Viral Infections and Associated Factors That Promote Acute Exacerbations of Asthma

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

Several studies have shown that viral infections precede bacterial infections of the upper and lower airways and may affect disease severity (e.g., increased invasive pneumococcal disease during high RV and RSV activity). 62 This may occur for several reasons, including virus-induced expression of airway receptors used by bacteria for cell invasion and disruption of airway epithelial layers. 63 Viruses and bacteria also increase release of inflammatory cytokines and mediators from epithelial cells and leukocytes, causing increased inflammation with a concomitant increase in symptoms and risk of asthma exacerbation. 3 Patients with stable asthma have even exhibited increased colonization of upper and lower airways with Proteobacteria, a group of bacteria predominantly composed of gram-negative species. 64 The possible role of bacteria in the early stages of asthma has been demonstrated by Bisgaard et al. 65 who found that S. pneumonia, H. influenzae, or M. catarrhalis colonization of the upper airway in early infancy was associated with increased risk of recurrent wheezing leading to asthma. Furthermore, wheezing illnesses in young children are similarly associated with detection of either viral or bacterial pathogens in the airway. 66 RV infections can promote increased detection of bacterial pathogens, and the combination of RV infection with detection of respiratory pathogens is associated with a greater risk for illness, including exacerbation of asthma. 3 Similarly, acute wheezing illnesses in infants or school-aged children are associated with both viral infections and airway microbiota that are dominated by bacterial pathogens. 67 This raises the possibility that selective use of antibiotics or vaccination could be useful in asthma. In wheezing infants, 2 controlled studies have reported that azithromycin produced clinical benefit in infants with acute wheezing. 68 Whether this is due to antimicrobial effects or anti-inflammatory effects of the macrolide is uncertain. Given that repeated antibiotic therapy could have adverse effects on commensal bacteria, and could also add to the problem of drug-resistant bacteria, more research is needed on long-term effects of this approach.