From systems biology to P4 medicine: applications in respiratory medicine.

Human health and disease are emergent properties of a complex, nonlinear, dynamic multilevel biological system: the human body. Systems biology is a comprehensive research strategy that has the potential to understand these emergent properties holistically. It stems from advancements in medical diagnostics, "omics" data and bioinformatic computing power. It paves the way forward towards "P4 medicine" (predictive, preventive, personalised and participatory), which seeks to better intervene preventively to preserve health or therapeutically to cure diseases. In this review, we: 1) discuss the principles of systems biology; 2) elaborate on how P4 medicine has the potential to shift healthcare from reactive medicine (treatment of illness) to predict and prevent illness, in a revolution that will be personalised in nature, probabilistic in essence and participatory driven; 3) review the current state of the art of network (systems) medicine in three prevalent respiratory diseases (chronic obstructive pulmonary disease, asthma and lung cancer); and 4) outline current challenges and future goals in the field.

Network medicine, multimorbidity and the lung in the elderly.

Noncommunicable diseases, including cardiovascular, metabolic and respiratory diseases, among others, are the major medical challenge of the 21st century. Most noncommunicable diseases are related to the ageing process and often co-occur in the same individual. However, it is unclear whether the index disease is somehow influencing the development of the other ones (comorbidity) or whether all of them (including the index disease) simply represent the clinical expression of pathological ageing (multimorbidity). The pathobiology of ageing, chronic obstructive pulmonary disease (COPD) and concomitant disorders is complex. A new field of research, known as systems biology if applied to model systems or network medicine if applied to human beings, has emerged over the past decade or so, to address biological complexity in a holistic, integrated way. It offers, therefore, great potential to decipher the relationship between ageing, COPD and comorbidities/multimorbidities. In this State of the Art review we present the basic concepts of systems biology, use some examples to illustrate the potential of network medicine to address complex medical problems, and review some recent publications that show how a systems-based research strategy can contribute to improve our understanding of multimorbidity and age-related respiratory diseases.