THE EVOLUTION OF ASTHMA MANAGEMENT: A BRIEF OVERVIEW

Dr Shuaib Nasser, Consultant in Allergy and Asthma, Cambridge University Hospitals NHS Foundation Trust, UK

Over the last 100 years asthma management has evolved considerably, thanks to increased understanding of the mechanism of disease and identification of new treatment targets. Here, we explore some of the key milestones that have shaped our understanding of asthma pathogenesis and the evolution of our approach to disease management in patients, from adrenergic bronchodilators to a new era of precision therapy.¹

“Prescientific” era [Pre 1930] First descriptions of asthma were recorded

With thanks to Prof Ian Pavord & Dr Simon Couillard for the original work of which this was adapted from.

1.

Asthma diagnosis and management were initially based on patient symptoms alone, as observed by the first description of asthma from Aretaeus of Cappadocia, a Greek physician. He described asthma as chest heaviness, difficulty breathing, tiredness and cough symptoms.2 Later, Sir William Osler further identified asthma as a spasm of the bronchial tubes and swelling of bronchial mucus membranes, closely related to hay fever. Asthma was also identified as disease beginning in childhood, with a possible genetic component.3 In the early 1900s, intrinsic and extrinsic asthma, now known as non-allergic and allergic asthma, were also described.4 Treatments during this era were focused on tackling symptoms rather than underlying disease. Direct adrenergic bronchodilators were one of the first treatments introduced for relief of asthma attacks.1

“Physiological” era [1930–1970]

Asthma diagnosis moved away from symptoms alone

Scientists gained improved understanding of how asthma affects the bronchial tubes and focused research on treatments that delivered bronchodilation for patients. Nebulised epinephrine was one of the first treatments to demonstrate effective bronchodilation for patients with asthma and emphysema.5 The role of eosinophils in asthma and immunoglobulin E (IgE) in mast cell activation were also discovered during this time.6,7 Once activated, mast cells were found to produce histamine which has a role in the asthmatic response.6 Short-acting ß2-agonists (SABAs) were recommended as an initial treatment for mild asthma.8,9

“Immunological” era [1970–2000]

Development in understanding of asthma inflammatory pathways

Further understanding of eosinophils and interleukin-5 (IL-5) led to a better understanding of patient responses to corticosteroid treatment, with eosinophilic and non-eosinophilic asthma described.6,10 These two inflammatory phenotypes were further characterised to identify different structural, physiological and clinical characteristics for each group.11 Systemic corticosteroids were the standard therapy for the treatment and prevention of asthma exacerbations.1 Inhaled corticosteroids (ICS) were first launched in 1978 and were found to reduce airway eosinophils, mast cells and inflammation.3,9 Leukotriene receptor antagonists (LTRAs) are approved for treating chronic asthma.12,13

“Phenotypes” era [2000–2010] Definition of asthma phenotypes

The phenotypes era saw the clustering of clinical phenotypes of asthma based on genetic and environmental factors.14 Antileukotriene and anti-IgE treatments specific to known endotypes of asthma were developed.1 In 2003, the first biologic therapy targeting IgE was approved as an add-on therapy for adults and children ≥6 years old with moderate-to-severe allergic asthma.15

“Endotypes” era [2010–2020]

Evolution of asthma endotypes

Asthma was classified by endotypes based on mechanisms that drive the disease phenotype. These included early onset allergic, late onset eosinophilic, exercise-induced, obesity-related, and neutrophilic asthma.16,17 Blood eosinophil counts were identified as predictive biomarkers for asthma exacerbations and responsiveness to ICS18, and precision medicine management approaches driven by patient phenotypes and endotypes were proposed.19 Clinical studies highlighted a clearer understanding of the role of eosinophils in the pathogenesis of severe exacerbations of asthma, and the role of thymic stromal lymphopoietin (TSLP) in asthma was first investigated.20,21 Anti-eosinophil agents such as IL-5 receptor and prostaglandin D2 receptor antagonists were found to reduce sputum eosinophilia.17 Short- or long-acting muscarinic antagonists (SAMAs/LAMAs) recommended as an alternative or add-on controller.8,22

“Epithelial” era [2010–Present]

New understanding of epithelial science

There is a growing understanding of the airway epithelium and epithelial cytokines. Associations between epithelial cytokine polymorphisms and asthma have been identified23–25, in addition to establishing the different components of type 2 inflammation from biomarkers26 to fractional exhaled nitric oxide (FeNO) and blood eosinophil counts.27,28 This precision treatment era has seen the more targeted treatments, including short- and long-acting ß2-agonists (SABAs/LABAs), used in combination with ICS, to relieve bronchoconstriction, improve asthma control, and prevent exacerbations. In the 2018 Global Initiative for Asthma (GINA) guidelines, ICS/LABAs are considered the first choice maintenance therapy for patients with moderate-to-severe asthma.8 More recently, therapies targeting TSLP are being developed due to the potential to treat more diverse phenotypes and endotypes of asthma.29,30

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©AstraZeneca 2023. All rights reserved, GB-45948 Date of preparation: June 2023.