Advertisement

Heterogeneity of Response to Therapy

  • William J. CalhounEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 795)

Abstract

As noted in prior chapters, US national and international guidelines provide a consistent approach to initial management of asthma, based on easily observed physical and physiologic findings, and a detailed history. From those data, a rational initial therapeutic regimen can be prescribed. In many cases, such therapy results in near complete control of asthma symptoms, restoration of normal lung physiology, and elimination of exacerbations. In fact, such improvement is frequent enough that therapeutic responsiveness to asthma treatments was thought to be nearly universal. However, it is not uncommon for patients to return with incomplete, or even trivial improvement in these clinical metrics of control (Langmack and Martin Curr Opin Pulm Med 16:13–18, 2010). In this chapter, we review the current literature on the variability of response to commonly used therapeutic agents in asthma.

Keywords

Asthma Therapeutic response Molecular phenotype Predictive phenotype Heterogeneity Inhaled steroid Montelukast Periostin IL-13 

References

  1. Bleecker ER, Postma DS, Lawrance RM, Meyers DA, Ambrose HJ, Goldman M (2007) Effect of ADRB2 polymorphisms on response to longacting beta2-agonist therapy: a pharmacogenetic analysis of two randomised studies. Lancet 370:2118–2125PubMedCrossRefGoogle Scholar
  2. Bleecker ER, Nelson HS, Kraft M, Corren J, Meyers DA, Yancey SW, Anderson WH, Emmett AH, Ortega HG (2010) Beta2-receptor polymorphisms in patients receiving salmeterol with or without fluticasone propionate. Am J Respir Crit Care Med 181:676–687PubMedCrossRefGoogle Scholar
  3. Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, Harris JM, Scheerens H, Wu LC, Su Z, Mosesova S, Eisner MD, Bohen SP, Matthews JG (2011) Lebrikizumab treatment in adults with asthma. N Engl J Med 365:1088–1098PubMedCrossRefGoogle Scholar
  4. Drazen JM, Yandava CN, Dubé L, Szczerback N, Hippensteel R, Pillari A, Israel E, Schork N, Silverman ES, Katz DA, Drajesk J (1999) Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet 22:168–170PubMedCrossRefGoogle Scholar
  5. Green RH, Brightling CE, Woltmann G, Parker D, Wardlaw AJ, Pavord ID (2002) Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax 57:875–879PubMedCrossRefGoogle Scholar
  6. Hoffmann HJ, Nielsen LP, Harving H, Heinig JH, Dahl R (2008) Asthmatics able to step down from inhaled corticosteroid treatment without loss of asthma control have low serum eotaxin/CCL11. Clin Respir J 2:149–157PubMedCrossRefGoogle Scholar
  7. Israel E, Chinchilli VM, Ford JG, Boushey HA, Cherniack R, Craig TJ, Deykin A, Fagan JK, Fahy JV, Fish J, Kraft M, Kunselman SJ, Lazarus SC, Lemanske RF Jr, Liggett SB, Martin RJ, Mitra N, Peters SP, Silverman E, Sorkness CA, Szefler SJ, Wechsler ME, Weiss ST, Drazen JM, National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network (2004) Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomized, placebo-controlled, cross-over trial. Lancet 364:1505–1512PubMedCrossRefGoogle Scholar
  8. Langmack EL, Martin RJ (2010) Heterogeneity of response to asthma controller therapy: clinical implications. Curr Opin Pulm Med 16:13–18PubMedCrossRefGoogle Scholar
  9. Lazarus SC, Chinchilli VM, Rollings NJ, Boushey HA, Cherniack R, Craig TJ, Deykin A, DiMango E, Fish JE, Ford JG, Israel E, Kiley J, Kraft M, Lemanske RF Jr, Leone FT, Martin RJ, Pesola GR, Peters SP, Sorkness CA, Szefler SJ, Wechsler ME, Fahy JV, National Heart Lung and Blood Institute’s Asthma Clinical Research Network (2007) Smoking affects response to inhaled corticosteroids and leukotriene receptor antagonist in asthma. Am J Respir Crit Care Med 175:783–790PubMedCrossRefGoogle Scholar
  10. Lima JJ (2007) Treatment heterogeneity in asthma: genetics of response to leukotriene modifiers. Mol Diagn Ther 11:97–104PubMedCrossRefGoogle Scholar
  11. Malmstrom K, Rodriguez-Gomez G, Guerra J, Villaran C, Piñeiro A, Wei LX, Seidenberg BC, Reiss TF (1999) Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group. Ann Intern Med 130:487–495PubMedCrossRefGoogle Scholar
  12. Martin RJ, Szefler SJ, King TS (2007) The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial. J Allergy Clin Immunol 119:73–80PubMedCrossRefGoogle Scholar
  13. Matsumura Y (2010) Heterogeneity of glucocorticoid resistance in patients with bronchial asthma. Int J Biomed Sci 6:158–166PubMedGoogle Scholar
  14. Montuschi P, Barnes PJ (2011) New perspectives in pharmacological treatment of mild persistent asthma. Drug Discov Today 16:1084–1091PubMedCrossRefGoogle Scholar
  15. Sally Wenzel W, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, Wang L, Kirkesseli S, Rocklin R, Bock B, Hamilton J, Ming JE, Radin A, Stahl N, Yancopoulos GD, Graham N, Pirozzi G (2013) Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med 368(26):2455–2466. doi: 10.1056/NEJMoa1304048 PubMedCrossRefGoogle Scholar
  16. Silverman ES, Drazen JM (2000) Genetic variations in the 5-lipoxygenase core promoter. Description and functional implications. Am J Respir Crit Care Med 161:S77–S80PubMedCrossRefGoogle Scholar
  17. Szefler SJ, Martin RJ, King TS, Boushey HA, Cherniack RM, Chinchilli VM, Craig TJ, Dolovich M, Drazen JM, Fagan JK, Fahy JV, Fish JE, Ford JG, Israel E, Kiley J, Kraft M, Lazarus SC, Lemanske RF Jr, Mauger E, Peters SP, Sorkness CA, Asthma Clinical Research Network of the National Heart Lung, and Blood Institute (2002) Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol 109:410–418PubMedCrossRefGoogle Scholar
  18. Tantisira KG, Drazen JM (2009) Genetics and pharmacogenetics of leukotriene pathway. J Allergy Clin Immunol 124:422–427PubMedCrossRefGoogle Scholar
  19. Tantisira KG, Lake S, Silverman ES, Palmer LJ, Lazarus R, Silverman EK, Liggett SB, Gelfand EW, Rosenwasser LJ, Richter B, Israel E, Wechsler M, Gabriel S, Altshuler D, Lander E, Drazen J, Weiss ST (2004a) Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids. Hum Mol Genet 13:1353–1359PubMedCrossRefGoogle Scholar
  20. Tantisira KG, Hwang ES, Raby BA, Silverman ES, Lake SL, Richter BG, Peng SL, Drazen JM, Glimcher LH, Weiss ST (2004b) TBX21: a functional variant predicts improvement in asthma with the use of inhaled corticosteroids. Proc Natl Acad Sci USA 101:18099–18104PubMedCrossRefGoogle Scholar
  21. Telleria JJ, Blanco-Quiros A, Varillas D, Armentia A, Fernandez-Carvajal I, Jesus Alonso M, Diez I (2008) ALOX5 promoter genotype and response to montelukast in moderate persistent asthma. Respir Med 102:857–861PubMedCrossRefGoogle Scholar
  22. Wechsler ME, Kunselman SJ, Chinchilli VM, Bleecker E, Boushey HA, Calhoun WJ, Ameredes BT, Castro M, Craig TJ, Denlinger L, Fahy JV, Jarjour N, Kazani S, Kim S, Kraft M, Lazarus SC, Lemanske RF Jr, Markezich A, Martin RJ, Permaul P, Peters SP, Ramsdell J, Sorkness CA, Sutherland ER, Szefler SJ, Walter MJ, Wasserman SI, Israel E, National Heart, Lung and Blood Institute’s Asthma Clinical Research Network (2009) Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial. Lancet 374:1754–1764PubMedCrossRefGoogle Scholar
  23. Zheng X, Guan W, Zheng J, Ye P, Liu S, Zhou J, Xiong Y, Zhang Q, Chen Q (2012) Smoking influences response to inhaled corticosteroids in patients with asthma: a meta-analysis. Curr Med Res Opin 28:1791–1798PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Internal MedicineUniversity of Texas Medical BranchGalvestonUSA

Personalised recommendations