title: Wound healing and infection in surgery:  the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review.
abstract: OBJECTIVE
  The aim was to clarify how smoking and nicotine affects wound healing processes and to establish if smoking cessation and nicotine replacement therapy reverse the mechanisms involved.
  
  
  BACKGROUND
  Smoking is a recognized risk factor for healing complications after surgery, but the pathophysiological mechanisms remain largely unknown.
  
  
  METHODS
  Pathophysiological studies addressing smoking and wound healing were identified through electronic databases (PubMed, EMBASE) and by hand-search of articles' bibliography. Of the 1460 citations identified, 325 articles were retained following title and abstract reviews. In total, 177 articles were included and systematically reviewed.
  
  
  RESULTS
  Smoking decreases tissue oxygenation and aerobe metabolism temporarily. The inflammatory healing response is attenuated by a reduced inflammatory cell chemotactic responsiveness, migratory function, and oxidative bactericidal mechanisms. In addition, the release of proteolytic enzymes and inhibitors is imbalanced. The proliferative response is impaired by a reduced fibroblast migration and proliferation in addition to a downregulated collagen synthesis and deposition. Smoking cessation restores tissue oxygenation and metabolism rapidly. Inflammatory cell response is reversed in part within 4 weeks, whereas the proliferative response remains impaired. Nicotine does not affect tissue microenvironment, but appears to impair inflammation and stimulate proliferation.
  
  
  CONCLUSIONS
  Smoking has a transient effect on the tissue microenvironment and a prolonged effect on inflammatory and reparative cell functions leading to delayed healing and complications. Smoking cessation restores the tissue microenvironment rapidly and the inflammatory cellular functions within 4 weeks, but the proliferative response remain impaired. Nicotine and nicotine replacement drugs seem to attenuate inflammation and enhance proliferation but the effect appears to be marginal.
authors.affiliation: Copenhagen Wound Healing Center and Department of Surgery K, Bispebjerg Hospital, University of Copenhagen, Denmark. lts@dadlnet.dk
authors.forename: Lars Tue
authors.initials: LT
authors.lastname: Sørensen
mesh_terms: D006801:Humans; D012307:Risk Factors; D012907:Smoking / Q000276:immunology / Q000503:physiopathology*; D016540:Smoking Cessation; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D013530:Surgical Wound Infection / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D061485:Tobacco Use Cessation Devices; D014945:Wound Healing / Q000276:immunology / Q000502:physiology*