The role of viruses in acute exacerbations of asthma

Abstract

Viral respiratory infections are the most common cause of an acute asthma exacerbation in both children and adults and represent a significant global health burden. An increasing body of evidence supports the hypothesis that these infections cause a greater degree of morbidity in asthmatic subjects than in the healthy population, emphasizing a discrepancy in the antiviral response of asthmatics. In this review we discuss why such a discrepancy might exist, examining the role of the bronchial epithelium as well as the main inflammatory cells, mediators, and molecular pathways that are involved in the immune response. In addition, the potential impact of virus-induced asthma exacerbations on airway remodelling is reviewed and we explore which therapeutic options might be of benefit in preventing the deterioration of asthma control seen following viral infection.

Fig 1

Epithelial and immune cell responses to rhinovirus infection. Following infection a wide range of mediators are secreted including pro-inflammatory cytokines, chemokines, interferons, and growth factors. This leads to eosinophilic, neutrophilic, and lymphocytic inflammation, as well as mucus hypersecretion and likely airway remodelling. CCL, CC chemokine ligand; CCL5, RANTES (Regulated on Activation Normal T-cell Expressed and Secreted); CCL11, eotaxin; CCL24, eotaxin-2; CXCL, CXC chemokine ligand; CXCL 1, GRO-α (growth-related oncogene α); CXCL-5, ENA-78 (epithelial neutrophil activating protein-78); CXCL10, IP-10 (IFN-γ-inducible protein 10); DC, dendritic cell; FGF-2, fibroblast growth factor-2; GMCSF, granulocyte macrophage-colony stimulating factor; ICAM-1, intercellular adhesion molecule-1; IFN, interferon; IL, interleukin; LDLR, low density lipoprotein receptor; RV, rhinovirus; TC1, cytotoxic CD8+ T lymphocyte type 1; TH1, T-helper 1 CD4+ T lymphocyte; TNF-α, tumour necrosis factor-α; VEGF, vascular endothelial growth factor.