Arthritis manifests as sustained inflammation of the synovium, and uncontrolled arthritis may cause permanent joint damage, stiffness, reduced mobility, impaired functionality, and other extra-articular complications. (Scott et al., 2010). In the United States, approximately 54.4 million adults suffer from arthritis diseases, which equates to about 25% of the population, and the number is projected to be 78 million (25.9%) by 2040 (Barbour et al., 2017). Arthritis creates a profound economic burden for the person and society. In 2013, the total national arthritis-attributable medical care costs and earnings losses among adults with arthritis were $303.5 billion or 1% of the 2013 US Gross Domestic Product (Murphy et al., 2018).

E-cigarettes quickly rose in popularity in the early part of this decade, with many users viewing them as a less harmful nicotine delivery alternative to combustible cigarettes. These battery-operated devices aerosolized, commonly called “vapor” by heating a liquid mixture, which usually contains nicotine, tetrahydrocannabinol, cannabinoid oils, flavorings, and other additives. Although, at much lower levels than found in cigarette smoke, e-cigarette aerosol has been found to contain ultrafine particles and known toxins, such as acetaldehyde, acrolein, toluene, and formaldehyde (Goniewicz et al., 2014). Recently, a growing body of evidence demonstrated that e-cigarette use is associated with numerous short- and long-term deleterious health consequences, including asthma, cardiovascular, oral, brain, kidney, and pulmonary diseases (Antoniewicz et al., 2016; Martin et al., 2016; Osei et al., 2019a; Osei et al., 2019b; Huilgol et al., 2019).

Given the rapidly increasing prevalence and controversy surrounding the use of e-cigarettes in general, there is a concern about whether e-cigarettes may be associated with arthritis diseases. We used the 2016–2018 Behavioral Risk Factor Surveillance System (BRFSS), which is a nationally representative sample in the United States, to determine if e-cigarette usage is associated with an increased risk of inflammatory arthritis diseases.

Of the 924,882 persons aged 18 years or older in our study sample in the BRFSS, 314,190 had arthritis diseases, for an overall weighted prevalence of 25.9% (95% CI, 25.7–26.1%). These data correspond to approximately 79.7 million individuals aged 18 years or older in the US population in 2010. There were 30,569 (3.3%) current e-cigarette users, and 20.2% of the e-cigarette users were 25–34 years of age. (Table 1). Compared with never e-cigarette users, current e-cigarette users were more likely to be men, with lower education levels, and lower annual income.

Among participants with inflammatory arthritis, the weighted prevalence of current e-cigarette and combustible cigarette users were 3.7 and 16.2%, respectively (Table 2). The weighted prevalence rates were 13.2 and 8.9% for participants without inflammatory arthritis, respectively.

In the fully adjusted model, the odds ratio (OR) (95% confidence interval) of self-reported inflammatory arthritis diseases was 1.81 (95% CI, 1.70-1.93) for current e-cigarette users compared with never e-cigarette users (Table 3). The ORs of self-reported inflammatory arthritis diseases was 2.06 (95% CI, 1.93-2.20) for current e-cigarette users compared with never combustible cigarette and e-cigarette users. The ORs of self-reported inflammatory arthritis diseases were 1.31 (95% CI, 1.18-1.47), and 1.55 (95% CI, 1.42-1.69) among sole e-cigarette and dual users compared with never e-cigarette users, respectively (Table 4).

In subgroup analyses, the ORs of inflammatory arthritis diseases were stronger in younger participants compared to older participants, and in males compared to females (Figure 2). In sensitivity analysis, the ORs did not results in substantially different when we restricted the analyses among participants under 35 years old (Supplementary Table S1).

In this representative of the U.S. adult population, we found e-cigarette usage was associated with an increased risk of inflammatory arthritis, and the results were consistent in both sole e-cigarette users and dual users. The findings from the present study have yielded several socially and clinically relevant findings.

It is noteworthy that cigarette smoking is one of the major risk factors suggested to play a crucial role in the development of arthritis due to its involvement in the pathogenesis of autoimmune diseases (Rydell et al., 2018). However, to our knowledge, no previous study has examined the impact of e-cigarette usage on inflammatory arthritis diseases. We found that current e-cigarette users have a higher risk of inflammatory arthritis compared with never e-cigarette users, especially in the current combustible cigarette group (dual users). This finding has a significant public health implication, because, initially, using e-cigarette as a potential smoking cessation tool and harm reduction strategy, the higher risks of inflammatory arthritis in dual users might indicate the undermining efforts at smoking cessation. While among the dual users, there were smokers who initiate use of e-cigarettes intending to quit may inadvertently prolong and/or sustain their nicotine addiction. Thus, exposure to an overwhelming amount of nicotine may be the potential mechanism that dual users have a high risk of arthritis in our population.

In the rapidly evolving landscape of e-cigarettes, public authorities concern that e-cigarette can become a “gateway” to smoking, teenagers may never switch to smoking but will become nicotine-dependent adults who vape, or some may initiate use of e-cigarettes in lieu of combustible cigarettes (Thorndike, 2019). In this study, sole e-cigarette users have a higher risk of inflammatory arthritis diseases, which might highlight the potential need to regulate sales and marketing of e-cigarettes to protect this vulnerable population from the onset of inflammatory arthritis diseases.

We found that current women e-cigarette smokers have a higher risk of inflammatory arthritis diseases compared to men. However, this was a subgroup analysis of our data and should be interpreted with caution. Nevertheless, female cigarette smokers face more health risks than male smokers do; they are more likely to develop lung cancer, myocardial infarction, and cognitive impairment (Risch et al., 1993; Prescott et al., 1998; Rosengren et al., 2004; Park et al., 2013). Although, current smoking was higher among men at 15.6% than women at 12.0%, the prevalence of current use of e-cigarettes was about the same for men and women in the United States (Schoenborn and Gindi, 2015; Creamer et al., 2019). Therefore, e-cigarette may be considered a risk factor inflammatory arthritis diseases for both sex, but particularly for the women who currently use of e-cigarettes.

E-cigarette use may increase inflammatory arthritis risk through gene-environment interactions, increasing inflammation and citrullination locally in pulmonary/oral mucosa or systemically, thereby inducing arthritis-related autoimmunity. Nicotine, the main constituent in e-cigarette, may have a pathogenic role in the development of arthritis diseases due to its ability to induce osteoblast apoptosis and sustained tissue hypoxia, which consequently induces osteoclast activity and bone resorption (Chaumont et al., 2018; Marinucci et al., 2018). In addition, e-cigarette use can lead to oxidative stress, altered cellular senescence, impaired host response and dysregulated repair mechanisms that can lead to arthritis diseases (Carnevale et al., 2016; Scott et al., 2018).

Although we observed e-cigarette usage was a major risk of inflammatory arthritis, our findings should be interpreted with caution because unadjusted residual confounding might remain and attenuate the association. Moreover, another caution is needed because these associations were shown epidemiologically and could not translate directly to clinical risks. Our current study has several limitations, some of which are inherent to the BRFSS data set, such as the exclusion of institutionalized individuals and lack of distinction among specific inflammatory arthritis types, including osteoarthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia. As the chance of developing osteoarthritis increases with age, we restricted our analyses among young adults under 35 years old. The findings were consistent with finding from all participants. As the prevalence of e-cigarette usage was high in the youth, this finding support e-cigarette usage was a major risk of inflammatory arthritis. Additionally, the cross-sectional nature of the BRFSS precludes us from drawing firm conclusions regarding the temporality of the observed risk factor associations. Finally, the prospective cohort studies are needed to track the changes in use patterns among dual users of combustible and electronic cigarettes, which we can estimate whether combustible cigarette smokers will benefit from the substituting e-cigarettes.

In the United States, approximately 1 of every four persons aged 18 years or older estimated to have arthritis diseases. We observed that e-cigarette usage was associated with an increased risk of inflammatory arthritis diseases, with consistent results among sole e-cigarette and dual users. Given the rapidly increasing prevalence of e-cigarette usage, public policies for regulating the sale, marketing, and use of e-cigarettes, as well as relevant policies and regulations (for example, prohibit flavored e-cigarettes), are critical to improve the overall health and reduce the prevalence of arthritis diseases in the United States.