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      Initial Evaluation of the Effects of Aerosolized Florida Red Tide Toxins (Brevetoxins) in Persons with Asthma

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          Abstract

          Florida red tides annually occur in the Gulf of Mexico, resulting from blooms of the marine dinoflagellate Karenia brevis. K. brevis produces highly potent natural polyether toxins, known as brevetoxins, that activate voltage-sensitive sodium channels. In experimental animals, brevetoxins cause significant bronchoconstriction. A study of persons who visited the beach recreationally found a significant increase in self-reported respiratory symptoms after exposure to aerosolized Florida red tides. Anecdotal reports indicate that persons with underlying respiratory diseases may be particularly susceptible to adverse health effects from these aerosolized toxins. Fifty-nine persons with physician-diagnosed asthma were evaluated for 1 hr before and after going to the beach on days with and without Florida red tide. Study participants were evaluated with a brief symptom questionnaire, nose and throat swabs, and spirometry approved by the National Institute for Occupational Safety and Health. Environmental monitoring, water and air sampling (i.e., K. brevis, brevetoxins, and particulate size distribution), and personal monitoring (for toxins) were performed. Brevetoxin concentrations were measured by liquid chromatography mass spectrometry, high-performance liquid chromatography, and a newly developed brevetoxin enzyme-linked immunosorbent assay. Participants were significantly more likely to report respiratory symptoms after Florida red tide exposure. Participants demonstrated small but statistically significant decreases in forced expiratory volume in 1 sec, forced expiratory flow between 25 and 75%, and peak expiratory flow after exposure, particularly those regularly using asthma medications. Similar evaluation during nonexposure periods did not significantly differ. This is the first study to show objectively measurable adverse health effects from exposure to aerosolized Florida red tide toxins in persons with asthma. Future studies will examine the possible chronic effects of these toxins among persons with asthma and other chronic respiratory impairment.

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          Most cited references37

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          Lung function testing: selection of reference values and interpretative strategies. American Thoracic Society.

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            Comparative deposition of inhaled aerosols in experimental animals and humans: a review.

            The biological effects of inhaled aerosols are often related to their site(s) of deposition within the respiratory tract. However, deposition patterns may differ between humans and those experimental animals commonly used in inhalation toxicology studies, making cross-species risk extrapolations difficult. This paper reviews the factors that control deposition and synthesizes much of the available data on comparative regional deposition.
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              Natural and Derivative Brevetoxins: Historical Background, Multiplicity, and Effects

              Symptoms consistent with inhalation toxicity have long been associated with Florida red tides, and various causal agents have been proposed. Research since 1981 has centered on a group of naturally occurring trans-fused cyclic polyether compounds called brevetoxins that are produced by a marine dinoflagellate known as Karenia brevis. Numerous individual brevetoxins have been identified from cultures as well as from natural bloom events. A spectrum of brevetoxin derivatives produced by chemical modification of the natural toxins has been prepared to examine the effects of functional group modification on physiologic activity. Certain structural features of natural and synthetic derivatives of brevetoxin appear to ascribe specific physiologic consequences to each toxin. Differential physiologic effects have been documented with many of the natural toxins and derivatives, reinforcing the hypothesis that metabolism or modification of toxin structures modulates both the specific toxicity (lethality on a per milligram basis) and potentially the molecular mechanism(s) of action. A series of naturally occurring fused-ring polyether compounds with fewer rings than brevetoxin, known as brevenals, exhibit antagonistic properties and counteract the effects of the brevetoxins in neuronal and pulmonary model systems. Taken together, the inhalation toxicity of Florida red tides would appear to depend on the amount of each toxin present, as well as on the spectrum of molecular activities elicited by each toxin. Toxicity in a bloom is diminished by the amount brevenal present.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institue of Environmental Health Sciences
                0091-6765
                May 2005
                10 February 2005
                : 113
                : 5
                : 650-657
                Affiliations
                1National Institute of Environmental Health Sciences Marine and Freshwater Biomedical Sciences Center, University of Miami Rosenstiel School of Marine and Atmospheric Sciences, Miami, Florida, USA;
                2University of Miami School of Medicine, Miami, Florida, USA;
                3Mote Marine Laboratory, Sarasota, Florida, USA;
                4National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA;
                5Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio, USA;
                6Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA;
                7Center for Marine Science Research, University of North Carolina at Wilmington, Wilmington, North Carolina, USA;
                8Florida Department of Health, Tallahassee, Florida, USA;
                9Harbor Branch Oceanographic Institution, Fort Pierce, Florida, USA;
                10Twin Cities Hospital, Niceville, Florida, USA
                Author notes
                Address correspondence to L.E. Fleming, c/o Department of Epidemiology and Public Health, University of Miami School of Medicine, 1801 NW 9th Ave., Highland Professional Building, Suite 200 (R 669), Miami, FL 33136 USA. Telephone: (305) 243-5912. Fax: (305) 243-3384. E-mail: lfleming@med.miami.edu

                This article is part of the mini-monograph “Aerosolized Florida Red Tide Toxins (Brevetoxins).”

                This study could not have been performed without the help of numerous volunteer investigators, including T.C. Fleming, C. Fleming, M. Johnson, W. Quirino, M. Friedman, D. Squicciarini, L. Pitman, and T. Pitman (University of Miami National Institute of Environmental Health Sciences Center); J. Horton, J. Howell, R. Sabogal, C. Bell (Centers for Disease Control and Prevention); P. Stack, G. Kirkpatrick, and C. Higham (Mote Marine Laboratory, Sarasota, FL). We also thank A. Weidner from the University of North Carolina at Wilmington for her help with the enzyme-linked immunosorbent assay analysis. Environmental monitoring was performed with help from S. Campbell (University of North Carolina at Wilmington); T. Blum, S. Hamel, B. Turton (Mote Marine Laboratory); D.A. Kracko, J. McDonald, and C.M. Irvin (Lovelace Respiratory Research Institute). We also thank the Mote Marine Laboratory, Sarasota County Parks and Recreation Department, the Coquina and Helmseley hotels, and all our volunteer participants and their families in Sarasota, Florida.

                This research was supported by National Institute of Environmental Health Sciences (NIEHS) grant P01 ES 10594 and a Minority Supplement to the P01 also from the NIEHS, as well as by the Centers for Disease Control and Prevention, the Florida Harmful Bloom Taskforce, and the Florida Department of Health.

                The authors declare they have no competing financial interests.

                Article
                ehp0113-000650
                10.1289/ehp.7500
                1257563
                15866779
                ea1dea07-de0b-44c8-9802-13668661a17a
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 2 August 2004
                : 19 January 2005
                Categories
                Mini-Monograph: Brevetoxins

                Public health
                copd,asthma,brevetoxins,red tides,sensitive populations,karenia brevis,spirometry,harmful algal blooms (habs)

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