Complexity and emergent phenomena.

Complex biological systems operate under non-equilibrium conditions and exhibit emergent properties associated with correlated spatial and temporal structures. These properties may be individually unpredictable, but tend to be governed by power-law probability distributions and/or correlation. This article reviews the concepts that are invoked in the treatment of complex systems through a wide range of respiratory-related examples. Following a brief historical overview, some of the tools to characterize structural variabilities and temporal fluctuations associated with complex systems are introduced. By invoking the concept of percolation, the notion of multiscale behavior and related modeling issues are discussed. Spatial complexity is then examined in the airway and parenchymal structures with implications for gas exchange followed by a short glimpse of complexity at the cellular and subcellular network levels. Variability and complexity in the time domain are then reviewed in relation to temporal fluctuations in airway function. Next, an attempt is given to link spatial and temporal complexities through examples of airway opening and lung tissue viscoelasticity. Specific examples of possible and more direct clinical implications are also offered through examples of optimal future treatment of fibrosis, exacerbation risk prediction in asthma, and a novel method in mechanical ventilation. Finally, the potential role of the science of complexity in the future of physiology, biology, and medicine is discussed.