Effect of Ozone Exposure on Airway Responses to Inhaled Allergen in Asthmatic Subjects

Background: Controlled human exposure studies have produced conflicting results regarding the effect of ozone on the early bronchoconstrictor response to inhaled allergen in specifically sensitized asthmatic subjects. Spirometric parameters do not necessarily reflect the airway inflammatory effects of inhaled ozone or allergen. Objective: This study was designed to investigate whether exposure to ozone enhances the late airway inflammatory response, as well as the early bronchoconstrictor response, to inhaled house dust mite allergen in sensitized asthmatic subjects. Design: Randomized, counter-balanced, cross-over study. Setting: Human exposure laboratory. Methods: Fourteen subjects were exposed to 0.2 ppm O3 or filtered air, on separate days, for 1 h during exercise. After each exposure, the subjects were challenged with doubling doses of Dermatophagoides farinae (DF) allergen (provocative concentration of DF causing a 15% decrease in FEV1 [PC15]). At 6 h after allergen challenge, bronchoscopy with BAL, proximal airway lavage (PAL), and endobronchial biopsy were performed. The second exposure/allergen challenge/bronchoscopy sequence was performed at least 4 weeks after the first sequence. Results: No significant difference in cellular or biochemical markers of the late inflammatory response after allergen was found between the ozone and air exposures (although a trend toward increased neutrophils was noted after ozone exposure in the PAL fluid, p 0.06). For the group as a whole, no significant difference in PC15 was demonstrated after ozone exposure compared to air exposure. However, subjects with the greatest ozone-induced decrements in FEV1 tended to have lower PC15 values after ozone exposure. Conclusion: Exposure to a relatively low-level concentration of ozone does not enhance the late inflammatory or early bronchoconstrictor response to inhaled antigen in most allergic asthmatic subjects. Our results do suggest, however, that a subgroup of asthmatics may acquire increased sensitivity to aeroallergens after exposure to ozone. (CHEST 2004; 125:2328 –2335) Abbreviations: AU allergen units; DF Dermatophygoides farinae; ECP eosinophil cationic protein; GMCSF granulocyte-macrophage colony-stimulating factor; IL interleukin; MPO neutrophil myeloperoxidase; PAL proximal airway lavage; PC15 concentration of Dermatophygoides farinae causing a 15% decrease in FEV1 from the post-saline solution baseline; PC20 concentration of methacholine causing a 20% decrease in FEV1 from the post-saline solution baseline; Sraw specific airway resistance