Predicting the future from the past Agustí, Alvar
European respiratory journal/The European respiratory journal,
01/2017, Letnik:
49, Številka:
1
Journal Article
Chronic obstructive pulmonary disease (COPD) is a complex disease at the clinical, cellular, and molecular levels. However, its diagnosis, assessment, and therapeutic management are based almost ...exclusively on the severity of airflow limitation. A better understanding of the multiple dimensions of COPD and its relationship to other diseases is very relevant and of high current interest. Recent theoretical (scale-free networks), technological (high-throughput technology, biocomputing), and analytical improvements (systems biology) provide tools capable of addressing the complexity of COPD. The information obtained from the integrated use of those techniques will be eventually incorporated into routine clinical practice. This review summarizes our current knowledge in this area and offers an insight into the elements needed to progress toward an integrated, multilevel view of COPD based on the novel scientific strategy of systems biology and its potential clinical derivative, P4 medicine (Personalized, Predictive, Preventive, and Participatory).
Cellular Senescence in Lung Fibrosis Hernandez-Gonzalez, Fernanda; Faner, Rosa; Rojas, Mauricio ...
International journal of molecular sciences,
07/2021, Letnik:
22, Številka:
13
Journal Article
Recenzirano
Odprti dostop
Fibrosing interstitial lung diseases (ILDs) are chronic and ultimately fatal age-related lung diseases characterized by the progressive and irreversible accumulation of scar tissue in the lung ...parenchyma. Over the past years, significant progress has been made in our incomplete understanding of the pathobiology underlying fibrosing ILDs, in particular in relation to diverse age-related processes and cell perturbations that seem to lead to maladaptation to stress and susceptibility to lung fibrosis. Growing evidence suggests that a specific biological phenomenon known as cellular senescence plays an important role in the initiation and progression of pulmonary fibrosis. Cellular senescence is defined as a cell fate decision caused by the accumulation of unrepairable cellular damage and is characterized by an abundant pro-inflammatory and pro-fibrotic secretome. The senescence response has been widely recognized as a beneficial physiological mechanism during development and in tumour suppression. However, recent evidence strengthens the idea that it also drives degenerative processes such as lung fibrosis, most likely by promoting molecular and cellular changes in chronic fibrosing processes. Here, we review how cellular senescence may contribute to lung fibrosis pathobiology, and we highlight current and emerging therapeutic approaches to treat fibrosing ILDs by targeting cellular senescence.
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.
Due to well-conducted epidemiological studies and advances in genetics, molecular biology, translational research, the advent of computed tomography of the lungs and bioinformatics, the diagnosis of ...chronic obstructive pulmonary disease (COPD) as a single entity caused by susceptibility to cigarette smoke is no longer tenable. Furthermore, the once-accepted concept that COPD results from a rapid and progressive loss of lung function over time is not true for a sizeable proportion of adults with the disease. Now we know that some genetic predisposition and/or different environmental interactions (nutritional, infectious, pollution and immunological) may negatively modulate post-natal lung development and lead to poorly reversible airflow limitation later in life, consistent with COPD. We believe it is time to rethink the taxonomy of this disease based on the evidence at hand. To do so, we have followed the principles outlined in the 1980s by J.D. Scadding who proposed that diseases can be defined by four key characteristics: 1) clinical description (syndrome), 2) disorder of structure (morbid anatomy), 3) disorder of function (pathophysiology) and 4) causation (aetiology). Here, we propose a pragmatic approach to the taxonomy of COPD based on different processes that result in a similar syndromic presentation. It can accommodate changes over time, as the pathobiology that may lead to COPD expands. We hope that stakeholders in the field may find it useful to better define the patients now boxed into one single entity, so that specific studies can be designed and conducted for each type of COPDs.
Chronic obstructive pulmonary disease (COPD) has been traditionally understood as a self-inflicted disease cause by tobacco smoking occurring in individuals older than 50-60 years. This traditional ...paradigm has changed over the last decade because new scientific evidence showed that there are many genetic (G) and environmental (E) factors associated with reduced lung function, that vary, accumulate, and interact over time (T), even before birth (G×E×T). This new perspective opens novel windows of opportunity for the prevention, early diagnosis, and personalized treatment of COPD. This review presents the evidence that supports this proposal, as well as its practical implications, with particular emphasis on the need that clinical histories in patients with suspected COPD should investigate early life events and that spirometry should be used much more widely as a global health marker.
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