title: Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach.
abstract: BACKGROUND
  Cigarette smoke contributes to a diverse range of diseases including chronic obstructive pulmonary disease (COPD), cardiovascular disorders and many cancers. There currently is a need for human challenge models, to assess the acute effects of a controlled cigarette smoke stimulus, followed by serial sampling of blood and respiratory tissue for advanced molecular profiling. We employ precision sampling of nasal mucosal lining fluid by absorption to permit soluble mediators measurement in eluates. Serial nasal curettage was used for transcriptomic analysis of mucosal tissue.
  
  
  METHODS
  Three groups of strictly defined patients will be studied: 12 smokers with COPD (GOLD Stage 2) with emphysema, 12 matched smokers with normal lung function and no evidence of emphysema, and 12 matched never smokers with normal spirometry. Patients in the smoking groups are current smokers, and will be given full support to stop smoking immediately after this study. In giving a controlled cigarette smoke stimulus, all patients will have abstained from smoking for 12 h, and will smoke two cigarettes with expiration through the nose in a ventilated chamber. Before and after inhalation of cigarette smoke, a series of samples will be taken from the blood, nasal mucosal lining fluid and nasal tissue by curettage. Analysis of plasma nicotine and metabolites in relation to levels of soluble inflammatory mediators in nasal lining fluid and blood, as well as assessing nasal transcriptomics, ex vivo blood platelet aggregation and leucocyte responses to toll-like receptor agonists will be undertaken.
  
  
  CONCLUSIONS
  Development of acute cigarette smoke challenge models has promise for the study of molecular effects of smoking in a range of pathological processes.
  
  
  BACKGROUND
  This study was approved by the West London National Research Ethics Committee (12/LO/1101). The study findings will be presented at conferences and will be reported in peer-reviewed journals.
authors: Imperial Clinical Respiratory Research Unit (ICRRU) and Biomedical Research Centre (BMRC), Centre for Respiratory Infection (CRI), St Mary's Hospital, Imperial College, London, UK.
authors: Clare L
authors: CL
authors: Ross
authors: National Heart and Lung Institute, Imperial College, London, UK.
authors: Neil
authors: N
authors: Galloway-Phillipps
authors: William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry, London, UK.
authors: Paul C
authors: PC
authors: Armstrong
authors: National Heart and Lung Institute, Imperial College, London, UK.
authors: Jane A
authors: JA
authors: Mitchell
authors: William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry, London, UK.
authors: Timothy D
authors: TD
authors: Warner
authors: Sunovion Pharmaceuticals Europe Ltd. (Sunovion Europe), London, UK.
authors: Christopher
authors: C
authors: Brearley
authors: Dainippon Sumitomo Pharma Co Ltd, Osaka, Japan Department of Molecular Regulation for intractable Diseases, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors: Mari
authors: M
authors: Ito
authors: Imperial Clinical Respiratory Research Unit (ICRRU) and Biomedical Research Centre (BMRC), Centre for Respiratory Infection (CRI), St Mary's Hospital, Imperial College, London, UK.
authors: Tanushree
authors: T
authors: Tunstall
authors: Imperial Clinical Respiratory Research Unit (ICRRU) and Biomedical Research Centre (BMRC), Centre for Respiratory Infection (CRI), St Mary's Hospital, Imperial College, London, UK.
authors: Sarah
authors: S
authors: Elkin
authors: Imperial Clinical Respiratory Research Unit (ICRRU) and Biomedical Research Centre (BMRC), Centre for Respiratory Infection (CRI), St Mary's Hospital, Imperial College, London, UK.
authors: Onn Min
authors: OM
authors: Kon
authors: Imperial Clinical Respiratory Research Unit (ICRRU) and Biomedical Research Centre (BMRC), Centre for Respiratory Infection (CRI), St Mary's Hospital, Imperial College, London, UK.
authors: Trevor T
authors: TT
authors: Hansel
authors: National Heart and Lung Institute, Imperial College, London, UK.
authors: Mark J
authors: MJ
authors: Paul-Clark
mesh_terms: D000280:Administration, Inhalation; D006801:Humans; D008954:Models, Biological; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism*; D011656:Pulmonary Emphysema / Q000276:immunology / Q000378:metabolism; D012107:Research Design; D012907:Smoking / Q000276:immunology* / Q000378:metabolism*
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