Cytochrome P450 Epoxygenase Pathway Regulation of Macrophage Function
Condition: Polymorphism; Lung Inflammation
MeSH terms: Pneumonia; Inflammation
Study type: Observational

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.
    

Detailed description: 
      This is a prospective, cross-sectional study designed to provide a consistent method for
      obtaining biological samples and respiratory health-related information from participants for
      use in research that evaluates lung function (e.g., responses to environmental agents such as
      air pollution particles, engineered nanomaterials, or immune ligands; the role of genetics on
      cellular responses or functioning).

      Study participants will be adult volunteers, ages 18-65 (inclusive), who meet eligibility
      criteria to undergo bronchoscopy. Potential participants will be prescreened and scheduled
      for a final eligibility visit that will include medical history review, vital signs, physical
      examination, blood draw, and pulmonary function tests. After eligibility is confirmed, the
      participant will be scheduled for biological sample collections, which will include a blood
      draw and bronchoscopy.

      The objective of this protocol is to investigate the role of cytochrome P450 (CYP)
      epoxygenase pathway enzymes, including the soluble epoxide hydrolase (sEH; encoded by EPHX2)
      and CYP2J2 proteins, in macrophage function and inflammatory responses. The primary outcome
      measure will evaluate macrophage phagocytosis in an ex vivo assay, comparing groups of
      individuals with and without EPHX2 and CYP2J2 polymorphisms of interest. Secondary outcomes
      will include evaluations of ex vivo gene expression of inflammatory receptors and cytokines
      in stimulated macrophages (alveolar and peripheral blood monocyte-derived), assessment of the
      lower airway microbiome from bronchoalveolar lavage (BAL) fluid, and measurement of
      eicosanoids and cytokines in serum and BAL fluid.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Healthy volunteers
      
Keywords: Bronchoscopy; Pollutants; Human Pulmonary Cells; Macrophage Function; Soluble Epoxide Hydrolase; Natural History