Cytokine-targeted therapies for asthma and COPD

Abstract

Asthma affects over 300 million people worldwide and its prevalence is increasing. COPD is the third leading cause of death globally. Asthma and COPD are complex inflammatory diseases of the airways in which impaired host defences lead to increased susceptibility to pathogens, pollutants and allergens. There is a constant interplay between host and the environment. Environmental exposures can alter the lung microbiome and influence the development of sensitisation by disrupting normal immunoregulation. The underlying airway inflammation in severe asthma is heterogeneous, with upregulation of type 2 cytokines in most cases but increased neutrophilic inflammation and activated T-helper 17 mediated immunity in others. COPD may also comprise several different phentoypes that are driven by different molecular mechanisms or endotypes. This disease heterogeneity is affected by comorbidities, treatments and environmental exposures. Recent intervention trials have shed light on the pathways beyond type 2 inflammation that can lead to beneficial outcomes versus potentially deleterious effects. We have made a great deal of progress over the last 10 years in terms of immunology and the pathophysiology of asthma and this has led to the development of novel treatments and major improvements in severe asthma outcomes. In COPD, however, no targeted treatments have demonstrated great improvements. This article reviews the mechanism of action and efficacy of the available biologics in asthma and COPD.

FIGURE 1

Airway inflammation in severe asthma and COPD. CXCL: C-X-C motif ligand; Eosino: eosinophil; IFN-γ: interferon-γ; IL: interleukin; ILC2: innate lymphoid cell type 2; MMP: matrix metalloproteinase; Neutro: neutrophil; TNF-α: tumour necrosis factor-α; TSLP: thymic stromal lymphopoietin.