Table 1.

Summaries of studies on Karenia brevis aerosols and health (n = 15).

Author and year	Location	Exposure assessment method	Population and study period	measured outcome	Findings summary
Backer 2003	Sarasota and Jacksonville, Florida, USA	Seawater samples were collected twice per day to measure the concentrations of K.brevis cells and brevetoxins. To obtain spatial brevetoxin distribution over the beach and surrounding areas, six high-volume air samplers were placed. Brevetoxin analyses were performed by High Performance Liquid Chromatography (HPLC). Exposure was then categorized into three levels according to K. brevis cells or brevetoxin concentrations: low/no exposure, moderate exposure, and high.	129 adults (≥18 years) who spent time (10 min to ∼8 h; average of 71 min) on beaches in Sarasota or Jacksonville during February and October 1999.	Pre- and post-beach visits. Spirometry test values: peak expiratory flow (PEF); forced expiratory volume in 1s (FEV1); forced vital capacity (FVC); and the ratio of FEV1 to forced vital capacity (FEV1/FVC). Upper respiratory symptoms (eye and throat irritation, nasal congestion, cough), lower respiratory symptoms (chest tightness; wheezing; shortness of breath), and other symptoms (itchy skin; headaches; and others) as measured by questionnaires. The nasal–pharyngeal swabs were collected to compare the inflammatory response, as measured by the relative percentages of neutrophils vs. chronic inflammatory cells (e.g., macrophages, lymphocytes, plasma cells).	After exposure to aerosolized brevetoxins during red tide events, participants experienced upper and lower respiratory irritation. Those with high or medium exposure reported more symptoms than low/no exposure participants. An increase in inflammation (mostly acute and sub-acute in nature) in the nose and/or throat swab sample was observed in 49% and 39% of participants sampled on high and moderate exposure days, respectively. No significant changes in pulmonary function were reported.
Backer 2005	Sarasota and Manatee, Florida, USA	For cell counts, water samples were collected three times per each day from the surf zone adjacent to the study high-volume air sampler locations. To assess lifeguard exposure to brevetoxins in the air, samples were collected using high-volume air samplers and personal breathing zone samplers. Brevetoxins from the environmental and personal air samplers were analysed via liquid chromatography-mass spectrometry (LC-MS) and enzyme-linked immunosorbent assay (ELISA).	28 healthy lifeguards (≥18 years) who are occupationally exposed to red tide toxins during daily work activities. Unexposed period: May 2002, January 2003; exposed period: September 2001, March 2003.	Spirometry and symptoms before and after 8-hr shifts during an unexposed period and again during an exposure period. Spirometry tests: FVC; FEV1; FEV1/FVC percentage; FEF25–75%; and PEF. Upper respiratory symptoms (eye and throat irritation, nasal congestion, cough), lower respiratory symptoms (chest tightness; wheezing; shortness of breath), and other symptoms (itchy skin; headache; and other) measured by questionnaires.	Brevetoxin concentration levels displayed spatial and temporal variability. Compared with unexposed periods, the group of lifeguards reported upper respiratory symptoms and headache during the periods of aerosolized brevetoxin exposure but did not report lower respiratory symptoms. No impact of exposure on pulmonary function, with or without mild exercise, was reported.
Fleming 2005	Sarasota, Florida, USA	For cell counts, water samples were collected three times per each day from the surf zone adjacent to the study high-volume air sampler locations. Samples were collected using high-volume air samplers equipped to capture aerosol particles by size, and personal breathing zone samplers. Concentrations of brevetoxins on portions of the samplers, as well as the nasal and throat swabs, were analysed by LC-MS and ELISA.	59 persons (≥12 years) with physician-diagnosed asthma. The use of asthma medications within 12 h before going to the beach was used as a surrogate for asthma severity. Unexposed period: January 2003; exposed period: March 2003.	Spirometry test values before and after 1 h exposure: FVC; FEV1; FEV1/FVC percentage; FEF25–75%; and PEF. Respiratory symptoms (cough; wheezing; shortness of breath; chest tightness), and other symptoms (throat irritation; nasal congestion; eye irritation; headache; itchy skin; and diarrhoea) measured by questionnaires. The nose and throat swabs taken pre- and post- beach trips were analysed for neutrophils and chronic inflammatory cells, protein transudation, amount of fibrin, and percentage of reactive epithelial cells	Participants were significantly more likely to report respiratory symptoms and report respiratory impairment after Florida red tide exposure. Participants demonstrated small but statistically significant decreases in FEV1 FEF25–75%, and PEF; stronger effects were seen among those regularly using asthma medications. Increased but not statistically significant levels for inflammation were seen.
Kirkpatrick 2006	Sarasota, Florida, USA	The red tide cell count data were provided by the Phytoplankton Ecology Program at Mote Marine Laboratory, Sarasota, FL. This program routinely monitors a minimum of two shore locations on its campus. Water samples are analysed weekly during non-bloom conditions and daily during blooms; blooms are defined as when cell counts are over 100,000 cells/L.	Emergency room (ER) visits between two time periods; October 1–December 31, 2001 (red tide period) and October 1–December 31, 2002 (non-red tide period) in Sarasota, FL.	Using the ICD-9 codes (460–519), diagnoses were categorized as pneumonia, bronchitis, asthma, upper airway disease, or all other primary diagnoses.	A significant increase in the rate of annual ER admissions were found for respiratory diseases (pneumonia – by 31%, bronchitis – 56%, asthma – 44%, and upper airway disease – 64%) during the 2001 red tide exposure period vs. the 2002 non-red tide period in the coastal areas. No increases were seen in the non-coastal areas.
Milian 2007	Sarasota, Florida, USA	Six high volume air samplers collecting brevetoxin levels and particle size were placed on the beach in the same area where study participants walked for 1 h. Near shore water samples were collected 3 times per day and evaluated for cell counts and brevetoxin concentrations. Every participant carried a personal air sampler during their beach walk to determine an individualized aerosol dose. Brevetoxin analyses for all environmental monitoring were performed by HPLC and by ELISA.	97 persons (≥12 years) with physician-diagnosed asthma (unexposed period: March 2003 and, March 2005; exposed period: January 2003, May 2004 October 2004).	Respiratory symptoms (e.g., eye and/or throat irritation; nasal congestion; cough; wheeze; chest tightness; and shortness of breath) and other symptoms designed to identify people who over-report symptoms (e.g., headache; itchy skin and/or diarrhoea), as well as the use of asthma medications, were recorded before and after each 1-h beach walk. The participants further categorized and scored their symptom intensity.	Inhalation of aerosolized brevetoxins during exposure events resulted in statistically significant increases in the respiratory symptom intensity scores; both coastal and inland residents both reacted significantly, suggesting that location of residence does not modify the observed relationships. Asthmatics who use medications reported fewer changes in respiratory symptom intensity compared with non-medicated asthmatics when exposed to aerosolized brevetoxins.
Fleming 2007	Sarasota, Florida, USA	Water samples were collected twice daily and analysed for K. brevis cell counts and for brevetoxin using both the ELISA and LC-MS analyses. To sample air for toxin and particulate size, three types of samplers were used: high-volume air samplers; high volume air with impactors to capture aerosol particles by size; and personal breathing zone monitors.	97 persons (≥12 years) with physician-diagnosed asthma (unexposed period: March 2003 and, March 2005; exposed period: January 2003, May 2004 October 2004).	Respiratory (cough, wheezing, shortness of breath, chest tightness); other (throat irritation, nasal congestion, eye irritation, headache, itchy skin, diarrhoea) symptoms. Spirometry test values pre- and post-beach visit (FVC; FEV1; FEV1/FVC percentage; FEF25–75%; and PEF.) The use of asthma medications within 12 h before going to the beach was used as a surrogate for increased asthma severity.	Participants were significantly more likely to report respiratory symptoms after brevetoxin aerosol exposure than before exposure. Participants demonstrated small, but statistically significant, decreases in FEV1, FEF25–75%, and PEF after brevetoxin exposures, particularly among those participants regularly using asthma medications.
Fleming 2009	Sarasota, Florida, USA	Water samples were collected twice daily and analysed for K. brevis cell counts and for brevetoxin using both the ELISA and LC-MS analyses. To sample air for toxin and particulate size, three types of samplers were used: high-volume air samplers; high volume air with impactors to capture aerosol particles by size; and personal breathing zone monitors.	87 persons (≥12 years) with physician-diagnosed asthma. Florida red tide exposure periods in March 2005 and September 2006.	Respiratory (cough, wheezing, shortness of breath, chest tightness); other (throat irritation, nasal congestion, eye irritation, headache, itchy skin, diarrhoea) symptoms. Spirometry test values pre- and post-beach visit (FVC; FEV1; FEV1/FVC percentage; FEF25–75%; and PEF.) The use of asthma medications within 12 h before going to the beach was used as a surrogate for increased asthma severity.	After 1-hr of exposure to low concentrations of brevetoxin aerosols, asthmatics had statistically significant increases in self-reported respiratory symptoms and total symptom scores. Pulmonary function changes were not observed. Symptoms increased significantly in those not using asthma medication and those living inland.
Hoagland 2009	Sarasota, Florida, USA	In situ K. brevis cell counts in the ocean served as a proxy for aerosolized brevetoxin concentrations. Water samples were collected at two Sarasota Bay locations and analysed weekly during non-bloom conditions and daily during blooms. The in situ cell count was averaged from the two stations.	The total number of daily emergency department (ED) visits for respiratory diagnoses (October 2001–September 2006)	Hospital emergency department visits (2001–2006) at Sarasota Memorial Hospital for total of all four respiratory diseases (pneumonia, bronchitis, asthma, upper airway disease UAD) and a combination of UAD and bronchitis.	The statistical models showed that the number of emergency department visits for respiratory ailments was positively associated with 1-week lagged K. brevis cell counts after adjustment for confounders (e.g., temperature, Flu season, pollen counts, tourist visits). The models estimated the marginal costs of illness for respiratory ED visits associated with blooms to be ranging from $0.5 to $4 million, depending on the bloom severity.
Kirkpatrick 2010	Sarasota, Florida, USA	The red tide cell count data were provided by the Phytoplankton Ecology Program at Mote Marine Laboratory, Sarasota, FL. This program routinely monitors a minimum of two shore locations on its campus. Water samples are analysed weekly during non-bloom conditions and daily during blooms	The total number of emergency room (ER) admissions during the Florida red tide bloom period was during the fall of 2001 (September 1–December 31, 2001), and the non-bloom period during the fall of 2002 (September 1–December 31, 2002). The number of ER admissions was similar (21,308 in 2001 vs. 22,270 in 2002).	ER admission diagnosis with the ICD-9 codes for gastrointestinal (GI) diseases (530–579). Further classification for selected outcomes most consistent with exposure to brevetoxins: gastritis, duodenitis, and non-infectious enteritis and colitis (acute, chronic, unspecified, and other) (ICD 535.0–537.9 and 557.0–558.0).	ER admissions rates (adjusted for age) were not significantly different between the 2 years for all GI diseases (RR = 1.01; 95% CI: 0.92–1.10). ER admissions rates for the selected gastrointestinal diagnoses (RR = 1.40; 95% CI: 1.06–1.84) were significantly different for the Florida red tide bloom period compared to the no red tide period. No significant difference between the 2 time periods for the ER admission rates for all other gastrointestinal diagnoses (1.04; 0.94–1.16).
Bean 2011	Sarasota, Florida, USA	Participants spent ≥1 h at the beach with field/personal environmental monitoring. Each participant had at least evaluation during an active bloom (exposure period) and during a period without a bloom (non-exposure period) each. Measures of red tide toxins were through monitoring (cell counts for K. brevis > 100,000 cells/L in the sampled water), brevetoxins detected via ELISA, and/or LCMS in both water and air.	125 asthmatic participants (self-reported diagnosis by a physician; ≥12 years old; smoked for ≤10 years; able to walk ≥30 min on the beach; resident of the Sarasota, Florida for ≥6 months) in a cohort of asthmatics over 7 years. 38 participants with 1 exposure study (Group 1) were compared to 36 who participated in ≥4 studies (Group 2).	Pre- and post-exposure pulmonary functions measured by spirometry (the pre-exposure percent predicted values for FEV1, PEF, and FEF25–75%). A respiratory symptom intensity score – mild (1), moderate (2), and severe (3).	There were no significant changes in the pulmonary functions associated with exposure over a 7-year period among the participants who participated in ≥4 exposure evaluations, indicating that living in areas with occasional K. brevis blooms do not exhibit long-term respiratory effects from repeated, intermittent exposures to brevetoxin aerosols.
Kirkpatrick 2011	Sarasota, Florida, USA	Water samples were collected twice daily at Siesta Key beach during the main beach study and throughout the 5 days follow-up study. The water samples were analysed for K. brevis cell counts and for brevetoxin concentrations, using brevetoxin ELISA and LC–MS analyses. During the primary beach study, air samples for toxin and aerosol particle size were collected using two types of high-volume samplers and a personal sampler of the subjects' breathing zones.	52 participants (≥12 years) with self-report of physician-diagnosed asthma and who agreed to do study activities over 5 additional days after the day of their initial 1 h beach exposure.	The spirometry values included the peak expiratory flow (PEF). Respiratory symptoms established as relevant to brevetoxin exposure in past studies (cough, wheeze, throat irritation, shortness of breath, chest tightness, nasal congestion, eye irritation, and headache) were asked before and after spending 1 h on the beach, as well as in the follow-up interviews and symptom diaries. Categorized as severe asthmatics vs. controlled asthmatics based on the use of asthma medications within 12 h before going to the beach.	Asthmatics may continue to experience increased symptoms and suppressed respiratory function suppression for several days after 1 h of exposure to the brevetoxin aerosols. After exposure during an active bloom, subjects had elevated mean symptoms which did not return to the pre-exposure baseline for at least 4 days. The PEF measurements decreased after the initial beach exposure, with a subsequent additional delayed effect within 24 h, and continued to be suppressed after 5 days. Most pronounced effects were seen in severe asthmatics and those living inland.
Hoagland 2014	6 counties in Southwest Florida, USA	Two measures of red tides: (1) opportunistic water sampling of the number of K. brevis cells per litre of seawater within 15 km of the coast collected once blooms were known to occur; and (2) the closures of individual shellfish harvesting areas to mitigate illnesses resulting from the consumption of contaminated shellfish.	Monthly emergency department (ED) data 2005–2009 and monthly hospital inpatient data from 1999 to 2009 in older (≥55 years) patients	Diseases of the respiratory system (ICD-9 codes 460.0–519.2) and diseases of the digestive system (520.0–579.9) using a time-series model using monthly data at the county level	Adverse respiratory and digestive health effects were significantly associated with increases in two measures of red tides. Annual costs of illness ranged from $60,000 to $700,000, potentially exceeding $1 million per year for severe red tide blooms
Diaz 2019	6 counties in Southwest Florida, USA	Measures of red tide blooms were compiled using counts of K. brevis cells obtained through opportunistic water sampling efforts along the Gulf coast during the study period. These included all K. brevis counts greater than 103 cell counts/L within 15 km of waters of the counties. As sampling was not consistent across space and time, the maximum cell count in a month and county was used to represent bloom severity.	Emergency department (ED) visits in older (≥55 years) patients between 2005 and 2009	Headache (ICD-9 784.0) as a primary diagnosis	Significant increases in ED visits for headaches as the primary diagnosis were observed during coastal K. brevis blooms
Abdullah 2022	5 counties in Southwest Florida, USA	A surrogate variable for aerosolized brevetoxin was developed, which generated an estimate of exposure derived from K. brevis cell counts in coastal waters in relation to the participants' home location.	Data on past medical history and medical symptoms were collected from n = 258 participants enrolled between June 2019 and August 2021; n = 70 were seen twice.	Upper respiratory tract symptoms (coughing, sneezing, sore throat, nasal congestion); neurological (headaches and dizziness); and systemic outcomes (fever, chills, nausea).	A linear dose-dependent relationship between the magnitude of K. brevis blooms and upper respiratory tract symptoms was seen. Linear dose–response relationship between exposure and neurotoxin shellfish poisoning-like symptoms (weakness, headaches, dizziness, muscle pain, stiff neck, metallic taste); no impact of seafood consumption on this relationship, suggesting that brevetoxin aerosols can induce these symptoms.
Stumpf 2022	Sarasota and Manatee Counties, Florida, USA	Monthly and annual bloom severity indices (BSI) derived from the historical cell count observations along the southwest Florida shoreline.	Beach Conditions Reporting System (BCRS) provided respiratory irritation reports based on the intensity of the coughing as routinely reported by volunteers. Eight beach sites in Sarasota and Manatee Counties, Florida; August 2006–January 2019	Respiratory irritation conditions reported once or twice daily by the volunteers were used to determine the respiratory measure falling into the 4 categories (none, slight, moderate, high) for each beach site. A monthly respiratory irritation index (RI) was developed using the sum of days with respiratory irritation observations across the eight beach sites over a month divided by the number of sites and the number of days for a given month.	The seasonality of RI mirrors that of the BSI with a peak in the fall, decreasing in winter and lowest frequency in the spring. RI generally corresponded with BSI, but discrepancies were observed. The onshore wind anomalies were related to such discrepancies between the monthly BSI and RI, indicating their influence in predicting respiratory irritation due to blooms.