< 70% of predicted
• 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)
• 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
• Sickle cell disease or GP6 deficiency
• Facial deformity or major facial surgery
• Asthma exacerbation or respiratory infection 4 weeks prior to study visit

Sponsors & Collaborators

• National Institute of Environmental Health Sciences (NIEHS): lead

Study Sites (1)

NIEHS, Research Triangle Park

Research Triangle Park, North Carolina, 27709, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pneumonia

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Darryl C Zeldin, M.D.

  National Institute of Environmental Health Sciences (NIEHS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2016
• First Posted: April 19, 2016
• Study Start: January 8, 2019
• Primary Completion: December 18, 2019
• Study Completion: September 21, 2023
• Last Updated: April 29, 2026

Record last verified: 2026-04-03

Locations

US (1)