Moving toward consensus on diagnosis and management of severe asthma in adults

References

• Martinez FD, Vercelli D. Asthma. Lancet 2013;382:1360-72
   PubMed Web of Science ®Google Scholar
• The Global Asthma Report 2014. Auckland, New Zealand: Global Asthma Network, 2014. Available at: http://www.globalasthmareport.org/resources/Global_Asthma_Report_2014.pdf [Last Accessed 3 January 2017]
   Google Scholar
• Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014;43:343-73
   PubMed Web of Science ®Google Scholar
• Bush A, Zar HJ. WHO universal definition of severe asthma. Curr Opin Allergy Clin Immunol 2011;11:115-21
   PubMed Web of Science ®Google Scholar
• Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2016. Available at: http://www.ginasthma.org/ [Last accessed 20 April 2017]
   Google Scholar
• Holgate ST, Polosa R. The mechanisms, diagnosis, and management of severe asthma in adults. Lancet 2006;368:780-93
   PubMed Web of Science ®Google Scholar
• Peters SP, Ferguson G, Deniz Y, et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med 2006;100:1139-51
   PubMed Web of Science ®Google Scholar
• Bel EH. Clinical phenotypes of asthma. Curr Opin Pulm Med 2004;10:44-50
   PubMed Web of Science ®Google Scholar
• Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet 2006;368:804-13
   PubMed Web of Science ®Google Scholar
• Custovic A, Johnston SL, Pavord I, et al. EAACI position statement on asthma exacerbations and severe asthma. Allergy 2013;68:1520-31
   PubMed Web of Science ®Google Scholar
• Del Giacco SR, Bakirtas A, Bel E, et al. Allergy in severe asthma. Allergy 2017;72:207-20
   PubMed Web of Science ®Google Scholar
• Cisneros Serrano C, Melero Moreno C, Almonacid Sánchez C, et al. Guidelines for severe uncontrolled asthma. Arch Bronconeumol 2015;51:235-46
   PubMed Web of Science ®Google Scholar
• Desai M, Oppenheimer J. Elucidating asthma phenotypes and endotypes: progress towards personalized medicine. Ann Allergy Asthma Immunol 2016;116:394-401
   PubMed Web of Science ®Google Scholar
• Adcock IM, Caramori G, Chung KF. New targets for drug development in asthma. Lancet 2008;372:1073-87
   PubMed Web of Science ®Google Scholar
• van Buul AR, Taube C. Treatment of severe asthma: entering the era of targeted therapy. Expert Opin Biol Ther 2015;15:1713-25
   PubMed Web of Science ®Google Scholar
• Gupta S, Paolucci E, Kaplan A, et al. Contemporaneous international asthma guidelines present differing recommendations: an analysis. Can Respir J 2016;2016:3085065
   PubMedGoogle Scholar
• Chung KF, Godard P, Adelroth E, 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. Eur Respir J 1999;13:1198-208
   PubMed Web of Science ®Google Scholar
• O’Byrne PM, Naji N, Gauvreau GM. Severe asthma: future treatments. Clin Exp Allergy 2012;42:706-11
   PubMed Web of Science ®Google Scholar
• Haselkorn T, Borish L, Miller DP, et al. High prevalence of skin test positivity in severe or difficult-to-treat asthma. J Asthma 2006;43:745-52
   PubMed Web of Science ®Google Scholar
• Rabe KF, Adachi M, Lai CK, et al. Worldwide severity and control of asthma in children and adults: the global asthma insights and reality surveys. J Allergy Clin Immunol 2004;114:40-7
   PubMed Web of Science ®Google Scholar
• Liard R, Leynaert B, Zureik M, et al. Using Global Initiative for Asthma guidelines to assess asthma severity in populations. Eur Respir J 2000;16:615-20
   PubMed Web of Science ®Google Scholar
• Braido F. Failure in asthma control: reasons and consequences. Scientifica (Cairo) 2013;2013:549252
   PubMedGoogle Scholar
• Neffen H, Fritscher C, Schacht FC, et al. Asthma control in Latin America: the Asthma Insights and Reality in Latin America (AIRLA) survey. Rev Panam Salud Publica 2005;17:191-7
   PubMed Web of Science ®Google Scholar
• Zainudin BM, Lai CK, Soriano JB, et al. Asthma Insights and Reality in Asia-Pacific (AIRIAP) Steering Committee. Asthma control in adults in Asia-Pacific. Respirology 2005;10:579-86
   PubMed Web of Science ®Google Scholar
• Vermeire PA, Rabe KF, Soriano JB, et al. Asthma control and differences in management practices across seven European countries. Respir Med 2002;96:142-9
   PubMed Web of Science ®Google Scholar
• Adams RJ, Fuhlbrigge A, Guilbert T, et al. Inadequate use of asthma medication in the United States: results of the Asthma in America national population survey. J Allergy Clin Immunol 2002;110:58-64
   PubMed Web of Science ®Google Scholar
• Maspero JF, Jardim JR, Aranda A, et al. Insights, attitudes, and perceptions about asthma and its treatment: findings from a multinational survey of patients from Latin America. World Allergy Organ J 2013;6:19
   PubMedGoogle Scholar
• The ENFUMOSA Study Group. The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma. Eur Respir J 2003;22:470-7
   PubMed Web of Science ®Google Scholar
• Barranco P, Pérez-Francés C, Quirce S, et al. Consensus document on the diagnosis of severe uncontrolled asthma. J Investig Allergol Clin Immunol 2012;22:460-75
   PubMed Web of Science ®Google Scholar
• Rodrigo GJ, Plaza V, Neffen H, et al. Relationship between the characteristics of hospitalised acute asthma patients and the severity of their asthma. A case-control study. Allergol Immunopathol (Madr) 2009;37:225-9
   PubMed Web of Science ®Google Scholar
• Hankin CS, Cox L, Bronstone A, Wang Z. Allergy immunotherapy: reduced health care costs in adults and children with allergic rhinitis. J Allergy Clin Immunol 2013;131:1084-91
   PubMed Web of Science ®Google Scholar
• Siroux V, Boudier A, Anto JM, et al. Quality-of-life and asthma-severity in general population asthmatics: results of the ECRHS II study. Allergy 2008;63:547-54
   PubMed Web of Science ®Google Scholar
• Bisaccioni C, Aun MV, Cajuela E, et al. Comorbidities in severe asthma: frequency of rhinitis, nasal polyposis, gastroesophageal reflux disease, vocal cord dysfunction and bronchiectasis. Clinics (Sao Paulo). 2009;64:769-73
   PubMed Web of Science ®Google Scholar
• Moore WC, Bleecker ER, Curran-Everett D, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol. 2007;119:405-13
   PubMed Web of Science ®Google Scholar
• Gaga M, Papageorgiou N, Yiourgioti G, et al. Risk factors and characteristics associated with severe and difficult to treat asthma phenotype: an analysis of the ENFUMOSA group of patients based on the ECRHS questionnaire. Clin Exp Allergy. 2005;35:954-9
   PubMed Web of Science ®Google Scholar
• Burrows B, Martinez FD, Halonen M, et al. Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med. 1989;320:271-7
   PubMed Web of Science ®Google Scholar
• Bousquet J, Chanez P, Lacoste JY, et al. Eosinophilic inflammation in asthma. N Engl J Med 1990;323:1033-9
   PubMed Web of Science ®Google Scholar
• Fahy JV. Type 2 inflammation in asthma—present in most, absent in many. Nat Rev Immunol. 2015;15:57-65
   PubMed Web of Science ®Google Scholar
• Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med 2012;18:693-704
   PubMed Web of Science ®Google Scholar
• Samitas K, Lötvall J, Bossios A. B cells: from early development to regulating allergic diseases. Arch Immunol Ther Exp 2010;58:209-25
   PubMed Web of Science ®Google Scholar
• Gould HJ, Sutton BJ. IgE in allergy and asthma today. Nat Rev Immunol 2008;8:205-17
   PubMed Web of Science ®Google Scholar
• Oettgen HC, Geha RS. IgE in asthma and atopy: cellular and molecular connections. J Clin Invest 1999;104:829-35
   PubMed Web of Science ®Google Scholar
• Morjaria JB, Gnanakumaran G, Babu KS. Anti-IgE in allergic asthma and rhinitis: an update. Expert Opin Biol Ther 2007;7:1739-47
   PubMed Web of Science ®Google Scholar
• Stone KD, Prussin C, Metcalfe DD. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 2010;125(Suppl 2):S73-S80
   PubMed Web of Science ®Google Scholar
• Murdoch JR, Lloyd CM. Chronic inflammation and asthma. Mutat Res 2010;690:24-39
   PubMed Web of Science ®Google Scholar
• Gill MA, Palucka AK, Barton T, et al. Mobilization of plasmacytoid and myeloid dendritic cells to mucosal sites in children with respiratory syncytial virus and other viral respiratory infections. J Infect Dis 2005;191:1105-15
   PubMed Web of Science ®Google Scholar
• Colonna M, Trinchieri G, Liu YJ. Plasmacytoid dendritic cells in immunity. Nat Immunol 2004;5:1219-26
   PubMed Web of Science ®Google Scholar
• Gill MA, Bajwa G, George TA, et al. Counterregulation between the FceRI pathway and antiviral responses in human plasmacytoid dendritic cells. J Immunol 2010;184:5999-6006
   PubMed Web of Science ®Google Scholar
• Schroeder JT, Bieneman AP, Xiao H, et al. TLR9- and FceRI-mediated responses oppose one another in plasmacytoid dendritic cells by down-regulating receptor expression. J Immunol 2005;175:5724-31
   PubMed Web of Science ®Google Scholar
• Durrani SR, Montville DJ, Pratt AS, et al. Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children. J Allergy Clin Immunol 2012;130:489-95
   PubMed Web of Science ®Google Scholar
• Cohn L, Elias JA, Chupp GL. Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol 2004;22:789-815
   PubMed Web of Science ®Google Scholar
• Doherty T, Broide D. Cytokines and growth factors in airway remodeling in asthma. Curr Opin Immunol 2007;19:676-80
   PubMed Web of Science ®Google Scholar
• Campbell AM, Vachier I, Chanez P, et al. Expression of the high-affinity receptor for IgE on bronchial epithelial cells of asthmatics. Am J Respir Cell Mol Biol 1998;19:92-7
   PubMed Web of Science ®Google Scholar
• Gounni AS, Wellemans V, Yang J, et al. Human airway smooth muscle cells express the high affinity receptor for IgE (FcεRI): a critical role of FcεRI in human airway smooth muscle cell function. J Immunol 2005;175:2613-21
   PubMed Web of Science ®Google Scholar
• Roth M, Zhong J, Zumkeller C, et al. The role of IgE-receptors in IgE-dependent airway smooth muscle cell remodelling. PLoS One 2013;8:e56015
   PubMed Web of Science ®Google Scholar
• Roth M, Tamm M. The effects of omalizumab on IgE-induced cytokine synthesis by asthmatic airway smooth muscle cells. Ann Allergy Asthma Immunol 2010;104:152-60
   PubMed Web of Science ®Google Scholar
• Kay AB, Phipps S, Robinson DS. A role for eosinophils in airway remodelling in asthma. Trends Immunol 2004;25:477-82
   PubMed Web of Science ®Google Scholar
• Menzies-Gow A, Flood-Page P, Sehmi R, 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;111:714-19
   PubMed Web of Science ®Google Scholar
• Munitz A, Brandt EB, Mingler M, et al. Distinct roles for IL-13 and IL-4 via IL-13 receptor-1 and the type II IL-4 receptor in asthma pathogenesis. Proc Natl Acad Sci USA 2008;105:7240-5
   PubMed Web of Science ®Google Scholar
• Walsh ER, Stokes K, August A. The role of eosinophils in allergic airway inflammation. Discov Med 2010;9:357-62
   PubMed Web of Science ®Google Scholar
• Xue L, Barrow A, Pettipher R. Novel function of CRTH2 in preventing apoptosis of human Th2 cells through activation of the phosphatidylinositol 3-kinase pathway. J Immunol 2009;182:7580-6
   PubMed Web of Science ®Google Scholar
• Li W, Gao P, Zhi Y, et al. Periostin: its role in asthma and its potential as a diagnostic or therapeutic target. Respir Res 2015;16:57
   PubMed Web of Science ®Google Scholar
• Merriam-Webster’s dictionary (Merriam-Webster Inc.) 2016. Available at: http://www.merriam-webster.com/dictionary/phenotype [Last accessed 24 October 2016]
   Google Scholar
• Walker C, Bode E, Boer L, et al. Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis 1992;146:109-15
   PubMed Web of Science ®Google Scholar
• Rackemann F. A working classification of asthma. Am J Med 1947;3:601-6
   PubMed Web of Science ®Google Scholar
• Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 2012;18:716-25
   PubMed Web of Science ®Google Scholar
• Romanet-Manent S, Charpin D, Magnan A, et al. Allergic vs nonallergic asthma: what makes the difference? Allergy 2002;57:607-13
   PubMed Web of Science ®Google Scholar
• ten Brinke A, Zwinderman AH, Sterk PJ, et al. “Refractory” eosinophilic airway inflammation in severe asthma: effect of parenteral corticosteroids. Am J Respir Crit Care Med 2004;170:601-5
   PubMed Web of Science ®Google Scholar
• Moore WC, Meyers DA, Wenzel SE, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 2010;181:315-23
   PubMed Web of Science ®Google Scholar
• Tan DJ, Walters EH, Perret JL, et al. Clinical and functional differences between early-onset and late-onset adult asthma: a population-based Tasmanian Longitudinal Health Study. Thorax 2016;71:981-7
   PubMed Web of Science ®Google Scholar
• Tan DJ, Walters EH, Perret JL, et al. Age-of-asthma onset as a determinant of different asthma phenotypes in adults: a systematic review and meta-analysis of the literature. Expert Rev Respir Med 2015;9:109-23
   PubMed Web of Science ®Google Scholar
• Lötvall J, Akdis CA, Bacharier LB, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 2011;127:355-60
   PubMed Web of Science ®Google Scholar
• Siroux V, Garcia-Aymerich J. The investigation of asthma phenotypes. Curr Opin Allergy Clin Immunol 2011;11:393-9
   PubMed Web of Science ®Google Scholar
• Agache I, Akdis C, Jutel M, et al. Untangling asthma phenotypes and endotypes. Allergy 2012;67:835-46
   PubMed Web of Science ®Google Scholar
• Siroux V, Basagaña X, Boudier A, et al. Identifying adult asthma phenotypes using a clustering approach. Eur Respir J 2011;38:310-17
   PubMed Web of Science ®Google Scholar
• Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008;31:143-78
   PubMed Web of Science ®Google Scholar
• Lucas AE, Smeenk FW, Smeele IJ, et al. Overtreatment with inhaled corticosteroids and diagnostic problems in primary care patients, an exploratory study. Fam Pract 2008;25:86-91
   PubMed Web of Science ®Google Scholar
• Tilles SA. Differential diagnosis of adult asthma. Med Clin North Am 2006;90:61-76
   PubMed Web of Science ®Google Scholar
• Moore WC, Bleecker ER, Curran-Everett D, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol 2007:405-13
   PubMed Web of Science ®Google Scholar
• Skloot GS, Busse PJ, Braman SS, et al. An official American Thoracic Society workshop report: evaluation and management of asthma in the elderly. Ann Am Thorac Soc 2016;13(11):2064-77
   PubMed Web of Science ®Google Scholar
• Majd S, Apps LD, Hudson N, et al. Protocol for a feasibility study to inform the development of a multicentre randomised controlled trial of asthma-tailored pulmonary rehabilitation versus usual care for individuals with severe asthma. BMJ Open 2016;6:e010574
   PubMed Web of Science ®Google Scholar
• Boulet LP, Boulay ME. Asthma-related comorbidities. Expert Rev Respir Med 2011;5:377-93
   PubMed Web of Science ®Google Scholar
• Chipps BE, Zeiger RS, Borish L, et al. Key findings and clinical implications from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. J Allergy Clin Immunol 2012;130:332-42
   PubMed Web of Science ®Google Scholar
• Shaw DE, Sousa AR, Fowler SJ, et al. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. Eur Respir J 2015;46:1308-21
   PubMed Web of Science ®Google Scholar
• Schleich F, Brusselle G, Louis R, et al. Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR). Respir Med 2014;108:1723-32
   PubMed Web of Science ®Google Scholar
• Kankaanranta H, Kauppi P, Tuomisto LE, et al. Emerging comorbidities in adult asthma: risks, clinical associations, and mechanisms. Mediators Inflamm 2016;2016:690628690628
   Google Scholar
• Luján M, Gallardo X, Amengual MJ, et al. Prevalence of bronchiectasis in asthma according to oral steroid requirement: influence of immunoglobulin levels. Biomed Res Int 2013;2013:109219
   PubMed Web of Science ®Google Scholar
• Baiardini I, Sicuro F, Balbi F, et al. Psychological aspects in asthma: do psychological factors affect asthma management? Asthma Res Pract 2015;1:7
   PubMedGoogle Scholar
• Ledford DK, Lockey RF. Asthma and comorbidities. Curr Opin Allergy Clin Immunol 2013;13:78-86
   PubMed Web of Science ®Google Scholar
• Tay TR, Radhakrishna N, Hore-Lacy F, et al. Comorbidities in difficult asthma are independent risk factors for frequent exacerbations, poor control and diminished quality of life. Respirology 2016;21:1384-90
   PubMed Web of Science ®Google Scholar
• Chen W, Lynd LD, FitzGerald JM, et al. Excess medical costs in patients with asthma and the role of comorbidity. Eur Respir J 2016;48:1584-92
   PubMed Web of Science ®Google Scholar
• Cazzola MM, Segreti A, Calzetta L, et al. Comorbidities of asthma: current knowledge and future research needs. Curr Opin Pulm Med 2013;19:36-41
   PubMed Web of Science ®Google Scholar
• Wark PA, Hew M, Maltby S, et al. Diagnosis and investigation in the severe asthma clinic. Expert Rev Respir Med 2016;10:491-503
   PubMed Web of Science ®Google Scholar
• van der Meer AN, Pasma H, Kempenaar-Okkema W, et al. A 1-day visit in a severe asthma centre: effect on asthma control, quality of life and healthcare use. Eur Respir J 2016;48:726-33
   PubMed Web of Science ®Google Scholar
• Radhakrishna N, Tay TR, Hore-Lacy F, et al. Validated questionnaires heighten detection of difficult asthma comorbidities. J Asthma 2017;54:294-9
   PubMed Web of Science ®Google Scholar
• Fahy JV. Eosinophilic and neutrophilic inflammation in asthma: insights from clinical studies. Proc Am Thorac Soc 2009;6:256-9
   PubMedGoogle Scholar
• Gemicioglu B, Musellim B, Dogan I, et al. Fractional exhaled nitric oxide (FeNo) in different asthma phenotypes. Allergy Rhinol (Providence) 2014;5:157-61
   PubMedGoogle Scholar
• Westerhof GA, Korevaar DA, Amelink M, et al. Biomarkers to identify sputum eosinophilia in different adult asthma phenotypes. Eur Respir J 2015;46:688-96
   PubMed Web of Science ®Google Scholar
• Gibeon D, Heaney LG, Brightling CE, et al. Dedicated severe asthma services improve health-care use and quality of life. Chest 2015;148:870-6
   PubMed Web of Science ®Google Scholar
• Löwhagen O. Diagnosis of asthma – a new approach. Allergy 2012;67:713-17
   PubMed Web of Science ®Google Scholar
• Robinson DS, Campbell DA, Durham SR, et al. Systematic assessment of difficult-to-treat asthma. Eur Respir J 2003;22:478-83
   PubMed Web of Science ®Google Scholar
• Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, November 1986. Am Rev Respir Dis 1987;136:225-44
   PubMed Web of Science ®Google Scholar
• Antunes J, Fernandes A, Borrego LM, et al. Cystic fibrosis, atopy, asthma and ABPA. Allergol Immunopathol (Madr) 2010;38:278-84
   PubMed Web of Science ®Google Scholar
• McCormack MC, Enright PL. Making the diagnosis of asthma. Respir Care 2008;53:583-90
   PubMed Web of Science ®Google Scholar
• Chanez P, Wenzel SE, Anderson GP, et al. Severe asthma in adults: what are the important questions? J Allergy Clin Immunol 2007;119:1337-48
   PubMed Web of Science ®Google Scholar
• Gamble J, Stevenson M, Heaney LG. A study of a multi-level intervention to improve non-adherence in difficult to control asthma. Respir Med 2011;105:1308-15
   PubMed Web of Science ®Google Scholar
• Agusti A, Bel E, Thomas M, et al. Treatable traits: toward precision medicine of chronic airway diseases. Eur Respir J 2016;47:410-19
   PubMed Web of Science ®Google Scholar
• Bousquet J, Mantzouranis E, Cruz AA, et al. Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organization Consultation on Severe Asthma. J Allergy Clin Immunol 2010;126:926-38
   PubMed Web of Science ®Google Scholar
• Lommatzsch M, Virchow JC. Severe asthma: definition, diagnosis and treatment. Dtsch Arztebl Int 2014;111:847-55
   PubMed Web of Science ®Google Scholar
• Heaney LG, Conway E, Kelly C, et al. Predictors of therapy resistant asthma: outcome of a systematic evaluation protocol. Thorax 2003;58:561-66
   PubMed Web of Science ®Google Scholar
• National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma – summary report 2007. J Allergy Clin Immunol 2007;120(5Suppl):S94-S138
   Web of Science ®Google Scholar
• Ohta K, Ichinose M, Nagase H, et al. Japanese guideline for adult asthma 2014. Allergol Int 2014;63:293-333
   PubMed Web of Science ®Google Scholar
• Domingo C, Sans-Torres J, Solà J, et al. Effectiveness and efficiency of a specialized unit in the care of patients with chronic obstructive pulmonary disease and respiratory insufficiency. Arch Bronconeumol 2006;42:104-12
   PubMed Web of Science ®Google Scholar
• Weiss ST. New approaches to personalized medicine for asthma: where are we? J Allergy Clin Immunol 2012;129:327-34
   PubMed Web of Science ®Google Scholar
• Trejo Bittar HE, Yousem SA, Wenzel SE. Pathobiology of severe asthma. Ann Rev Pathol 2015;10:511-45
   PubMed Web of Science ®Google Scholar
• Darveaux J, Busse WW. Biologics in asthma – the next step toward personalized treatment. J Allergy Clin Immunol Pract 2015;3:152-60
   PubMed Web of Science ®Google Scholar
• AstraZeneca’s new asthma drug to take on GSK, Teva and Novartis after clearing clinical hurdles. 5 September 2016. Available at: http://www.telegraph.co.uk/business/2016/09/05/astrazenecas-new-asthma-drug-to-take-on-gsk-teva-and-novartis-af/ [Last accessed 9 August 2017]
   Google Scholar
• Busse W, Corren J, Lanier BQ, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J. Allergy Clin Immunol 2001;108:184-90
   PubMed Web of Science ®Google Scholar
• Normansell R, Walker S, Milan SJ, et al. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev 2014;1:CD003559
   PubMed Web of Science ®Google Scholar
• Domingo C. Omalizumab for severe asthma: efficacy beyond the atopic patient? Drugs 2014;74:521-33
   PubMed Web of Science ®Google Scholar
• Humbert M, Beasley R, Ayres 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;60:309-16
   PubMed Web of Science ®Google Scholar
• Hanania NA, Alpan O, Hamilos DL, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med 2011;154:573-82
   PubMed Web of Science ®Google Scholar
• Domingo C, Moreno A, José Amengual M, et al. Omalizumab in the management of oral corticosteroid-dependent IGE-mediated asthma patients. Curr Med Res Opin 2011;27:45-53
   PubMed Web of Science ®Google Scholar
• Hanania NA, Wenzel S, Rosén K, 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;187:804-11
   PubMed Web of Science ®Google Scholar
• de Groot JC, Ten Brinke A, Bel EH. Management of the patient with eosinophilic asthma: a new era begins. ERJ Open Res 2015;1:pii00024-2015
   Google Scholar
• Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012;380:651-9
   PubMed Web of Science ®Google Scholar
• Castro M, Mathur S, Hargreave F, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med 2011;184:1125-32
   PubMed Web of Science ®Google Scholar
• Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014;371:1198-207
   PubMed Web of Science ®Google Scholar
• Corren J, Weinstein S, Janka L, et al. Phase 3 study of reslizumab in patients with poorly controlled asthma: effects across a broad range of eosinophil counts. Chest 2016;150:799-810
   PubMed Web of Science ®Google Scholar
• Ghazi A, Trikha A, Calhoun WJ. Benralizumab – a humanized mAb to IL-5Ralpha with enhanced antibody-dependent cell-mediated cytotoxicity – a novel approach for the treatment of asthma. Expert Opin Biol Ther 2012;12:113-18
   PubMed Web of Science ®Google Scholar
• FitzGerald JM, Bleecker ER, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor α 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;388:2128-41
   PubMed Web of Science ®Google Scholar
• Saco TV, Pepper AN, Lockey RF. Benralizumab for the treatment of asthma. Expert Rev Clin Immunol 2017;13:405-13
   PubMed Web of Science ®Google Scholar
• Santini G, Mores N, Malerba M, et al. Dupilumab for the treatment of asthma. Expert Opin Investig Drugs 2017;26:357-66
   PubMed Web of Science ®Google Scholar
• Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med 2013;368:2455-66
   PubMed Web of Science ®Google Scholar
• Wenzel S, Castro M, Corren J, 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 β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet 2016;388:31-44
   PubMed Web of Science ®Google Scholar
• Kerstjens HA, Engel M, Dahl R, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med 2012;367:1198-207
   PubMed Web of Science ®Google Scholar
• Brusselle GG, Vanderstichele C, Jordens P, et al. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax 2013;68:322-9
   PubMed Web of Science ®Google Scholar
• Domingo C, Moreno A, Amengual MJ, et al. Twelve years’ experience with methotrexate for GINA treatment step 5 asthma patients. Curr Med Res Opin 2009;25:367-74
   PubMed Web of Science ®Google Scholar
• Castro M, Rubin AS, Laviolette M, 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;181:116-24
   PubMed Web of Science ®Google Scholar
• Torrego A, Solà I, Munoz AM, et al. Bronchial thermoplasty for moderate or severe persistent asthma in adults. Cochrane Database Syst Rev 2014;3:CD009910
   PubMed Web of Science ®Google Scholar
• Levy ML, Thomas M, Small I, et al. Summary of the 2008 BTS/SIGN British guideline on the management of asthma. Prim Care Respir J 2009;18(Suppl 1):S1-S16
   PubMedGoogle Scholar
• Lin CH, Cheng SL. A review of omalizumab for the management of severe asthma. Drug Des Devel Ther 2016;10:2369-78
   PubMed Web of Science ®Google Scholar
• Bousquet J, Siergiejko Z, Swiebocka E, et al. Persistency of response to omalizumab therapy in severe allergic (IgE-mediated) asthma. Allergy 2011;66:671-8
   PubMed Web of Science ®Google Scholar
• Mepolizumab for treating severe refractory eosinophilic asthma. Technology appraisal guidance [TA431]. Published date: 25 January 2017. Available at: https://www.nice.org.uk/guidance/ta431/chapter/1-recommendations [Last accessed 3 January 2017]
   Google Scholar
• Reslizumab for treating eosinophilic asthma inadequately controlled on inhaled corticosteroids. Technology appraisal guidance [ID872]. 2017. Available at: https://www.nice.org.uk/guidance/GID-TA10036/documents/committee-papers [Last accessed 3 January 2017]
   Google Scholar
• McDonald VM, Vertigan AE, Gibson PG. How to set up a severe asthma service. Respirology 2011;16:900-11
   PubMed Web of Science ®Google Scholar
• Baren JM, Shofer FS, Ivey B, et al. A randomized, controlled trial of a simple emergency department intervention to improve the rate of primary care follow-up for patients with acute asthma exacerbations. Ann Emerg Med 2001;38:115-22
   PubMed Web of Science ®Google Scholar
• Fortuna AM, Feixas T, González M, et al. Diagnostic utility of inflammatory biomarkers in asthma: exhaled nitric oxide and induced sputum eosinophil count. Respir Med 2007;101:2416-21
   PubMed Web of Science ®Google Scholar
• Schatz M, Kazzi AA, Brenner B, et al. Introduction. Proc Am Thorac Soc 2009;6:353-6
   PubMedGoogle Scholar
• Domingo C. Overlapping effects of new monoclonal antibodies for severe asthma. Drugs 2017: published online 25 September 2017, doi: 10.1007/s40265-017-0810-5. [Epub ahead of print]
   PubMed Web of Science ®Google Scholar