Effects of inhaled brevetoxins in allergic airways: Toxin-allergen interactions and pharmacologic intervention

William M. Abraham, Andrea J. Bourdelais, Ashfaq Ahmed, Irakli Serebriakov, Daniel G. Baden

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)632-637
Number of pages6
JournalEnvironmental Health Perspectives
Volume113
Issue number5
DOIs
StatePublished - May 2005

Keywords

  • Animal models
  • Asthma
  • Brevetoxin
  • Bronchoconstriction
  • Clinical therapies

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

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