Viral Infections and Associated Factors That Promote Acute Exacerbations of Asthma

Kim, Chang-Keun; Callaway, Zak; Gern, James E.

In both adults and children, RV is the most frequently identified virus associated with acute asthma exacerbation. 31 RV enters the body through the respiratory route and infects and replicates in epithelial cells. It was first thought that RV infected only the upper airway, but it is now known that it can also infect the lower airway. 32 One of the proposed reasons why asthmatics are predisposed to viral infection is damaged epithelium, which may increase susceptibility to infection and ultimately lead to airway obstruction. Cellular mechanisms involved in this response include higher intracellular adhesion molecule-1 (ICAM-1) expression on respiratory epithelial cells, disruption of epithelial barrier function, impaired apoptosis, increased cell lysis, deficient Th1 response (e.g., interferon [IFN]-γ), and enhanced neutrophil recruitment. 7 RV infection also induces proinflammatory mediators, including interleukin (IL)-6, IL-8, tumor necrosis factor-α (TNF-α), IL-β, regulated on activation normal T expressed and secreted (RANTES), and granulocytemacrophage colony stimulating factor (GM-CSF). 33 In addition to increasing airway neutrophils, RV-induced asthma exacerbation can also be associated with increases in airway eosinophils (Eos). 2 Airway Eos bind to RV and may participate in virus-specific immune responses through antigen presentation and T cell activation. 34 Eos may contribute to antiviral responses to RSV in vitro, 35 but the clinical significance of these effects is unclear. Eos can have immunomodulating effects, including inducing T cell activation, and eosinophilic cationic protein (ECP) can upregulate ICAM-1 expression on respiratory epithelial cells. 36 It should be noted that 90% of RV-A and RV-B serotypes use ICAM-1 as a receptor, which has a pivotal role in movement of inflammatory cells into the airways. 37 RV-C types bind to cadherin-related protein-3 (CDHR3), and the corresponding gene has been linked to childhood asthma associated with severe wheezing episodes in early life. 38