Skip to main content
SpringerLink
Log in

Defining Phenotypes in Asthma: A Step Towards Personalized Medicine

  • Current Opinion
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Asthma is a common disease with a complex pathophysiology. It can present in various clinical forms and with different levels of severity. Unbiased cluster analytic methods have unravelled several phenotypes in cohorts representative of the whole spectrum of severity. Clusters of severe asthma include those on high-dose corticosteroid treatment, often with both inhaled and oral treatment, usually associated with severe airflow obstruction. Phenotypes with concordance between symptoms and sputum eosinophilia have been reported, including an eosinophilic inflammation-predominant group with few symptoms and late-onset disease who have a high prevalence of rhinosinusitis, aspirin sensitivity, and exacerbations. Sputum eosinophilia is also a biomarker that can predict therapeutic responses to antibody-based treatments to block the effects of the T-helper (Th)-2 cytokine, interleukin (IL)-5. Low Th2-expression has been predictive of poor therapeutic response to inhaled corticosteroid therapy. Current asthma schedules emphasise a step-up approach to treating asthma in relation to increasing severity, but, in more severe disease, phenotyping or endotyping of asthma will be necessary to determine new treatment strategies as severe asthma is recognized as being a particularly heterogeneous disease. Much less is known about ‘non-eosinophilic’ asthma. Phenotypic characterisation of corticosteroid insensitivity and chronic airflow obstruction of severe asthma is also needed. Phenotype-driven treatment of asthma will be further boosted by the advent of transcriptomic and proteomic technologies, with the application of systems biology or medicine approaches to defining phenotypes and biomarkers of disease and therapeutic response. This will pave the way towards personalized medicine and healthcare for asthma.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bel EH. Clinical phenotypes of asthma. Curr Opin Pulmonary Med. 2004;10(1):44–50.

    Article  Google Scholar 

  2. Chung KF, Godard P, Adelroth E, Ayres J, Barnes N, Barnes P, et al. Difficult/therapy-resistant asthma: the need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies. ERS Task Force on Difficult/Therapy-Resistant Asthma European Respiratory Society. Eur Respir J. 1999;13(5):1198–208.

    CAS  PubMed  Google Scholar 

  3. Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. American Thoracic Society. Am J Respir Crit Care Med. 2000;162(6):2341–51.

  4. Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet. 2008;372(9643):1107–19.

    Article  PubMed  Google Scholar 

  5. Lotvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127(2):355–60.

    Article  PubMed  Google Scholar 

  6. Prosperi MC, Sahiner UM, Belgrave D, Sackesen C, Buchan IE, Simpson A, et al. Challenges in identifying asthma subgroups using unsupervised statistical learning techniques. Am J Respir Crit Care Med. 2013;188(11):1303–12.

    Article  PubMed  Google Scholar 

  7. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. 2010;181(4):315–23.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Fitzpatrick AM, Teague WG, Meyers DA, Peters SP, Li X, Li H, et al. Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program. J Allergy Clin Immunol. 2011;127(2):382–389.e1-13.

    Article  PubMed Central  PubMed  Google Scholar 

  9. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Siroux V, Basagana X, Boudier A, Pin I, Garcia-Aymerich J, Vesin A, et al. Identifying adult asthma phenotypes using a clustering approach. Eur Respir J. 2011;38(2):310–7.

    Article  CAS  PubMed  Google Scholar 

  11. Kim TB, Jang AS, Kwon HS, Park JS, Chang YS, Cho SH, et al. Identification of asthma clusters in two independent Korean adult asthma cohorts. Eur Respir J. 2013;41(6):1308–14.

    Article  PubMed  Google Scholar 

  12. Kaneko Y, Masuko H, Sakamoto T, Iijima H, Naito T, Yatagai Y, et al. Asthma phenotypes in Japanese adults—their associations with the CCL5 and ADRB2 genotypes. Allergol Int. 2013;62(1):113–21.

    Article  CAS  PubMed  Google Scholar 

  13. Patrawalla P, Kazeros A, Rogers L, Shao Y, Liu M, Fernandez-Beros ME, Shang S, Reibman J. Application of the asthma phenotype algorithm from the Severe Asthma Research Program to an urban population. PLoS ONE. 2012;7(9):e44540.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Chang TS, Lemanske RF Jr, Mauger DT, Fitzpatrick AM, Sorkness CA, Szefler SJ, et al. Childhood asthma clusters and response to therapy in clinical trials. J Allergy Clin Immunol. 2014;133:363–9.

    Article  PubMed  Google Scholar 

  15. Schatz M, Hsu JW, Zeiger RS, Chen W, Dorenbaum A, Chipps BE, et al. Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma. J Allergy Clin Immunol. 2013 Dec 3 [Epub ahead of print].

  16. Jang AS, Kwon HS, Cho YS, Bae YJ, Kim TB, Park JS, et al. Identification of subtypes of refractory asthma in Korean patients by cluster analysis. Lung. 2013;191(1):87–93.

    Article  PubMed  Google Scholar 

  17. Sutherland ER, Goleva E, King TS, Lehman E, Stevens AD, Jackson LP, et al. Cluster analysis of obesity and asthma phenotypes. PLoS ONE. 2012;7(5):e36631.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Gibeon D, Batuwita K, Osmond M, Heaney LG, Brightling CE, Niven R, et al. Obesity-associated severe asthma represents a distinct clinical phenotype: analysis of the British Thoracic Society Difficult Asthma Registry Patient cohort according to BMI. Chest. 2013;143(2):406–14.

    Article  CAS  PubMed  Google Scholar 

  19. Amelink M, de Nijs SB, de Groot JC, van Tilburg PM, van Spiegel PI, Krouwels FH, et al. Three phenotypes of adult-onset asthma. Allergy. 2013;68(5):674–80.

    Article  CAS  PubMed  Google Scholar 

  20. Boudier A, Curjuric I, Basagana X, Hazgui H, Anto JM, Bousquet J, et al. Ten-year follow-up of cluster-based asthma phenotypes in adults. A pooled analysis of three cohorts. Am J Respir Crit Care Med. 2013;188(5):550–60.

    Article  PubMed  Google Scholar 

  21. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med. 2004;170(8):836–44.

    Article  PubMed  Google Scholar 

  22. Chung KF, Caramori G, Adcock IM. Inhaled corticosteroids as combination therapy with beta-adrenergic agonists in airways disease: present and future. Eur J Clin Pharmacol. 2009;65(9):853–71.

    Article  CAS  PubMed  Google Scholar 

  23. 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;43:343–73.

    Article  CAS  PubMed  Google Scholar 

  24. Deykin A, Lazarus SC, Fahy JV, Wechsler ME, Boushey HA, Chinchilli VM, et al. Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids. J Allergy Clin Immunol. 2005;115(4):720–7.

    Article  CAS  PubMed  Google Scholar 

  25. Cowan DC, Cowan JO, Palmay R, Williamson A, Taylor DR. Effects of steroid therapy on inflammatory cell subtypes in asthma. Thorax. 2010;65(5):384–90.

    Article  PubMed  Google Scholar 

  26. Dente FL, Bacci E, Bartoli ML, Cianchetti S, Costa F, Di Franco A, et al. Effects of oral prednisone on sputum eosinophils and cytokines in patients with severe refractory asthma. Ann Allergy Asthma Immunol. 2010;104(6):464–70.

    Article  CAS  PubMed  Google Scholar 

  27. Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002;360(9347):1715–21.

    Article  PubMed  Google Scholar 

  28. Moore WC, Hastie AT, Li X, Li H, Busse WW, Jarjour NN, et al. Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis. J Allergy Clin Immunol. 2013 Dec 8 [Epub ahead of print].

  29. Israel E, Chervinsky PS, Friedman B, van Bavel J, Skalky CS, Ghannam AF, et al. Effects of montelukast and beclomethasone on airway function and asthma control. J Allergy Clin Immunol. 2002;110(6):847–54.

    Article  CAS  PubMed  Google Scholar 

  30. Jatakanon A, Uasuf C, Maziak W, Lim S, Chung KF, Barnes PJ. Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med. 1999;160(5 Pt 1):1532–9.

    Article  CAS  PubMed  Google Scholar 

  31. 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.

    Article  PubMed  Google Scholar 

  32. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Wysocki K, Park SY, Bleecker E, Busse W, Castro M, Chung KF, et al. Characterization of factors associated with systemic corticosteroid use in severe asthma: data from the Severe Asthma Research Program. J Allergy Clin Immunol. 2014;133:915–8.

    Article  CAS  PubMed  Google Scholar 

  34. Chang PJ, Bhavsar PK, Michaeloudes C, Khorasani N, Chung KF. Corticosteroid insensitivity of chemokine expression in airway smooth muscle of patients with severe asthma. J Allergy Clin Immunol. 2012;130(4):877–885.e5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Bhavsar P, Khorasani N, Hew M, Johnson M, Chung KF. Effect of p38 MAPK inhibition on corticosteroid suppression of cytokine release in severe asthma. Eur Respir J. 2010;35(4):750–6.

    Article  CAS  PubMed  Google Scholar 

  36. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J. 2001;15(6):1110–2.

    CAS  PubMed  Google Scholar 

  37. Irusen E, Matthews JG, Takahashi A, Barnes PJ, Chung KF, Adcock IM. p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol. 2002;109(4):649–57.

    Article  CAS  PubMed  Google Scholar 

  38. Leung DYM, Hamid Q, Vottero A, Szefler SJ, Surs W, Minshall E, et al. Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor beta. J Exp Med. 1997;186(9):1567–74.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. McGrath KW, Icitovic N, Boushey HA, Lazarus SC, Sutherland ER, Chinchilli VM, et al. A large subgroup of mild-to-moderate asthma is persistently noneosinophilic. Am J Respir Crit Care Med. 2012;185(6):612–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Wenzel SE, Schwartz LB, Langmack EL, Halliday JL, Trudeau JB, Gibbs RL, et al. Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics. Am J Respir Crit Care Med. 1999;160(3):1001–8.

    Article  CAS  PubMed  Google Scholar 

  41. Baines KJ, Simpson JL, Wood LG, Scott RJ, Gibson PG. Transcriptional phenotypes of asthma defined by gene expression profiling of induced sputum samples. J Allergy Clin Immunol. 2011;127(1):153–160.e1-9.

    Article  CAS  PubMed  Google Scholar 

  42. Hastie AT, Moore WC, Meyers DA, Vestal PL, Li H, Peters SP, et al. Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes. J Allergy Clin Immunol. 2010;125(5):1028–1036.e13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Zhang Q, Illing R, Hui CK, Downey K, Carr D, Stearn M, et al. Bacteria in sputum of stable severe asthma and increased airway wall thickness. Respir Res. 2012;13:35.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Wood LG, Simpson JL, Hansbro PM, Gibson PG. Potentially pathogenic bacteria cultured from the sputum of stable asthmatics are associated with increased 8-isoprostane and airway neutrophilia. Free Radic Res. 2010;44(2):146–54.

    Article  CAS  PubMed  Google Scholar 

  45. Fitzpatrick AM, Holguin F, Teague WG, Brown LA. Alveolar macrophage phagocytosis is impaired in children with poorly controlled asthma. J Allergy Clin Immunol. 2008;121(6):1372–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Huynh ML, Malcolm KC, Kotaru C, Tilstra JA, Westcott JY, Fadok VA, et al. Defective apoptotic cell phagocytosis attenuates PGE2 and 15-HETE in severe asthma alveolar macrophages. Am J Respir Crit Care Med. 2005;172:972–9.

    Article  PubMed  Google Scholar 

  47. Nguyen LT, Lim S, Oates T, Chung KF. Increase in airway neutrophils after oral but not inhaled corticosteroid therapy in mild asthma. Respir Med. 2005;99(2):200–7.

    Article  PubMed  Google Scholar 

  48. Shannon J, Ernst P, Yamauchi Y, Olivenstein R, Lemiere C, Foley S, et al. Differences in airway cytokine profile in severe asthma compared to moderate asthma. Chest. 2008;133(2):420–6.

    Article  CAS  PubMed  Google Scholar 

  49. Al-Ramli W, Prefontaine D, Chouiali F, Martin JG, Olivenstein R, Lemiere C, et al. T(H)17-associated cytokines (IL-17A and IL-17F) in severe asthma. J Allergy Clin Immunol. 2009;123(5):1185–7.

    Article  CAS  PubMed  Google Scholar 

  50. 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 USA. 2007;104(40):15858–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009;180(5):388–95.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Peters MC, Mekonnen ZK, Yuan S, Bhakta NR, Woodruff PG, Fahy JV. Measures of gene expression in sputum cells can identify T2-high and T2-low subtypes of asthma. J Allergy Clin Immunol. 2014;133:388–94.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Adcock IM, Caramori G, Chung KF. New targets for drug development in asthma. Lancet. 2008;372(9643):1073–87.

    Article  CAS  PubMed  Google Scholar 

  54. Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012;18(5):673–83.

    Article  CAS  PubMed  Google Scholar 

  55. Chung KF. New treatments for severe treatment-resistant asthma: targeting the right patient. Lancet Respir Med. 2013;1:639–52.

    Article  CAS  PubMed  Google Scholar 

  56. 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.

    Article  CAS  PubMed  Google Scholar 

  57. Busse WW, Morgan WJ, Gergen PJ, Mitchell HE, Gern JE, Liu AH, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011;364(11):1005–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Hanania NA, Alpan O, Hamilos DL, Condemi JJ, Reyes-Rivera I, Zhu J, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med. 2011;154(9):573–82.

    Article  PubMed  Google Scholar 

  59. 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.

    Article  CAS  PubMed  Google Scholar 

  60. Flood-Page P, Swenson C, Faiferman I, Matthews J, Williams M, Brannick L, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med. 2007;176(11):1062–71.

    Article  CAS  PubMed  Google Scholar 

  61. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2011;184(10):1125–32.

    Article  CAS  PubMed  Google Scholar 

  63. 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.

    Article  CAS  PubMed  Google Scholar 

  64. 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.

    Article  CAS  PubMed  Google Scholar 

  65. Maes T, Joos GF, Brusselle GG. Targeting interleukin-4 in asthma: lost in translation? Am J Respir Cell Mol Biol. 2012;47(3):261–70.

    Article  CAS  PubMed  Google Scholar 

  66. Corren J, Busse W, Meltzer EO, Mansfield L, Bensch G, Fahrenholz J, et al. A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in patients with asthma. Am J Respir Crit Care Med. 2010;181(8):788–96.

    Article  CAS  PubMed  Google Scholar 

  67. Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368:2455–66.

    Article  CAS  PubMed  Google Scholar 

  68. 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.

    Article  CAS  PubMed  Google Scholar 

  69. Piper E, Brightling C, Niven R, Oh C, Faggioni R, Poon K, et al. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J. 2013;41(2):330–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Nair P, Gaga M, Zervas E, Alagha K, Hargreave FE, O’Byrne PM, et al. Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial. Clin Exp Allergy. 2012;42(7):1097–103.

    Article  CAS  PubMed  Google Scholar 

  71. Simpson JL, Powell H, Boyle MJ, Scott RJ, Gibson PG. Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am J Respir Crit Care Med. 2008;177(2):148–55.

    Article  CAS  PubMed  Google Scholar 

  72. 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.

    Article  PubMed  Google Scholar 

  73. Busse WW, Holgate S, Kerwin E, Chon Y, Feng J, Lin J, et al. Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma. Am J Respir Crit Care Med. 2013;188(11):1294–302.

    Article  CAS  PubMed  Google Scholar 

  74. Gibeon D, Chung KF. The investigation of severe asthma to define phenotypes. Clin Exp Allergy. 2012;42(5):678–92.

    Article  CAS  PubMed  Google Scholar 

  75. Chung KF. Inflammatory biomarkers in severe asthma. Curr Opin Pulmonary Med. 2012;18(1):35–41.

    Article  CAS  Google Scholar 

  76. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602–15.

    Article  CAS  PubMed  Google Scholar 

  77. Jia G, Erickson RW, Choy DF, Mosesova S, Wu LC, Solberg OD, et al. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol. 2012;130(3):647–654.e10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Kanemitsu Y, Matsumoto H, Izuhara K, Tohda Y, Kita H, Horiguchi T, et al. Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids. J Allergy Clin Immunol. 2013;132(2):305–312.e3.

    Article  CAS  PubMed  Google Scholar 

  79. Saito J, Zhang Q, Hui C, Macedo P, Gibeon D, Menzies-Gow A, et al. Sputum hydrogen sulfide as a novel biomarker of obstructive neutrophilic asthma. J Allergy Clin Immunol. 2013;131(1):232–234.e1-3.

    Article  CAS  PubMed  Google Scholar 

  80. Kabesch M, Adcock IM. Epigenetics in asthma and COPD. Biochimie. 2012;94(11):2231–41.

    Article  CAS  PubMed  Google Scholar 

  81. Tsitsiou E, Williams AE, Moschos SA, Patel K, Rossios C, Jiang X, et al. Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma. J Allergy Clin Immunol. 2012;129(1):95–103.

    Article  CAS  PubMed  Google Scholar 

  82. O’Neil SE, Sitkauskiene B, Babusyte A, Krisiukeniene A, Stravinskaite-Bieksiene K, Sakalauskas R, et al. Network analysis of quantitative proteomics on asthmatic bronchi: effects of inhaled glucocorticoid treatment. Respir Res. 2011;12:124.

    Article  PubMed Central  PubMed  Google Scholar 

  83. Hwang S, Son SW, Kim SC, Kim YJ, Jeong H, Lee D. A protein interaction network associated with asthma. J Theor Biol. 2008;252(4):722–31.

    Article  CAS  PubMed  Google Scholar 

  84. Auffray C, Adcock IM, Chung KF, Djukanovic R, Pison C, Sterk PJ. An integrative systems biology approach to understanding pulmonary diseases. Chest. 2010;137(6):1410–6.

    Article  PubMed  Google Scholar 

  85. Chen R, Snyder M. Systems biology: personalized medicine for the future? Curr Opin Pharmacol. 2012;12(5):623–8.

    Article  CAS  PubMed  Google Scholar 

  86. Landau DA, Carter SL, Stojanov P, McKenna A, Stevenson K, Lawrence MS, et al. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell. 2013;152(4):714–26.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Hamburg MA, Collins FS. The path to personalized medicine. N Engl J Med. 2010;363(4):301–4.

    Article  CAS  PubMed  Google Scholar 

  88. Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180(1):59–99.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The author has no potential conflicts of interest to declare in relation to the contents of this review. The author is funded through the Innovative Medicines Initiative in terms of the UBIOPRED project, which is looking into a systems biology approach to severe asthma. No funding was obtained for the writing of this manuscript.

Author information

Authors and Affiliations

  1. Experimental Studies, National Heart and Lung Institute, Imperial College London, Dovehouse St, London, SW3 6LY, UK

    Kian Fan Chung

  2. Royal Brompton NIHR Biomedical Research Unit, London, UK

    Kian Fan Chung

Authors
  1. Kian Fan Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kian Fan Chung.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chung, K.F. Defining Phenotypes in Asthma: A Step Towards Personalized Medicine. Drugs 74, 719–728 (2014). https://doi.org/10.1007/s40265-014-0213-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-014-0213-9

Keywords

Search

Navigation