European Respiratory Society
Severe Asthma

Severe asthma is a form of asthma that responds poorly to currently available medication, and its patients represent those with greatest unmet needs. In the last 10 years, substantial progress has been made in terms of understanding some of the mechanisms that drive severe asthma; there have also been concomitant advances in the recognition of specific molecular phenotypes. This ERS Monograph covers all aspects of severe asthma – epidemiology, diagnosis, mechanisms, treatment and management – but has a particular focus on recent understanding of mechanistic heterogeneity based on an analytic approach using various ‘omics platforms applied to clinically well-defined asthma cohorts. How these advances have led to improved management targets is also emphasised. This book brings together the clinical and scientific expertise of those from around the world who are collaborating to solve the problem of severe asthma.

  • ERS Monograph
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  4. Page 1
    Abstract
    William W. Busse, University of Wisconsin Hospital, K4/910 CSC, MC 9988, 600 Highland Avenue, Madison, WI 53792, USA. E-mail: wwb@medicine.wisc.edu

    Although severe asthma is a small fraction of all asthma, its impact on patient burden and healthcare costs is high. To identify this high-risk group for both research and treatment, a clear definition of severe asthma is needed. The European Respiratory Society/American Thoracic Society Task Force on Severe Asthma has provided that direction and defines this phenotype by the need for high-dose medication, including ICSs, to try to achieve control. The focus of the definition is on treatment required for asthma control.

    Cite as: Busse WW. Definition and impact. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 1–15 [https://doi.org/10.1183/2312508X.10022418].

  5. Page 16
    Abstract
    Vanessa M. McDonald, Level 2 West Wing, 1 Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia. E-mail: vanessa.mcdonald@newcastle.edu.au

    Severe asthma has a significant impact on the lives of people with the disease. The burden is both physical and emotional, with patients struggling to control symptoms of their asthma, as well as the significant comorbidities that exist with severe disease. These physical impacts lead to an emotional burden that has an impact not only on the individual but also on their relationships with loved ones, friends and work colleagues. Adverse effects from medications also negatively affect their experience of living with severe asthma. Together, the physical, emotional and medication burdens lead to people with severe asthma feeling isolated, alone and battling with their own identify. However, despite these negative impacts, people with severe asthma can also identify strategies to adapt to this disabling disease and demonstrate resilience. Understanding the experience of patients with severe asthma is imperative and can be aided by the use of patient-reported outcome measures. Strategies aimed at improving patient experience are a priority.

    Cite as: McDonald VM, Kennington E, Hyland ME. Understanding the experience of people living with severe asthma. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 16–29 [https://doi.org/10.1183/2312508X.10022618].

  6. Page 30
    Abstract
    Liam Heaney, Centre for Experimental Medicine, Wellcome-Wolfson Institute for Experimental Medicine, Queens's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK. E-mail: l.heaney@qub.ac.uk

    Asthma control may remain elusive for reasons apart from severe asthma biology.

    Several comorbidities which worsen asthma control, mimic poor asthma control or both, are highly prevalent in severe asthma cohorts. These comorbidities impact breathing perception and control the upper airway (nasal and sinus cavities), the middle airway (oropharynx and larynx), and the lower airway (including the tracheobronchial tree). The detection and management of these comorbidities is, therefore, a key aspect of severe asthma management.

    At the same time, asthma control may also be impacted by social, psychological and behavioural factors. These factors may impede access to, and engagement with, healthcare services, prevent effective asthma self-management, or interfere with the effectiveness of pharmacological and non-pharmacological therapies. Chief among these is poor adherence to prescribed medication, with significant challenges in both detecting and managing the issue.

    Clinicians who seek to manage severe asthma patients should develop and employ a consistent, comprehensive, multidisciplinary approach to these comorbidities and psychosocial factors (including adherence) ideally delivered by a dedicated severe asthma service. Such a systematic approach is associated with improved patient outcomes.

    Cite as: Hew M, Heaney LG. The contribution of comorbidities, psychosocial factors and adherence to the presentation of severe asthma. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 30–47 [https://doi.org/10.1183/2312508X.10022718].

  7. Page 48
    Abstract
    Elisabeth H. Bel, Dept of Pulmonology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands. E-mail: e.h.bel@amc.uva.nl

    Classification of asthma into phenotypes is an important first step towards precision medicine. Over the last century, clinicians and researchers have made great efforts to classify severe asthma into different subtypes, and several classification systems have been used. These include classification based on clinical features (presence of fixed airflow limitation or frequent exacerbations), the type of airway inflammation (eosinophilic, neutrophilic, mixed eosinophilic/neutrophilic or paucigranulocytic), and biased and unbiased cluster analysis techniques. Many of the phenotypes identified with these techniques correspond to well-described and accepted clinical phenotypes that are based on pattern recognition by clinicians. These include early onset allergic asthma, adult-onset eosinophilic asthma, aspirin-exacerbated asthma, obesity-associated asthma, occupational asthma, smoking-related asthma and asthma in athletes. This chapter will review the characteristics of these severe asthma phenotypes and inform the clinician on how to use clinical phenotypes in clinical practice.

    Cite as: Kim T-B, Bel EH, Moore W. Clinical phenotypes: adults. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 48–63 [https://doi.org/10.1183/2312508X.10035518].

  8. Page 64
    Abstract
    W. Gerald Teague, Child Health Research Center, University of Virginia School of Medicine, 409 Lane Road, Building MR4, Room 2114, Charlottesville, VA 22908, USA. E-mail: wgt2p@virginia.edu

    Severe asthma is a complex syndrome with heterogeneous clinical features that change with development. Pre-school children manifest a phenotype characterised by repeated episodes of multitrigger wheeze and sensitisation to environmental allergens. School-age children may manifest a phenotype of severe wheeze and airflow limitation that can persist and potentially culminate in COPD. School-age children with severe asthma can be sorted by cluster analysis into phenotypes differentiated by young age of onset, sensitisation to multiple allergens and by the presence or absence of airflow limitation. Pre-school children are more likely to transition from one phenotype to another compared to school-age children. Unlike “neutrophilic” asthma in adults, lung neutrophilia in childhood asthma is highly informed by microbial pathogens and has fewer morbid features. Future phenotypic classification methods will evolve to recognition of endotypes, defined by common molecular patterns of inflammation, and will guide specific therapies.

    Cite as: Teague WG, Roberts G. Clinical phenotypes: children. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 64–81 [https://doi.org/10.1183/2312508X.10023018].

  9. Page 82
    Abstract
    Nizar N. Jarjour, 600 Highland Ave, Madison, WI, 53792-9988, USA. E-mail: njarjour@uwhealth.org

    Patients with severe asthma suffer frequent exacerbations associated with increased symptoms and airway obstruction. They constitute a significant burden to patients, families and healthcare systems. Understanding the mechanisms of asthma exacerbations and how best to prevent them is an important step to reduce asthma morbidity and associated healthcare costs. In most patients, airway obstruction in asthma is reversible; however, a subset of asthma patients has a fixed component of their airflow limitation. Potential causes include epithelial injury during asthma exacerbations with altered repair leading to excess fibrosis and smooth muscle hypertrophy. Understanding and addressing asthma exacerbations and fixed airway obstruction represent important challenges in the management of severe asthma. Important advances have included the development of biological therapeutics targeting specific inflammatory pathways in asthma. When used in properly selected patients, these treatments reduce exacerbations and improve asthma control. Future efforts need to focus on reversing fixed airway obstruction and treatment of patients with type 2-low asthma.

    Cite as: Jarjour NN, Konno S. Mechanisms underlying fixed airflow obstruction and exacerbations. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 82–92 [https://doi.org/10.1183/2312508X.10022818].

  10. Page 93
    Abstract
    Parameswaran Nair, Firestone Institute for Respiratory Health, St Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, ON, L8N 4A6, Canada. E-mail: parames@mcmaster.ca

    Strategies to manage severe asthma have evolved in order to consider the components of airways disease and endotype-specific disease mechanisms that may govern progression and response to treatment. This paradigm shift has been enabled in part by the use of noninvasive biomarkers that are likely to be impressive in the clinical management of patients with more severe forms of the disease, and are currently limited to simple measurements such as serum IgE, blood and sputum eosinophil numbers, and FeNO. The focus of recent literature and ongoing multicentre initiatives surrounds the discovery, clinical validation and clinical utility of biomarkers to stratify asthmatics according to their endotype, predict disease progression, titrate treatment dose and select patients who are likely to respond to targeted therapies. Application of medical imaging and 'omics technology, and systems biology approaches to synthesise this data, with the development of point-of-care tests using novel lab-on-chip technologies, are likely to revolutionise the care of asthma.

    Cite as: Svenningsen S, Fowler SJ, Nair P. Clinical biomarkers and noninvasive assessment. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 93–112 [https://doi.org/10.1183/2312508X.10023118].

  11. Page 113
    Abstract
    Christopher E. Brightling, Institute for Lung Health, University of Leicester, Leicester, LE3 9QP, UK. E-mail: ceb17@leicester.ac.uk

    Imaging plays a central role in the clinical management of severe asthma, particularly in identifying important comorbidities that have an impact on acute and chronic care. Qualitative assessment of chest radiographs and CT are part of the standard of care. Beyond the standard of care, there are multimodality lung imaging platforms and software algorithms capable of quantifying regional airway structure and function, as well as airway inflammation. This chapter describes how state-of-the-art and novel imaging modalities are beginning to be applied in severe asthma research. The application of these imaging approaches contributes to our ability to dissect the heterogeneity of severe asthma and is likely to inform future clinical management towards precision medicine.

    Cite as: Siddiqui S, Castro M, Brightling CE. Imaging. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 113–131 [https://doi.org/10.1183/2312508X.10023218].

  12. Page 132
    Abstract
    Ian M. Adcock, Respiratory Division, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Dovehouse Street, London SW3 6LY, UK. E-mail: ian.adcock@imperial.ac.uk

    Invasive measures have shown that severe asthma patients have characteristic features, such as prominent airway smooth muscle, enlarged submucosal mucous glands and inflammation, with reduced airway lumen size due to airway smooth muscle constriction, folding of the basement membrane and high mucus levels. Sputum granulocytes are used to define subtypes of severe asthma into eosinophilic, neutrophilic, mixed and pauci-granulocytic. Eosinophilic asthma, associated with type 2 (T2) allergic inflammation, responds well to ICSs, although eosinophilic asthma is seen in some subjects despite high doses of ICSs or even OCSs. Asthma pathology is influenced by infection and/or environmental pollution in non-T2 subjects, which has identified potential drug targets such as monoclonal antibodies directed against the alarmins IL-33 and TSLP, and against inflammasome-related factors such as IL-1. Pauci-granulocytic asthma involves distinct types of T-cells and macrophages, which may be targeted by antibodies against IL-6, IL-17 and IFNs. The development of noninvasive measures is needed to provide greater insight into pathophysiological changes over time.

    Cite as: Adcock IM, Mumby S. Pathophysiology. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 132–151 [https://doi.org/10.1183/2312508X.10023318].

  13. Page 152
    Abstract
    Scott S. Wagers, BioSci Consulting, Rijksweg 328, Maasmechelen 3630, Belgium. E-mail: scottwagers@biosciconsulting.com

    The U-BIOPRED project was one of the first Innovative Medicines Initiative-funded projects. The vision of U-BIOPRED is that by integrating different types of “’omics” data with clinical and patient-reported outcome data to generate “handprints”, we will be able to identify subphenotypes of severe asthma that will be grounded on mechanistic insights. Several U-BIOPRED publications have advanced our clinical and mechanistic understanding of severe asthma. There continue to be ongoing efforts to analyse U-BIOPRED data.

    The most important organisational lesson of U-BIOPRED is that it is important to have a flexible structure that enables collaboration across the consortium on the issues that block progress, deploying adequate resources for the data and knowledge management, focusing more on the depth of patient characterisation instead of size of the cohort and, most importantly, that with the right effort, multiple stakeholders, including patients, can effectively work together with a true collaborative spirit.

    Cite as: Wagers SS, Adcock IM. The lessons from U-BIOPRED. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 152–166 [https://doi.org/10.1183/2312508X.10023418].

  14. Page 167
    Abstract
    Deborah Meyers, Dept of Medicine, University of Arizona, 1230 N. Cherry, BSRL 251, PO Box 210242, Tucson, AZ 85721, USA. E-mail: dameyers@email.arizona.edu

    In this chapter, the aims and accomplishments of the National Heart, Lung, and Blood Institute SARP are presented with emphasis on the importance of disease heterogeneity within asthma, and within severe asthma. This overview is limited to only some of the research accomplishments since the SARP investigators have published over 100 manuscripts on inflammation, genomics, subphenotypes, biomarkers and imaging in severe asthma. The initial rationale for SARP was to address the unmet needs of patients with severe or refractory asthma by the development of networks of centres to perform standardised in-depth clinical characterisation with collection of multiple samples. To dissect disease heterogeneity in severe asthma, statistical approaches that allow the data to be "grouped" into similar subsets without prior assumptions were utilised. Clinical cluster analysis was performed in SARP 1 and, subsequently, various analyses have addressed disease heterogeneity utilising more than clinical data alone by incorporating biomarkers such as sputum (airway) cells, imaging and response to corticosteroids. The important findings from SARP 3 systemic corticosteroid-induced phenotype emphasises the observed clinical and biologic responses that imply relative resistance to corticosteroids in some patients with severe asthma. Finally, multiple genetic studies have been performed identifying genes and genetic pathways important in asthma susceptibility and severity including genomic studies integrating DNA data with RNA expression from the primary disease organ of interest: lung airways cells. Understanding disease heterogeneity is essential in understanding the pathogenesis and represents the basis for targeted therapies for severe asthma.

    Cite as: Meyers DA, Wenzel SE, Bleecker ER. SARP: dissecting subphenotypes and endotypes. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 167–183 [https://doi.org/10.1183/2312508X.10023518].

  15. Page 184
    Abstract
    Kian Fan Chung, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK. E-mail: f.chung@imperial.ac.uk

    Asthma has long been recognised by clinicians as being a heterogeneous disease. Unbiased clustering approaches using clinical, physiological and inflammatory markers have enabled the definition of phenotypes based on age at asthma onset, BMI, clinical traits (such as airflow obstruction and recurrent exacerbations) and blood or sputum eosinophilia. Phenotyping based on analysis of the transcripts or proteins expressed in different compartments (“molecular phenotyping”) has brought a new dimension, as this may lead to the description of endotypes, which are phenotypes recognised through their driving mechanism. A type 2-high inflammation cluster characterised by expression of transcripts that are induced in epithelial cells exposed to IL-13 has been identified in severe asthma with recurrent exacerbations and eosinophilia. Type 2-low phenotypes have been described in connection with the IFN pathway, inflammasome activation and mitochondrial oxidative phosphorylation pathways. A systems biology approach is needed to establish the links between these pathways or mechanisms, and the clinical/physiological features. Molecular phenotyping leading to directed therapy will achieve better treatment for severe asthma.

    Cite as: Chung KF, Pavlidis S, Adcock I. Molecular phenotypes. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 184–194 [https://doi.org/10.1183/2312508X.10001019].

  16. Page 195
    Abstract
    Anne E. Dixon, Given D209, 89 Beaumont Avenue, Burlington, VT 05405, USA. E-mail: anne.dixon@uvmheatlh.org

    Obesity is a major risk factor for asthma, and those patients with metabolic dysfunction tend to have severe, difficult-to-control disease. This chapter will discuss how factors causing weight gain and metabolic dysregulation: 1) contribute to the pathogenesis of de novo airway disease, and 2) alter the pathophysiology of disease in those with pre-existing asthma. Factors pertinent to metabolic dysregulation and the pathogenesis of asthma include genetics, environmental exposures (including diet), the microbiome, altered growth and physiology, systemic and local metabolic dysregulation, immune function and comorbidities that afflict the patient. Treatment of asthma in patients with obesity and/or metabolic dysfunction requires careful evaluation and treatment of factors related to the obese state that contribute to airway disease, as well as optimisation of conventional asthma medications.

    Cite as: Dixon AE, Holguin F. Metabolic dysfunction. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 195–210 [https://doi.org/10.1183/2312508X.10023718].

  17. Page 211
    Abstract
    Pankaj Bhavsar, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK. E-mail: p.bhavsar@imperial.ac.uk

    The majority of patients with asthma are well controlled by current combination therapy consisting of ICSs and LABAs. Patients with severe asthma continue to have uncontrolled asthma symptoms despite being established on high-dose ICSs and often need additional OCS therapy. These patients are relatively insensitive to the therapeutic benefits of corticosteroids, which highlights the need for the development of new treatments to overcome corticosteroid resistance. A number of conditions have been associated with corticosteroid insensitivity in severe asthma, including obesity, cigarette smoking, vitamin D deficiency and possibly respiratory infections. Understanding the underlying mechanisms driving the relative corticosteroid insensitivity would be of benefit in order to identify the defects that lead to impaired response in asthmatic cells. Corticosteroids mediate their effects through the glucocorticoid receptor. Molecular mechanisms identified to date include: impaired nuclear translocation of glucocorticoid receptor; activation of the mitogen-activated protein kinase (MAPK) pathways, in particular p38 MAPK; activation of transcription factors by IFN-γ; or increased oxidative stress resulting in a reduction in histone deacetylase expression and activity.

    Cite as: Bhavsar P, Harmer G, Adcock IM. Corticosteroid responsiveness and resistance. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 211–230 [https://doi.org/10.1183/2312508X.10024218].

  18. Page 231
    Abstract
    Stanley Szefler, Pediatric Asthma Research Program, Breathing Institute, Section of Pediatric Pulmonary Medicine, Children's Hospital Colorado, 13123 E 16th Ave, Aurora, CO 80045, USA. E-mail: stanley.szefler@childrenscolorado.org

    Severe asthma affects <5% of asthmatic children but carries the majority of asthma morbidity and mortality due to asthma. Although severe asthma is recognised as a heterogeneous disease, recent studies have identified some molecular and histopathological features that may be shared among atopic children with severe therapy-resistant asthma. These include exaggerated eosinophilic inflammation, airway remodelling and activation of the alarmin IL-33 in the subepithelial layer, as well as neutrophils in the epithelial layer of the airway wall. The emergence of treatments to specifically target cytokines and their receptors has reaffirmed the redundancy and complexity of effector functions in mounting type 2 immune responses in severe asthma. The further development of predictive and monitoring biomarkers for treatment success and failure may allow clinicians to identify children at risk for severe asthma early and to intervene effectively with currently available and novel personalised treatment approaches.

    Cite as: Mattes J, Szefler S. Mechanisms in children. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 231–245 [https://doi.org/10.1183/2312508X.10024318].

  19. Page 246
    Abstract
    Louise Fleming, National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK. E-mail: l.fleming@rbht.nhs.uk

    Most children with asthma will have their symptoms controlled if inhaled steroids are regularly and correctly administered. Although only a small number have severe asthma, they consume disproportionate healthcare resources. Careful evaluation and characterisation is essential to correctly diagnose severe asthma and to implement appropriate management strategies. The main objectives of management are to control symptoms, optimise activity and minimise the risk of asthma attacks and medication side-effects. In order to achieve this, several challenges must be addressed; these include comorbidities, inadequate medical therapy, psychosocial factors and environmental exposures. For those who remain poorly controlled despite attention to these basics, a biologic should be considered; however, the range of biologics currently available is limited compared to adults with severe asthma. Although there has been considerable progress in our understanding of severe asthma in children, there remain significant knowledge gaps about the determinants of severe asthma and appropriate therapeutic targets. Better definition and understanding of asthma phenotypes in children to enable individualised targeted therapies have the potential to lead to improved outcomes.

    Cite as: Haktanir Abul M, Naja AS, Fitzpatrick A, Phipatanakul W, Fleming L. Evaluation and management in children. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 246–264 [https://doi.org/10.1183/2312508X.10024418].

  20. Page 265
    Abstract
    Elliot Israel, Brigham & Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. E-mail: Eisrael@partners.org

    This chapter reviews how to evaluate difficult-to-treat and severe asthma. We outline how to confirm a diagnosis of asthma and the evaluation of factors that can make asthma appear resistant to treatment, and discuss comorbidities and other factors that are not necessarily part of asthma but that can make asthma difficult to treat. We also review how to characterise patients who have severe asthma so that the most appropriate treatment can be considered.

    Cite as: Israel E, Reddel H. Evaluation of difficult-to-treat and severe asthma in adults. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 265–284 [https://doi.org/10.1183/2312508X.10024518].

  21. Page 285
    Abstract
    Ian D. Pavord, Respiratory Medicine Unit and NIHR Respiratory BRC, Nuffield Department of Medicine, NDM Research Building, Old Road Campus, University of Oxford, Oxford, OX3 7FZ, UK. E-mail: Ian.pavord@ndm.ox.ac.uk

    Asthma is characterised by typical symptoms in combination with variable airway obstruction and, in many cases, eosinophilic airway inflammation. Most patients with asthma have well-controlled symptoms and a low risk of asthma exacerbations when treated with ICSs. However, ∼5–10% remain symptomatic and/or at risk of asthma exacerbations despite maximum inhaled therapy with ICSs and long-acting β2-agonists. Such patients with severe asthma are responsible for a significant proportion of healthcare costs attributable to asthma and have a large unmet need for better treatment. An important advance in recent years has been the recognition that severe asthma is heterogeneous with respect to clinical presentation, response to treatment and the pattern of lower airway inflammation. Type 2-high airway inflammation is seen in >50% of patients with severe asthma and is driven by innate and adaptive immune mechanism and associated mediators, including IgE, IL-5, IL-13 and IL-4, resulting in the presence of airway eosinophilia. Biological agents blocking IgE, IL-5, and both IL-4 and IL-13 are effective treatments in selected patients with severe asthma with type 2 airway inflammation.

    Cite as: Pavord ID, Shrimanker R, Hanania NA. Biologics targeting type 2 inflammation. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 285–303 [https://doi.org/10.1183/2312508X.10024618].

  22. Page 304
    Abstract
    Michael E. Wechsler, Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, and The NJH Cohen Family Asthma Institute, 1400 Jackson Street, Denver, CO 80206, USA. E-mail: wechslerm@njhealth.org

    While targeted pharmacological therapies are the mainstay of treatment for severe asthma, several nonpharmacological approaches have been shown to improve symptoms, reduce exacerbations and reduce healthcare utilisation. As anxiety, dysfunctional breathing and altered airway smooth muscle all contribute to symptoms and repetitive exacerbations in this small, yet heavily burdened, proportion of asthmatic patients, breathing techniques, anxiety management, physical and dietary interventions, and attempts to reverse and prevent further progression of airway remodelling via bronchial thermoplasty are offered as potential adjuncts to inhaler and biological therapies in severe asthma.

    Cite as: Guntur VP, Wechsler ME. Nonpharmacological interventions: behavioural and interventional approaches. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 304–314 [https://doi.org/10.1183/2312508X.10024718].

  23. Page 315
    Abstract
    Peter G. Gibson, Level 2 West Wing, 1 Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia. E-mail: peter.gibson@hnehealth.nsw.gov.au

    Severe asthma has a high illness burden. It is a complex and heterogeneous disease that is refractory to standard treatment and is complicated by multiple comorbidities and risk factors. Systematic assessment can identify many issues in a person with severe asthma and can allow a personalised treatment plan to be formulated. People with severe asthma require assessment of the inflammatory phenotype, risk factors, behavioural issues, pulmonary comorbidities and extrapulmonary comorbidities. Targeted and individualised management can be implemented in several ways, such as by a multidimensional severe asthma clinic, a case manager, the use of a structured checklist, or a combination of these approaches. In this chapter, we describe a practical approach to the assessment and management of patients with severe asthma.

    Cite as: Gibson PG, Chung KF, Israel E. Management in adults. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 315–326 [https://doi.org/10.1183/2312508X.10035718].

  24. Page 327
    Abstract
    Kian F. Chung, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, SW3 6LY, UK. E-mail: f.chung@imperial.ac.uk

    Progress has been made in defining and managing severe asthma, and in the next 10 years, difficult-to-treat patients will be investigated in specialist severe asthma clinics, where the factors that make asthma difficult to treat can be determined. The ability to predict the onset of asthma worsening by self-monitoring will be useful in allowing preventive actions. The use of antibodies blocking type 2 (T2) targets such as IgE, IL-5, IL-5 receptor α (IL-5Rα) and IL-4Rα for those with severe allergic and severe eosinophilic asthma is the most important advance. These therapies may be introduced at an earlier stage of severe asthma prior to the introduction of OCSs. Molecular phenotypes or endotypes will be described across the spectrum of severe asthma, not just the current T2-high phenotypes. More T2-high targeted therapies will be introduced, and T2-low targeted therapies will also become available. A wider range of bedside biomarkers either measured in the blood, urine or exhaled breath will be used to determine the endotype and the specific treatment required for each individual patient. In the future, severe asthma clinics will have the task of molecular phenotyping and selecting the right targeted treatments. We should be looking to improve the control of asthma and severity while reducing the side-effects of corticosteroids. The possibility of endotyping leading to early identification of patients at risk of progressive severe asthma needs to be investigated.

    Cite as: Chung KF, Israel E, Gibson PG. The next decade of continuing progress. In: Chung KF, Israel E, Gibson PG, eds. Severe Asthma (ERS Monograph). Sheffield, European Respiratory Society, 2019; pp. 327–333 [https://doi.org/10.1183/2312508X.10035818].

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