Syndromic Surveillance for E-Cigarette, or Vaping, Product Use–Associated Lung Injury

Study Design

Syndromic surveillance analysts at state health departments and the CDC collaborated to develop two queries of ED data.⁸ We assessed exposure to e-cigarette (or vaping) products as well as the incidence of acute lung injury occurring from January 1, 2017, to December 7, 2019.

Exposure Query — E-Cigarette Product Use

The first query was developed to search the field regarding the reason for the visit for words related to the use of e-cigarette products, including slang terms, among all persons who presented to an ED (Section S2). The query was not limited to lung injuries. The query attempted to exclude injuries unrelated to EVALI, such as device explosions and accidental ingestion of e-cigarette liquid. However, it did not exclude potentially related syndromes such as acute intoxication from THC or nicotine poisoning.

Outcome Query — Acute Lung Injury

The lung injury query included the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), codes that were recommended by the CDC on October 17, 2019, for the identification of EVALI (Sections S3 and S4).⁹ This query included persons who presented to an ED and were not discharged home, and it excluded discharge diagnosis codes and terms regarding the reason for the visit for infectious diseases, cystic fibrosis, and other potential causes of acute lung injury. Because 78% of the reported cases involved persons 34 years of age or younger, and 95% of the cases involved hospitalization,² the diagnostic query was limited to patients 11 to 34 years of age who were admitted to the hospital, were transferred to another facility, or died in the ED. This age cutoff improved specificity by reducing noise from ED visits involving unclear causes, such as unexplained pneumonia, which are more common in older adults.

Confirmed or Probable Cases

We overlaid the ED visit trend on the trend for confirmed and probable cases of EVALI that were reported by state health departments to the CDC.⁴ Reported cases were considered to be complete through the week of November 24, 2019, with declines in more recent weeks resulting in part from lags in reporting.

Google Trends

The weekly time series of ED visits and reported cases were overlaid on Google search engine data, as a measure of public awareness of the outbreak. Data were visualized with the use of Google Trends^10,11 for U.S. searches related to e-cigarette or vaping products (Section S1). Google Trends scores range from 0 to 100, with a score of 100 indicating peak interest and a score of 50 indicating that the search term is half as popular as at its peak.

Statistical Analysis

Longer-term trends were assessed as the ED visits returned by each query per 1 million reported ED visits (Section S1). To identify weeks when the trend in ED visit rates changed for each query, we identified knots with the use of the segmented package in R software, version 3.6.^12,13 Piecewise linear splines were fit between knots to estimate the change in visit rates during each period of interest.

For the exposure query, we used the tidytext package in R software, version 3.6,¹⁴ to analyze which symptoms were most commonly described in the reasons given for the visit involving e-cigarette product use. This method counts adjacent word pairs in the comments about the reason for the visit, excluding uninformative words such as “of” and “the.”

For the outcome query, we compared the relative frequency of hospitalizations with EVALI-related codes among persons 11 to 34 years of age beginning June 9, 2019. We estimated separate incidence ratios among male and female patients with the use of the epiR package (R software, version 3.6).¹⁵

Exposure Query

Figure 1. Figure 1. Emergency Department (ED) Visits with Electronic Cigarette (E-Cigarette) Product Use as the Reason for the Visit, According to Age Group.

Shown are data from the National Syndromic Surveillance Program, from January 1, 2017, to December 7, 2019, regarding ED visits in the United States in which e-cigarette or vaping product use was mentioned as the reason for the visit. The query regarding the reason for the visit was specified as such in an attempt to exclude injuries related to e-cigarette product use, such as device explosions or accidental ingestion of e-cigarette liquid. However, potentially related syndromes such as acute intoxication from tetrahydrocannabinol or nicotine poisoning were not excluded.

Figure 2. Figure 2. Comparison of Weekly Counts of ED Visits Related to E-Cigarette Product Use.

Shown is a comparison of the weekly counts of ED visits in the National Syndromic Surveillance Program with e-cigarette product use as the reason for the visit with other reports, including discharge diagnoses related to e-cigarette, or vaping, product use–associated lung injury (EVALI), online search interest, and cases reported to the Centers for Disease Control and Prevention (CDC). Online search interest was measured by the Google Trends (https://trends.google.com) interest score for terms for e-cigarette or vaping from U.S. searches. Google search terms were “vaping,” “vap,” “e-cig,” “e-cigarette,” “ecig,” and “electronic cigarette.” Google Trends scores range from 0 to 100, with a score of 100 indicating peak interest and a score of 50 indicating that the search term is half as popular as at its peak. Confirmed or probable cases of EVALI were reported to the CDC through December 10, 2019, for dates of admission between April 1, 2019, and December 7, 2019. The CDC-recommended diagnostic codes for EVALI include the following: J68.0 (bronchitis and pneumonitis due to chemicals, gases, fumes, and vapors), J69.1 (pneumonitis due to inhalation of oils and essences; includes lipoid pneumonia), J80 (acute respiratory distress syndrome), J82 (pulmonary eosinophilia, not elsewhere classified), J84.114 (acute interstitial pneumonitis), J84.89 (other specified interstitial pulmonary disease), and J68.9 (unspecified respiratory condition due to chemicals, gases, fumes, and vapors).

The incidence of ED visits with e-cigarette product–related terms mentioned in the reasons given for the visit gradually increased between the first week of January 2017 and the week of August 11, 2019, particularly among patients 10 to 19 years of age (Figure 1). In this age group, the weekly ED visit rate steadily increased from 4 visits per 1 million in the first week of January 2017 to 83 visits per 1 million during the week of August 4, 2019. Across all age groups, the trend sharply increased between August 11, 2019, and September 8, 2019 (Figure 2) by a mean of 26 visits (95% confidence interval [CI], 19 to 32) per 1 million each week. The weekly visit rate peaked at 116 visits per 1 million during the week of September 8, 2019, and then decreased by a weekly mean of 6 visits (95% CI, 5 to 6) per 1 million. The overall trend mirrored the trend in admission dates among patients with cases of EVALI reported to the CDC, which peaked during the week of September 15, and in U.S. Google searches for the specified terms, which peaked during the week of September 8, 2019 (Figure 2).

Figure 3. Figure 3. Trend in the Word Pair “Shortness Breath.”

Shown is the trend in the adjacent word pair “shortness breath” from January 1, 2017, to December 7, 2019, as found in records returned by the search for e-cigarette product use in the comments about the reason for the visit. The trend is represented as the monthly count of the word pair “shortness breath” divided by the total number of all adjacent word pairs in records returned by the search that month.

From January 1, 2017, to December 7, 2019, the adjacent word pairs for symptoms that appeared most frequently in the query for use of e-cigarette products were “shortness breath” and “chest pain.” Among records of patients with e-cigarette use, the terms “shortness” and “breath” appeared together in 21% (95% CI, 20 to 23) of visits during the period from June 2, 2019, to December 7, 2019 — an increase from 8% (95% CI, 7 to 9) in the period from January 1, 2017, to June 1, 2019 (Figure 3). Use of the word pair “chest pain” similarly increased to 18% (95% CI, 16 to 19) for the period starting on June 2, 2019, from 8% (95% CI, 6 to 9) in the period before June 2, 2019.

Outcome Query

The trend in ED visits with EVALI-related diagnostic codes changed in the week of June 9, 2019. From the week of June 9, 2019, to the week of September 29, 2019, the use of these codes increased weekly by an average of 6 visits (95% CI, 4 to 7) per 1 million. Among male patients, the incidence of ED visits with EVALI-related codes was higher in the period starting on June 9, 2019, than it was during the period from January 1, 2017, to June 8, 2019 (incidence ratio, 3.7; 95% CI, 3.2 to 4.3). The incidence was also higher among female patients in the period starting on June 9, 2019, than during the period from January 1, 2017, to June 8, 2019 (incidence ratio, 2.1; 95% CI, 1.8 to 2.5), although the increase was not as large as among male patients.

Figure 4. Figure 4. ED Visits among Persons 11 to 34 Years of Age Who Received Diagnoses Potentially Related to EVALI, According to Sex.

Shown are data from the National Syndromic Surveillance Program for the period from January 1, 2017, to December 7, 2019, for patients 11 to 34 years of age with potential EVALI who were admitted to the hospital, were transferred to another facility, or died in the ED. CDC-recommended diagnostic codes for EVALI were used.

This increase in the number of visits among persons with a potential EVALI-related discharge diagnosis began during the week of June 9, 2019 (Figure 4), close to the same time that the adjacent word pair “shortness breath” was increasingly seen in records of reasons for the visit related to e-cigarette products (Figure 3) Although the incidence of visits with these codes has decreased since peaking during the week of September 29, they remain higher than at any time before June 2019.

These analyses suggest that ED visits associated with EVALI began to spike in June 2019, peaked with cases reported to the CDC in September, and have decreased since then. From January 2017 to June 2019, there was a gradual increase in the incidence of ED visits that involved mentions of e-cigarette product use. In the first week of June 2019, the incidence of reasons for the visit that included mention of these products and shortness of breath began to increase sharply, which suggests that this EVALI-related symptom was appearing more often in persons using e-cigarette products. Also in early June, the incidence of discharge diagnoses with codes that the CDC would later recommend for EVALI began to increase nationwide among persons 11 to 34 years of age. These increases that occurred in June 2019 coincided with the first known cluster of EVALI cases.¹ As with cases reported to the CDC² and a previous analysis in Illinois,¹ the ED visit rates were higher among male patients than among female patients. This analysis of ED data suggests that the incidence of EVALI increased sharply in the summer of 2019 and had not been occurring at the same level over a longer period without detection.

There are many exposures that might have contributed to the gradual increase in the incidence of a report of e-cigarette product use as the reason for the visit during the period from January 1, 2017, to June 1, 2019, especially among patients 10 to 19 years of age. The ED visits could include sporadic cases from the same products or substances that later contributed to the wider outbreak when they became more commonly used. Another possibility is the increasing use of e-cigarettes containing nicotine. The percentage of U.S. high school students reporting e-cigarette use in the previous 30 days increased from 11.7% in 2017 to 27.5% in 2019.¹⁶ Newer-generation e-cigarettes use nicotine salts,¹⁷ which allow more nicotine to be inhaled with less irritation.¹⁸ Nicotine salts may increase the risk of adverse effects to the lungs owing to more frequent and stronger inhalation or may increase the risks of other health effects, such as nicotine poisoning or effects from other potential toxicants such as flavoring agents. The rise also coincided with the increased use of cannabinoid (CBD) oil in these products.¹⁹ The increase in the incidence of these ED visits may also be driven by acute intoxication from THC (which increased in availability over this time period), synthetic cannabinoids, or other drugs. Because the causes of the earlier increase are not yet known, more study is needed to understand the increase between January 2017 and June 2019.

The number of ED visits with e-cigarette product use mentioned in the reasons for the visit peaked during the week of September 8, 2019, which was the same week as a peak in Google searches for similar terms, after there was widespread national media attention about this issue. This spike could reflect a real increase in EVALI cases over time. Results for the outcome query regarding lung injury, which relied on the use of specific diagnostic codes, increased in early June 2019 and peaked during the week of September 29, 2019, before the CDC recommended these codes for use on October 17. The slower increase and later peak with the outcome query than with the exposure query might have been caused by more gradual uptake of certain diagnostic codes. Alternatively, some of the ED visits with e-cigarette product use mentioned in the reason for the visit but without an EVALI-related diagnosis may represent less severe effects or were early signs of more serious injury, such as shortness of breath that later progressed to respiratory failure.

This study has limitations. First, both the exposure query and the outcome query returned records that were unrelated to the current injury and in which e-cigarette use was incidental to the visit. Second, the exposure query was probably affected by public and clinical awareness of the outbreak, which increased the likelihood that e-cigarette products would be mentioned in the reasons given for the visit. Third, the outcome query relied on the use of specific codes and probably underestimated the number of visits for EVALI. The magnitude of the underestimate cannot be assessed at the national level. In Illinois, an analysis of confirmed and probable cases showed that 23% of 159 patients 11 to 34 years of age seen in an ED that participated in syndromic surveillance had a CDC-recommended discharge diagnosis, so these cases would have been captured by the outcome query. Finally, NSSP coverage is not uniform across or within all states, and health care facilities contributing data to the system change over time as new hospitals are added to the system and, more rarely, when they close. From the first week of June 2019 through the first week of November 2019, the number of facilities sending data to NSSP increased from 3109 to 3247.

Despite these limitations, syndromic surveillance also has important strengths, including timeliness, automated reporting, the ability to examine local and national trends rapidly, and the flexibility to change syndrome definitions rapidly without changing data collection, which make ED data a valuable complement to traditional epidemiologic investigations. In the future, it may be possible to use ED data in combination with reports from clinicians to understand any spikes that may be caused by increasing exposure to e-cigarette products. The CDC announced in November 2019 that it would no longer request EVALI case reports for patients who were not hospitalized; data from ED visits that do not lead to hospitalization can thus offer insight on trends in less severe cases.

ED data suggested that the incidence of EVALI increased sharply between early June and early September 2019. Although the incidence of ED visits for which reasons given for the visit and discharge diagnosis codes included terms associated with EVALI has decreased since the peak, the incidence has not decreased to the rates that were observed before June 2019; therefore, there is a need for continued monitoring and prevention.