Role of Infection in the Development and Exacerbation of Asthma

Interactions between Viral Infections & Allergy
Theresa W Guilbert, MD†

The effect of allergic sensitization on the asthmatic airway response to viral infection has been a topic of much research. The relationship between these two factors appear to be bidirectional, as the atopic state can alter the lower airway response to viral infections,[13,153] viral infections can affect the development of allergen sensitization,[154,155] and synergistic interactions can emerge when individuals are exposed concurrently to both allergens and viruses.[11,156,157] As previously suggested, atopic individuals may have both altered host defenses that increase susceptibility to bacterial and viral infections, and an increased risk of developing asthma.[3,78–82]

Atopy is a risk factor for the development of childhood asthma after virus-induced wheezing illnesses and many investigative groups have explored the mechanisms of this relationship.[158] It has also been proposed that atopy may be an important predisposing factor for the development of acute bronchiolitis during RSV epidemics.[159] Some investigators have reported that atopic parents increase the likelihood of children developing persistent wheezing,[159–161] whereas others have not observed this.[162,163] Similarly, there is controversy over whether personal atopy is more prevalent after bronchiolitis.[12,154,163,164] Albeit, it is clear that children who wheeze in early life and have atopic features such as allergic sensitization, atopic dermatitis and either blood eosinophilia or allergen-specific IgE are at the highest risk for later asthma. These findings have led to the development of predictive indices to estimate the risk of asthma after wheezing in infancy.[165,166]

There are data to support that allergic sensitization is a risk factor for wheezing with common cold infections in later childhood.[17,167] In an emergency department setting, risk factors associated with acute wheezing episodes were reported.[14] These included the detection of a respiratory virus, most commonly HRV, positive allergen-specific IgE, and the presence of eosinophilia.

Notably, viral infections and allergic inflammation synergistically augmented the risk of wheezing. Moreover, experimental inoculation with HRV is more likely to increase airway responsiveness in allergic individuals compared with nonallergic individuals.[168]
Finally, the risk of hospitalization among virus-infected individuals is amplified in patients who are both sensitized and exposed to respiratory allergens.[17] These results imply that individuals with respiratory allergies or eosinophilic airway inflammation are at increased risk for viral-induced wheezing. However, this theory has not been confirmed with experimentally induced colds, as allergen administration before viral inoculation did not increase cold symptoms.[136,169]

Viral infections are proposed to interact with allergic inflammation, leading to airway dysfunction through several mechanisms. Viral infections could potentially damage the barrier function of the airway epithelium, leading to an enhanced absorption of aeroallergens across the airway wall and subsequent inflammation.[170] Moreover, the production of various cytokines (TNF-α, IL-1β and IL-6), chemokines (CCL3/MIP-1α, CCL5/RANTES, CCL2/MCP-1 and CXCL8/IL-8), leukotrienes and adhesion molecules (ICAM-1) may further upregulate cellular recruitment, cell activation and the ongoing inflammatory response.[171]

Several studies have also demonstrated that HRV infection increases airway hyperresponsiveness in patients with atopy and asthma.[156,167,168,172] Finally, a recent study has demonstrated that the use of prednisolone was associated with less recurrent wheezing in young children with HRV infection but not those with RSV or non-HRV/RSV infections. Thus, HRV infection may be a marker for wheezing children that will respond favorably to corticosteroid treatment.[50]