Virus infection-induced bronchial asthma exacerbation

Abstract

Infection with respiratory viruses, including rhinoviruses, influenza virus, and respiratory syncytial virus, exacerbates asthma, which is associated with processes such as airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. In patients with viral infections and with infection-induced asthma exacerbation, inflammatory mediators and substances, including interleukins (ILs), leukotrienes and histamine, have been identified in the airway secretions, serum, plasma, and urine. Viral infections induce an accumulation of inflammatory cells in the airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Viral infections also enhance the production of inflammatory mediators and substances in airway epithelial cells, mast cells, and other inflammatory cells, such as IL-1, IL-6, IL-8, GM-CSF, RANTES, histamine, and intercellular adhesion molecule-1. Viral infections affect the barrier function of the airway epithelial cells and vascular endothelial cells. Recent reports have demonstrated augmented viral production mediated by an impaired interferon response in the airway epithelial cells of asthma patients. Several drugs used for the treatment of bronchial asthma reduce viral and pro-inflammatory cytokine release from airway epithelial cells infected with viruses. Here, I review the literature on the pathogenesis of the viral infection-induced exacerbation of asthma and on the modulation of viral infection-induced airway inflammation.

Figure 1

Time course changes in peak expiratory flow rate (PEFR) in asthmatic patients (n = 30) before acute asthma exacerbations (baseline) and after treatment with oral glucocorticoids. ↑: the start of treatment of acute asthma exacerbations with oral glucocorticoids. Means and ranges are indicated by open circles with bars. Significant differences from baseline are indicated by **P < 0.01. Significant differences from acute asthma exacerbations are indicated by ⁺ P < 0.05 and ⁺⁺ P < 0.01. (Cited from [19]).

Figure 2

Concentrations of urinary LTE₄ (a) and plasma histamine (b) in control subjects (Control, n = 30) and patients with bronchial asthma (n = 30) at a stable condition (Stable), during exacerbations (Exacerbation) and after 21 days of treatment with oral glucocorticoids when patients showed evidence of clinical improvement (Recovery). Mean values ± S.E.M. are indicated by closed circles with error bars. NS, not significant. (Cited from [19]).

Figure 3

Summary of our findings on the effects of viral infection on the pathogenesis of viral infection-induced asthma exacerbation and on the inhibitory effects of drugs on viral infection. RV: rhinovirus, RSV: respiratory syncytial virus, IL: interleukin, TNF: tumor necrosis factor, GM-CSF: granulocyte-macrophage colony stimulating factor. (Cited from [, , , , , –, –46, 49, 53, 55, 56, 61, 72, 77, 80, 84]).

Figure 4

Histamine release into supernatants of the cell lines from human mast cells (HMC-1) (left side) and basophils (KU812) (right side) in the presence of immunoglobulin E (IgE) plus anti-IgE (IgE + a-IgE) after type 14 rhinovirus (RV14) or sham (control) infection. Results are reported as means ± S.E.M. from 7 samples. Significant differences from RV14 infection alone are indicated by **P < 0.01 and ***P < 0.001. Significant differences from stimulation with IgE + a-IgE alone are indicated by ⁺⁺ P < 0.01 (Cited from [53]).

Figure 5

Effects of dexamethasone (DEX, 1 μM) on release of IL-1β (a) and IL-6 (b) in supernatants after type 14 rhinovirus (RV14), or sham (control) infection. Effects of DEX were examined at maximal production of each cytokine after RV14 infection. Results are reported as means ± S.E.M. from 7 samples. Significant difference from corresponding control values are indicated by ∗P < 0.05, **P < 0.01, ***P < 0.001. Significant difference from RV infection alone are indicated by ⁺⁺ P < 0.01 (Cited from [36]).

Figure 6

Replication of viral RNA in human tracheal epithelial cells at 1 day (24 h) or 3 days (72 h) after infection with type 14 rhinovirus in the presence of procaterol (0.1 μM) (RV + Proc), vehicle (0.01% ethanol) (Control; RV), ICI 118551 (1 μM) (RV + ICI) or the presence of procaterol (0.1 μM) plus ICI 118551 (1 μM) (RV + Proc + ICI) as detected by real-time quantitative RT-PCR. The epithelial cells isolated from the same donors were treated with either procaterol, vehicle, ICI 118551, or procaterol plus ICI 118551. The results are expressed as the relative amount of RNA expression (%) compared with that of maximal rhinovirus RNA at day 3 (72 h) in the cells treated with vehicle, and reported as means ± S.E.M. from 5 samples (2 ex-smokers and 3 non-smokers). Significant differences from treatment with a vehicle (RV) at each time are indicated by *P < 0.05. (Cited from [39]).