| Effects of Inhaled Brevetoxins in Allergic Airways: Toxin-Allergen Interactions and Pharmacologic Intervention William M. Abraham,1 Andrea J. Bourdelais,2 Ashfaq Ahmed,1 Irakli Serebriakov,1 and Daniel G. Baden2 1Division of Pulmonary and Critical Care Medicine, University of Miami at Mount Sinai Medical Center, Miami Beach, Florida, USA; 2Center for Marine Science, University of North Carolina at Wilmington, Wilmington, North Carolina, USA Abstract
During a Florida red tide, brevetoxins produced by the dinoflagellate Karenia brevis become aerosolized and cause airway symptoms in humans, especially in those with pre-existing airway disease (e.g., asthma) . To understand these toxin-induced airway effects, we used sheep with airway hypersensitivity to Ascaris suum antigen as a surrogate for asthmatic patients and studied changes in pulmonary airflow resistance (RL) after inhalation challenge with lysed cultures of K. brevis (crude brevetoxins) . Studies were done without and with clinically available drugs to determine which might prevent/reverse these effects. Crude brevetoxins (20 breaths at 100 pg/mL ; n = 5) increased RL 128 ± 6% (mean ± SE) over baseline. This bronchoconstriction was significantly reduced (% inhibition) after pretreatment with the glucocorticosteroid budesonide (49%) , the β2 adrenergic agent albuterol (71%) , the anticholinergic agent atropine (58%) , and the histamine H1-antagonist diphenhydramine (47%) . The protection afforded by atropine and diphenhydramine suggests that both cholinergic (vagal) and H1-mediated pathways contribute to the bronchoconstriction. The response to cutaneous toxin injection was also histamine mediated. Thus, the airway and skin data support the hypothesis that toxin activates mast cells in vivo. Albuterol given immediately after toxin challenge rapidly reversed the bronchoconstriction. Toxin inhalation increased airway kinins, and the response to inhaled toxin was enhanced after allergen challenge. Both factors could contribute to the increased sensitivity of asthmatic patients to toxin exposure. We conclude that K. brevis aerosols are potent airway constrictors. Clinically available drugs may be used to prevent or provide therapeutic relief for affected individuals. Key words: animal models, asthma, brevetoxin, bronchoconstriction, clinical therapies. Environ Health Perspect 113: 632-637 (2005) . doi:10.1289/ehp.7498 available via http://dx.doi.org/ [Online 10 February 2005]
This article is part of the mini-monograph "Aerosolized Florida Red Tide Toxins (Brevetoxins) ." Address correspondence to W.M. Abraham, Department of Research, Mount Sinai Medical Center, 4300 Alton Rd., Miami Beach, FL 33140 USA. Telephone: (305) 674-2790. Fax: (305) 674-2790. E-mail: abraham@msmc.com This research was supported by National Institute of Environmental Health Sciences grant P01 ES 10594. The authors declare they have no competing financial interests. Received 2 August 2004 ; accepted 13 January 2005.
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