RESUMEN

Los factores de riesgo y desencadenantes del asma son múltiples, los más relevantes en la actualidad son los genéticos, infecciosos (virales, bacterianos, fúngicos y parasitarios), ambientales (alergenos, tabaquismo, irritantes, contaminantes de autos, industrias, ambiente laboral, etc.) y obesidad. La gravedad del asma se ve influenciada por la edad, sexo, embarazo, inmadurez del sistema inmunológico y la marcha atópica. La patogenia del proceso inflamatorio alérgico más que un desequilibrio Th1/Th2, células cebadas, eosinófilos e IgE, actualmente incluye la importante participación de otros elementos como Th17 ó IL-17, IL-23, IL-25, IL-27, T regs, TLRs, NODs, MAs, DCs, células del epitelio bronquial, neurocininas, quimiocinas, ICAM-1, NO (iNO). Además de otros elementos que influyen en la amplificación de la respuesta inflamatoria y en la remodelación del epitelio de la vía aérea.

PALABRAS CLAVE

Edad, genéticos, infecciones, linfocitos Th1, linfocitos Th2, células T reguladoras, Th17, interleucinas, receptores tipo toll.

REFERENCIAS

1. Wiesch DG, Meyers DA, Bleecker ER. Genetics of asthma. J Allergy Clin Immunol 1999; 104(5): 895-901.

2. Zhang J, Paré PD, Sandford AJ. Recent advances in asthma genetics. Respir Res 2008; 9: 4.

3. Bouzigon E, Demenais F, Kauffmann F. Genetics of asthma and atopy: How many genes? Bull Acad Natl Med 2005; 189(7): 1435-48.

4. Corydon TJ, Haagerup A, Jensen TG, Binderup HG, Petersen MS, Kaltoft K, et al. A functional CD86 polymorphism associated with asthma and related allergic disorders. J Med Genet 2007; 44(8): 509-15.

5. Ryu HJ, Jung HY, Park JS, Ryu GM, Heo JY, Kim JJ, et al. Gene-based single nucleotide polymorphisms and linkage disequilibrium patterns of 29 asthma candidate genes in the chromosome 5q31-33 region in Koreans. Int Arch Allergy Immunol. 2006; 139(3): 209-16.

6. Munthe-Kaas MC, Carlsen KL, Carlsen KH, Egeland T, Håland G, Devulapalli CS, et al. HLA Dr-Dq haplotypes and the TNFA-308 polymorphism: associations with asthma and allergy. Allergy 2007; 62(9): 991-8.

7. Laitinen T, Daly MJ, Rioux JD, Kauppi P, Laprise C, Petäys T, et al. A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population. Nat Genet 2001; 28(1): 87-91.

8. Chan A, Newman DL, Shon AM, Schneider DH, Kuldanek S, Ober C. Variation in the type I interferon gene cluster on 9p21 influences susceptibility to asthma and atopy. Genes Immun. 2006; 7(2): 169-78.

9. Bégin P, Tremblay K, Daley D, Lemire M, Claveau S, Salesse C, et al. Association of urokinase-type plasminogen activator with asthma and atopy. Am J Respir Crit Care Med 2007; 175(11): 1109-16.

10. Pinto LA, Stein RT, Kabesch M. Impact of genetics in childhood asthma. J Pediatr (Rio J) 2008; 84(4 Suppl): S68-75.

11. Zhang Y, Leaves NI, Anderson GG, Ponting CP, Broxholme J, Holt R, et al. Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma. Nat Genet 2003; 34(2): 181–6.

12. Wjst M, Kruse S, Illig T, Deichmann K. Asthma and IL-4 receptor alpha gene variants. Eur J Immunogenet 2002; 29(3): 263-8.

13. Morita H, Nagai R. Smoking exposure, 17q21 variants, and early-onset asthma. N Engl J Med 2008; 359(19): 1985-94.

14. Barton SJ, Koppelman GH, Vonk JM, Browning CA, Nolte IM, Stewart CE, et al. PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline. J Allergy Clin Immunol 2009; 123(6): 1391-400.

15. Van Eerdewegh P, Little RD, Dupuis J, Del Mastro RG, Falls K, Simon J, et al. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature 2002; 418(6896): 426–30.

16. Blakey JD, Sayers I, Ring SM, Strachan DP, Hall IP. Positionally cloned asthma susceptibility gene polymorphisms and disease risk in the British 1958 Birth Cohort. Thorax 2009; 64(5): 381-7.

17. Brasch-Andersen C, Møller MU, Haagerup A, Vestbo J, Kruse TA. Evidence for an asthma risk locus on chromosome Xp: a replication linkage study. Allergy 2008; 63(9): 1235-8.

18. Mota Pinto A, Todo-Bom A. The role of the epithelial cell in asthma. Rev Port Pneumol 2009; 15(3): 461-72.

19. Huckabee MM, Peebles RS Jr. Novel concepts in virally induced asthma. Clin Mol Allergy 2009; 7: 2.

20. Kallal L, Lukas N. The Role of Chemokines in virus- associated asthma exacerbations. Curr Allergy Asthma Rep 2008; 8(5): 443-50.

21. Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med 2008; 178(7): 667-72.

22. Ramsey CD, Celedón JC. The hygiene hypothesis and asthma. Curr Opin Pulm Med 2005; 11(1): 14-20.

23. Abdo RA, Cué BM, Álvarez CM. Asma bronquial: factores de riesgo de las crisis y factores preventivos. Rev Cubana Med Gen Integr 2007; 23(3).

24. Dreborg S. The implications of nomenclature. Ann Allergy Asthma Immunol 2002; 89(6 Suppl 1): 83-5.

25. Furrie E. Probiotics and allergy. Proc Nutr Soc 2005; 64(4): 465-9.

26. Reed CE, Kita H. The role of protease activation of inflammation in allergic respiratory diseases. J Allergy Clin Immunol 2004; 114(5): 997-1008.

27. Larché M, Robinson DS, Kay AB. The role of T Lymphocites in the pathogenesis of asthma. J Allergy Clin Immunol 2003; 111(3): 450-63.

28. Siddiqui S, Martin JG. Structural aspects of airway remodeling in asthma. Curr Allergy Asthma Rep 2008; 8(6): 540-7.

29. Robinson DS. Regulatory T cells and asthma. Clin Exp Allergy 2009; 39(9): 1314-23.

30. Suarez CJ, Parker NJ, Finn PW. Innate immune mechanism in allergic asthma. Curr Allergy and Asthma Rep 2008; 8(5): 451-9.

31. Afzali B, Lombardi G, Lechler GI, Lord GM. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exp Immunol 2007; 148(1): 32–46.

32. Lazarus SC, Chinchilli VM, Rollings NJ, Boushey HA, Cherniack R, Craig TJ, et al. Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma. Am J Respir Crit Care Med 2007; 175(8): 783-90.

33. Jindal SK, Gupta D. The relationship between tobacco smoke & bronchial asthma. Indian J Med Res 2004; 120(5): 443-53.

34. Mortimer K, Neugebauer R, Lurmann F, Alcorn S, Balmes J, Tager I. Air pollution and pulmonary function in asthmatic children: Effects of prenatal and lifetime exposures. Epidemiology 2008; 19(4): 550-7.

35. Joos GF. The role of neuroeffector mechanisms in the pathogenesis of asthma. Curr Allergy Asthma Rep 2001; 1(2): 134-43.

36. Schwela D. Air pollution and health in urban areas. Rev Environ Health 2000; 15(1-2): 13-42.

37. Boulet LP, Lemière C, Gautrin D, Cartier A. New insights into occupational asthma. Curr Opin Allergy Clin Immunol 2007; 7(1): 96-101.

38. Rodrigo GJ, Plaza V. Body mass index and response to emergency department treatment in adults with severe asthma exacerbations: a prospective cohort study. Chest 2007; 132(5): 1513-9.

39. Shore SA. Obesity and asthma: possible mechanisms. J Allergy Clin Immunol 2008; 121(5): 1087-93.

40. Vandenbulcke L, Bachert C, Van Cauwenberge P, Claeys S. The innate immune system and its role in allergic disorders. Int Arch Allergy Immunol 2006; 139: 159-65.

41. Conroy ME, Shi HN, Walker WA. The long-term health effects of neonatal microbial flora. Curr Opin Allergy Clin Immunol 2009; 9(3): 197-201.

42. Venter C. Infant atopy and allergic diseases: an introduction to dietary aspects. J Fam Health Care 2009; 19(3): 92-6.

43. Pilette Ch, Nouri- Aria KT,Jacobson M R , Wilcock LK, Detry B, Walker SM, et al. Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-b expression. J Immunol 2007; 178: 4658-66.

44. Wahn U. What drives the allergic march? Allergy 2000; 55(7): 591-9.

45. Aviña FJA, Castañeda GD. Marcha alérgica: El camino de la atopia. Alergia e Inmunol Pediat 2006; 15(2): 50-6.

46. Jones AC, Miles EA, Warner JO, Colwell BM, Bryant TN, Warner JA. Fetal peripheral blood mononuclear cell proliferative responses to mitogenic and allergenic stimuli during gestation. Pediatr Allergy Immunol 1996; 7(3): 109-16.

47. Kjellman NI, Nilsson L. From food allergy and atopic dermatitis to respiratory allergy. Pediatr Allergy Immunol 1998; 9(11 Suppl): 13-7.

48. Spergel JM, Paller AS. Atopic dermatitis and the atopic march. J Allergy Clin Immunol 2003; 112(6 Suppl): S118-27.

49. Guilbert TW, Morgan WJ, Zeiger RS, Bacharier LB, Boehmer SJ, Krawiec M, et al. Atopic characteristics of children with recurrent wheezing at high risk for the development of childhood asthma. J Allergy Clin Immunol 2004; 114(6): 1282-7.

50. Sansoni P, Vescovini R, Fagnoni F, Biasini C, Zanni F, Zanlari L, et al. The immune system in extreme longevity. Exp Gerontol 2008; 43(2): 61-5.

51. Baena Cagnani CE, Lockey RF, Passalacqua G, Canonica GW. Inmunoterapia en América Latina. Del pasado al futuro. Rev Alerg Mex 2008; 55(1): 33-7.