Skip to main content
SpringerLink
Log in

Heterogeneity of Treatment Response to Asthma

  • Chapter
  • First Online:
Precision Approaches to Heterogeneity in Asthma

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1426))

Abstract

The definition of asthma has evolved over the years with significant heterogeneity of the disease increasingly recognized. Complex gene and environment interactions result in different pheno-endotypes of asthma that respond differently to the same treatment. Multiple studies have revealed pharmacogenomic and endophenotypic factors that predict treatment response to standard therapies for asthma. Recent advances in biologic medications have enabled a more tailored approach to the care of patients with moderate to severe asthma, taking into consideration clinical traits and measurable biomarkers. This chapter will review heterogeneity in treatment response to different medication classes for asthma: inhaled and systemic corticosteroids, beta-2 agonists, leukotriene modifiers, muscarinic antagonists, macrolides, and biologics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Global Initiative for Asthma. Global strategy for asthma management and prevention. 2022. Available from: www.ginasthma.org. Accessed on 30 Aug 2022.

  2. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group | NHLBI, NIH. 2021. Available from: https://www.nhlbi.nih.gov/resources/2020-focused-updates-asthma-management-guidelines. Accessed on 30 Aug 2022.

  3. Drazen JM, Silverman EK, Lee TH. Heterogeneity of therapeutic responses in asthma. Br Med Bull. 2000;56(4):1054–70.

    CAS  PubMed  Google Scholar 

  4. Hall IP. Pharmacogenetics of asthma. Eur Respir J. 2000;15(3):449–51.

    CAS  PubMed  Google Scholar 

  5. van Boven JFM, Dierick BJH, Usmani OS. When biology meets behaviour: can medication adherence mask the contribution of pharmacogenetic effects in asthma? Eur Respir J. 2021;58(3):2100304.

    PubMed  Google Scholar 

  6. Wechsler ME, Israel E. How pharmacogenomics will play a role in the management of asthma. Am J Respir Crit Care Med. 2005;172(1):12–8.

    PubMed  Google Scholar 

  7. Meyers DA, Bleecker ER, Holloway JW, Holgate ST. Asthma genetics and personalised medicine. Lancet Respir Med. 2014;2(5):405–15.

    PubMed  PubMed Central  Google Scholar 

  8. Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008;178(3):218–24.

    PubMed  Google Scholar 

  9. Kelly RS, Mendez KM, Huang M, Hobbs BD, Clish CB, Gerszten R, et al. Metabo-endotypes of asthma reveal differences in lung function: discovery and validation in two TOPMed cohorts. Am J Respir Crit Care Med. 2022;205(3):288–99.

    CAS  PubMed  Google Scholar 

  10. Malmstrom K, Rodriguez-Gomez G, Guerra J, Villaran C, Pineiro A, Wei LX, et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group. Ann Intern Med. 1999;130(6):487–95.

    CAS  PubMed  Google Scholar 

  11. Chan MT, Leung DY, Szefler SJ, Spahn JD. Difficult-to-control asthma: clinical characteristics of steroid-insensitive asthma. J Allergy Clin Immunol. 1998;101(5):594–601.

    CAS  PubMed  Google Scholar 

  12. Martin RJ, Szefler SJ, King TS, Kraft M, Boushey HA, Chinchilli VM, et al. The predicting response to inhaled corticosteroid efficacy (PRICE) trial. J Allergy Clin Immunol. 2007;119(1):73–80.

    PubMed  PubMed Central  Google Scholar 

  13. Tantisira KG, Lake S, Silverman ES, Palmer LJ, Lazarus R, Silverman EK, et al. Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids. Hum Mol Genet. 2004;13(13):1353–9.

    CAS  PubMed  Google Scholar 

  14. Dijkstra A, Koppelman GH, Vonk JM, Bruinenberg M, Schouten JP, Postma DS. Pharmacogenomics and outcome of asthma: no clinical application for long-term steroid effects by CRHR1 polymorphisms. J Allergy Clin Immunol. 2008;121(6):1510–3.

    CAS  PubMed  Google Scholar 

  15. Tantisira KG, Hwang ES, Raby BA, Silverman ES, Lake SL, Richter BG, et al. TBX21: a functional variant predicts improvement in asthma with the use of inhaled corticosteroids. Proc Natl Acad Sci U S A. 2004;101(52):18099–104.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Tantisira KG, Lasky-Su J, Harada M, Murphy A, Litonjua AA, Himes BE, et al. Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma. N Engl J Med. 2011;365(13):1173–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Hosking L, Bleecker E, Ghosh S, Yeo A, Jacques L, Mosteller M, et al. GLCCI1 rs37973 does not influence treatment response to inhaled corticosteroids in white subjects with asthma. J Allergy Clin Immunol. 2014;133(2):587–9.

    CAS  PubMed  Google Scholar 

  18. Tantisira KG, Damask A, Szefler SJ, Schuemann B, Markezich A, Su J, et al. Genome-wide association identifies the T gene as a novel asthma pharmacogenetic locus. Am J Respir Crit Care Med. 2012;185(12):1286–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Sharma S, Kho AT, Chhabra D, Qiu W, Gaedigk R, Vyhlidal CA, et al. Glucocorticoid genes and the developmental origins of asthma susceptibility and treatment response. Am J Respir Cell Mol Biol. 2015;52(5):543–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Baines KJ, Simpson JL, Wood LG, Scott RJ, Fibbens NL, Powell H, et al. Sputum gene expression signature of 6 biomarkers discriminates asthma inflammatory phenotypes. J Allergy Clin Immunol. 2014;133(4):997–1007.

    CAS  PubMed  Google Scholar 

  21. Park HW, Dahlin A, Tse S, Duan QL, Schuemann B, Martinez FD, et al. Genetic predictors associated with improvement of asthma symptoms in response to inhaled corticosteroids. J Allergy Clin Immunol. 2014;133(3):664–9.e5.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Xiao C, Biagini Myers JM, Ji H, Metz K, Martin LJ, Lindsey M, et al. Vanin-1 expression and methylation discriminate pediatric asthma corticosteroid treatment response. J Allergy Clin Immunol. 2015;136(4):923–31.e3.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. McGeachie MJ, Clemmer GL, Hayete B, Xing H, Runge K, Wu AC, et al. Systems biology and in vitro validation identifies family with sequence similarity 129 member A (FAM129A) as an asthma steroid response modulator. J Allergy Clin Immunol. 2018;142(5):1479–88.e12.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Green RH, Brightling CE, Woltmann G, Parker D, Wardlaw AJ, Pavord ID. Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax. 2002;57(10):875–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Zeiger RS, Szefler SJ, Phillips BR, Schatz M, Martinez FD, Chinchilli VM, et al. Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. J Allergy Clin Immunol. 2006;117(1):45–52.

    CAS  PubMed  Google Scholar 

  26. Barnes PJ. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2013;131(3):636–45.

    CAS  PubMed  Google Scholar 

  27. Al Heialy S, Ramakrishnan RK, Hamid Q. Recent advances in the immunopathogenesis of severe asthma. J Allergy Clin Immunol. 2022;149(2):455–65.

    PubMed  Google Scholar 

  28. Hew M, Bhavsar P, Torrego A, Meah S, Khorasani N, Barnes PJ, et al. Relative corticosteroid insensitivity of peripheral blood mononuclear cells in severe asthma. Am J Respir Crit Care Med. 2006;174(2):134–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Woodruff PG, Boushey HA, Dolganov GM, Barker CS, Yang YH, Donnelly S, et al. Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc Natl Acad Sci U S A. 2007;104(40):15858–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Irvin C, Zafar I, Good J, Rollins D, Christianson C, Gorska MM, et al. Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma. J Allergy Clin Immunol. 2014;134(5):1175–86.e7.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhang X, Biagini Myers JM, Yadagiri VK, Ulm A, Chen X, Weirauch MT, et al. Nasal DNA methylation differentiates corticosteroid treatment response in pediatric asthma: a pilot study. PLoS One. 2017;12(10):e0186150.

    PubMed  PubMed Central  Google Scholar 

  32. Fayon M, Lacoste-Rodrigues A, Barat P, Helbling JC, Nacka F, Berger P, et al. Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children. PLoS One. 2017;12(5):e0177051.

    PubMed  PubMed Central  Google Scholar 

  33. Clemmer GL, Wu AC, Rosner B, McGeachie MJ, Litonjua AA, Tantisira KG, et al. Measuring the corticosteroid responsiveness endophenotype in asthmatic patients. J Allergy Clin Immunol. 2015;136(2):274–81.e8.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Chaudhuri R, Livingston E, McMahon AD, Thomson L, Borland W, Thomson NC. Cigarette smoking impairs the therapeutic response to oral corticosteroids in chronic asthma. Am J Respir Crit Care Med. 2003;168(11):1308–11.

    PubMed  Google Scholar 

  36. Sutherland ER, Goleva E, Strand M, Beuther DA, Leung DY. Body mass and glucocorticoid response in asthma. Am J Respir Crit Care Med. 2008;178(7):682–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Forno E, Lescher R, Strunk R, Weiss S, Fuhlbrigge A, Celedon JC, et al. Decreased response to inhaled steroids in overweight and obese asthmatic children. J Allergy Clin Immunol. 2011;127:741–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Wells KE, Cajigal S, Peterson EL, Ahmedani BK, Kumar R, Lanfear DE, et al. Assessing differences in inhaled corticosteroid response by self-reported race-ethnicity and genetic ancestry among asthmatic subjects. J Allergy Clin Immunol. 2016;137(5):1364–9.e2.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Hernandez-Pacheco N, Farzan N, Francis B, Karimi L, Repnik K, Vijverberg SJ, et al. Genome-wide association study of inhaled corticosteroid response in admixed children with asthma. Clin Exp Allergy. 2019;49(6):789–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Mosteller M, Hosking L, Murphy K, Shen J, Song K, Nelson M, et al. No evidence of large genetic effects on steroid response in asthma patients. J Allergy Clin Immunol. 2017;139(3):797–803.e7.

    CAS  PubMed  Google Scholar 

  41. Qiu W, Guo F, Glass K, Yuan GC, Quackenbush J, Zhou X, et al. Differential connectivity of gene regulatory networks distinguishes corticosteroid response in asthma. J Allergy Clin Immunol. 2018;141(4):1250–8.

    CAS  PubMed  Google Scholar 

  42. Sears MR, Taylor DR, Print CG, Lake DC, Li QQ, Flannery EM, et al. Regular inhaled beta-agonist treatment in bronchial asthma. Lancet. 1990;336(8728):1391–6.

    CAS  PubMed  Google Scholar 

  43. Drazen JM, Israel E, Boushey HA, Chinchilli VM, Fahy JV, Fish JE, 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(12):841–7.

    CAS  PubMed  Google Scholar 

  44. Hancox RJ, Sears MR, Taylor DR. Polymorphism of the beta2-adrenoceptor and the response to long-term beta2-agonist therapy in asthma. Eur Respir J. 1998;11(3):589–93.

    CAS  PubMed  Google Scholar 

  45. Israel E, Drazen JM, Liggett SB, Boushey HA, Cherniack RM, Chinchilli VM, et al. The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma. Am J Respir Crit Care Med. 2000;162(1):75–80.

    CAS  PubMed  Google Scholar 

  46. Israel E, Chinchilli VM, Ford JG, Boushey HA, Cherniack R, Craig TJ, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet. 2004;364(9444):1505–12.

    CAS  PubMed  Google Scholar 

  47. Bleecker ER, Yancey SW, Baitinger LA, Edwards LD, Klotsman M, Anderson WH, et al. Salmeterol response is not affected by beta2-adrenergic receptor genotype in subjects with persistent asthma. J Allergy Clin Immunol. 2006;118(4):809–16.

    CAS  PubMed  Google Scholar 

  48. Bleecker ER, Postma DS, Lawrance RM, Meyers DA, Ambrose HJ, Goldman M. Effect of ADRB2 polymorphisms on response to longacting beta2-agonist therapy: a pharmacogenetic analysis of two randomised studies. Lancet. 2007;370(9605):2118–25.

    CAS  PubMed  Google Scholar 

  49. Bleecker ER, Nelson HS, Kraft M, Corren J, Meyers DA, Yancey SW, et al. Beta2-receptor polymorphisms in patients receiving salmeterol with or without fluticasone propionate. Am J Respir Crit Care Med. 2010;181(7):676–87.

    CAS  PubMed  Google Scholar 

  50. Wechsler ME, Kunselman SJ, Chinchilli VM, Bleecker E, Boushey HA, Calhoun WJ, et al. 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. 2009;374(9703):1754–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Basu K, Palmer CN, Tavendale R, Lipworth BJ, Mukhopadhyay S. Adrenergic beta(2)-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol. J Allergy Clin Immunol. 2009;124(6):1188–94.e3.

    CAS  PubMed  Google Scholar 

  52. Zuurhout MJ, Vijverberg SJ, Raaijmakers JA, Koenderman L, Postma DS, Koppelman GH, et al. Arg16 ADRB2 genotype increases the risk of asthma exacerbation in children with a reported use of long-acting beta2-agonists: results of the PACMAN cohort. Pharmacogenomics. 2013;14(16):1965–71.

    CAS  PubMed  Google Scholar 

  53. Turner S, Francis B, Vijverberg S, Pino-Yanes M, Maitland-van der Zee AH, Basu K, et al. Childhood asthma exacerbations and the Arg16 beta2-receptor polymorphism: a meta-analysis stratified by treatment. J Allergy Clin Immunol. 2016;138(1):107–13.e5.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Lipworth BJ, Basu K, Donald HP, Tavendale R, Macgregor DF, Ogston SA, et al. Tailored second-line therapy in asthmatic children with the Arg(16) genotype. Clin Sci (Lond). 2013;124(8):521–8.

    CAS  PubMed  Google Scholar 

  55. Ruffles T, Jones CJ, Palmer C, Turner S, Grigg J, Tavendale R, et al. Asthma prescribing according to Arg16Gly beta-2 genotype: a randomised trial in adolescents. Eur Respir J. 2021;58(2):2004107.

    CAS  PubMed  Google Scholar 

  56. Ortega VE, Hawkins GA, Moore WC, Hastie AT, Ampleford EJ, Busse WW, et al. Effect of rare variants in ADRB2 on risk of severe exacerbations and symptom control during longacting beta agonist treatment in a multiethnic asthma population: a genetic study. Lancet Respir Med. 2014;2(3):204–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Litonjua AA, Lasky-Su J, Schneiter K, Tantisira KG, Lazarus R, Klanderman B, et al. ARG1 is a novel bronchodilator response gene: screening and replication in four asthma cohorts. Am J Respir Crit Care Med. 2008;178(7):688–94.

    PubMed  PubMed Central  Google Scholar 

  58. Duan QL, Gaume BR, Hawkins GA, Himes BE, Bleecker ER, Klanderman B, et al. Regulatory haplotypes in ARG1 are associated with altered bronchodilator response. Am J Respir Crit Care Med. 2011;183(4):449–54.

    CAS  PubMed  Google Scholar 

  59. Israel E, Lasky-Su J, Markezich A, Damask A, Szefler SJ, Schuemann B, et al. Genome-wide association study of short-acting beta2-agonists. A novel genome-wide significant locus on chromosome 2 near ASB3. Am J Respir Crit Care Med. 2015;191(5):530–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Drake KA, Torgerson DG, Gignoux CR, Galanter JM, Roth LA, Huntsman S, et al. A genome-wide association study of bronchodilator response in Latinos implicates rare variants. J Allergy Clin Immunol. 2014;133(2):370–8.

    PubMed  Google Scholar 

  61. Mak ACY, White MJ, Eckalbar WL, Szpiech ZA, Oh SS, Pino-Yanes M, et al. Whole-genome sequencing of pharmacogenetic drug response in racially diverse children with asthma. Am J Respir Crit Care Med. 2018;197(12):1552–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Drazen JM, Yandava CN, Dube L, Szczerback N, Hippensteel R, Pillari A, et al. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet. 1999;22(2):168–70.

    CAS  PubMed  Google Scholar 

  63. Lima JJ, Zhang S, Grant A, Shao L, Tantisira KG, Allayee H, et al. Influence of leukotriene pathway polymorphisms on response to montelukast in asthma. Am J Respir Crit Care Med. 2006;173(4):379–85.

    CAS  PubMed  Google Scholar 

  64. Telleria JJ, Blanco-Quiros A, Varillas D, Armentia A, Fernandez-Carvajal I, Jesus Alonso M, et al. ALOX5 promoter genotype and response to montelukast in moderate persistent asthma. Respir Med. 2008;102(6):857–61.

    PubMed  Google Scholar 

  65. Tantisira KG, Lima J, Sylvia J, Klanderman B, Weiss ST. 5-lipoxygenase pharmacogenetics in asthma: overlap with Cys-leukotriene receptor antagonist loci. Pharmacogenet Genomics. 2009;19(3):244–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Dahlin A, Litonjua A, Lima JJ, Tamari M, Kubo M, Irvin CG, et al. Genome-wide association study identifies novel pharmacogenomic loci for therapeutic response to montelukast in asthma. PLoS One. 2015;10(6):e0129385.

    PubMed  PubMed Central  Google Scholar 

  67. Maroteau C, Espuela-Ortiz A, Herrera-Luis E, Srinivasan S, Carr F, Tavendale R, et al. LTA4H rs2660845 association with montelukast response in early and late-onset asthma. PLoS One. 2021;16(9):e0257396.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Edelman JM, Turpin JA, Bronsky EA, Grossman J, Kemp JP, Ghannam AF, et al. Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction. A randomized, double-blind trial. Exercise Study Group. Ann Intern Med. 2000;132(2):97–104.

    CAS  PubMed  Google Scholar 

  69. Dahlen SE, Malmstrom K, Nizankowska E, Dahlen B, Kuna P, Kowalski M, et al. Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial. Am J Respir Crit Care Med. 2002;165(1):9–14.

    PubMed  Google Scholar 

  70. Peters SP, Kunselman SJ, Icitovic N, Moore WC, Pascual R, Ameredes BT, et al. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med. 2010;363(18):1715–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Peters SP, Bleecker ER, Kunselman SJ, Icitovic N, Moore WC, Pascual R, et al. Predictors of response to tiotropium versus salmeterol in asthmatic adults. J Allergy Clin Immunol. 2013;132(5):1068–1074.e1.

    CAS  PubMed  Google Scholar 

  72. Lazarus SC, Krishnan JA, King TS, Lang JE, Blake KV, Covar R, et al. Mometasone or tiotropium in mild asthma with a low sputum eosinophil level. N Engl J Med. 2019;380(21):2009–19.

    PubMed  PubMed Central  Google Scholar 

  73. Brusselle GG, Vanderstichele C, Jordens P, Deman R, Slabbynck H, Ringoet V, et al. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax. 2013;68(4):322–9.

    PubMed  Google Scholar 

  74. Gibson PG, Yang IA, Upham JW, Reynolds PN, Hodge S, James AL, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390(10095):659–68.

    CAS  PubMed  Google Scholar 

  75. Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43(2):343–73.

    CAS  PubMed  Google Scholar 

  76. Desai D, Newby C, Symon FA, Haldar P, Shah S, Gupta S, et al. Elevated sputum interleukin-5 and submucosal eosinophilia in obese individuals with severe asthma. Am J Respir Crit Care Med. 2013;188(6):657–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. McGregor MC, Krings JG, Nair P, Castro M. Role of biologics in asthma. Am J Respir Crit Care Med. 2019;199(4):433–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Brusselle GG, Koppelman GH. Biologic therapies for severe asthma. N Engl J Med. 2022;386(2):157–71.

    CAS  PubMed  Google Scholar 

  79. Khurana S, Bush A, Holguin F. Management of severe asthma: summary of the European Respiratory Society/American Thoracic Society task force report. Breathe (Sheff). 2020;16:200058. https://doi.org/10.1183/20734735.0058-2020.

    Article  PubMed  Google Scholar 

  80. Busse W, Corren J, Lanier BQ, McAlary M, Fowler-Taylor A, Cioppa GD, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108(2):184–90.

    CAS  PubMed  Google Scholar 

  81. Humbert M, Beasley R, Ayres J, Slavin R, Hebert J, Bousquet J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. 2005;60(3):309–16.

    CAS  PubMed  Google Scholar 

  82. Bousquet J, Rabe K, Humbert M, Chung KF, Berger W, Fox H, et al. Predicting and evaluating response to omalizumab in patients with severe allergic asthma. Respir Med. 2007;101(7):1483–92.

    CAS  PubMed  Google Scholar 

  83. Hanania NA, Wenzel S, Rosen K, Hsieh HJ, Mosesova S, Choy DF, et al. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med. 2013;187(8):804–11.

    CAS  PubMed  Google Scholar 

  84. Casale TB, Luskin AT, Busse W, Zeiger RS, Trzaskoma B, Yang M, et al. Omalizumab effectiveness by biomarker status in patients with asthma: evidence from PROSPERO, a prospective real-world study. J Allergy Clin Immunol Pract. 2019;7(1):156–64.e1.

    PubMed  Google Scholar 

  85. Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360(10):973–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009;360(10):985–93.

    CAS  PubMed  Google Scholar 

  87. Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):651–9.

    CAS  PubMed  Google Scholar 

  88. Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198–207.

    PubMed  Google Scholar 

  89. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371(13):1189–97.

    PubMed  Google Scholar 

  90. Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015;3(5):355–66.

    CAS  PubMed  Google Scholar 

  91. Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115–27.

    CAS  PubMed  Google Scholar 

  92. Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376(25):2448–58.

    CAS  PubMed  Google Scholar 

  93. FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, et al. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128–41.

    CAS  PubMed  Google Scholar 

  94. FitzGerald JM, Bleecker ER, Menzies-Gow A, Zangrilli JG, Hirsch I, Metcalfe P, et al. Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies. Lancet Respir Med. 2018;6(1):51–64.

    CAS  PubMed  Google Scholar 

  95. Nair P, O’Byrne PM. The interleukin-13 paradox in asthma: effective biology, ineffective biologicals. Eur Respir J. 2019;53(2):1802250.

    CAS  PubMed  Google Scholar 

  96. Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365(12):1088–98.

    CAS  PubMed  Google Scholar 

  97. Hanania NA, Korenblat P, Chapman KR, Bateman ED, Kopecky P, Paggiaro P, et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med. 2016;4(10):781–96.

    CAS  PubMed  Google Scholar 

  98. Castro M, Corren J, Pavord ID, Maspero J, Wenzel S, Rabe KF, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378(26):2486–96.

    CAS  PubMed  Google Scholar 

  99. Rabe KF, Nair P, Brusselle G, Maspero JF, Castro M, Sher L, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med. 2018;378(26):2475–85.

    CAS  PubMed  Google Scholar 

  100. Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting beta2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388(10039):31–44.

    CAS  PubMed  Google Scholar 

  101. Corren J, Parnes JR, Wang L, Mo M, Roseti SL, Griffiths JM, et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377(10):936–46.

    CAS  PubMed  Google Scholar 

  102. Menzies-Gow A, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. 2021;384(19):1800–9.

    CAS  PubMed  Google Scholar 

  103. Wechsler ME, Menzies-Gow A, Brightling CE, Kuna P, Korn S, Welte T, et al. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study. Lancet Respir Med. 2022;10:650.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Rochester School of Medicine and Dentistry, Division of Pulmonary and Critical Care Medicine, Rochester, NY, USA

    Tetsuro Maeda & Sandhya Khurana

Authors
  1. Tetsuro Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandhya Khurana
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sandhya Khurana .

Editor information

Editors and Affiliations

  1. Department of Medicine, Division of Endocrinology Institute for Clinical and Translational Research, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Allan R. Brasier

  2. Department of Medicine, Division of Allergy, Pulmonary and Critical Care, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Nizar N. Jarjour

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Maeda, T., Khurana, S. (2023). Heterogeneity of Treatment Response to Asthma. In: Brasier, A.R., Jarjour, N.N. (eds) Precision Approaches to Heterogeneity in Asthma. Advances in Experimental Medicine and Biology, vol 1426. Springer, Cham. https://doi.org/10.1007/978-3-031-32259-4_7

Download citation

Publish with us

Policies and ethics

Search

Navigation