title: Animal models for anti-emphysema drug discovery.
abstract: BACKGROUND
  Emphysema is characterized by an abnormal and permanent enlargement of airspaces accompanied by destruction of their walls. Up to now, there is no cure for emphysema, and animal models may be important for new drug discovery.
  
  
  METHODS
  Herein, the authors review animal models of emphysema since the protease-antiprotease hypothesis as well as the results obtained with compounds tested in these models. Of particular importance are animal models of cigarette smoke exposure since it is the most important risk factor of emphysema. The authors also analyze two approaches to drug testing, that is, the approach aimed at preventing emphysema and the one aimed at reversing it.
  
  
  CONCLUSIONS
  It has been suggested that early and late interventions do not have the same protective effect and that late interventions are much more likely to reveal treatments beneficial in humans. However, this is not always the case, and a compound that prevents emphysema when administered as an early intervention can also have the same protective effect when given as a late intervention. Furthermore, the fact that a compound detected by means of early intervention is now in clinical practice shows that early intervention studies can be predictive for efficacy in humans.
authors.affiliation: University of Siena, Department of Molecular and Developmental Medicine , Via Aldo Moro 2 - Siena , Italy +39 0 577 234002 ; concetta.gardi@unisi.it.
authors.forename: Concetta
authors.initials: C
authors.lastname: Gardi
authors.forename: Blerta
authors.initials: B
authors.lastname: Stringa
authors.forename: Piero A
authors.initials: PA
authors.lastname: Martorana
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D004646:Emphysema / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
keywords: animal models of emphysema; anti-inflammatory agents; antioxidants; chronic obstructive pulmonary disease; cigarette smoke exposure; emphysema; mouse strains; protease inhibitors; reversal of emphysema; α-1-antitrypsin