RESUMEN

En los últimos años se han estudiado un gran número de biomarcadores en asma y enfermedad pulmonar obstructiva crónica (EPOC). Un biomarcador debe tener las siguientes características: a) relevancia clínica, b) sensibilidad y especificidad, c) confiabilidad y reproducibilidad, d) facilidad en su medición y obtención. Las muestras en las que se pueden determinar los biomarcadores pueden provenir de diferentes fuentes (lavado bronquioalveolar, esputo, aire exhalado y sangre) y ofrecen información complementaria para establecer diagnóstico, estadio, progresión y actividad de una enfermedad, así como la respuesta al tratamiento. Se realizó una búsqueda de artículos publicados entre los años 1989-2013 utilizando la base de datos Medline. En el presente artículo se resumen los principales biomarcadores en asma y EPOC.

PALABRAS CLAVE

Biomarcadores, asma, EPOC, tratamiento.

REFERENCIAS

1. Dasgupta A, Nair P. When are biomarkers useful in the management of airway diseases? Pol Arch Med Wewn 2013;123:183-188.

2. Lesko LJ, Atkinson AJ Jr. Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: criteria, validation, strategies. Annu Rev Pharmacol Toxicol 2001;41:347-366.

3. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 2012;18:716-725.

4. O’Byrne PM. Global guidelines for asthma management: summary of the current status and future challenges. Pol Arch Med Wewn 2010;120:511-517.

5. Disponible en: http://www.ginasthma.org/uploads/users/files/GINA Fecha de consulta: abril 2011.

6. Decramer M, Janssens W, Miravitlles M. Chronic obstructive pulmonary disease. Lancet 2012;379:1341-1351.

7. Disponible en: http://www.goldcopd.org/uploads/users/files/GOLD_Report_2013_Feb20.pdf

8. Taylor DR, Pavord ID. Biomarkers in the assessment and management of airways diseases. Postgrad Med J 2008;84:628-634.

9. Patel AR, Hurst JR, Wedzicha JA. The potential value of biomarkers in diagnosis and staging of COPD and exacerbations. Semin Respir Crit Care Med 2010;31:267-275.

10. Bafadhel M, McKenna S, Terry S, et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med 2011;184:662-671.

11. Hurst J. Phenotype-based care in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012;186:935-936.

12. Pinto-Plata V, Casanova C, Müllerova H, et al. Inflammatory and repair serum biomarker pattern: association to clinical outcomes in COPD. Respir Res 2012;13:71.

13. Smith AD, Cowan JO, Filsell S, et al. Diagnosing asthma: comparisons between exhaled nitric oxide measurements and conventional tests. Am J Respir Crit Care Med 2004;169:473-478.

14. Bommarito L, Migliore E, Bugiani M, et al. Exhaled nitric oxide in a population sample of adults. Respiration 2008;75:386-392.

15. Dweik RA, Boggs PB, Erzurum SC, et al.; American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 2011;184:602-615.

16. Pike K, Selby A, Price S, et al. Exhaled nitric oxide monitoring does not reduce exacerbation frequency or inhaled corticosteroid dose in paediatric asthma: a randomised controlled trial. Clin Respir J 2012;doi:10.1111/j.

17. Jartti T, Wendelin-Saarenhovi M, Heinonen I, Hartiala J, Vanto T. Childhood asthma management guided by repeated FeNO measurements: a meta-analysis. Paediatr Respir Rev 2012;13:178-183.

18. Zeiger RS, Schatz M, Zhang F, et al. Association of exhaled nitric oxide to asthma burden in asthmatics on inhaled corticosteroids. J Asthma 2011;48:8-17.

19. Hillas G, Kostikas K, Mantzouranis K, et al. Exhaled nitric oxide and exhaled breath condensate pH as predictors of sputum cell counts in optimally treated asthmatic smokers. Respirology 2011;16:811-818.

20. Bazeghi N, Gerds TA, Budtz-Jørgensen E, Hove J, Vestbo J. Exhaled nitric oxide measure using multiple flows in clinically relevant subgroups of COPD. Respir Med 2011;105:1338-1344.

21. Antus B, Barta I, Horvath I, Csiszer E. Relationship between exhaled nitric oxide and treatment response in COPD patients with exacerbations. Respirology 2010;15:472-477.

22. Kersul AL, Iglesias A, Ríos Á, et al. Molecular mechanisms of inflammation during exacerbations of chronic obstructive pulmonary disease. Arch Bronconeumol 2011;47:176-183.

23. Cai C, Yang J, Hu S, Zhow M, Guo W. Relationship between urinary cysteinyl leukotriene E4 levels and clinical response to antileukotriene treatment in patients with asthma. Lung 2007;185:105-112.

24. Rabinovitch N, Zhang L, Gelfand EW. Urine leukotriene E4 levels are associated with decreased pulmonary function in children with persistent airway obstruction. J Allergy Clin Immunol 2006;118:635-640.

25. Jayaram L, Pizzichini MM, Cook RJ, et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J 2006;27:483-494.

26. Gibson PG, Simpson JL, Hankin R, Powell H, Henry RL. Relationship between induced sputum eosinophils and the clinical pattern of childhood asthma. Thorax 2003;58:116-121.

27. Fleming L, Wilson N, Regamey N, Bush A. Use of sputum eosinophil counts to guide management in children with severe asthma. Thorax 2012;67:193-198.

28. Kim S, Nadel JA. Role of neutrophils in mucus hypersecretion in COPD and implications for therapy. Treat Respir Med 2004;3:147-159.

29. Pavord ID, Pizzichini MM, Pizzichini E, Hargreave FE. The use of induced sputum to investigate airway inflammation. Thorax 1997;52:498-501.

30. Hoffmeyer F, Raulf-Heimsoth M, Brüning T. Exhaled breath condensate and airway inflammation. Curr Opin Allergy Clin Immunol 2009;9:16-22.

31. Accordino R, Visentin A, Bordin A, et al. Long-term repeatability of exhaled breath condensate pH in asthma. Respiratory Med 2008;102:377-381.

32. Carraro S, Giordano G, Reniero F, et al. Asthma severity in childhood and metabolomic profiling of breath condensate. Allergy 2013;68:110-117.

33. Warwick G, Thomas PS, Yates DH. Non-invasive biomarkers in exacerbations of obstructive lung disease. Respirology 2013;18:874-884.

34. Takayama G, Arima K, Kanaji T, et al. Periostin: A novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals. J Allergy Clin Immunol 2006;118:98-104.

35. Jia G, Erickson RW, Choy DF, et al; Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) Study Group. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol 2012;130:647-654.

36. Dahl M, Vestbo J, Lange P, et al. C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;175:250-255.

37. De Torres JP, Pinto-Plata V, Casanova C, et al. C-reactive protein levels and survival in patients with moderate to very severe COPD. Chest 2008;133:1336-1343.

38. Hurst JR, Donaldson GC, Perera WR, et al. Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006;174:867-874.

39. Deraz TE, Kamel TB, El-Kerdany TA, El-Ghazoly HM. High-sensitivity C reactive protein as a biomarker for grading of childhood asthma in relation to clinical classification, induced sputum cellularity, and spirometry. Pediatr Pulmonol 2012;47:220-225.

40. Kishimoto T. The biology of interleukin-6. Blood 1989;74:1-10.

41. Rincon M, Irvin CG. Role of IL-6 in asthma and other inflammatory pulmonary diseases. Int J Biol Sci 2012;8:1281-1290.

42. Bucchioni E, Kharitonov SA, Allegra L, Barnes PJ. High levels of interleukin-6 in the exhaled breath condensate of patients with COPD. Respir Med 2003;97:1299-1302.

43. Djoba-Siawaya JF, Roberts T, Babb C, et al. An evaluation of commercial fluorescent bead-based luminex cytokine assays. PLoS One. 2008;3:e2535.

44. Dahl M, Tybjaerg-Hansen A, Vestbo J, Lange P, Nordestgaard BG. Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;164:1008-1011.

45. Thomsen M, Dahl M, Lange P, Vestbo J, Nordestgaard BG. Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012;186:982-988.

46. Groenewegen KH, Postma DS, Hop WC, et al. COSMIC Study Group. Increased systemic inflammation is a risk factor for COPD exacerbations. Chest 2008;133:350-357.

47. Fibrinogen Studies Collaboration, Danesh J, Lewington S, Thompson SG, et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA 2005;294:1799-1809.

48. Broeckaert F, Clippe A, Knoops B, Hermans C, Bernard A. Clara cell secretory protein (CC16): features as a peripheral lung biomarker. Ann N Y Acad Sci 2000;923:68-77.

49. Lakind JS, Holgate ST, Ownby DR, et al. A critical review of the use of Clara cell secretory protein (CC16) as a biomarker of acute or chronic pulmonary effects. Biomarkers 2007;12:445-467.

50. Lomas DA, Silverman EK, Edwards LD, et al; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators. Evaluation of serum CC-16 as a biomarker for COPD in the ECLIPSE cohort. Thorax 2008;63:1058-1063.

51. Andreeva AV, Kutuzov MA, Voyno-Yasenetskaya TA. Regulation of surfactant secretion in alveolar type II cells. Am J Physiol Lung Cell Mol Physiol 2007;293:L259-L271.

52. Lomas DA, Silverman EK, Edwards LD, et al. Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD. Eur Respir J 2009;34:95-102.

53. Sin DD, Leung R, Gan WQ, Man SPBMC. Circulating surfactant protein D as a potential lung-specific biomarker of health outcomes in COPD: a pilot study. BMC Pulm Med 2007;7:13.

54. Foreman MG, Kong X, DeMeo DL, et al. Polymorphisms in surfactant protein-D are associated with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2011;44:316-322.

55. Cheng G, Ueda T, Numao T, et al. Increased levels of surfactant protein A and D in bronchoalveolar lavage fluids in patients with bronchial asthma. Eur Respir J 2000;16:831-835.

56. Bode W. Structural basis of matrix metalloproteinase function. Biochem Soc Symp 2003;(70):1-14.

57. Finlay GA, Russell KJ, McMahon KJ, et al. Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients. Thorax 1997;52:502-506.

58. Higashimoto Y, Yamagata Y, Iwata T, et al. Increased serum concentrations of tissue inhibitor of metalloproteinase-1 in COPD patients. Eur Respir J 2005;25:885-890.

59. Kwiatkowska S, Noweta K, Zieba M, Nowak D, Bialasiewicz p. Enhanced exhalation of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in patients with COPD exacerbation: a prospective study. Respiration 2012;84:231-241.

60. Foster JA, Curtiss SW. The regulation of lung elastin synthesis. Am J Physiol 1990;259(2 Pt 1):L13-23.

61. Lindberg CA, Engström G, de Verdier MG, et al. Total desmosines in plasma and urine correlate with lung function. Eur Respir J 2012;39:839-845.

62. Huang JT, Chaudhuri R, Albarbarawi O, et al. Clinical validity of plasma and urinary desmosine as biomarkers for chronic obstructive pulmonary disease. Thorax 2012;67:502-508.