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Vol. 46. Issue 8.
Pages 433-438 (January 2010)
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Vol. 46. Issue 8.
Pages 433-438 (January 2010)
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Why do We Look at Asthma through the Keyhole?
¿Por qué miramos el asma a través del ojo de la cerradura?
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Miguel Perpiñá Tordera
Servicio de Neumología, Hospital Universitario La Fe, Valencia, Spain
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Abstract

As happens with the rest of pathology, the study of asthma has been traditionally conducted from postulates set by reductionist science. That model still provides answers to theoretical and practical questions that establish diseases, but does not offer us a complete view of their complexity and multidimensionality. To overcome this limitation has emerged medicine directed towards systems based on the application of biological systems concepts and tools. Biological systems is a cross-disciplinary strategy which, from the data generated by the “-omic” sciences, helps to relate the elements of an organism or biological system, to understand the properties arising from the same and to generate mathematical models capable of predicting their dynamic behaviour. The application of biological systems to asthma starts is starting to make ground. The main challenge today is to understand the need to change focus. The starting point is to abandon the idea that asthma is exclusively an airways disease and considering that the whole lung is involved and, even more, the possibility that it is, at least in part, a systemic process. In view of our current limitations, to understand asthma and design personalised treatment strategies for each patient, requires thinking of systems medicine.

Keywords:
Asthma
Systems oriented medicine
Biology systems
Omic sciences
Resumen

Al igual que sucede con el resto de la patología, el estudio del asma se ha venido realizando tradicionalmente desde los postulados marcados por la ciencia reduccionista. Ese modelo sigue aportando respuestas a las preguntas teóricas y prácticas que las enfermedades plantean pero no nos ofrece una visión completa de su complejidad y multidimensionalidad. Para superar esta limitación surge la medicina orientada hacia sistemas basada en la aplicación de los conceptos y herramientas de la biología de sistemas. La biología de sistemas es una estrategia analítica transdisciplinar que, a partir de los datos generados por las ciencias ómicas, permite relacionar los elementos de un organismo o sistema biológico, comprender las propiedades emergentes del mismo y generar modelos matemáticos capaces de predecir su comportamiento dinámico. La aplicación de la biología de sistemas al asma comienza a dar ya los primeros pasos. Hoy el reto principal es comprender la necesidad del cambio de enfoque. El punto de partida pasa por abandonar la idea del asma como enfermedad exclusiva de la vía aérea considerando que en su patogenia participa todo el pulmón y, aún más, que posiblemente se trate, al menos en parte, de un proceso sistémico. Vistas nuestras limitaciones actuales, entender el asma y diseñar estrategias terapéuticas personalizadas para cada paciente exige pensar en medicina de sistemas.

Palabras clave:
Asma
Medicina orientada hacia sistemas
Biología de sistemas
Ciencias ómicas
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References
[1]
Y. Bossé, T.J. Hudson.
Toward a comprehensive set of asthma susceptibility genes.
Annu Rev Med, 57 (2007), pp. 171-184
[2]
S. Guerra, F.D. Martínez.
Asthma genetics: From linear to multifactorial approach.
[3]
E. von Mutius.
Gene-environment interactions in asthma.
J Allergy Clin Immunol, 123 (2009), pp. 3-11
[4]
P.J. Barnes.
Immunology of asthma and chronic obstructive pulmonary disease.
Nature Rev, 8 (2008), pp. 183-192
[5]
S.T. Holgate.
The airway epithelium is central to the pathogenesis of asthma.
Allergol Int, 57 (2008), pp. 1-10
[6]
A.S. Abdulamir, R.R. Hafidh, F. Abubakar, K.A. Abbas.
Changing survival, memory cell compartment, and T-helper balance of lymphocytes between severe asthma and mild asthma.
BMC Immunoly, 9 (2008), pp. 73
[7]
S.E. Wenzel.
Asthma: defining of the persistent adult phenotypes.
[8]
J. Kiley, R. Smith, P. Noel.
Asthma phenotypes.
Curr Opin Pulm Med, 13 (2007), pp. 19-23
[9]
P. Haldar, I.D. Pavord, D.E. Shaw, M.A. Berry, M. Thomas, C.E. Brightling, et al.
Cluster analysis and clinical phenotypes.
Am J Respir Crit Care Med, 178 (2008), pp. 218-224
[10]
A. ten Brinke, P.J. Sterk, A.A. Masclee, P. Spinhoven, J.T. Schmidt, A.H. Zwinderman, et al.
Risk factors of frequent exacerbations in difficult-to-treat asthma.
Eur Respir J, 5 (2005), pp. 812-818
[11]
L.P. Boulet.
Influence of comorbid conditions on asthma.
Eur Respir J, 33 (2009), pp. 897-906
[12]
I.D. Pavord, S.S. Birring, M. Berry, R.H. Green, C.E. Brightling, A.J. Wardlaw.
Multiple inflammatory hits and the pathogenesis of severe airway disease.
Eur Respir J, 27 (2006), pp. 884-888
[13]
L. Bjermer.
Time for a paradigm shift in asthma treatment: From relieving bronchospasm to controlling systemic inflammation.
J Allergy Clin Immunol, 120 (2007), pp. 1269-1275
[14]
M. Perpiñá Tordera.
La complejidad en el asma: inflamación y redes libres de escala.
Arch Bronconeumol, 45 (2009), pp. 459-465
[15]
D. Getahun, K. Dermissie, G.C. Rhoads.
Recent trends in asthma hospitalization and mortality in the United States.
J Asthma, 42 (2005), pp. 373-378
[16]
M. Sánchez Bahíllo, L. García Marcos, V. Pérez Fernández, A.L. Martínez Torres, M. Sánchez Solís.
Evolución de la mortalidad por asma en España (1960-2005).
Arch Bronconeumol, 45 (2009), pp. 123-128
[17]
M.HV. Van Regenmortel.
Reductionism and complexity in molecular biology.
EMBO Rep, 5 (2004), pp. 1016-1020
[18]
H. Kitano.
Systems biology: a brief overview.
Science, 295 (2002), pp. 1662-1664
[19]
A.C. Ahn, M. Tewari, C.S. Poon, R.S. Phillips.
The clinical applications of a systems approach.
[20]
T. Lemberger.
Systems biology in human health and disease.
Mol Syst Biol, 3 (2007), pp. 136
[21]
Auffray C, Chen Z, Hood L. Systems medicine: the future of medical genomics and healthcare. Genome Med. 2009;1:2 [epub ahead of print].
[22]
A.C. Ahn, M. Tewari, C.S. Poon, R.S. Phillips.
The limits of reductionism in medicine: could systems biology offer an alternative?.
[23]
D. Noble.
The music of life.
Oxford University Press, (2006),
[24]
D. Noble.
Claude Bernard, the first systems biologist, and the future of physiology.
Exp Physiol, 93 (2008), pp. 16-28
[25]
S. Wuchty, E. Ravasz, A.L. Barabási.
The architecture of biological networks.
Complex systems in biomedicine, pp. 1-30
[26]
L.F. Costa, F.A. Rodrigues, A.S. Cristino.
Complex networks: The key to systems biology.
Genet Mol Biol, 31 (2008), pp. 591-601
[27]
A.JE. Seely, N.V. Christou.
Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear systems.
Crit Care Med, 28 (2000), pp. 2193-2200
[28]
G.M. Edelman, J.A. Gally.
Degeneracy and complexity in biological systems.
Proc Natl Acad Sci U S A, 98 (2001), pp. 13763-13768
[29]
H. Kitano.
Biological robustness.
Nat Rev Genet, 5 (2004), pp. 826-837
[30]
H. Kitano.
Towards a theory of biological robustness.
Mol Syst Biol, 3 (2007), pp. 137
[31]
J. Macia, R.V. Solé.
Distributed robustness in cellular networks: insightts from synthetic evolved circuits.
J R Soc Interface, 6 (2009), pp. 393-400
[32]
A.L. Goldberger.
Complex systems.
Proc Am Thorac Soc, 3 (2006), pp. 467-472
[33]
A. Aderem.
Systems biology: its practice and challenges.
[34]
H. Kitano.
Computational systems biology.
Nature, 420 (2002), pp. 206-210
[35]
M. López, G. Ruiz Romero, M. Vega.
Biología de sistemas.
Genoma España/FUAM, (2007),
[36]
A. Pandey, M. Mann.
Proteomics to study genes and genomes.
Nature, 405 (2000), pp. 837-846
[37]
A.R. Joyce, B.Ø. Palsson.
The model organism as a system: integrating “omics” data sets.
Nat Rev Mol Cell Biol, 7 (2006), pp. 198-210
[38]
F. Klauschen, B.R. Angermann, M. Meier-Schellersheim.
Understanding diseases by mouse click: the promise and potential of computational approaches in systems biology.
Clin Exp Immunol, 149 (2007), pp. 424-429
[39]
J. Wright, A. Wagner.
The systems biology research tool: evolvable open-source software.
BMC Systems Biology, 2 (2008), pp. 55
[40]
J.W. Haefner.
Modeling biological systems: principles and applications.
2a ed., Springer, (2005),
[41]
A.J. Lusis.
A Thematic review series: systems biology approaches to metabolic and cardiovascular disorders.
J Lipid Res, 47 (2006), pp. 1887-1890
[42]
E.T. Liu, V.A. Kuznetsov, L.D. Miller.
In the pursuit of complexity: systems medicine in cancer biology.
Cancer Cell, 9 (2006), pp. 245-247
[43]
S.M. Studer, N. Kaminsky.
Towards systems biology of human pulmonary fibrosis.
Proc Am Thorac Soc, 4 (2007), pp. 85-91
[44]
Y. Vodovotz, M. Csete, J. Bartels, S. Chang, G. An.
Translational systems biology of inflammation.
Plos Comput Biol, 4 (2008), pp. 1e000014
[45]
D. Young, J. Stark, D. Kirschner.
Systems biology of persistent infection: tuberculosis as a case study.
Nat Rev Microbiol, 6 (2008), pp. 520-528
[46]
B.S. Abrahams, D.H. Geschwind.
Advances in autism genetics: on the threshold of a new neurobiology.
Nat Rev Genet, 9 (2008), pp. 341-355
[47]
J.A. Miller, M.C. Oldham, D.H. Gerschwind.
A systems level analysis of transcriptional changes in Alzheimer?s disease and normal aging.
J Neurosci, 28 (2008), pp. 1410-1420
[48]
J.I. Richens, R.A. Urbanowicz, E.A. Lunt, R. Metcalf, J. Corne, L. Fairclough, et al.
Systems biology coupled with label-free high-throughput detection as a novel approach for diagnosis of chronic obstructive pulmonary disease.
Respir Res, 10 (2009), pp. 29
[49]
Adams KF. Systems biology and heart failure: concepts, methods, and potential reasearch implications. Heart Fail Rev. 2009 [epub ahead of print].
[50]
J.L. Gardy, D.J. Lynn, F.SL. Brinkman, R.EW. Hancock.
Enabling a systems biology approach to immunology: focus on innate immunity.
Trends Immunol, 30 (2009), pp. 249-262
[51]
X. Lu, V.V. Jain, P.W. Finn, D.L. Perkins.
Hubs in biological interaction networks exhibit low changes in expression in experimental asthma.
Mol Syst Biol, 3 (2007), pp. 98
[52]
N. Novershtern, Z. Itzhaki, O. Manor, N. Friedman, N. Kaminiski.
A functional and regulatory map of asthma.
Am J Respir Cell Mol Biol, 38 (2008), pp. 324-336
[53]
S. Hwang, S.W. Son, Y.J. Kim, H. Jeong, D. Lee.
A protein interaction network associated with asthma.
J Theor Biol, 252 (2008), pp. 722-731
[54]
V.V. Jain, D.L. Perkins, P.W. Finn.
Costimulation and allergic responses: immune and bioinformatic analyses.
Pharmacol and Therapeutics, 117 (2008), pp. 385-392
[55]
S. Pussi, C. Incovaia.
Allergy as an organ and systemic disease.
Clin Exp Immunol, 153 (2008), pp. 1-2
[56]
N.F. Voelkel, S. Spiegel.
Why is effective treatment of asthma so difficult? An integrated systems biology hypothesis of asthma.
Immunol Cell Biol, (2009),
[57]
B.J. Undem, R. Kajekar, D.D. Hunter, A.C. Myers.
Neural integration and allergic disease.
J Allergy Clin Immunol, 106 (2000), pp. S213-S220
[58]
A. Togias.
Systemic effects of local allergic diseases.
J Allergy Clin Immunol, 113 (2004), pp. S8-S14

El contenido del presente artículo está basado en la conferencia del mismo título pronunciada por el autor durante el XXXV Simposio de Neumología (octubre 2009).

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