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LOW-DOSE AIRBORNE ENDOTOXIN EXPOSURE ENHANCES BRONCHIAL RESPONSIVENESS TO INHALED ALLERGEN IN ATOPIC ASTHMATICS
Citation:
Boehlecke, B. A., N. E. Alexis, M. J. Hazucha, R. Jacobs, P A. Bromberg, P. C. Reist, AND D. B. Peden. LOW-DOSE AIRBORNE ENDOTOXIN EXPOSURE ENHANCES BRONCHIAL RESPONSIVENESS TO INHALED ALLERGEN IN ATOPIC ASTHMATICS. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. Journal of Allergy Clinical Immunology, 112(6):1241-1243, (2003).
Impact/Purpose:
To evaluate the effect of endotoxin on the response to allergen
Description:
Endotoxin exposure has been associated with both protection against development of TH2-immune responses during childhood and exacerbation of asthma in persons who already have allergic airway inflammation.1 Occupational and experimental inhalation exposures to endotoxin have been reported to induce bronchospasm in both asthmatic and nonasthmatic persons, but it has been postulated that asthmatic persons have increased airway reactivity to endotoxin.1 Michel et al2 observed that asthma severity in mite-allergic asthmatic persons correlated better with levels of endotoxin than with mite allergen in dust samples recovered from their homes. Our group has demonstrated that allergen-induced inflammation enhances the response to endotoxin in the nasal airways and that baseline sputum eosinophilia is associated with neutrophilic response to inhaled endotoxin.3,4 These studies suggest that allergen and endotoxin may act synergistically in the airway. We have previously reported that ozone exposure enhances immediate airway response to inhaled allergen and hypothesized that inhaled endotoxin would have a similar effect.5
Teeuw et al6 reported increased symptoms in office workers exposed to ambient levels of endotoxin (100 to 408 ng/m3) that are considerably lower than those pres-ent in some occupational exposures (>5000 ng/m3 in very contaminated workplaces) or used in most human challenge experiments. We thought that it was important to determine if exposure to an endotoxin concentration approximating these indoor environments enhances response to inhaled allergens in mildly mite-sensitive asthmatic persons. Participants underwent double-blinded 4-hour chamber exposures to clean air and airborne particulate?associated endotoxin (approximate concentration, 500 ng/m3) in randomized order separated by at least 3 weeks. Approximately 1 hour after each exposure, they underwent a graded-dose inhaled allergen challenge, then were monitored by spirometry until stable and admitted to the General Clinical Research Center (GCRC) for overnight observation. The study was approved by the Committee for the Protection of the Rights of Human Subjects and the Clinical Research Advisory Committee of the GCRC of the University of North Carolina School of Medicine.