Rhinovirus Infections and Their Roles in Asthma: Etiology and Exacerbations

Abstract

Rhinovirus infections can cause wheezing illnesses in all age groups. In preschool children, rhinovirus infections frequently initiate acute wheezing illnesses. Children who wheeze with rhinoviruses are at increased risk to go on to develop asthma. Once asthma is established, rhinovirus infections are potent triggers for acute airway obstruction and exacerbations in children and adults. Paradoxically, for most individuals, rhinovirus infections commonly cause cold symptoms with little or no involvement of the lower airways. This paradox has led investigators to identify specific risk factors and mechanisms for rhinovirus wheezing, and this review will outline progress in 3 main areas. First, the 3 species of rhinoviruses have different patterns of infection and virulence. Second, personal factors such as lung function and immunity influence lower respiratory outcomes of rhinovirus infection. The mucosal immune response is critical, and the quality of the interferon response and allergic inflammation interacts to determine the risk for rhinovirus wheezing. Finally, rhinovirus infections can promote pathogen-dominated airway microbiota that increase the risk for wheezing. Although specific antivirals for rhinovirus are still not available, identifying risk factors for wheezing illnesses has provided several other potential targets and strategies for reducing the risk of rhinovirus-induced wheezing and exacerbations of asthma.

Keywords: Asthma; Exacerbation; Infection; Rhinovirus; Type 2 inflammation.

Figure 1.

Risk factors for RV wheezing illnesses and for progression from RV wheezing to childhood asthma.

Figure 2.

The pathogenesis of a rhinovirus-induced asthma exacerbation. Rhinovirus infects the respiratory epithelium leading to release of the epithelial derived cytokines IL-25, IL-33 and TSLP which drives downstream release of IL-4, IL-5 and IL-13 from Th2 cells and type 2 innate lymphoid cells (ILC2). IL-5 plays a key role in driving airway eosinophilia and is itself released by eosinophils; IL-13 is central for mucus hypersecretion and airway hyperresponsiveness and is additionally eosinophil-derived. Plasmocytoid dendritic cells (pDCs) are important sources of anti-viral type 1 interferon and their responsiveness to rhinovirus infection is impaired in the presence of allergic inflammation. ILC2 production of T2 cytokines is partly inhibited by type 1 interferon.

Figure 3.

Potentially modifiable risk factors for RV-induced wheezing and exacerbations of asthma.