Abstract
Respiratory diseases are highly complex, being driven by host-environment interactions and manifested by inflammatory, structural, and functional abnormalities that vary over time. Traditional reductionist approaches have contributed vastly to our knowledge of biological systems in health and disease to date; however, they are insufficient to provide an understanding of the behavior of the system as a whole. In this Pulmonary Perspective, we discuss systems biology approaches, especially but not limited to the study of the lung as a complex system. Such integrative approaches take into account the large number of dynamic subunits and their interactions found in biological systems. Borrowing methods from physics and mathematics, it is possible to study the collective behavior of these systems over time and in a multidimensional manner. We first examine the physiological basis for complexity in the respiratory system and its implications for disease. We then expand on the potential applications of systems biology methods to study complex systems, within the context of diagnosis and monitoring of respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD), and critical illness. We summarize the significant advances made in recent years using systems approaches for disease phenotyping, applied to data ranging from the molecular to clinical level, obtained from large-scale asthma and COPD networks. We describe new studies using temporal complexity patterns to characterize asthma and COPD and predict exacerbations as well as predict adverse outcomes in critical care. We highlight new methods that are emerging with this approach and discuss remaining questions that merit greater attention in the field.