Editorial [Hot Topic: Animal Models of Asthma (Guest Editor: Armin Braun)]

Allergic bronchial asthma is a disease of high prevalence in societies with western lifestyle. In recent years, substantial progress has been made in understanding the underlying mechanisms, and explanations have been developed why the disease prevalence has increased dramatically over the past decades. The most popular explanation is the so-called hygiene hypothesis, postulating that decreased bacterial infection and microbiological contact are responsible for an imbalanced immune response leading to an allergic predisposition. However, the physiological and immunological mechanisms in the lung leading to bronchial asthma are still not fully understood. Therefore, animal models of asthma have been established and improved to study the complex cellular and physiological interactions in vivo. It is the aim of this issue of CDT to give an overview of the current status of different models of asthma. In a first contribution, the clinicians Krug and Rabe describe their demands on a valuable animal model from a clinical point of view [1, this issue]. They state: “There is a marked discrepancy between numerous successful studies in animals and very few, rather disappointing clinical trials in patients. The currently available models are usually uniform models of an acute asthmatic attack in adult animals, which do not spontaneously develop asthma.” None of the animal models described so far is able to represent all features of the disease. In spite of these difficulties, pharmaceutical companies are interested in using predictive disease models to be able to develop new drugs for asthma treatment. Hahn and Erb [2, this issue] describe how companies deal with the complex drug discovery and development process. They state: “A particularly challenging aspect of developing novel chemical entities for the treatment of asthma is choosing and setting up in vivo models believed to be predictive of human disease,” and add: “An optimal animal disease model should accurately reproduce the clinical human disease pathology.” Since no single model at present completely fulfils this requirement, researchers have to choose models which reproduce the relevant aspects of the disease for a given specific compound or question they want to test. An approximated asthma phenotype can only be seen in larger animals, e.g. monkeys, dogs, cats, rats, or guinea pigs. Until the eighties, most of the pre-clinical research was performed using these physiologically relevant models showing a clear asthma phenotype [3]. Fabio et al. [4, this issue] explain that the guinea pig is one of the oldest and best models of asthma: "The guinea pig is the preferred choice for use as a model of allergic bronchial asthma in the evaluation of anti-asthmatic drugs, since the airway anatomy and the response to inflammatory mediators is similar to humans. Further, the great strength of this model is the direct anaphylactic bronchoconstriction upon antigen challenge. Under certain conditions a late asthmatic response can be measured, and airway hyperresponsiveness is observed in vitro and in vivo.” However, the major shortcoming of this model is that “guinea pigs are limited in terms of mechanistic studies, particularly those involving genetics, due to the low number of inbred strains and lack of guinea pig-specific reagents available”. The rat is another classical asthma model. Rats are used preferentially for the investigation of pharmacological and toxicological aspects of therapeutics for the disease [3]. Tschernig et al. [5, this issue] state: “The rat offers advantages in comparison to other species: the anatomical feature of the proprietary bronchial circulation, genetics and proteomics, lung function, and finally economical considerations.” According to our experience, the choice of the appropriate strain is critical. The widely used Brown Norway rat has significant and variable problems with endogenous granulomatous pneumonia [6]. Therefore, new models using e.g. Fischer rats have been developed [7]. Compared to guinea pig more reagents are available for the rat, but compared to mice the number of reagents especially for immunological targets is still very limited. Other, non-laboratory animal models involve similar problems regarding the availability of reagents and scientific tools. However, the article by Kirschvink and Reinhold [8, this issue] describes the advantages of such models: “Large animal species, however, present unique physiological and natural preconditions as well as experimental advantages that are of great value to develop alternative models of allergic and non-allergic chronic airway diseases. Despite the known disadvantages of being expensive and time consuming, large animal models are worth to be considered for their possible role as ‘functional models’.