Systems Biology and Clinical Practice in Respiratory Medicine. The Twain Shall Meet

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.

Complexity Analysis of Respiratory Dynamics

“…We read with interest the article by Thamrin and colleagues (1), which discussed systems biology approaches to study respiratory system, as a complex system, within the context of diagnosis and monitoring of diseases. A section of the article described previous studies that characterized the complex behavior of the lung in respiratory diseases using nonlinear analysis of the fluctuations of physiologic variables over time.…”

ERS International Congress 2017: preview of the “innovation in diagnosing and monitoring respiratory disease” symposium from the allied respiratory professionals assembly

“…This aims to discover the 'signal in the noise'. In other words: what previously was considered to be random variability, is now being analyzed in depth (e.g., by detrended fluctuation-or attractor analysis) demonstrating diagnostic or phenotypic signatures or fingerprints in the pattern of variation (16).…”

A good asthma catch by professional fishing

“…We know now that it is a very heterogeneous and complex disease, and one may even question as to whether asthma is a true entity or whether it merely refers to a shared clinical expression of several, only partially overlapping, biological conditions [1]. It is evident from research on the homeostasis and homeokinesis of so-called healthy and diseased states that the latter is becoming more and more likely [2]. There can be little doubt that this is exactly the reason for the plateau in the progress in research on the fundamental mechanisms of asthma in recent decades.…”

“…There can be little doubt that this is exactly the reason for the plateau in the progress in research on the fundamental mechanisms of asthma in recent decades. It just requires novel approaches for capturing these levels of complexity [2].…”

“…This is actually capturing "real-life" health and disease in all its day-to-day interplay. Of course, it is merely a snapshot, and does not include temporal variation [2], but still, it is the end result of the downstream metabolic processes, and that is what actually counts for a living organism here and now.…”