American Journal of Respiratory and Critical Care Medicine

To the Editor:

Randomized trials and cohort studies have shown that electronic nicotine delivery system (ENDS) use can promote abstinence from tobacco smoking, particularly when tobacco smokers switch to regular, exclusive ENDS use (14). However, dual use of ENDS with smoked (combustible) tobacco is common. Cross-sectional studies have reported an association between ENDS use and respiratory symptoms (510). These studies do not address whether ENDS use precedes and potentially causes respiratory symptoms. We therefore evaluated the association between ENDS use, tobacco smoking, dual use, and incident respiratory symptoms among people without baseline respiratory symptoms.

We analyzed data from the PATH (Population Assessment of Tobacco and Health) study, a U.S. nationally representative longitudinal survey. The population of interest were participants aged ⩾12 years who, at PATH wave 3 (2015–2016), reported no past 12-month respiratory symptoms. Per PATH questions, we defined respiratory symptoms as self-report of wheezing or whistling in the chest, or a nocturnal dry cough not associated with a cold or chest infection. We categorized participants by wave 3 self-reported ENDS use and tobacco smoking: non–current users (including former users), current exclusive ENDS users, current exclusive tobacco smokers, or current dual users of ENDS and smoked tobacco. Current ENDS use or current tobacco smoking was, for adults (ages ⩾18 yr), self-reported current some-day or every-day use of any ENDS product or smoked tobacco product, and for youth (ages 12–17 yr), self-reported past 30-day use. The outcome was incident respiratory symptoms, defined as wave 4 (2016–2018, target 1 yr after wave 3 survey) self-report of past 12-month respiratory symptoms. We performed multivariable logistic regression, adjusting for demographic factors and accounting for complex sampling per the PATH user guide. In three sensitivity analyses, we 1) incorporated chronic respiratory disease (wave 3 self-report of asthma, chronic obstructive pulmonary disease [COPD], chronic bronchitis, or emphysema) as a predictor; 2) limited the analysis to those whose categorization of ENDS and smoked tobacco use was the same in waves 3 and 4; and 3) limited the analysis to adults and added some-day versus every-day ENDS and/or smoked tobacco use to the model. Analyses were conducted in R 4.0.0 with the tidyverse 1.3.0 and survey 4.0 packages.

Of 20,882 participants without respiratory symptoms at wave 3, 81.6% were noncurrent users, 1.4% were exclusive ENDS users, 14.3% were exclusive tobacco smokers, and 2.7% were dual users (weighted, Table 1). Among adults, 54.8% of exclusive ENDS users and 22.2% of dual users reported every-day ENDS use, whereas 53.9% of exclusive tobacco smokers and 50.0% of dual users reported every-day tobacco smoking. Among adults who smoked tobacco cigarettes daily, the median (interquartile range) number smoked per day was 10 (7–20) cigarettes for both exclusive tobacco smokers and dual users.

Table 1. Characteristics of Those Who Reported No Past 12-Month Respiratory Symptoms at PATH Wave 3, by ENDS Use and Tobacco Smoking at PATH Wave 3

 Noncurrent Users
[N = 15,431 (81.6%)]
Exclusive ENDS Users
[N = 490 (1.4%)]
Exclusive Tobacco Smokers
[N = 4,061 (14.3%)]
Dual Users
[N = 900 (2.7%)]
Age, yr    
 12–249,341 (21.1)289 (39.5)1,121 (17.6)468 (37.9)
 25–544,195 (45.2)157 (44.8)2,171 (58.9)362 (51.6)
 ⩾551,894 (33.7)44 (15.7)769 (23.5)70 (10.5)
Sex    
 F7,817 (53.0)211 (40.0)1,753 (37.8)389 (39.8)
 M7,585 (47.0)279 (60.0)2,306 (62.2)511 (60.2)
Race    
 White10,481 (77.2)365 (80.7)2,736 (72.6)648 (74.3)
 Black2,284 (11.4)52 (9.8)831 (18.7)112 (13.7)
 Other1,922 (11.4)62 (9.5)396 (8.7)113 (12.0)
Ethnicity    
 Hispanic4,078 (18.9)96 (14.2)777 (16.3)177 (15.4)
 Not Hispanic11,067 (81.1)388 (85.8)3,220 (83.7)719 (84.6)
Self-reported history of asthma, COPD, chronic bronchitis, or emphysema    
 No13,992 (92.8)432 (89.6)3,516 (88.0)762 (85.5)
 Yes1,378 (7.2)56 (10.4)510 (12.0)129 (14.5)

Definition of abbreviations: COPD = chronic obstructive pulmonary disease; ENDS = electronic nicotine delivery systems; PATH = Population Assessment of Tobacco and Health.

Data are shown as n (weighted %).

Exclusive ENDS users and exclusive tobacco smokers reported either past 30-day use (youth) or current some-day or every-day use (adults). Dual use refers to both ENDS use and tobacco smoking.

At wave 4, incident respiratory symptoms were reported by 10.7% (95% confidence interval [CI], 9.8–11.6%) of wave 3 noncurrent users, 11.8% (8.4–16.4%) of exclusive ENDS users (adjusted odds ratio [AOR] vs. noncurrent users, 1.17; 95% CI, 0.79–1.74), 17.1% (15.9–18.4%) of exclusive tobacco smokers (AOR vs. noncurrent users, 1.78; 95% CI, 1.56–2.03), and 19.7% (16.7–23.0%) of dual users (AOR vs. noncurrent users, 2.22; 95% CI, 1.79–2.75) (Table 2). Dual users had significantly higher odds of incident respiratory symptoms compared with both exclusive ENDS users (AOR, 1.90; 95% CI, 1.23–2.93) and exclusive tobacco smokers (AOR, 1.24; 95% CI, 1.00–1.55).

Table 2. Past 12-Month Respiratory Symptoms at PATH Wave 4: Multivariable Logistic Regression Analysis

 Primary AnalysisLimited to Those with Consistent Exposure Categorization in Wave 3 and Wave 4*Limited to Adults (Age ⩾18 yr) and Adjusting for Frequency of ENDS Use and Tobacco Smoking
 Proportion Reporting Past 12-mo Respiratory Symptoms at Wave 4 (95% CI)Multivariable-adjusted Odds Ratio (95% CI)Proportion Reporting Past 12-mo Respiratory Symptoms at Wave 4 (95% CI)Multivariable-adjusted Odds Ratio (95% CI)Proportion Reporting Past 12-mo Respiratory Symptoms at Wave 4 (95% CI)Multivariable-adjusted Odds Ratio (95% CI)
ENDS use and tobacco smoking      
 Noncurrent users10.7 (9.8–11.6)10.6 (9.7–11.5)10.3 (9.4–11.3)
 Exclusive ENDS users11.8 (8.4–16.4)1.17 (0.79–1.74)10.4 (4.5–22.0)1.03 (0.42–2.55)10.2 (6.4–16.0)1.19 (0.62–2.26)
 Exclusive tobacco smokers17.1 (15.9–18.4)1.78 (1.56–2.03)17.5 (16.1–19.1)1.86 (1.59–2.17)17.0 (15.8–18.3)1.31 (1.09–1.56)
 Dual users19.7 (16.7–23.0)2.22 (1.79–2.75)23.2 (18.8–28.3)2.83 (2.11–3.79)19.3 (16.3–22.7)1.75 (1.33–2.29)
Dual users vs. exclusive ENDS users1.90 (1.23–2.93)2.74 (1.07–7.03)1.47 (0.79–2.76)
Dual users vs. exclusive tobacco smokers1.24 (1.00–1.55)1.53 (1.09–2.12)1.34 (1.03–1.74)
ENDS use frequency      
 Some day11.6 (10.8–12.5)
 Every day12.4 (8.9–17.1)0.88 (0.52–1.50)
Tobacco smoking frequency§      
 Some day10.5 (9.7–11.5)
 Every day21.6 (19.8–23.5)1.81 (1.46–2.26)
Age, yr      
 12–2412.1 (11.5–12.8)11.6 (10.9–12.4)10.6 (9.6–11.6)
 25–5411.0 (10.0–12.1)0.92 (0.81–1.03)10.7 (9.6–11.9)0.90 (0.78–1.05)11.0 (10.0–12.1)1.09 (0.94–1.25)
 ⩾5512.9 (11.4–14.6)1.16 (0.98–1.37)12.6 (11.0–14.3)1.13 (0.94–1.36)12.9 (11.4–14.6)1.37 (1.13–1.67)
Sex      
 F11.9 (11.0–13.0)11.6 (10.6–12.7)11.6 (10.6–12.8)
 M11.7 (10.7–12.8)0.95 (0.83–1.08)11.3 (10.3–12.5)0.94 (0.82–1.09)11.5 (10.5–12.7)0.97 (0.84–1.12)
Race      
 White11.4 (10.5–12.3)11.0 (10.1–12.0)11.2 (10.3–12.1)
 Black14.6 (12.6–16.9)1.26 (1.03–1.55)14.2 (12.3–16.4)1.26 (1.02–1.57)14.4 (12.2–16.9)1.25 (1.00–1.56)
 Other12.2 (9.9–15.0)1.12 (0.88–1.42)12.2 (9.9–15.0)1.15 (0.90–1.47)11.7 (9.2–14.8)1.11 (0.85–1.45)
Ethnicity      
 Hispanic11.2 (10.0–12.6)10.7 (9.4–12.2)11.0 (9.6–12.6)
 Not Hispanic12.0 (11.1–12.9)0.91 (0.76–1.09)11.6 (10.7–12.6)0.93 (0.76–1.13)11.7 (10.8–12.7)0.88 (0.72–1.08)

Definition of abbreviations: CI = confidence interval; ENDS = electronic nicotine delivery systems; PATH = Population Assessment of Tobacco and Health.

*Consistent exposure categorization signifies that an individual gave the same response at waves 3 and 4 for current use of ENDS (or nonuse) and gave the same response at waves 3 and 4 for current tobacco smoking (or nonuse).

Only adults were asked about some-day versus every-day ENDS use and tobacco smoking; youth were asked if they had used in the past 30 days.

ENDS use frequency was reported by adult exclusive ENDS users and by adult dual users.

§Tobacco smoking frequency was reported by adult exclusive tobacco smokers and by adult dual users.

In sensitivity analyses, results were similar when we included chronic respiratory disease as a predictor. Among those whose categorization of ENDS and smoked tobacco use was the same in waves 3 and 4, the AOR point estimates for incident respiratory symptoms among dual users compared with other categories were higher than those of the primary analysis (Table 2). When we included frequency of use among adults in the model, every-day versus some-day tobacco smoking was significantly associated with incident respiratory symptoms, but every-day versus some-day ENDS use was not. Odds of incident respiratory symptoms for dual users compared with exclusive tobacco smokers remained significantly higher (Table 2).

We found that dual use of ENDS and smoked tobacco is significantly associated with incident respiratory symptoms compared with use of either product alone or noncurrent use at baseline. The novelty of this study is twofold. First, despite similar frequency and intensity of tobacco smoking among exclusive tobacco smokers and dual users, dual users have a higher incidence of respiratory symptoms. ENDS use and tobacco smoking together may result in additive or synergistic pathology, although our results do not establish causation. Second, we analyzed youth and adults without past 12-month respiratory symptoms at baseline. The significant association between dual use and incident respiratory symptoms was even stronger after removing those whose dual use stopped by wave 4. In prior cross-sectional studies, causal inference is more limited: respiratory symptoms may prompt a tobacco smoker to start using ENDS in an attempt to quit smoking (510). A study using longitudinal PATH data found an association between ENDS use and incident respiratory conditions including COPD and asthma, but reverse causality remains possible—tobacco smokers with respiratory symptoms (not reported by that study) may have turned to ENDS (11). We focused on respiratory symptoms, which can develop more quickly than chronic diseases—COPD developing entirely within the relatively short timeframe of PATH is unlikely.

This analysis has limitations. ENDS use, tobacco smoking, and respiratory symptoms were self-reported, and inhalation practices and detailed past usage patterns were not captured. With approximately 1 year between wave 3 and wave 4 surveys, use patterns could have fluctuated in the interim, and respiratory symptoms could have developed at any time during that period. With tremendous heterogeneity in ENDS products, some may be more harmful than others, and intensity of ENDS use is challenging to capture. Waves 3 and 4 of PATH predate the rapid rise of pod-based ENDS like JUUL, which eventually dominated the ENDS market.

Our results indicate that dual use of ENDS and smoked tobacco is not without health risk. Those who use ENDS to stop smoking tobacco should be cautioned against dual use. For tobacco dependence, Food and Drug Administration–approved treatments such as varenicline remain preferred (12).

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*Corresponding author (e-mail: ).

Supported by awards from the National Institute on Drug Abuse of the NIH (K01 DA042687), the National Cancer Institute of the NIH and Food and Drug Administration Center for Tobacco Products (U54 CA229974), and the NHLBI of the NIH (K23 HL136854). The funding sources had no role in the study design, data collection, data analysis, data interpretation, or writing of the manuscript or in the decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration.

Originally Published in Press as DOI: 10.1164/rccm.202012-4441LE on April 15, 2021

Author disclosures are available with the text of this letter at www.atsjournals.org.

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