[Complexity in asthma: inflammation and scale-free networks]

Our understanding of asthma has traditionally been based on linear deterministic relationships of the type stimulus-bronchial hyperresponsiveness-obstruction-symptoms. This notion however neglects the fact that nonlinear relationships may be present. To better define the disease, some authors therefore suggest that we should think in terms of complex systems with a scale-free topology. The idea of multiple inflammatory hits proposed by the group of Pavord is in its broadest sense a further contribution to this line of thought. According to this theory, the coexistence of additional inflammatory stimuli, which may or may not be localized to the lungs, are responsible for deteriorating lung function. The effects of these stimuli may be additive or act in synergy with the underlying inflammation of asthma itself. In addition to the practical implications, this hypothesis serves as a reminder that the body is made up of interconnected parts and that the pathogenesis of asthma includes distinct elements linked together. If this hypothesis proves valid, future approaches should start to look for the hubs in this network that constitutes asthma, and attempt to integrate information from genomics, proteomics, and metabolomics.