Allergen-induced airway inflammation and its therapeutic intervention

Abstract

Allergen inhalation challenge has been useful for examining the mechanisms of allergen-induced airway inflammation and the associated physiological changes and for documenting the efficacy of drugs to treat asthma. Allergen inhalation by a sensitized subject results in acute bronchoconstriction, beginning within 15-30 min and lasting 1-3 hr, which can be followed by the development of a late asthmatic response. Individuals who develop both an early and late response after allergen have more marked increases in airway hyperresponsiveness, and greater increases in allergen-induced airway inflammation, particularly in airway eosinophils and basophils. All of the currently available and effective treatments for asthma modify some aspects of allergen-induced responses. These medications include short-acting and long-acting inhaled beta(2)-agonists, inhaled corticosteroids, cromones, methylxanthines, leukotriene inhibitors, and anti-IgE monoclonal antibody. In addition, allergen inhalation challenge has become a useful method which can, in a very limited number of patients, provide key information on the therapeutic potential of new drugs being developed to treat asthma.

Keywords: allergen; asthma; drug development; inflammation.

Fig. 1

The effect of therapy on the airway response to inhaled allergen; demonstrating time course of the mean (SD) decline in FEV₁ (expressed as percent of pre-challenge FEV₁ values) following allergen challenge to assess the efficacy of ten days of treatment with an inhaled corticosteroid (budesonide; 400 mcg daily) and a leukotriene antagonist (montelukast; 10 mg daily) on the early and late airway response to inhaled allergen in ten asthmatic subjects. Significant attenuation of the early response was observed with either montelukast or the combination of budesonide and montelukast when compared with placebo. Significant attenuation of the late airway response was observed by all three active treatment regimens when compared with placebo.

Fig. 2

The mean (SD) percentage of sputum eosinophils before and after an inhaled corticosteroid (budesonide) and a leukotriene antagonist (montelukast) before and following an allergen inhalation challenge. There was a subsequent reduction in the allergen-induced eosinophilia in the presence of all treatments. ^*Indicates significant difference from pre-allergen value in the same treatment group. Filled triangles indicate a significant difference from placebo at the same time point.