Skip to main content

Advertisement

SpringerLink
Log in

Management of Severe Asthma Beyond the Guidelines

  • Asthma (V Ortega, Section Editor)
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Asthma is one of the most common chronic respiratory diseases worldwide, yet only a small percentage of patients are categorized as having severe disease. Severe asthmatics, however, are responsible for the largest burden of healthcare costs and lost productivity. Several recent guidelines have addressed disease pathogenesis and treatment modalities for these complex patients. Herein, we review the severe asthma guidelines, compare the existing guidelines, address key areas that are yet to be addressed in the guidelines, and discuss future directions for severe asthma research.

Recent Findings

This is a narrative review of the 2019 European Respiratory Society/American Thoracic Society (ERS/ATS) and Global Initiative for Asthma (GINA) guidelines that specifically address the diagnosis and management of severe asthma. The pathophysiological mechanisms that underlie severe asthma are reviewed, and novel therapies that target specific pathophysiological pathways in severe asthma are discussed in detail. Although the guidelines address the use of novel biological therapies for patients with T2-mediated disease, data comparing these agents remain sparse. This review addresses several areas that are topics beyond the guidelines and highlight key areas where future research is warranted.

Summary

This review provides a comprehensive overview of the current state of severe asthma treatment and discusses potential avenues for future research for this patient population.

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

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163–96.

    PubMed  PubMed Central  Google Scholar 

  2. Hekking PP, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015;135(4):896–902.

    PubMed  Google Scholar 

  3. Varsano S, Segev D, Shitrit D. Severe and non-severe asthma in the community: a large electronic database analysis. Respir Med. 2017;123:131–9.

    PubMed  Google Scholar 

  4. Nagase H, Adachi M, Matsunaga K, Yoshida A, Okoba T, Hayashi N, et al. Prevalence, disease burden, and treatment reality of patients with severe, uncontrolled asthma in Japan. Allergol Int. 2019;69(1):53–60.

    PubMed  Google Scholar 

  5. 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  Google Scholar 

  6. Van Ganse E, Laforest L, Pietri G, Boissel JP, Gormand F, Ben-Joseph R, et al. Persistent asthma: disease control, resource utilisation and direct costs. Eur Respir J. 2002;20(2):260–7.

    PubMed  Google Scholar 

  7. Accordini S, Bugiani M, Arossa W, Gerzeli S, Marinoni A, Olivieri M, et al. Poor control increases the economic cost of asthma. A multicentre population-based study. Int Arch Allergy Immunol. 2006;141(2):189–98.

    PubMed  Google Scholar 

  8. 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 

  9. 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.

  10. •• Holguin F, Cardet JC, Chung KF, Diver S, Ferreira DS, Fitzpatrick A, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020;55(1):1900588 ERS/ATS guideline of severe asthma in which the use of biological agents for the treatment of severe asthma is reviewed.

    PubMed  Google Scholar 

  11. •• Global Initiative for Asthma (GINA). Difficult-to-treat & severe asthma in adolescent and adult patients. Diagnosis and management (updated April 2019). 2019. GINA severe asthma guideline in which biological agents, macrolides, and long-acting muscarinic agents are reviewed.

  12. Schleich F, Brusselle G, Louis R, Vandenplas O, Michils A, Pilette C, et al. Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR). Respir Med. 2014;108(12):1723–32.

    CAS  PubMed  Google Scholar 

  13. Zhang JY, Wenzel SE. Tissue and BAL based biomarkers in asthma. Immunol Allergy Clin N Am. 2007;27(4):623–32 vi.

    Google Scholar 

  14. Price D, Wilson AM, Chisholm A, Rigazio A, Burden A, Thomas M, et al. Predicting frequent asthma exacerbations using blood eosinophil count and other patient data routinely available in clinical practice. J Asthma Allergy. 2016;9:1–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Price DB, Rigazio A, Campbell JD, Bleecker ER, Corrigan CJ, Thomas M, et al. Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respir Med. 2015;3(11):849–58.

    PubMed  Google Scholar 

  16. Hancox RJ, Pavord ID, Sears MR. Associations between blood eosinophils and decline in lung function among adults with and without asthma. Eur Respir J. 2018;51(4):1702536.

    PubMed  Google Scholar 

  17. Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56(2):219–33.

    PubMed  PubMed Central  Google Scholar 

  18. • Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716–25 Excellent overview of asthma phenotypes and of endotype-driven treatment of asthma.

    CAS  Google Scholar 

  19. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 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 

  21. 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 

  22. •• 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 Use of Mepolizumab in patients with severe eosinophilic asthma reduces asthma exacerbation rates.

    PubMed  Google Scholar 

  23. 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  Google Scholar 

  24. 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  Google Scholar 

  25. 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 

  26. 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 

  27. Soler M, Matz J, Townley R, Buhl R, O'Brien J, Fox H, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;18(2):254–61.

    CAS  PubMed  Google Scholar 

  28. 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(26):2455–66.

    CAS  PubMed  Google Scholar 

  29. 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 

  30. 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.

    Google Scholar 

  31. •• 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 Randomized controlled trial demonstrating that in patients with glucoticoid-dependent severe asthma, use of Dupilumab decreased oral corticosteroid dose, reduced rates of severe exacerbations, and increased FEV1.

    CAS  PubMed  Google Scholar 

  32. Bjermer L, Lemiere C, Maspero J, Weiss S, Zangrilli J, Germinaro M. Reslizumab for inadequately controlled asthma with elevated blood eosinophil levels: a randomized phase 3 study. Chest. 2016;150(4):789–98.

    PubMed  Google Scholar 

  33. Chupp GL, Bradford ES, Albers FC, Bratton DJ, Wang-Jairaj J, Nelsen LM, et al. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med. 2017;5(5):390–400.

    Google Scholar 

  34. Buhl R, Hanf G, Soler M, Bensch G, Wolfe J, Everhard F, et al. The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma. Eur Respir J. 2002;20(5):1088–94.

    CAS  PubMed  Google Scholar 

  35. Kawakami T, Blank U. From IgE to Omalizumab. J Immunol. 2016;197(11):4187–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2010 (update). 2010.

  37. Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, et al. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125(6):1344–53 e2.

    CAS  PubMed  Google Scholar 

  38. Menzies-Gow A, Flood-Page P, Sehmi R, Burman J, Hamid Q, Robinson DS, et al. Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics. J Allergy Clin Immunol. 2003;111(4):714–9.

    CAS  PubMed  Google Scholar 

  39. Egan RW, Athwal D, Bodmer MW, Carter JM, Chapman RW, Chou CC, et al. Effect of Sch 55700, a humanized monoclonal antibody to human interleukin-5, on eosinophilic responses and bronchial hyperreactivity. Arzneimittelforschung. 1999;49(9):779–90.

    CAS  PubMed  Google Scholar 

  40. Pham TH, Damera G, Newbold P, Ranade K. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016;111:21–9.

    PubMed  Google Scholar 

  41. Harb H, Chatila TA. Mechanisms of dupilumab. Clin Exp Allergy. 2020;50(1):5–14.

    CAS  PubMed  Google Scholar 

  42. Hamelmann E, Bernstein JA, Vandewalker M, Moroni-Zentgraf P, Verri D, Unseld A, et al. A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J. 2017;49(1):1601100.

    PubMed  PubMed Central  Google Scholar 

  43. • Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012;367(13):1198–207 Randomized controlled trial demonstrating that in patients with poorly controlled asthma despite the use of inhaled glucocorticoids and long acting bronchodilators, the use of long acting muscarinic agents increased time to the first exacerbation.

    CAS  PubMed  Google Scholar 

  44. Timmer W, Moroni-Zentgraf P, Cornelissen P, Unseld A, Pizzichini E, Buhl R. Once-daily tiotropium Respimat(R) 5 μg is an efficacious 24-h bronchodilator in adults with symptomatic asthma. Respir Med. 2015;109(3):329–38.

    PubMed  Google Scholar 

  45. 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 

  46. Gibson PG, Yang IA, Upham JW, Reynolds PN, Hodge S, James AL, et al. Efficacy of azithromycin in severe asthma from the AMAZES randomised trial. ERJ Open Res. 2019;5(4):00056–2019.

    PubMed  PubMed Central  Google Scholar 

  47. Pavord ID, Cox G, Thomson NC, Rubin AS, Corris PA, Niven RM, et al. Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma. Am J Respir Crit Care Med. 2007;176(12):1185–91.

    CAS  PubMed  Google Scholar 

  48. Castro M, Rubin AS, Laviolette M, Fiterman J, De Andrade LM, Shah PL, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med. 2010;181(2):116–24.

    PubMed  PubMed Central  Google Scholar 

  49. Bourdin A, Husereau D, Molinari N, Golam S, Siddiqui MK, Lindner L, et al. Matching-adjusted indirect comparison of benralizumab versus interleukin-5 inhibitors for the treatment of severe asthma: a systematic review. Eur Respir J. 2018;52(5):1801393.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Casale TB, Pacou M, Mesana L, Farge G, Sun SX, Castro M. Reslizumab compared with benralizumab in patients with eosinophilic asthma: a systematic literature review and network meta-analysis. J Allergy Clin Immunol Pract. 2019;7(1):122–30 e1.

    PubMed  Google Scholar 

  51. Edris A, De Feyter S, Maes T, Joos G, Lahousse L. Monoclonal antibodies in type 2 asthma: a systematic review and network meta-analysis. Respir Res. 2019;20(1):179.

    PubMed  PubMed Central  Google Scholar 

  52. Ramonell RP, Iftikhar IH. Effect of anti-IL5, anti-IL5R, anti-IL13 therapy on asthma exacerbations: a network meta-analysis. Lung. 2020;198(1):95–103.

    CAS  PubMed  Google Scholar 

  53. Walford HH, Doherty TA. Diagnosis and management of eosinophilic asthma: a US perspective. J Asthma Allergy. 2014;7:53–65.

    PubMed  PubMed Central  Google Scholar 

  54. Arron JR, Choy DF, Scheerens H, Matthews JG. Noninvasive biomarkers that predict treatment benefit from biologic therapies in asthma. Ann Am Thorac Soc. 2013;10(Suppl):S206–13.

    PubMed  Google Scholar 

  55. Pavord ID, Afzalnia S, Menzies-Gow A, Heaney LG. The current and future role of biomarkers in type 2 cytokine-mediated asthma management. Clin Exp Allergy. 2017;47(2):148–60.

    CAS  PubMed  Google Scholar 

  56. Fowler SJ, Tavernier G, Niven R. High blood eosinophil counts predict sputum eosinophilia in patients with severe asthma. J Allergy Clin Immunol. 2015;135(3):822–4 e2.

    PubMed  Google Scholar 

  57. Gao J, Wu F. Association between fractional exhaled nitric oxide, sputum induction and peripheral blood eosinophil in uncontrolled asthma. Allergy, Asthma Clin Immunol. 2018;14:21.

    Google Scholar 

  58. Wagener AH, de Nijs SB, Lutter R, Sousa AR, Weersink EJ, Bel EH, et al. External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma. Thorax. 2015;70(2):115–20.

    CAS  PubMed  Google Scholar 

  59. Bleecker ER, Wechsler ME, FitzGerald JM, Menzies-Gow A, Wu Y, Hirsch I, et al. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018;52(4):1800936.

    PubMed  PubMed Central  Google Scholar 

  60. Castro M, Wenzel SE, Bleecker ER, Pizzichini E, Kuna P, Busse WW, et al. Benralizumab, an anti-interleukin 5 receptor alpha monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med. 2014;2(11):879–90.

    CAS  Google Scholar 

  61. Korevaar DA, Westerhof GA, Wang J, Cohen JF, Spijker R, Sterk PJ, et al. Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis. Lancet Respir Med. 2015;3(4):290–300.

    PubMed  Google Scholar 

  62. Hastie AT, Moore WC, Li H, Rector BM, Ortega VE, Pascual RM, et al. Biomarker surrogates do not accurately predict sputum eosinophil and neutrophil percentages in asthmatic subjects. J Allergy Clin Immunol. 2013;132(1):72–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Prazma CM, Bel EH, Price RG, Bradford ES, Albers FC, Yancey SW. Oral corticosteroid dose changes and impact on peripheral blood eosinophil counts in patients with severe eosinophilic asthma: a post hoc analysis. Respir Res. 2019;20(1):83.

    PubMed  PubMed Central  Google Scholar 

  64. Durrington HJ, Gioan-Tavernier GO, Maidstone RJ, Krakowiak K, Loudon ASI, Blaikley JF, et al. Time of day affects eosinophil biomarkers in asthma: implications for diagnosis and treatment. Am J Respir Crit Care Med. 2018;198:1578–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Shrimanker R, Keene O, Hynes G, Wenzel S, Yancey S, Pavord ID. Prognostic and predictive value of blood eosinophil count, fractional exhaled nitric oxide, and their combination in severe asthma: a post hoc analysis. Am J Respir Crit Care Med. 2019;200(10):1308–12.

    CAS  PubMed  Google Scholar 

  66. 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):647–54 e10.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Tajiri T, Matsumoto H, Gon Y, Ito R, Hashimoto S, Izuhara K, et al. Utility of serum periostin and free IgE levels in evaluating responsiveness to omalizumab in patients with severe asthma. Allergy. 2016;71(10):1472–9.

    CAS  PubMed  Google Scholar 

  68. 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 

  69. 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 

  70. Izuhara K, Ohta S, Ono J. Using periostin as a biomarker in the treatment of asthma. Allergy, Asthma Immunol Res. 2016;8(6):491–8.

    CAS  Google Scholar 

  71. Pandey G, Pandey OP, Rogers AJ, Ahsen ME, Hoffman GE, Raby BA, et al. A nasal brush-based classifier of asthma identified by machine learning analysis of nasal RNA sequence data. Sci Rep. 2018;8(1):8826.

    PubMed  PubMed Central  Google Scholar 

  72. • 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 Gene expression study of airway epithelial cells from asthmatic subjects demonstrates that IL-13 increased expression of CLCA1, periostin, and serpinB2, an effect that was suppressed by corticosteroids.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Peters MC, Mekonnen ZK, Yuan S, Bhakta NR, Woodruff PG, Fahy JV. Measures of gene expression in sputum cells can identify TH2-high and TH2-low subtypes of asthma. J Allergy Clin Immunol. 2014;133(2):388–94.

    CAS  PubMed  Google Scholar 

  74. Boudewijn IM, Lan A, Faiz A, Cox CA, Brouwer S, Schokker S, et al. Nasal gene expression changes with inhaled corticosteroid treatment in asthma. Allergy. 2019;75(1):191–4.

    PubMed  Google Scholar 

  75. Hochhaus G, Brookman L, Fox H, Johnson C, Matthews J, Ren S, et al. Pharmacodynamics of omalizumab: implications for optimised dosing strategies and clinical efficacy in the treatment of allergic asthma. Curr Med Res Opin. 2003;19(6):491–8.

    CAS  PubMed  Google Scholar 

  76. 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  Google Scholar 

  77. Perez de Llano LA, Cosio BG, Domingo C, Urrutia I, Bobolea I, Valero A, et al. Efficacy and safety of reslizumab in patients with severe asthma with inadequate response to omalizumab: a multicenter, open-label pilot study. J Allergy Clin Immunol Pract. 2019;7(7):2277–83 e2.

    PubMed  Google Scholar 

  78. Chapman KR, Albers FC, Chipps B, Munoz X, Devouassoux G, Bergna M, et al. The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma. Allergy. 2019;74(9):1716–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Kurosawa M, Sutoh E. Severe uncontrolled eosinophilic asthma, which responded to benralizumab after failure to respond to mepolizumab. Ann Allergy Asthma Immunol. 2019;122(4):431–3.

    PubMed  Google Scholar 

  80. Ortega G, Tongchinsub P, Carr T. Combination biologic therapy for severe persistent asthma. Ann Allergy Asthma Immunol. 2019;123(3):309–11.

    PubMed  Google Scholar 

  81. Fitzpatrick AM, Chipps BE, Holguin F, Woodruff PG. T2-"low" Asthma: overview and management strategies. J Allergy Clin Immunol Pract. 2020;8(2):452–63.

    PubMed  Google Scholar 

  82. 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):153–60 60 e1–9.

    CAS  PubMed  Google Scholar 

  83. Kuo CS, Pavlidis S, Loza M, Baribaud F, Rowe A, Pandis I, et al. T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED. Eur Respir J. 2017;49(2):1602135.

    PubMed  Google Scholar 

  84. National Asthma E, Prevention P. Expert panel report 3 (EPR-3): guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol. 2007;120(5 Suppl):S94–138.

    Google Scholar 

  85. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention, 2019. . 2019.

  86. British Thoracic Society (BTS) SIGNS. British guideline on the management of asthma. 2019.

  87. National Institute for Health Care and Excellence (NICE). Asthma: diagnosis, monitoring and chronic asthma management. 2020.

  88. Papadopoulos NG, Arakawa H, Carlsen KH, Custovic A, Gern J, Lemanske R, et al. International consensus on (ICON) pediatric asthma. Allergy. 2012;67(8):976–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Szefler SJ, Murphy K, Harper T 3rd, Boner A, Laki I, Engel M, et al. A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma. J Allergy Clin Immunol. 2017;140(5):1277–87.

    CAS  PubMed  Google Scholar 

  90. Hamelmann E, Bateman ED, Vogelberg C, Szefler SJ, Vandewalker M, Moroni-Zentgraf P, et al. Tiotropium add-on therapy in adolescents with moderate asthma: a 1-year randomized controlled trial. J Allergy Clin Immunol. 2016;138(2):441–50 e8.

    CAS  PubMed  Google Scholar 

  91. Vrijlandt E, El Azzi G, Vandewalker M, Rupp N, Harper T, Graham L, et al. Safety and efficacy of tiotropium in children aged 1-5 years with persistent asthmatic symptoms: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2018;6(2):127–37.

    CAS  PubMed  Google Scholar 

  92. Matsuno O, Ono E, Takenaka R, Okubo T, Takatani K, Ueno T, et al. Asthma and sinusitis: association and implication. Int Arch Allergy Immunol. 2008;147(1):52–8.

    PubMed  Google Scholar 

  93. Jarvis D, Newson R, Lotvall J, Hastan D, Tomassen P, Keil T, et al. Asthma in adults and its association with chronic rhinosinusitis: the GA2LEN survey in Europe. Allergy. 2012;67(1):91–8.

    CAS  PubMed  Google Scholar 

  94. Bresciani M, Paradis L, Des Roches A, Vernhet H, Vachier I, Godard P, et al. Rhinosinusitis in severe asthma. J Allergy Clin Immunol. 2001;107(1):73–80.

    CAS  PubMed  Google Scholar 

  95. Lin DC, Chandra RK, Tan BK, Zirkle W, Conley DB, Grammer LC, et al. Association between severity of asthma and degree of chronic rhinosinusitis. Am J Rhinol Allergy. 2011;25(4):205–8.

    PubMed  PubMed Central  Google Scholar 

  96. Ek A, Middelveld RJ, Bertilsson H, Bjerg A, Ekerljung L, Malinovschi A, et al. Chronic rhinosinusitis in asthma is a negative predictor of quality of life: results from the Swedish GA(2)LEN survey. Allergy. 2013;68(10):1314–21.

    CAS  PubMed  Google Scholar 

  97. Vashishta R, Soler ZM, Nguyen SA, Schlosser RJ. A systematic review and meta-analysis of asthma outcomes following endoscopic sinus surgery for chronic rhinosinusitis. Int Forum Allergy Rhinol. 2013;3(10):788–94.

    PubMed  Google Scholar 

  98. Ragab S, Scadding GK, Lund VJ, Saleh H. Treatment of chronic rhinosinusitis and its effects on asthma. Eur Respir J. 2006;28(1):68–74.

    CAS  PubMed  Google Scholar 

  99. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K, Kramper M, et al. Clinical practice guideline (update): adult sinusitis. Otolaryngol Head Neck Surg. 2015;152(2 Suppl):S1–S39.

    PubMed  Google Scholar 

  100. Australia’s National Asthma Council. Australian asthma handbook. 2019.

    Google Scholar 

  101. Mensah GA, Kiley JP, Gibbons GH. Generating evidence to inform an update of asthma clinical practice guidelines: perspectives from the National Heart, Lung, and Blood Institute. J Allergy Clin Immunol. 2018;142(3):744–8.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Mail Stop C272, 12700 E. 19th Avenue, Aurora, CO, 80045, USA

    Anne E. Reihman, Fernando Holguin & Sunita Sharma

Authors
  1. Anne E. Reihman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fernando Holguin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sunita Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sunita Sharma.

Ethics declarations

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Asthma

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reihman, A.E., Holguin, F. & Sharma, S. Management of Severe Asthma Beyond the Guidelines. Curr Allergy Asthma Rep 20, 47 (2020). https://doi.org/10.1007/s11882-020-00940-6

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11882-020-00940-6

Keywords

Search

Navigation