Clinical Pediatric Emergency Medicine
Volume 10, Issue 2 , Pages 95-102 , June 2009

Pharmacogenomics of Acute Asthma: The β2-Adrenergic Receptor Gene as a Model for Future Therapy

  • Kyle A. Nelson, MD, MPH

      Affiliations

    • Corresponding Author InformationReprint requests and correspondence: Kyle A. Nelson, MD, MPH, Division of Pediatric Emergency Medicine, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, A Level, Room AS01, Philadelphia, PA 19104.

References 

  1. Akinbami LJ. The state of childhood asthma, United States, 1980-2005. Advance data. From Vital and Health Statistics: No. 381. Hyattsville (Md): National Center for Health Statistics; 2006;
  2. National Asthma Education and Prevention Program . Expert Panel report 3: guidelines for the diagnosis and management of asthma—summary report 2007. J Allergy Clin Immunol. 2007;120:S94–S138
  3. Palmer LJ, Silverman ES, Weiss ST, et al. Pharmacogenetics of asthma. Am J Respir Crit Care Med. 2002;165:861–866
  4. Drazen JM, Silverman EK, Lee TH. Heterogeneity of therapeutic responses in asthma. Br Med Bull. 2000;56:1054–1070
  5. Hawkins GA, Weiss ST, Bleecker ER. Asthma pharmacogenomics. Immunol Allerg Clin North Am. 2005;25:723–742
  6. Halapi E, Hakonarson H. Recent developments in genomic and proteomic research for asthma. Curr Opin Pulm Med. 2003;10:22–30
  7. Hakonarson H, Wjst M. Current concepts on the genetics of asthma. Curr Opin Pediatr. 2001;13:267–277
  8. Wechsler ME, Israel E. How pharmacogenomics will play a role in the management of asthma. Am J Respir Crit Care Med. 2005;172:12–18
  9. Szalai C, Ungvari I, Pelyhe L, et al. Asthma from a pharmacogenomic point of view. Br J Pharmacol. 2008;153:1602–1614
  10. Warrier MR, Hershey GKK. Asthma genetics: personalizing medicine. J Asthma. 2008;45:257–264
  11. Reed CE. The natural history of asthma. J Allergy Clin Immunol. 2006;118:543–548
  12. Panettieri RA, Covar R, Grant E, et al. Natural history of asthma: persistence versus progression—does the beginning predict the end?. J Allergy Clin Immunol. 2008;121:607–613
  13. Cairns CB. Acute asthma exacerbations: phenotypes and management. Clin Chest Med. 2006;27:99–108
  14. Taussig LM, Wright AL, Holberg CJ, et al. Tucson Children's Respiratory Study: 1980 to present. J Allergy Clin Immunol. 2003;111:661–675
  15. Wright RJ, Cohen S, Carey V, et al. Parental stress as a predictor of wheezing in infancy: a prospective birth-cohort study. Am J Respir Crit Care Med. 2002;165:358–365
  16. Klinnert MD, Kraugars AS, Strand M, et al. Family psychological factors in relation to children's asthma status and adjustment at age 4. Fam Process. 2008;47:41–61
  17. Klinnert MD, Nelson HS, Price MR, et al. Onset and persistence of childhood asthma: predictors from infancy. Pediatrics. 2001;108:E69
  18. Kraugars AS, Klinnert MD, Bender BG. Family influences on pediatric asthma. J Pediatr Psychol. 2004;29:475–491
  19. Sandberg S, Paton JY, Ahola S, et al. The role of acute and chronic stress in asthma attacks in children. Lancet. 2000;356:982–987
  20. Sandberg S, Jarvenpaa S, Penttinen A, et al. Asthma exacerbations in children immediately following stressful life events: a Cox's hierarchical regression. Thorax. 2004;59:1046–1051
  21. Centers for Disease Control and Prevention (CDC) . Asthma prevalence and control characteristics by race/ethnicity—United States, 2002. Morb Mortal Wkly Rep. 2004;53:145–148
  22. Akinbami LJ, Schoendorf KC. Trends in childhood asthma: prevalence, health care utilization and mortality. Pediatrics. 2002;110:315–322
  23. Newacheck PW, Halfon N. Prevalence, impact, and trends in childhood disability due to asthma. Arch Pediatr Adolesc Med. 2000;154:287–293
  24. Miller JE. The effects of race/ethnicity and income on early childhood asthma prevalence and health care use. Am J Public Health. 2000;90:428–430
  25. Gold DR, Wright R. Population disparities in asthma. Annu Rev Public Health. 2005;26:89–113
  26. Illi S, von Mutius E, Lau S, et al. The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. J Allergy Clin Immunol. 2004;113:925–931
  27. Yawn BP, Wollan P, Kurland M, et al. A longitudinal study of prevalence of asthma in a community population of school-age children. J Pediatr. 2002;140:576–581
  28. Wu P, Dupont WD, Griffin MR, et al. Evidence of a causal role of winter virus infection during infancy in early childhood asthma. Am J Respir Crit Care Med. 2008;178:1123–1129
  29. Bouzigon E, Corda E, Aschard H, et al. Effect of 17q21 variants and smoking exposure in early-onset asthma. N Engl J Med. 2008;359:1985–1994
  30. Chipps BE, Spahn JD, Sorkness CA, et al. Variability in asthma severity in pediatric subjects with asthma previously receiving short-acting beta2-agonists. J Pediatr. 2006;148:517–521
  31. Calhoun WJ, Sutton LB, Emmett A, et al. Asthma variability in patients previously treated with beta2-agonists alone. J Allergy Clin Immunol. 2003;112:1088–1094
  32. Elizur A, Bacharier LB, Strunk RC. Pediatric asthma admissions: chronic severity and acute exacerbations. J Asthma. 2007;44:285–289
  33. Carroll CL, Schramm CM, Zucker AR. Severe exacerbations in children with mild asthma: characterizing a pediatric phenotype. J Asthma. 2008;45:513–517
  34. Woodruff PG, Emond SD, Singh AK, et al. Sudden-onset severe acute asthma: clinical features and responses to therapy. Acad Emerg Med. 1998;5:695–701
  35. Barr RB, Woodruff PG, Clark S, et al. Sudden-onset asthma exacerbations: clinical features, responses to therapy, and 2-week follow-up. Multicenter Airway Research Collaboration (MARC) investigators. Eur Respir J. 2000;15:266–273
  36. Sedik HA, Barr RG, Clark S, et al. Prospective study of sudden-onset asthma exacerbations in children. Pediatr Emerg Care. 2007;23:439–444
  37. Ramnath VR, Clark S, Carmargo CA. Multicenter study of clinical features of sudden-onset versus slower-onset asthma exacerbations requiring hospitalization. Respir Care. 2007;52:1013–1020
  38. Belessis Y, Dixon S, Thomsen A, et al. Risk factors for an intensive care unit admission in children with asthma. Pediatr Pulmonol. 2004;37:201–209
  39. Lyell PJ, Villanueva E, Burton D, et al. Risk factors for intensive care in children with acute asthma. Respirology. 2005;10:436–441
  40. Carroll CL, Schramm CM, Zucker AR. Slow-responders to IV beta2-adrenergic agonist therapy: defining a novel phenotype in pediatric asthma. Pediatr Pulmonol. 2008;43:627–633
  41. Weiss ST, Litonjua AA, Lange C, et al. Overview of the pharmacogenetics of asthma treatment. Pharmacogenomics J. 2006;6:311–326
  42. Liggett SB. Pharmacogenetics of the beta-1- and beta-2-adrenergic receptors. Pharmacology. 2000;61:167–173
  43. Martinez FD, Graves PE, Baldini S, et al. Association between genetic polymorphisms of the β-adrenoceptor and response to albuterol in children with and without a history of wheezing. J Clin Invest. 1997;100:3184–3188
  44. Lima JJ, Thomason DB, Mohamed MH, et al. Impact of genetic polymorphisms of the beta 2-adrenergic receptor on albuterol bronchodilator pharmacodynamics. Clin Pharmacol Ther. 1999;65:519–525
  45. Cho SH, Oh SY, Bahn JW, et al. Association between bronchodilating response to short-acting beta-agonist and non-synonymous single-nucleotide polymorphisms of beta-adrenoceptor gene. Clin Exp Allergy. 2005;35:1162–1167
  46. Silverman EK, Kwiatkowski DJ, Sylvia JS, et al. Family-based association analysis of beta 2-adrenergic receptor polymorphisms in the childhood asthma management program. J Allerg Clin Immunol. 2003;112:870–876
  47. Israel E, Drazen JM, Liggett SB, et al. The effect of polymorphisms of the β2-adrenergic receptor on the response to regular use of albuterol in asthma. Am J Respir Crit Care Med. 2000;162:75–80
  48. Choudry S, Ung N, Avila P, et al. Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma. Am J Respir Crit Care Med. 2005;171:563–570
  49. Drysdale CM, McGraw DW, Stack CB, et al. Complex promoter and coding region β2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. PNAS. 2000;97:10483–10488
  50. Taylor DR, Epton MJ, Kennedy MA, et al. Bronchodilator response in relation to β2-adrenoceptor haplotype in patients with asthma. Am J Respir Crit Care Med. 2005;172:700–703
  51. Drazen JM, Israel E, Boushey HA, et al. Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. Asthma clinical research network. N Engl J Med. 1996;335:841–847
  52. Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet. 2004;364:1505–1512
  53. Green SA, Turki J, Innes M, et al. Amino-terminal polymorphisms of the human β2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry. 1994;33:9414–9419
  54. Taylor DR, Drazen JM, Herbison GP, et al. Asthma exacerbations during long term beta agonist use: influence of beta(2) adrenergic receptor polymorphism. Thorax. 2000;55:762–767
  55. Telleria JJ, Blanco-Quiros A, Muntion S, et al. Tachyphylaxis to β2-agonists in Spanish asthmatic patients could be modulated by β2-adrenoceptor gene polymorphisms. Respir Med. 2006;100:1072–1078

PII: S1522-8401(09)00032-9

doi: 10.1016/j.cpem.2009.03.005

Clinical Pediatric Emergency Medicine
Volume 10, Issue 2 , Pages 95-102 , June 2009