Management of the patient with eosinophilic asthma: a new era begins

Abstract

Now that it is generally accepted that asthma is a heterogeneous condition, phenotyping of asthma patients has become a mandatory part of the diagnostic workup of all patients who do not respond satisfactorily to standard therapy with inhaled corticosteroids. Late-onset eosinophilic asthma is currently one of the most well-defined asthma phenotypes and seems to have a different underlying pathobiology to classical childhood-onset, allergic asthma. Patients with this phenotype can be identified in the clinic by typical symptoms (few allergies and dyspnoea on exertion), typical lung function abnormalities ("fixed" airflow obstruction, reduced forced vital capacity and increased residual volume), typical comorbidities (nasal polyposis) and a good response to systemic corticosteroids. The definitive diagnosis is based on evidence of eosinophilia in bronchial biopsies or induced sputum, which can be estimated with reasonable accuracy by eosinophilia in peripheral blood. Until recently, patients with eosinophilic asthma had a very poor quality of life and many suffered from frequent severe exacerbations or were dependent on oral corticosteroids. Now, for the first time, novel biologicals targeting the eosinophil have become available that have been shown to be able to provide full control of this type of refractory asthma, and to become a safe and efficacious substitute for oral corticosteroids.

FIGURE 1

Two different pathways lead to eosinophilic airway inflammation in asthma. In allergic asthma, dendritic cells present allergens to CD4⁺ T-cells, inducing T-helper (Th)2 cells, which produce interleukin (IL)-4, IL-5 and IL-13, and leading to IgE switching in B-cells, airway eosinophilia and mucous hypersecretion. In nonallergic eosinophilic asthma, air pollutants, microbes and glycolipids induce the release of epithelium-derived cytokines, including IL-33, IL-25 and thymic stromal lymphopoietin (TSLP), which activate innate lymphoid cells (ILCs) in an antigen-independent manner via their respective receptors (IL-17 receptor B (IL-17RB), ST2 and TSLP receptor (TSLPR)). Activated ILC2s produce high amounts of IL-5 and IL-13, leading to eosinophilia, mucus hypersecretion and airway hyperreactivity. CRTH2: chemoattractant receptor homologous molecule expressed on Th2 cells; ALX/FPR2: receptor for lipoxin A₄; FcεRI: high-affinity receptor for IgE; GATA3: GATA-binding protein 3; PG: prostaglandin; ROR: retinoic acid receptor-related orphan receptor; NK: natural killer; MHC: major histocompatibility complex; TCR: T-cell receptor. Reproduced from [51] with permission from the publisher.

FIGURE 2

Effect of high dose triamcinolone on sputum eosinophils. Effect of treatment with intramuscular triamcinolone or placebo on sputum eosinophil percentages in 22 patients with eosinophilic asthma. Horizontal lines represent median values. Reproduced and modified from [87] with permission from the publisher.