Fig. 1. –

a) An analytical reductionist approach and b) a system approach to the complex behaviour of asthma. The classical paradigm of asthma is based on the concept of an inducer or trigger causing airway inflammation, leading to bronchial hyperactivity and airway obstruction and resulting in symptoms (a). Although this analytical approach provides insight into the behaviour of mechanisms involved in cascades of reaction, it cannot explain all of the phenomena in a complex chronic disease such as asthma. Systems biology attempts to understand the behaviour of complete biological systems based on network considerations (b) [4]. This alternative systems approach to asthma is presented as an example of a fluctuating chronic disease with multiple components. It is proposed that, in such a complex system, the fluctuating output or symptoms are the result of noisy environmental inputs (such as allergen exposure, infection, air pollution, etc.), but modified by many interacting components of various subsystems (inflammatory system, immune system, lung mechanics, neurorespiratory control, etc.), each having internal feedback loop mechanisms. Some of these feedback mechanisms may act slowly over medium or long timescales of hours, weeks or months (e.g. the immune system), and some over short timescales of seconds or minutes (e.g. neurorespiratory control). It is important to note that such systems store information (memory) and can behave in a highly nonlinear manner. Thus, small perturbations may lead to exaggerated peak responses (e.g. in fatal asthma). In this model, even genetic adaptation to environmental pressure (i.e. evolutionary process) can be seen as a long-term effect [4]. Individual components of such systems cannot be described in detail, but statistical techniques are available for describing their overall properties.