Role of infection in the development and exacerbation of asthma

Abstract

Respiratory infections are associated with wheezing illnesses in all ages and may also impact the development and severity of asthma. Respiratory tract infections caused by viruses, Chlamydophila or Mycoplasma have been hypothesized to have significant roles in the pathogenesis of asthma. Progress is being made toward establishing the mechanisms by which these agents can cause acute wheezing and impact the pathophysiology of asthma. Host factors probably contribute to the risk of asthma inception and exacerbation, and these contributions may also vary with respect to early- versus adult-onset disease. This review discusses these various associations as they pertain to the development and exacerbation of asthma.

Keywords: asthma; asthma inception; exacerbation; respiratory infection; virus.

Figure 1. Model of infection-triggered airway epithelial cell injury with variable responses that may contribute to asthma symptoms

After upper airway infection and viral replication, epithelial cell lysis occurs, releasing virus particles and danger signals (including ATP), which act to stimulate resident antigen-presenting cells such as dendritic cells. Defense mechanisms include the epithelial cell production of interferons and initiation of apoptosis to limit viral productivity. Dendritic cell-derived chemokines initiate the recruitment of granulocytes and lymphocytes to assist with viral clearance. Attenuated IFN production and/or P2X7 pore function are correlated with less upper airway inflammation and a greater risk of acute asthma symptoms. This may result in lower airway infection with subsequent epithelial cell injury. The presence of IL-13 has been shown to delay epithelial tight junction formation, which may render the airway more susceptible to chronic asthmagenic environmental stimuli. Vitamin D has been shown to promote epithelial cell differentiation and has numerous innate immune effects; whether supplementation strategies affect asthma outcomes has not been evaluated. IFN: Interferon.