Clinical Toxicology (2014), 52, 542–548 Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 1556-3650 print / 1556-9519 online DOI: 10.3109/15563650.2014.913176
POISON CENTRE
Epidemiological trends in electronic cigarette exposures reported to U.S. Poison Centers J. P. VAKKALANKA, L. S. HARDISON, Jr., and C. P. HOLSTEGE Department of Emergency Medicine, University of Virginia Health System, Charlottesville, VA, USA
Context. The Centers for Disease Control and Prevention (CDC) has reported an increase in electronic cigarette (e-cigarette) use in both adults and adolescents. Poison Center calls provide data on exposures pertaining to e-cigarette devices and components (including nicotine-refill cartridges), potentially identifying epidemiological trends in reported exposures over time. Objective. To characterize the trends in e-cigarette exposures reported to United States (U.S.) Poison Centers between 01 June 2010 and 30 September 2013. Methods. We obtained data from the American Association of Poison Control Centers (AAPCC) for all exposures involving e-cigarettes reported to the National Poison Data System (NPDS) by U.S. Poison Centers and described trends in exposures over time, demographics, geographical characteristics, clinical effects and outcomes, management site, and exposure route. Results. A total of 1,700 exposures were reported to Poison Centers during this time. The most frequent age groups were children 5 years or below with 717 (42.2%) exposures and adults ages 20–39 years with 466 (27.4%) exposures. Temporal trends showed an increase of 1.36 exposures per month [95% CI: 1.16–1.56] from June 2010 through December 2012, after which exposures increased by 9.60 per month [95% CI: 8.64–10.55] from January through September 2013. The majority of patients who were followed reported that they had only minor effects. Conclusions. The majority of exposures to e-cigarette devices and components occurred in children of 5 years or below due to accidental exposure. Based on the available data, the reported exposures have resulted in minimal toxicity. Calls to Poison Centers regarding these products have rapidly increased since 2010, and continued surveillance may show changes in the epidemiological trends surrounding e-cigarette exposures. Keywords
E-cigarettes; Epidemiology; Poison Centers
cigarettes.6 In 2010 a federal appeals court ruled that ecigarettes may not be marketed as smoking cessation devices, and ought to be regulated like traditional tobacco products.6–8 This allowed e-cigarette manufacturers to continue to market their product without being subject to FDA regulation and propagated the widespread sales of e-cigarettes both over the counter in consumer stores and through internet sales. Recent studies report sales estimates would approach $1.7 billion in the U.S. in 2013.9 There has been an increased use of e-cigarettes among many current and former cigarette smokers as an alternative to traditional cigarettes.3,6,9,10 A 2011 study on a consumerbased survey showed that awareness of these products increased across all demographic groups between 2009 and 2010, and the proportion of adults who tried these products more than quadrupled in this timeframe.11 More alarmingly, the CDC reports that use of e-cigarettes is on the rise among 6–12th graders from 3.3% to 6.8% between 2011 and 2012.12 As research in the use of e-cigarettes continues to expand, a number of existing databases may be considered for markers of awareness, utilization, and impact of these products. U.S. Poison Centers serve as a gauge for public health concerns as they provide a data-rich source for surveillance of emerging exposures and trends. All U.S. Poison Centers upload their case information in real time to the National Poisoning Data
Introduction Electronic Nicotine Delivery Systems or e-cigarettes were first developed in China in 2003 and made their way into the U.S. market four years later.1–3 E-cigarettes are a novel nicotine delivery system that consist of a battery-powered heating coil “atomizer”, an air flow sensor, a cartridge containing a nicotine solution, and a light source that are all contained in a cigarette or cigar-shaped container.1,2,4 As the user inhales, an air flow sensor prompts the atomizer to heat the nicotine containing solution. The vapor is inhaled into the lungs much like a traditional cigarette smoke and then exhaled. The nicotine solution can be purchased separately as a prepackaged cartridge or as a refillable cartridge with variable refill solution volumes, flavors, and nicotine concentrations.5 For instance, a 5-mL vial of refill solution may contain 20 mg/mL or 100mg/vial of nicotine, or a 30-mL bottle of e-cigarette solution may contain more than 500mg of nicotine.5–7 E-cigarette vendors have marketed their product as a cheaper and safer smokeless alternative to traditional Received 20 January 2014; accepted 3 April 2014. Address correspondence to J. Priyanka Vakkalanka, Department of Emergency Medicine, University of Virginia Health System, Charlottesville, VA 22903, USA. Tel: (434) 243-7406. Fax: (434) 971-8657. E-mail: [email protected]
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Electronic cigarette exposures reported to NPDS 543 System (NPDS). This study aims to characterize the trends in e-cigarettes exposures reported to U.S. Poison Centers between 01 June 2010 and 30 September 2013.
Methods National Poison Data System This study was a retrospective evaluation of e-cigarette data (including the device as well as nicotine-containing solution) from the American Association of Poison Control Centers (AAPCC) NPDS, which contains records of calls received and documented by all U.S. Poison Centers. Calls to the Poison Centers may be classified as information (e.g., drug information, drug identification, poison information, environmental information, etc.) or a potential/actual exposure call (ingestion, inhalation, dermal, ocular, etc.). Exposures do not necessarily denote a poisoning or overdose by a specific product. Product information is entered by Poison Center personnel using AAPCC generic and product codes. While e-cigarettes have been on the market for several years in the U.S., AAPCC coding was updated in June 2010 to enable data collection of these products. NPDS data were queried for either generic code 0200620 (Electronic Cigarettes: Device and/or Cartridge Containing Nicotine) and/or product code 7033642 (Electronic Cigarettes), and generic code 0200622 (Electronic Cigarettes: Nicotine Liquid) for all exposures reported to U.S. Poison Centers from June 1, 2010 through September 30, 2013. All human exposures, including both intentional and unintentional reasons, were included in the analysis. Exposures involving additional substances were also included in the analysis. Data analysis Age (ⱕ 5, 6–12, 13–19, 20–39, 40–59, ⱖ 60 years, unknown child ⱕ 19 years, unknown adult ⬎ 20 years) and gender distribution were assessed. Pediatric cases were identified as those ⱕ 19 years of age. Missing values for age and gender were not included in cross tabulations. Exposure and clinical characteristics such as exposure route, exposure reason (adverse reactions, intentional, unintentional, and unknown), clinical effects (related, not related, and unknown if related), management site, treatments, and medical outcome were also assessed. The NPDS data provided by AAPCC included caller’s state as the geographical identifier. Data were analyzed by monthly summaries and geographical characteristics, where the exposures were aggregated at the state and regional level (Northeast: CT, DE, DC, ME, MD, MA, NJ, NH, NY, PA, RI, VT; Southeast: AL, AR, FL, GA, KY, LA, MS, NC, SC, TN, VA, WV; Midwest: IL, IN, IA, KS, MI, MN, MO, NE, ND, OH, SD, WI; Southwest: AZ, NM, OK, TX; and West: AK, CA, CO, HI, ID, MT, NV, OR, UT, WA, WY). Using the average of 2010–2012 U.S. Census American Community Survey data, human exposure penetrance (total exposures per 1,000,000 population) was evaluated for each state.13–15 Records where the caller’s state could not be identified or the caller was Copyright © Informa Healthcare USA, Inc. 2014
an overseas military/diplomatic were not included in the state- and regional-level analysis. Initial review of the temporal data showed an evident change in rates over time, with a sharp change in rate occurring after December 2012. As a result, temporal trends were measured during the two distinct periods (June 2010 through December 2012, and January 2013 through September 2013) using linear spline regression modeling to account for the two distinct linear rates (change in number of exposures per month). Temporal trends were further stratified by age categories described earlier for the two time periods. All data analyses were performed using SAS 9.3 software (SAS Institute Inc., Cary, NC). This study was approved by the University of Virginia Institutional Review Board.
Results Demographics The characteristics of e-cigarette exposures are presented in Table 1. There were 840 pediatric exposures, accounted for 49.4% of all reported exposures to NPDS. Among all pediatric exposures, 717 (85.4%) were among children 5 years or below. There were 466 exposures reported among adults ages 20–39, accounting for 27.4% of the whole population and 55% of all adults. Overall distribution by gender was fairly similar, with slightly more exposures reported among males (n ⫽ 888; 52.2%) than females (n ⫽ 804; 47.3%). Stratifying by age group, however, there were more exposures reported among males in the 13- to 19-year (n ⫽ 60; 72.3%) and 20- to 39-year (n ⫽ 277; 59.44%) age groups. Women accounted for the majority of reported exposures among the 40- to 49-year (n ⫽ 130; 64.7%) and ⱖ 60-year (n ⫽ 39; 69.6%) age groups. Temporal and geographical trends There were two distinct periods for exposures pertaining to e-cigarettes between June 2010 and September 2013. Trends showed an increase of 1.36 additional exposures per month (95% CI: 1.16–1.56) from June 2010 through December 2012. From January 2013 through September 2013, the rate Table 1. Characteristics of population. Demographics Total Age (years) ⱕ5 6–12 13–19 20–39 40–59 ⱖ 60 Unknown child (ⱕ 19) Unknown adult (ⱖ 20) Unknown age Gender Female Male
n
%
1700
100.0
717 36 83 466 201 56 4 125 12
42.2 2.1 4.9 27.4 11.8 3.3 0.2 7.4 0.7
804 888
47.3 52.2
544
J. P. Vakkalanka et al. Table 2. Changes in monthly call volume, by age, region, and time period*. June 2010–December 2012 Age group
Change in monthly call volume
ⱕ5 6–12 13–19 20–39 40–59 ⱖ 60
0.55 0.01 0.01 0.38 0.16 0.03
Region
Change in monthly call volume 0.15 0.29 0.28 0.27 0.31
January 2013–September 2013 Change in monthly call volume
95% CI 0.39–0.72 ⫺ 0.06–0.86 ⫺ 0.04–0.07 0.23–0.53 0.09–0.23 ⫺ 0.04–0.10
June 2010–December 2012
Northeast Southeast Midwest Southwest West
6.03 0.35 0.57 1.54 0.55 0.05
95% CI 5.26–6.80 0.12–0.59 0.32–0.82 0.85–2.23 0.23–0.87 ⫺ 0.22–0.33
January 2013–September 2013
95% CI
Change in monthly call volume
95% CI
0.06–0.25 0.17–0.41 0.17–0.39 0.15–0.38 0.16–0.46
0.60 1.61 1.81 2.17 3.43
0.17–1.02 1.04–2.18 1.30–2.32 1.71–2.64 2.73–4.12
*Rate of exposures is defined as the slope (or change in exposures per month). For example, for children ⱕ 5 years, the exposure rate between June 2010 and December 2012 was 0.55 more exposures per month. Between January 2013 through September 2013, however, there were 6.03 more exposures per month reported for this age group.
of exposure increased to 9.60 exposures per month (95% CI: 8.64–10.55). Between January through September 2013, the change in exposure rate was high in children of 5 years or below, from 0.55 exposures per month (95% CI: 0.39–0.72) to 6.03 exposures per month (95% CI: 5.26–6.80; Table 2). The monthly exposure volume is presented in Fig. 1. Human exposures and penetrance (exposures per 1,000,000 population) by state are presented in Table 3. While there was an average of 33 exposures (median: 25)
across the U.S., Texas (n ⫽ 135), California (n ⫽ 117), and Washington (n ⫽ 96) were identified as the most frequent caller states. When adjusting for population, penetrance was greatest in Utah, Hawaii, and Oklahoma (29.5, 20.3, and 19.5 exposures per 1,000,000 population, respectively). When analyzing regional trends over time, all regions maintained a steady increase in reported human exposures through December 2012. At the regional level, there was a greater increase per month beginning in January 2013
160
140
120
Exposures (N)
100
80
60
40
20
0 Jun '10 Sep '10 Dec '10 Mar '11 Jun '11 Sep '11 Dec '11 Mar '12 Jun '12 Sep '12 Dec '12 Mar '13 Jun '13 Sep '13 Month, Year
Fig. 1. Monthly exposures reported to U.S. Poison Centers. Clinical Toxicology vol. 52 no. 5 2014
Electronic cigarette exposures reported to NPDS 545 Table 3. E-Cigarette exposures and penetrance by state, June 2010– September 2013*§. State
N Penetrance
Alabama Alaska Arizona Arkansas
17 5 50 14
3.5 6.9 7.7 4.8
117 39 6 1 0
3.1 7.6 1.7 1.1 –
80 35 28 22 50 44 15 17 46 19 9 23 13 39 66 1 53
4.2 3.6 20.3 13.9 3.9 6.8 4.9 5.9 10.5 4.2 6.8 3.9 2.0 4.0 12.4 0.3 8.8
California Colorado Connecticut Delaware District of Columbia Florida Georgia Hawaii Idaho Illinois Indiana Iowa Kansas Kentucky Louisiana Maine Maryland Massachusetts Michigan Minnesota Mississippi Missouri
State
N
Penetrance
Montana Nebraska Nevada New Hampshire New Jersey New Mexico New York North Carolina North Dakota
6 9 15 3
6.0 4.9 5.5 2.3
28 33 77 52 0
3.2 15.9 4.0 5.4 –
Ohio 43 Oklahoma 74 Oregon 35 Pennsylvania 48 Rhode Island 7 South Carolina 17 South Dakota 3 Tennessee 29 Texas 135 Utah 83 Vermont 7 Virginia 42 Washington 96 West Virginia 7 Wisconsin 25 Wyoming 8
3.7 19.5 9.1 3.8 6.7 3.6 3.6 4.5 5.3 29.5 11.2 5.2 14.1 3.8 4.4 14.1
*Does not include unknown locations (n ⫽ 8), foreign country (n ⫽ 1), or the U.S. Virgin Islands (n ⫽ 1). §Penetrance measured as human exposure calls per 1,000,000 population.
(Table 2), and the greatest rate was observed in the western states with an increase of 3.43 additional exposures per month (95% CI: 2.73–4.12). Exposure and clinical characteristics Exposure site, caller site, and exposure reasons Exposure and call characteristics by age group are presented in Table 4. The vast majority of exposures (n ⫽ 1,621; 95.4%) occurred at a residence, followed by a workplace (n ⫽ 18; 1.1%) and schools (n ⫽ 11; 0.6%). Caller site was more frequently from a residence (n ⫽ 1,364; 80.2%) or a healthcare facility (n ⫽ 213; 12.5%). For exposure reasons, most were classified as unintentional general exposures (n ⫽ 1,037; 61.0%), unintentional misuse (n ⫽ 252; 14.8%), and adverse drug reactions (n ⫽ 99; 5.8%); however, reasons varied by age as 732 (90.7%) pediatric exposures were classified as unintentional exposures compared to 269 (31.7%) adult exposures. While two-thirds of overall exposures occurred due to ingestion, exposure through ingestion occurred in 704 (83.8%) pediatric exposures compared to 396 (46.7%) adult exposures. Management, medical outcomes, clinical effects, and duration Table 5 presents the management and medical outcomes. The majority of cases were managed onsite (n ⫽ 1,157; 68.1%) Copyright © Informa Healthcare USA, Inc. 2014
Table 4. Call and exposure characteristics. Pediatric Adults (ⱕ 19 years) (⬎ 19 years) n Exposure site Residence (Own/Other) Workplace School Public area Other Unknown Caller site Residence (Own/Other) Healthcare facility Workplace Public area School Restaurant/Food service Other Unknown Exposure reason** Adverse reaction Drug Other Intentional Abuse Misuse Suspected suicide Unknown Unintentional Environmental General Misuse Occupational Therapeutic error Unknown Other Contamination/ Tampering Malicious Withdrawal Unknown reason Exposure route Ingestion Inhalation/Nasal Dermal Ocular Parenteral Unknown Vaginal
%
n
%
Total* n
%
815 0 11 6 6 2
97.0 795 0.0 18 1.3 0 0.7 7 0.7 14 0.2 14
93.8 1,621 95.4 2.1 18 1.1 0.0 11 0.6 0.8 13 0.8 1.7 20 1.2 1.7 17 1.0
663 119 4 2 2 2 45 3
78.9 691 14.2 94 0.5 14 0.2 1 0.2 0 0.2 0 5.4 44 0.4 4
81.5 1,364 80.2 11.1 213 12.5 1.7 18 1.1 0.1 3 0.2 0.0 2 0.1 0.0 2 0.1 5.2 90 5.3 0.5 8 0.5
10 6 4 34 14 18 0 2 791 1 762 20 0 8 0 4 3
1.2 0.7 0.5 4.0 1.7 2.1 0.0 0.2 94.2 0.1 90.7 2.4 0.0 1.0 0.0 0.5 0.4
179 89 90 90 27 48 12 3 563 10 269 232 3 44 5 6 4
21.1 194 11.4 10.5 99 5.8 10.6 95 5.6 10.6 125 7.4 3.2 42 2.5 5.7 66 3.9 1.4 12 0.7 0.4 5 0.3 66.4 1,360 80.0 1.2 11 0.6 31.7 1,037 61.0 27.4 252 14.8 0.4 3 0.2 5.2 52 3.1 0.6 5 0.3 0.7 10 0.6 0.5 7 0.4
1 0 1
0.1 0.0 0.1
0 2 10
704 89 69 34 1 1 0
83.8 396 10.6 306 8.2 98 4.0 103 0.1 4 0.1 2 0.0 1
0.0 0.2 1.2
1 2 11
0.1 0.1 0.6
46.7 1,103 64.9 36.1 404 23.8 11.6 167 9.8 12.1 137 8.1 0.5 5 0.3 0.2 3 0.2 0.1 1 0.1
*Total values include 12 individuals with unknown age. **Bolded values represent overall exposure categories. represent a breakdown of each exposure category.
Italicized values
followed by cases who were in/en-route or referred to a healthcare facility by the Poison Center (n ⫽ 512; 31.1%). Most cases (n ⫽ 731; 43%) were not followed by Poison Centers, particularly those where no more than minor clinical effects were expected (n ⫽ 576; 33.9%). Following this, the most frequent outcomes included minor effects (n ⫽ 435; 25.6%) or no effects (n ⫽ 353; 20.8%) were reported. One death due to suicide was reported in this time period, a single substance parenteral exposure in a 29-year old male. The patient injected the refilling liquid intravenously, resulting in nicotine toxicity, seizures, and cardiopulmonary arrest.
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Table 5. Management and medical outcome.
Management site Managed on site Patient in/en route to healthcare facility Patient referred by poison center to healthcare facility Other Unknown Medical outcome No effect Minor effect Moderate effect Major effect Death Not followed/Unable to follow* Judged as nontoxic exposure (clinical effects not expected) Minimal clinical effects possible (no more than minor effect possible) Judged as a potentially toxic exposure Confirmed nonexposure Unrelated effect, exposure was probably not responsible for the effects
n
%
1157 264 248
68.1 15.5 14.6
20 11
1.2 0.6
353 435 76 3 1 731 63
20.8 25.6 4.5 0.2 0.1 43.0 3.7
576
33.9
92 4 97
5.4 0.2 5.7
*Italicized values represent a breakdown of exposures not followed.
A wide range of clinical effects were identified, of which vomiting (n ⫽ 267; 15.7%), nausea (n ⫽ 216; 12.7%), ocular irritation/pain (n ⫽ 102; 6.0%), and dizziness/vertigo (n ⫽ 92; 5.4%) were the most frequently reported symptoms (Table 6). Only one-quarter of records indicated the duration of clinical effects, of which ⱕ 2 h (n ⫽ 251, 58.0%) or 2–8 h (n ⫽ 118; 27.3%) were most frequently reported.
Discussion This study captures national-level Poison Center data and reveals several noteworthy trends. First, exposures reported Table 6. Most frequently identified clinical effects. Clinical effects Vomiting Nausea Ocular–irritation/pain Dizziness/vertigo Tachycardia Agitated/Irritable Headache Red eye/conjunctivitis Diaphoresis Oral irritation Drowsiness/lethargy Cough/choke Abdominal pain Throat irritation Diarrhea Tremor Chest pain (noncardiac) Dermal–irritation/pain Dyspnea Pallor
Not Unknown Related related if related 219 155 100 58 60 46 39 56 44 49 26 30 22 24 16 17 11 22 7 15
17 18 0 11 6 5 7 1 4 1 15 6 7 5 10 1 7 2 6 3
31 43 2 23 10 16 20 1 7 4 11 8 10 10 7 10 9 1 8 2
Total
%
267 216 102 92 76 67 66 58 55 54 52 44 39 39 33 28 27 25 21 20
15.7 12.7 6.0 5.4 4.5 3.9 3.9 3.4 3.2 3.2 3.1 2.6 2.3 2.3 1.9 1.6 1.6 1.5 1.2 1.2
to NPDS have escalated because coding and documentation of these products were initiated in 2010. The exposures were originally rising at a rate of 1.36 additional exposures per month until December 2012. At this point, there was a seven-fold increase in the rate of exposures per month until the end of the study period in September 2013. While Poison Centers may receive more calls initially due to unfamiliarity of new products in the community, these findings may also reflect trends in increased use of e-cigarettes in the U.S. It is uncertain whether this trend will continue in the future, as exposures may rise due to increased prevalence in the U.S. or plateau as increased familiarity with the products lead to decreased dependence on Poison Centers. Second, children 5 years or below represented both the largest proportion of exposures and the group with the greatest increase in number of exposures per month. Adults ages 20–39 years represented the next largest exposure group, accounting for 27.4% of all exposures. Furthermore, approximately 80% of exposures occurred at a residence compared to other common sites such as the workplace, restaurants, and other public spaces. We speculate that these two age groups and the site of exposure may be associated as adults ages 20–39 years are most likely to have children 5 years or below. With the increasing availability of these products in households, children may have greater access to e-cigarettes devices or their nicotine-refill components. While the true prevalence of exposure in the general public cannot be measured from Poison Center data, these trends serve as a marker for availability and acceptance of e-cigarettes among American consumers. Finally, the majority of exposures indicated only minor effects, with nausea and vomiting being most commonly reported. Furthermore, only 25% of exposures had the duration of effects recorded, as the majority of cases were not followed potentially due to minimal toxicity expected. This finding is in contrast to the concerns raised by several organizations, including the World Health Organization, in regards to the potential for death following ingestion of these solutions by children.16 While we share the same concerns over potential toxicity of these products, the data reported to U.S. Poison Centers do not reflect these outcomes. These differences may be a result of under-reporting in cases where the cause of toxicity is unknown or the event was never reported. A majority of the exposures reported were safely managed at home. These data support the findings of a previous, but more limited analysis, which suggested that adverse effects and accidental exposures to e-cigarettes were unlikely to result in serious toxicity.17,18 There remains concern that as the popularity of these products continues to increase, there will be more nicotinerelated exposures resulting in harmful effects. Refill solutions seem to represent the largest area for concern as they vary in volume and composition in regards to nicotine and other components.19 E-cigarettes are not currently FDAapproved devices, and therefore the concentration of nicotine that is contained in these cartridges or refill solutions are not regulated.20 This gives rise to concern over potentially toxic/lethal ingestions, especially in the pediatric population, Clinical Toxicology vol. 52 no. 5 2014
Electronic cigarette exposures reported to NPDS 547 where nicotine toxicity, characterized by nausea, vomiting, diaphoresis, potential dysrhythmias and seizures, can develop with ingestion of 10–30 mg of nicotine(the equivalent of one whole traditional cigarette) or as little as 1 mL of solution.21 The estimated LD50 for nicotine in humans is 1mg/kg, a level that could be easily achieved in children ingesting small amounts of the higher nicotine concentration solutions.21 Fortunately, exposures have resulted in mainly minor effects being reported to Poison Centers. Possible explanations for these findings would include a limited access to large amounts of solution, unpleasant taste of the solution, poor bioavailability, and under-reporting of all exposures. The true reason that the majority of reported exposure resulted in only mild effects has yet to be determined. Limitations to this study were that NPDS is a passive surveillance system that is dependent on exposures self-reported to Poison Centers. This results in an underestimate of the true prevalence in the general population. Furthermore, there is potential for reporting bias, as exposures among children are more likely to be reported to Poison Centers than those in adults. The e-cigarette exposures presented in this study are dependent on the current coding practices for generic and product codes utilized by Poison Center personnel. There may be variation across all Poison Centers in distinguishing between codes used for e-cigarette devices and the nicotinerefill solutions used for these devices, suggesting additional review or validation. As a result, the data presented reflect either the device or nicotine-containing solution. In addition, the extent to which other data points are gathered is dependent upon information requested by Poison Center personnel and upon available details given by patients or healthcare providers. As a result, practices may vary both across and within Poison Centers, and records may contain missing fields for demographics, clinical effects, or true outcomes; however, the use of standard definitions and data fields with drop-down options may reduce the extent of bias. This study does not examine the measures of dose reported in exposures, which may be associated with clinical effects. Finally, all data (such as the codes used for products) reported for 2013 are considered preliminary as a Poison Center may update a case anytime during the year if new information is obtained. While changes occur in only a small number of cases each year, the data are not locked until the fall of the next year after which no additional changes are permitted. Sales and marketing of e-cigarettes have significantly increased in popularity since being introduced to the U.S. market. Seated in this growing market is a public health dispute of global scale. The primary concern is that the products are increasing in availability to a younger population, potentially enticing them to initiate a seemingly safer alternative to smoking traditional cigarettes.6,22 Furthermore, insufficient research on the safety of these products are at the heart of this controversy. Although some reports and the public heath literature tout the potential benefits as a “safe” smoking alternative, the risk of accidental and long-term exposures are not known. Despite their growing popularity, several cities including Boston have restricted the use while cities such as Copyright © Informa Healthcare USA, Inc. 2014
New York are preparing a ban on the use of e-cigarettes in the workplace, indoor places, and in certain other public venues (e.g., parks, beaches, pedestrian plazas, etc.).9,23 While the regulation of marketing and the use of these products continue to develop, it is perceivable that e-cigarette sales will maintain a presence in the U.S. culture.
Conclusions E-cigarette exposures reported to U.S. Poison Centers are currently increasing over time. The greatest increases in exposure rates have been observed in children of 5 years or below as well as adults 20–39 years of age. Continued surveillance of Poison Center data may continue to describe the epidemiology of e-cigarette exposures over time and to provide additional information regarding toxicity of these products.
Disclaimer The American Association of Poison Control Centers (www. aapcc.org) maintains the national database of information logged by the 57 U.S. Poison Control Centers. Case records in this database are from self-reported calls; they reflect only information provided when the public or health care professionals report an actual or potential exposure to a substance (e.g., an ingestion, inhalation, or topical exposure) or request information. Exposures are not necessarily poisonings or overdoses. The AAPCC is not able to completely verify the accuracy of every report made to member centers. Additional exposures may go unreported to Poison Control Centers, and data referenced from the AAPCC should not be construed to represent the complete incidence of national exposures to any substance(s).
Acknowledgments We would like to thank Elise Bailey and Asma Madad with the National Poison Data System for assisting and providing the data.
Declaration of interest The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
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5. Indiana Tobacco Prevention and Cessation (2013). Electronic Cigarettes. Available at: http://www.in.gov/itpc/files/ECigarettes.pdf. Accessed 04 March 2014. 6. Palazzolo DL. Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review. Front Public Health 2013; 1:56. 7. Cameron JM, Howell DN, White JR, Andrenyak DM, Layton ME, Roll JM. Variable and potentially fatal amounts of nicotine in ecigarette nicotine solutions. Tob Control 2014; 23:77–78. 8. Sottera Inc. Doing business as NJOY v. Food and Drug Administration, et al. Available at: http://www.cadc.uscourts.gov/internet/ opinions.nsf/D02F9D2CA50299F0852577F20070BCC2/$file/10– 5032-1281606.pdf. Accessed 10 January 2014. 9. Fairchild AL, Bayer R, Colgrove J. The renormalization of smoking? E-cigarettes and the tobacco “endgame”. N Engl J Med 2014; 370:293–295. 10. Sutfin EL, McCoy TP, Morrell HER, Hoeppner BB, Wolfson M. Electronic cigarette use by college students. Drug Alcohol Depend 2013; 131:214–221. 11. Regan AK, Promoff G, Dube SR, Arrazola R. Electronic nicotine delivery systems: adult use and awareness of the ‘e-cigarette’ in the USA. Tob Control 2013; 22:19–23. 12. Centers for Disease Control and Prevention (CDC). Notes from the field: electronic cigarette use among middle and high school students United States, 2011–2012. MMWR Morb Mortal Wkly Rep 2013; 62:729–730. 13. US Census Bureau (2010). 2010 American community survey 1-year estimates. Available at: http://factfinder2.census.gov/faces/nav/jsf/ pages/index.xhtml. Accessed 18 March 2013.
14. US Census Bureau (2011). 2011 American community survey 1-year estimates. Available at: http://factfinder2.census.gov/faces/nav/jsf/ pages/index.xhtml. Accessed 18 March 2013. 15. US Census Bureau (2012). 2012 American community survey 1-year estimates. Available at: http://factfinder2.census.gov/faces/nav/jsf/ pages/index.xhtml. Accessed 18 March 2013. 16. World Health Organization (2013). Questions and answers on electronic cigarettes or electronic nicotine delivery systems (ENDS). Available at: http://www.who.int/tobacco/communications/ statements/eletronic_cigarettes/en/. Accessed 04 March 2014. 17. Cantrell FL. E-cigarette exposures-nothing to get choked up about [abstract]. Clin Toxicol 2013; 51:684–685. Abstract 241. 18. Ordonez J, Forrester MB, Kleinschmidt K. Electronic cigarette exposures reported to poison centers [abstract]. Clin Toxicol 2013; 51:685. Abstract 242. 19. Kirschner RI, Gerona R, Jacobitz KL. Nicotine content of liquid for electronic cigarettes [abstract]. Clin Toxicol 2013; 51:684. Abstract 240. 20. U.S. FDA (2014). Electronic cigarettes (e-Cigarettes). Available at: http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm172906.htm Accessed 04 March 2014. 21. Nicotine SS. (Chapter 84). In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE, eds. Goldfrank’s Toxicologic Emergencies. 9th ed. New York: McGraw Hill Medical; 2011:1187. 22. Noel JK, Rees VW, Connolly GN. Electronic cigarettes: a new ‘tobacco’ industry? Tob Control 2011; 20:81. 23. McCarthy M. New york city votes to ban e-cigarettes from public places. BMJ 2013; 347:f7677.
Clinical Toxicology vol. 52 no. 5 2014
Copyright of Clinical Toxicology (15563650) is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
POISON CENTRE
Epidemiological trends in electronic cigarette exposures reported to U.S. Poison Centers J. P. VAKKALANKA, L. S. HARDISON, Jr., and C. P. HOLSTEGE Department of Emergency Medicine, University of Virginia Health System, Charlottesville, VA, USA
Context. The Centers for Disease Control and Prevention (CDC) has reported an increase in electronic cigarette (e-cigarette) use in both adults and adolescents. Poison Center calls provide data on exposures pertaining to e-cigarette devices and components (including nicotine-refill cartridges), potentially identifying epidemiological trends in reported exposures over time. Objective. To characterize the trends in e-cigarette exposures reported to United States (U.S.) Poison Centers between 01 June 2010 and 30 September 2013. Methods. We obtained data from the American Association of Poison Control Centers (AAPCC) for all exposures involving e-cigarettes reported to the National Poison Data System (NPDS) by U.S. Poison Centers and described trends in exposures over time, demographics, geographical characteristics, clinical effects and outcomes, management site, and exposure route. Results. A total of 1,700 exposures were reported to Poison Centers during this time. The most frequent age groups were children 5 years or below with 717 (42.2%) exposures and adults ages 20–39 years with 466 (27.4%) exposures. Temporal trends showed an increase of 1.36 exposures per month [95% CI: 1.16–1.56] from June 2010 through December 2012, after which exposures increased by 9.60 per month [95% CI: 8.64–10.55] from January through September 2013. The majority of patients who were followed reported that they had only minor effects. Conclusions. The majority of exposures to e-cigarette devices and components occurred in children of 5 years or below due to accidental exposure. Based on the available data, the reported exposures have resulted in minimal toxicity. Calls to Poison Centers regarding these products have rapidly increased since 2010, and continued surveillance may show changes in the epidemiological trends surrounding e-cigarette exposures. Keywords
E-cigarettes; Epidemiology; Poison Centers
cigarettes.6 In 2010 a federal appeals court ruled that ecigarettes may not be marketed as smoking cessation devices, and ought to be regulated like traditional tobacco products.6–8 This allowed e-cigarette manufacturers to continue to market their product without being subject to FDA regulation and propagated the widespread sales of e-cigarettes both over the counter in consumer stores and through internet sales. Recent studies report sales estimates would approach $1.7 billion in the U.S. in 2013.9 There has been an increased use of e-cigarettes among many current and former cigarette smokers as an alternative to traditional cigarettes.3,6,9,10 A 2011 study on a consumerbased survey showed that awareness of these products increased across all demographic groups between 2009 and 2010, and the proportion of adults who tried these products more than quadrupled in this timeframe.11 More alarmingly, the CDC reports that use of e-cigarettes is on the rise among 6–12th graders from 3.3% to 6.8% between 2011 and 2012.12 As research in the use of e-cigarettes continues to expand, a number of existing databases may be considered for markers of awareness, utilization, and impact of these products. U.S. Poison Centers serve as a gauge for public health concerns as they provide a data-rich source for surveillance of emerging exposures and trends. All U.S. Poison Centers upload their case information in real time to the National Poisoning Data
Introduction Electronic Nicotine Delivery Systems or e-cigarettes were first developed in China in 2003 and made their way into the U.S. market four years later.1–3 E-cigarettes are a novel nicotine delivery system that consist of a battery-powered heating coil “atomizer”, an air flow sensor, a cartridge containing a nicotine solution, and a light source that are all contained in a cigarette or cigar-shaped container.1,2,4 As the user inhales, an air flow sensor prompts the atomizer to heat the nicotine containing solution. The vapor is inhaled into the lungs much like a traditional cigarette smoke and then exhaled. The nicotine solution can be purchased separately as a prepackaged cartridge or as a refillable cartridge with variable refill solution volumes, flavors, and nicotine concentrations.5 For instance, a 5-mL vial of refill solution may contain 20 mg/mL or 100mg/vial of nicotine, or a 30-mL bottle of e-cigarette solution may contain more than 500mg of nicotine.5–7 E-cigarette vendors have marketed their product as a cheaper and safer smokeless alternative to traditional Received 20 January 2014; accepted 3 April 2014. Address correspondence to J. Priyanka Vakkalanka, Department of Emergency Medicine, University of Virginia Health System, Charlottesville, VA 22903, USA. Tel: (434) 243-7406. Fax: (434) 971-8657. E-mail: [email protected]
542
Electronic cigarette exposures reported to NPDS 543 System (NPDS). This study aims to characterize the trends in e-cigarettes exposures reported to U.S. Poison Centers between 01 June 2010 and 30 September 2013.
Methods National Poison Data System This study was a retrospective evaluation of e-cigarette data (including the device as well as nicotine-containing solution) from the American Association of Poison Control Centers (AAPCC) NPDS, which contains records of calls received and documented by all U.S. Poison Centers. Calls to the Poison Centers may be classified as information (e.g., drug information, drug identification, poison information, environmental information, etc.) or a potential/actual exposure call (ingestion, inhalation, dermal, ocular, etc.). Exposures do not necessarily denote a poisoning or overdose by a specific product. Product information is entered by Poison Center personnel using AAPCC generic and product codes. While e-cigarettes have been on the market for several years in the U.S., AAPCC coding was updated in June 2010 to enable data collection of these products. NPDS data were queried for either generic code 0200620 (Electronic Cigarettes: Device and/or Cartridge Containing Nicotine) and/or product code 7033642 (Electronic Cigarettes), and generic code 0200622 (Electronic Cigarettes: Nicotine Liquid) for all exposures reported to U.S. Poison Centers from June 1, 2010 through September 30, 2013. All human exposures, including both intentional and unintentional reasons, were included in the analysis. Exposures involving additional substances were also included in the analysis. Data analysis Age (ⱕ 5, 6–12, 13–19, 20–39, 40–59, ⱖ 60 years, unknown child ⱕ 19 years, unknown adult ⬎ 20 years) and gender distribution were assessed. Pediatric cases were identified as those ⱕ 19 years of age. Missing values for age and gender were not included in cross tabulations. Exposure and clinical characteristics such as exposure route, exposure reason (adverse reactions, intentional, unintentional, and unknown), clinical effects (related, not related, and unknown if related), management site, treatments, and medical outcome were also assessed. The NPDS data provided by AAPCC included caller’s state as the geographical identifier. Data were analyzed by monthly summaries and geographical characteristics, where the exposures were aggregated at the state and regional level (Northeast: CT, DE, DC, ME, MD, MA, NJ, NH, NY, PA, RI, VT; Southeast: AL, AR, FL, GA, KY, LA, MS, NC, SC, TN, VA, WV; Midwest: IL, IN, IA, KS, MI, MN, MO, NE, ND, OH, SD, WI; Southwest: AZ, NM, OK, TX; and West: AK, CA, CO, HI, ID, MT, NV, OR, UT, WA, WY). Using the average of 2010–2012 U.S. Census American Community Survey data, human exposure penetrance (total exposures per 1,000,000 population) was evaluated for each state.13–15 Records where the caller’s state could not be identified or the caller was Copyright © Informa Healthcare USA, Inc. 2014
an overseas military/diplomatic were not included in the state- and regional-level analysis. Initial review of the temporal data showed an evident change in rates over time, with a sharp change in rate occurring after December 2012. As a result, temporal trends were measured during the two distinct periods (June 2010 through December 2012, and January 2013 through September 2013) using linear spline regression modeling to account for the two distinct linear rates (change in number of exposures per month). Temporal trends were further stratified by age categories described earlier for the two time periods. All data analyses were performed using SAS 9.3 software (SAS Institute Inc., Cary, NC). This study was approved by the University of Virginia Institutional Review Board.
Results Demographics The characteristics of e-cigarette exposures are presented in Table 1. There were 840 pediatric exposures, accounted for 49.4% of all reported exposures to NPDS. Among all pediatric exposures, 717 (85.4%) were among children 5 years or below. There were 466 exposures reported among adults ages 20–39, accounting for 27.4% of the whole population and 55% of all adults. Overall distribution by gender was fairly similar, with slightly more exposures reported among males (n ⫽ 888; 52.2%) than females (n ⫽ 804; 47.3%). Stratifying by age group, however, there were more exposures reported among males in the 13- to 19-year (n ⫽ 60; 72.3%) and 20- to 39-year (n ⫽ 277; 59.44%) age groups. Women accounted for the majority of reported exposures among the 40- to 49-year (n ⫽ 130; 64.7%) and ⱖ 60-year (n ⫽ 39; 69.6%) age groups. Temporal and geographical trends There were two distinct periods for exposures pertaining to e-cigarettes between June 2010 and September 2013. Trends showed an increase of 1.36 additional exposures per month (95% CI: 1.16–1.56) from June 2010 through December 2012. From January 2013 through September 2013, the rate Table 1. Characteristics of population. Demographics Total Age (years) ⱕ5 6–12 13–19 20–39 40–59 ⱖ 60 Unknown child (ⱕ 19) Unknown adult (ⱖ 20) Unknown age Gender Female Male
n
%
1700
100.0
717 36 83 466 201 56 4 125 12
42.2 2.1 4.9 27.4 11.8 3.3 0.2 7.4 0.7
804 888
47.3 52.2
544
J. P. Vakkalanka et al. Table 2. Changes in monthly call volume, by age, region, and time period*. June 2010–December 2012 Age group
Change in monthly call volume
ⱕ5 6–12 13–19 20–39 40–59 ⱖ 60
0.55 0.01 0.01 0.38 0.16 0.03
Region
Change in monthly call volume 0.15 0.29 0.28 0.27 0.31
January 2013–September 2013 Change in monthly call volume
95% CI 0.39–0.72 ⫺ 0.06–0.86 ⫺ 0.04–0.07 0.23–0.53 0.09–0.23 ⫺ 0.04–0.10
June 2010–December 2012
Northeast Southeast Midwest Southwest West
6.03 0.35 0.57 1.54 0.55 0.05
95% CI 5.26–6.80 0.12–0.59 0.32–0.82 0.85–2.23 0.23–0.87 ⫺ 0.22–0.33
January 2013–September 2013
95% CI
Change in monthly call volume
95% CI
0.06–0.25 0.17–0.41 0.17–0.39 0.15–0.38 0.16–0.46
0.60 1.61 1.81 2.17 3.43
0.17–1.02 1.04–2.18 1.30–2.32 1.71–2.64 2.73–4.12
*Rate of exposures is defined as the slope (or change in exposures per month). For example, for children ⱕ 5 years, the exposure rate between June 2010 and December 2012 was 0.55 more exposures per month. Between January 2013 through September 2013, however, there were 6.03 more exposures per month reported for this age group.
of exposure increased to 9.60 exposures per month (95% CI: 8.64–10.55). Between January through September 2013, the change in exposure rate was high in children of 5 years or below, from 0.55 exposures per month (95% CI: 0.39–0.72) to 6.03 exposures per month (95% CI: 5.26–6.80; Table 2). The monthly exposure volume is presented in Fig. 1. Human exposures and penetrance (exposures per 1,000,000 population) by state are presented in Table 3. While there was an average of 33 exposures (median: 25)
across the U.S., Texas (n ⫽ 135), California (n ⫽ 117), and Washington (n ⫽ 96) were identified as the most frequent caller states. When adjusting for population, penetrance was greatest in Utah, Hawaii, and Oklahoma (29.5, 20.3, and 19.5 exposures per 1,000,000 population, respectively). When analyzing regional trends over time, all regions maintained a steady increase in reported human exposures through December 2012. At the regional level, there was a greater increase per month beginning in January 2013
160
140
120
Exposures (N)
100
80
60
40
20
0 Jun '10 Sep '10 Dec '10 Mar '11 Jun '11 Sep '11 Dec '11 Mar '12 Jun '12 Sep '12 Dec '12 Mar '13 Jun '13 Sep '13 Month, Year
Fig. 1. Monthly exposures reported to U.S. Poison Centers. Clinical Toxicology vol. 52 no. 5 2014
Electronic cigarette exposures reported to NPDS 545 Table 3. E-Cigarette exposures and penetrance by state, June 2010– September 2013*§. State
N Penetrance
Alabama Alaska Arizona Arkansas
17 5 50 14
3.5 6.9 7.7 4.8
117 39 6 1 0
3.1 7.6 1.7 1.1 –
80 35 28 22 50 44 15 17 46 19 9 23 13 39 66 1 53
4.2 3.6 20.3 13.9 3.9 6.8 4.9 5.9 10.5 4.2 6.8 3.9 2.0 4.0 12.4 0.3 8.8
California Colorado Connecticut Delaware District of Columbia Florida Georgia Hawaii Idaho Illinois Indiana Iowa Kansas Kentucky Louisiana Maine Maryland Massachusetts Michigan Minnesota Mississippi Missouri
State
N
Penetrance
Montana Nebraska Nevada New Hampshire New Jersey New Mexico New York North Carolina North Dakota
6 9 15 3
6.0 4.9 5.5 2.3
28 33 77 52 0
3.2 15.9 4.0 5.4 –
Ohio 43 Oklahoma 74 Oregon 35 Pennsylvania 48 Rhode Island 7 South Carolina 17 South Dakota 3 Tennessee 29 Texas 135 Utah 83 Vermont 7 Virginia 42 Washington 96 West Virginia 7 Wisconsin 25 Wyoming 8
3.7 19.5 9.1 3.8 6.7 3.6 3.6 4.5 5.3 29.5 11.2 5.2 14.1 3.8 4.4 14.1
*Does not include unknown locations (n ⫽ 8), foreign country (n ⫽ 1), or the U.S. Virgin Islands (n ⫽ 1). §Penetrance measured as human exposure calls per 1,000,000 population.
(Table 2), and the greatest rate was observed in the western states with an increase of 3.43 additional exposures per month (95% CI: 2.73–4.12). Exposure and clinical characteristics Exposure site, caller site, and exposure reasons Exposure and call characteristics by age group are presented in Table 4. The vast majority of exposures (n ⫽ 1,621; 95.4%) occurred at a residence, followed by a workplace (n ⫽ 18; 1.1%) and schools (n ⫽ 11; 0.6%). Caller site was more frequently from a residence (n ⫽ 1,364; 80.2%) or a healthcare facility (n ⫽ 213; 12.5%). For exposure reasons, most were classified as unintentional general exposures (n ⫽ 1,037; 61.0%), unintentional misuse (n ⫽ 252; 14.8%), and adverse drug reactions (n ⫽ 99; 5.8%); however, reasons varied by age as 732 (90.7%) pediatric exposures were classified as unintentional exposures compared to 269 (31.7%) adult exposures. While two-thirds of overall exposures occurred due to ingestion, exposure through ingestion occurred in 704 (83.8%) pediatric exposures compared to 396 (46.7%) adult exposures. Management, medical outcomes, clinical effects, and duration Table 5 presents the management and medical outcomes. The majority of cases were managed onsite (n ⫽ 1,157; 68.1%) Copyright © Informa Healthcare USA, Inc. 2014
Table 4. Call and exposure characteristics. Pediatric Adults (ⱕ 19 years) (⬎ 19 years) n Exposure site Residence (Own/Other) Workplace School Public area Other Unknown Caller site Residence (Own/Other) Healthcare facility Workplace Public area School Restaurant/Food service Other Unknown Exposure reason** Adverse reaction Drug Other Intentional Abuse Misuse Suspected suicide Unknown Unintentional Environmental General Misuse Occupational Therapeutic error Unknown Other Contamination/ Tampering Malicious Withdrawal Unknown reason Exposure route Ingestion Inhalation/Nasal Dermal Ocular Parenteral Unknown Vaginal
%
n
%
Total* n
%
815 0 11 6 6 2
97.0 795 0.0 18 1.3 0 0.7 7 0.7 14 0.2 14
93.8 1,621 95.4 2.1 18 1.1 0.0 11 0.6 0.8 13 0.8 1.7 20 1.2 1.7 17 1.0
663 119 4 2 2 2 45 3
78.9 691 14.2 94 0.5 14 0.2 1 0.2 0 0.2 0 5.4 44 0.4 4
81.5 1,364 80.2 11.1 213 12.5 1.7 18 1.1 0.1 3 0.2 0.0 2 0.1 0.0 2 0.1 5.2 90 5.3 0.5 8 0.5
10 6 4 34 14 18 0 2 791 1 762 20 0 8 0 4 3
1.2 0.7 0.5 4.0 1.7 2.1 0.0 0.2 94.2 0.1 90.7 2.4 0.0 1.0 0.0 0.5 0.4
179 89 90 90 27 48 12 3 563 10 269 232 3 44 5 6 4
21.1 194 11.4 10.5 99 5.8 10.6 95 5.6 10.6 125 7.4 3.2 42 2.5 5.7 66 3.9 1.4 12 0.7 0.4 5 0.3 66.4 1,360 80.0 1.2 11 0.6 31.7 1,037 61.0 27.4 252 14.8 0.4 3 0.2 5.2 52 3.1 0.6 5 0.3 0.7 10 0.6 0.5 7 0.4
1 0 1
0.1 0.0 0.1
0 2 10
704 89 69 34 1 1 0
83.8 396 10.6 306 8.2 98 4.0 103 0.1 4 0.1 2 0.0 1
0.0 0.2 1.2
1 2 11
0.1 0.1 0.6
46.7 1,103 64.9 36.1 404 23.8 11.6 167 9.8 12.1 137 8.1 0.5 5 0.3 0.2 3 0.2 0.1 1 0.1
*Total values include 12 individuals with unknown age. **Bolded values represent overall exposure categories. represent a breakdown of each exposure category.
Italicized values
followed by cases who were in/en-route or referred to a healthcare facility by the Poison Center (n ⫽ 512; 31.1%). Most cases (n ⫽ 731; 43%) were not followed by Poison Centers, particularly those where no more than minor clinical effects were expected (n ⫽ 576; 33.9%). Following this, the most frequent outcomes included minor effects (n ⫽ 435; 25.6%) or no effects (n ⫽ 353; 20.8%) were reported. One death due to suicide was reported in this time period, a single substance parenteral exposure in a 29-year old male. The patient injected the refilling liquid intravenously, resulting in nicotine toxicity, seizures, and cardiopulmonary arrest.
546
J. P. Vakkalanka et al.
Table 5. Management and medical outcome.
Management site Managed on site Patient in/en route to healthcare facility Patient referred by poison center to healthcare facility Other Unknown Medical outcome No effect Minor effect Moderate effect Major effect Death Not followed/Unable to follow* Judged as nontoxic exposure (clinical effects not expected) Minimal clinical effects possible (no more than minor effect possible) Judged as a potentially toxic exposure Confirmed nonexposure Unrelated effect, exposure was probably not responsible for the effects
n
%
1157 264 248
68.1 15.5 14.6
20 11
1.2 0.6
353 435 76 3 1 731 63
20.8 25.6 4.5 0.2 0.1 43.0 3.7
576
33.9
92 4 97
5.4 0.2 5.7
*Italicized values represent a breakdown of exposures not followed.
A wide range of clinical effects were identified, of which vomiting (n ⫽ 267; 15.7%), nausea (n ⫽ 216; 12.7%), ocular irritation/pain (n ⫽ 102; 6.0%), and dizziness/vertigo (n ⫽ 92; 5.4%) were the most frequently reported symptoms (Table 6). Only one-quarter of records indicated the duration of clinical effects, of which ⱕ 2 h (n ⫽ 251, 58.0%) or 2–8 h (n ⫽ 118; 27.3%) were most frequently reported.
Discussion This study captures national-level Poison Center data and reveals several noteworthy trends. First, exposures reported Table 6. Most frequently identified clinical effects. Clinical effects Vomiting Nausea Ocular–irritation/pain Dizziness/vertigo Tachycardia Agitated/Irritable Headache Red eye/conjunctivitis Diaphoresis Oral irritation Drowsiness/lethargy Cough/choke Abdominal pain Throat irritation Diarrhea Tremor Chest pain (noncardiac) Dermal–irritation/pain Dyspnea Pallor
Not Unknown Related related if related 219 155 100 58 60 46 39 56 44 49 26 30 22 24 16 17 11 22 7 15
17 18 0 11 6 5 7 1 4 1 15 6 7 5 10 1 7 2 6 3
31 43 2 23 10 16 20 1 7 4 11 8 10 10 7 10 9 1 8 2
Total
%
267 216 102 92 76 67 66 58 55 54 52 44 39 39 33 28 27 25 21 20
15.7 12.7 6.0 5.4 4.5 3.9 3.9 3.4 3.2 3.2 3.1 2.6 2.3 2.3 1.9 1.6 1.6 1.5 1.2 1.2
to NPDS have escalated because coding and documentation of these products were initiated in 2010. The exposures were originally rising at a rate of 1.36 additional exposures per month until December 2012. At this point, there was a seven-fold increase in the rate of exposures per month until the end of the study period in September 2013. While Poison Centers may receive more calls initially due to unfamiliarity of new products in the community, these findings may also reflect trends in increased use of e-cigarettes in the U.S. It is uncertain whether this trend will continue in the future, as exposures may rise due to increased prevalence in the U.S. or plateau as increased familiarity with the products lead to decreased dependence on Poison Centers. Second, children 5 years or below represented both the largest proportion of exposures and the group with the greatest increase in number of exposures per month. Adults ages 20–39 years represented the next largest exposure group, accounting for 27.4% of all exposures. Furthermore, approximately 80% of exposures occurred at a residence compared to other common sites such as the workplace, restaurants, and other public spaces. We speculate that these two age groups and the site of exposure may be associated as adults ages 20–39 years are most likely to have children 5 years or below. With the increasing availability of these products in households, children may have greater access to e-cigarettes devices or their nicotine-refill components. While the true prevalence of exposure in the general public cannot be measured from Poison Center data, these trends serve as a marker for availability and acceptance of e-cigarettes among American consumers. Finally, the majority of exposures indicated only minor effects, with nausea and vomiting being most commonly reported. Furthermore, only 25% of exposures had the duration of effects recorded, as the majority of cases were not followed potentially due to minimal toxicity expected. This finding is in contrast to the concerns raised by several organizations, including the World Health Organization, in regards to the potential for death following ingestion of these solutions by children.16 While we share the same concerns over potential toxicity of these products, the data reported to U.S. Poison Centers do not reflect these outcomes. These differences may be a result of under-reporting in cases where the cause of toxicity is unknown or the event was never reported. A majority of the exposures reported were safely managed at home. These data support the findings of a previous, but more limited analysis, which suggested that adverse effects and accidental exposures to e-cigarettes were unlikely to result in serious toxicity.17,18 There remains concern that as the popularity of these products continues to increase, there will be more nicotinerelated exposures resulting in harmful effects. Refill solutions seem to represent the largest area for concern as they vary in volume and composition in regards to nicotine and other components.19 E-cigarettes are not currently FDAapproved devices, and therefore the concentration of nicotine that is contained in these cartridges or refill solutions are not regulated.20 This gives rise to concern over potentially toxic/lethal ingestions, especially in the pediatric population, Clinical Toxicology vol. 52 no. 5 2014
Electronic cigarette exposures reported to NPDS 547 where nicotine toxicity, characterized by nausea, vomiting, diaphoresis, potential dysrhythmias and seizures, can develop with ingestion of 10–30 mg of nicotine(the equivalent of one whole traditional cigarette) or as little as 1 mL of solution.21 The estimated LD50 for nicotine in humans is 1mg/kg, a level that could be easily achieved in children ingesting small amounts of the higher nicotine concentration solutions.21 Fortunately, exposures have resulted in mainly minor effects being reported to Poison Centers. Possible explanations for these findings would include a limited access to large amounts of solution, unpleasant taste of the solution, poor bioavailability, and under-reporting of all exposures. The true reason that the majority of reported exposure resulted in only mild effects has yet to be determined. Limitations to this study were that NPDS is a passive surveillance system that is dependent on exposures self-reported to Poison Centers. This results in an underestimate of the true prevalence in the general population. Furthermore, there is potential for reporting bias, as exposures among children are more likely to be reported to Poison Centers than those in adults. The e-cigarette exposures presented in this study are dependent on the current coding practices for generic and product codes utilized by Poison Center personnel. There may be variation across all Poison Centers in distinguishing between codes used for e-cigarette devices and the nicotinerefill solutions used for these devices, suggesting additional review or validation. As a result, the data presented reflect either the device or nicotine-containing solution. In addition, the extent to which other data points are gathered is dependent upon information requested by Poison Center personnel and upon available details given by patients or healthcare providers. As a result, practices may vary both across and within Poison Centers, and records may contain missing fields for demographics, clinical effects, or true outcomes; however, the use of standard definitions and data fields with drop-down options may reduce the extent of bias. This study does not examine the measures of dose reported in exposures, which may be associated with clinical effects. Finally, all data (such as the codes used for products) reported for 2013 are considered preliminary as a Poison Center may update a case anytime during the year if new information is obtained. While changes occur in only a small number of cases each year, the data are not locked until the fall of the next year after which no additional changes are permitted. Sales and marketing of e-cigarettes have significantly increased in popularity since being introduced to the U.S. market. Seated in this growing market is a public health dispute of global scale. The primary concern is that the products are increasing in availability to a younger population, potentially enticing them to initiate a seemingly safer alternative to smoking traditional cigarettes.6,22 Furthermore, insufficient research on the safety of these products are at the heart of this controversy. Although some reports and the public heath literature tout the potential benefits as a “safe” smoking alternative, the risk of accidental and long-term exposures are not known. Despite their growing popularity, several cities including Boston have restricted the use while cities such as Copyright © Informa Healthcare USA, Inc. 2014
New York are preparing a ban on the use of e-cigarettes in the workplace, indoor places, and in certain other public venues (e.g., parks, beaches, pedestrian plazas, etc.).9,23 While the regulation of marketing and the use of these products continue to develop, it is perceivable that e-cigarette sales will maintain a presence in the U.S. culture.
Conclusions E-cigarette exposures reported to U.S. Poison Centers are currently increasing over time. The greatest increases in exposure rates have been observed in children of 5 years or below as well as adults 20–39 years of age. Continued surveillance of Poison Center data may continue to describe the epidemiology of e-cigarette exposures over time and to provide additional information regarding toxicity of these products.
Disclaimer The American Association of Poison Control Centers (www. aapcc.org) maintains the national database of information logged by the 57 U.S. Poison Control Centers. Case records in this database are from self-reported calls; they reflect only information provided when the public or health care professionals report an actual or potential exposure to a substance (e.g., an ingestion, inhalation, or topical exposure) or request information. Exposures are not necessarily poisonings or overdoses. The AAPCC is not able to completely verify the accuracy of every report made to member centers. Additional exposures may go unreported to Poison Control Centers, and data referenced from the AAPCC should not be construed to represent the complete incidence of national exposures to any substance(s).
Acknowledgments We would like to thank Elise Bailey and Asma Madad with the National Poison Data System for assisting and providing the data.
Declaration of interest The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
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Clinical Toxicology vol. 52 no. 5 2014
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