Comparison of the effects of repetitive low-dose and single-dose antigen challenge on airway inflammation

Background: Airway allergen provocation provides a model to study allergic inflammation in relationship to pulmonary physiology. Allergen provocation is usually administered as a relatively large single-dose challenge that might not reflect a chronic, natural, low-dose airborne allergen exposure. Objective: We sought to compare the magnitude, characteristic features, and kinetics of airway inflammation induced by means of repetitive low-dose antigen challenges with those factors induced by means of an equivalent single-dose allergen challenge in allergic asthma. Methods: This was a 2-period crossover study. During separate phases, each subject was administered either a predetermined single-dose antigen challenge or 25% of that dose on each of 4 consecutive days. The airway response to allergen challenge was determined by means of measurement of pulmonary function and sputum features of inflammation, including eosinophil, eosinophil derived neurotoxin, and fibronectin levels. Results: Both models of antigen challenge caused significant and equivalent sputum eosinophilia. The immediate decrease in FEV1 and the FEV1/forced vital capacity ratio and the increase in sputum eosinophilia, eosinophil-derived neurotoxin, and fibronectin levels occurred gradually over the first 3 low doses and then reached a plateau or tended to decrease with the fourth antigen exposure. Conclusion: Our data suggest that although the 2 challenge models had similar quantitative effects on lung function and sputum eosinophilia, the qualitative responses and kinetics of these changes were distinct. Repetitive low doses of antigen, as might mimic natural allergy exposure, produced an equivalent inflammatory response to the large single-dose challenge but with a smaller amount of antigen, suggesting that priming and accumulative effects might have occurred. Moreover, our limited data also suggest that immunologic tolerance might be induced by frequent challenges.