Associations between Electronic Cigarettes, Smokeless Tobacco, and Age-related Macular Degeneration in the 2017 United States National Health Interview Survey

Abstract

Purpose: To investigate the association of cigarette-alternative tobacco products with age-related macular degeneration (AMD). Methods: The 2017 National Health Interview Survey, comprising epidemiologic data from a nationally representative sample of the US adult population, was queried to identify all participants who reported using electronic cigarettes (e-cigarettes) and smokeless tobacco and whether or not they had AMD. Participant characteristics were analyzed and a multivariable regression was performed to determine predictors of AMD, adjusting for age, sex, race/ethnicity, number of packs of cigarettes smoked per day, and body mass index. Results: The final analytic sample included 26 689 survey respondents, representing the US national population of 246 242 859 adults. The weighted prevalence of AMD was 1.9% (95% confidence interval [95% CI], 1.8–2.1%). Compared to those without AMD, adults with AMD were significantly older, more often female, and disproportionately non-Hispanic White (P < .0001). In adjusted models (including adjustment for number of packs of cigarettes smoked per day), the odds ratios for developing AMD were 1.49 (95% CI, 1.02 to 2.18) in adults who used smokeless tobacco products and 1.08 (95% CI, 0.73 to 1.60) in adults who used e-cigarettes, compared to those who had never used these products. Conclusions: This study identified smokeless tobacco use as a novel factor associated with AMD among a nationally representative sample, suggesting its avoidance may reduce the risk of developing AMD. Additional studies are needed to better understand the long-term effects of e-cigarettes on AMD.

Introduction

Age-related macular degeneration (AMD) is the leading cause of blindness in individuals older than age 65 years in the US. ¹ Most risk factors for AMD, such as age and race, are not modifiable. Cigarette smoking, however, is the most important modifiable exposure. ² Addressing modifiable risk factors at the individual patient level is essential and merits attention at the public health policy level to reduce disease prevalence and blindness.

While cigarette smoking is a well-established risk factor for AMD, tobacco and nicotine exposure through other methods is less well-studied. Namely, data on the effects of electronic cigarettes (e-cigarettes) and smokeless tobacco (such as chewing tobacco and snuff) on the risk of developing AMD are limited. E-cigarettes, which are devices that produce an aerosol by heating a solution, typically nicotine-containing, that users inhale, or vape, are the tobacco product gaining the most popularity in the US, especially among adolescents. In this age group, use of e-cigarettes has increased 10-fold in recent years, exceedig the use of traditional cigarette smoking among adolescents. ³ Despite their popularity, the effect of e-cigarettes on health is largely unknown. Although smokeless tobacco has been in use for longer than e-cigarettes and is known to be associated with increased risk of cancers, ⁴ its effect on AMD remains understudied.

To better understand the effect of e-cigarettes and smokeless tobacco products on the risk of AMD, we analyzed data from the National Health Interview Survey (NHIS), an epidemiologic survey of a nationally representative sample of the US adult population. To our knowledge this study is the first to present national data on the use of cigarette-alternative tobacco products among patients with AMD in the US. Additionally, adjusted statistical models were applied to assess their effects beyond those of established risk factors for AMD (eg, cigarette smoking).

Methods

The NHIS is an in-person cross-sectional household survey designed to secure accurate and current statistical information on the amount, distribution, and effects of illness and disability in the US. ⁵ It has been conducted annually since 1957 by the Centers for Disease Control and Prevention National Center for Health Statistics, and the survey content is updated every 15 years to incorporate advances in survey methodology and coverage of health topics. The survey is distributed to noninstitutionalized civilians across all 50 states and the District of Columbia. Survey responses are weighted based on reciprocal probability of selection, ratio, nonresponse, and poststratification adjustments (adjusted for age, sex, and race/ethnicity among other covariates) based on population estimates produced by the US Census Bureau to generate national estimates.

In the present study, we queried the 2017 NHIS database to identify all participants who reported using e-cigarettes and smokeless tobacco (including chewing tobacco, snuff, dip, snus, or dissolvable tobacco). The primary outcome was a self-reported history of AMD. The following variables were analyzed as possible explanatory factors: age, sex, race/ethnicity, number of packs of cigarettes smoked per day, and body mass index (BMI).

The weighted distribution of participant characteristics was compared using chi-square tests for categorical variables and Wald tests for continuous variables. Unadjusted and adjusted logistic regression models were used to assess associations between e-cigarette exposure, smokeless tobacco exposure, and self-reported AMD in separate models, adjusting for age, sex, race/ethnicity, number of packs of cigarettes smoked per day, and BMI. Data were analyzed using STATA version 14 (StataCorp). Associations of e-cigarette and smokeless tobacco exposure with AMD are reported as unadjusted and adjusted odd ratios (ORs) with 95% confidence intervals (95% CIs). Statistical significance was set at P < .05.

Results

The final analytic sample included 26 689 survey respondents, representing the US national population of 246 242 859 adults. Table 1 presents the characteristics of the survey respondents. The weighted prevalence of AMD was 1.9% (95% CI, 1.8% to 2.1%). Adults with AMD were significantly older, more often female, and disproportionately non-Hispanic White (P < .0001) compared to those without AMD. In addition, adults with AMD had a marginally lower BMI (29.3 kg/m² versus 30.4 kg/m² for those without AMD; P = .015).

Table 1.

Characteristics of the 2017 National Health Interview Survey Respondents (n) With or Without Age-Related Macular Degeneration Among the Total Population (N) of US Adults.

	Without Age-Related Macular Degeneration (n = 25 980)(N = 241 536 187)		With Age-Related Macular Degeneration (n = 709) (N = 4 706 672)		Total Population (n = 26 689) (N = 246 242 859)
Characteristic	Estimate	95% CI	Estimate	95% CI	Estimate	95% CI	P
Age (mean years)	47.0	46.6 to 47.3	70.9	69.6 to 72.1	47.5	47.1 to 47.8	<.0001
Sex (%)
Male	48.4	47.6 to 49.2	39.9	35.5 to 44.6	48.3	47.5 to 49.0	<.0001
Female	51.6	50.8 to 52.4	60.1	55.4 to 64.6	51.8	51.0 to 52.5
Race/ethnicity (%)
Non-Hispanic White	63.6	61.9 to 65.3	83.7	79.2 to 87.4	64.0	62.2 to 65.7	<.0001
Black	12.0	11.0 to 13.1	3.7	2.4 to 5.7	11.8	10.8 to 12.9
AIAN	0.7	0.4 to 1.2	1.7	0.7 to 4.1	0.7	0.4 to 1.2
Asian	6.0	5.4 to 6.7	2.1	1.1 to 4.2	5.9	5.3 to 6.6
More than 1 race	1.6	0.1 to 1.8	1.8	0.8 to 3.8	1.6	1.4 to 1.8
Hispanic	16.2	14.8 to 17.7	7.0	4.5 to 10.6	16.0	14.6 to 17.5
Cigarette smoking status (%)
Never smoker	86.3	85.7 to 86.9	89.8	87.1 to 92.0	86.4	85.8 to 87.0	.1268
At least 0.5 pack per day	8.5	8.1 to 9.0	4.5	3.2 to 6.5	8.5	8.0 to 8.9
0.6–1.0 packs per day	4.4	4.1 to 4.7	4.9	3.4 to 7.1	4.4	4.1 to 4.7
1.1–1.5 packs per day	0.5	0.4 to 0.6	0.5	0.2 to 1.6	0.5	0.4 to 0.6
≥1.6 packs per day	0.3	0.2 to 0.3	0.3	0.0 to 0.8	0.3	0.2 to 0.3
BMI (mean kg/m2)	30.4	30.1 to 30.6	29.3	28.4 to 30.2	30.4	30.1 to 30.6	.0150
Ever e-cigarette use (%)
No	85.4	84.7 to 86.1	93.0	90.7 to 94.8	85.5	84.9 to 86.2	<.0001
Yes	14.6	14.0 to 15.3	7.0	5.2 to 9.3	14.5	13.8 to 15.1
Ever smokeless tobacco use (%)
No	90.0	89.4 to 90.6	90.4	86.9 to 93.0	90.0	89.4 to 90.6	.8108
Yes	10.0	9.5 to 10.6	9.6	7.0 to 13.1	10.0	9.5 to 10.6

Abbreviations: 95% CI, 95% confidence interval; AIAN, American Indian and Alaska Native; BMI = body mass index; e-cigarette, electronic cigarette.

Table 2 presents the results of the multivariate regression models predicting the development of AMD based on ever use of e-cigarettes and smokeless tobacco. Adults who were exposed to e-cigarettes had an unadjusted OR for developing AMD of 0.44 (95% CI, 0.32 to 0.60; P < .001) compared to those who had never used e-cigarettes; after adjusting for covariates (age, sex, race/ethnicity, number of cigarette packs smoked per day, and BMI), the adjusted OR was 1.08 (95% CI, 0.73 to 1.60; P < .692). Adults who were exposed to smokeless tobacco products, compared to those who had never used smokeless tobacco products, had an unadjusted OR for developing AMD of 0.96 (95% CI, 0.68 to 1.36; P < .811); in models adjusted for the same covariates as above (including number of cigarette packs smoked per day), the adjusted OR for AMD was 1.49 (95% CI, 1.02 to 2.18; P < .039).

Table 2.

Logistic Regression Models Assessing Associations Between Use of Tobacco Alternatives and Age-Related Macular Degeneration.

Exposure, Models	OR for AMD	95% CI	P
E-cigarettes (relative to never used)
Unadjusted	0.44	0.32 to 0.60	<.001
Adjusted a	1.08	0.73 to 1.60	.692
Smokeless tobacco (relative to never used)
Unadjusted	0.96	0.68 to 1.36	.811
Adjusted a	1.49	1.02 to 2.18	.039

Abbreviations: 95% CI, confidence interval; AMD, age-related macular degeneration; e-cigarette, electronic cigarette; OR, odds ratio.

^aAdjusted for age, sex, race/ethnicity, number of packs of cigarettes smoked per day, and body mass index.

Discussion

In this study, we present national data, not previously published, on the effects of e-cigarettes and smokeless tobacco on AMD. After the logistic regression analyses were controlled for covariates such as number of cigarette packs smoked per day, smokeless tobacco emerged as an independent risk factor for AMD in our study population. This finding coincides with a rise in cigarette-alternative tobacco products in the US, with some states reporting a frequency of current smokeless tobacco use among adults of 7.0% to 8.8%. ⁶

This novel finding helps broaden our knowledge of the effect of tobacco products on AMD. The association between cigarette smoking and AMD is well-established. Cigarette smoking increases the risk of the development and progression of AMD. ² However, in 2021, the prevalence of cigarette smoking in the US reached its lowest level since 1965. ⁷ Conversely, the use of other tobacco products has persisted or increased. Regardless of the method of consumption of tobacco and tobacco-derived products, they likely share the same pathway to retinal damage, promoting oxidative damage to the retinal pigment epithelium (RPE), which contributes to the development of AMD. ⁸ Evidence of structural damage to the deep capillary plexus and choriocapillaris has been observed on ocular coherence tomography angiography among smokeless tobacco users when compared to non–tobacco users. ⁹ While clinical studies are limited on this topic, a cohort study in South India reported an increased risk of late development of AMD among smokeless tobacco users compared to those who have not used smokeless tobacco. ¹⁰ Although our study took place in the US, where environmental factors and the popular forms of smokeless tobacco differ, we confirmed an association between smokeless tobacco and AMD. Additionally, the present study did not exclude those who had ever smoked cigarettes. Instead, we used adjusted models, allowing for the identification of smokeless tobacco as an independent risk factor, with the findings showing that smokeless tobacco use conferred a higher risk for AMD compared to cigarette smoking alone.

We interpret with caution the apparent lack of association of e-cigarettes with AMD in the present study. E-cigarettes contain nicotine, derived from tobacco, which has been shown to alter the function of human RPE cells and enhance angiogenesis in vivo. ¹¹ Additionally, exposure to e-cigarette vapor has been shown to promote inflammatory and angiogenic reactions in the RPE and choroid in animal models. ¹² Given that e-cigarettes have become most popular over approximately the last decade and that they are most popular among younger users, the association with AMD may be influenced by the limited duration of exposure and by younger users not yet reaching the peak years for the development of AMD. Confounding factors that make e-cigarettes difficult to study are the heterogeneity of products available, including variability in nicotine concentration, heating mechanisms, and the volume and ingredients of different carrier solutions. Another factor that may conceal a relationship between AMD and e-cigarettes is the lack of data on the amount and duration of exposure. It may be that a dose-dependent effect is present, as seen with conventional cigarette smoking. However, the present dataset lacks the granularity to investigate this possibility.

The strengths of this study include providing US national population–based estimates of the number of adults with AMD, utilizing a standardized method of data collection, and assessing a large sample size. The NHIS is also a principal source for tracking tobacco use in the US. ⁷ However, this study also has limitations. The NHIS does not include data on institutionalized populations or those without a fixed US household address. The data are based on in-person interview responses and self-reported characteristics. Self-reporting is a common method for obtaining medical data, even though it is subject to biases such as variations in healthcare access, social desirability, and recall. Previous research has found self-reporting of ophthalmic diseases to have a low sensitivity and high specificity. ¹³ Therefore, the prevalence of AMD and use of e-cigarettes and smokeless tobacco reported herein may be an underestimate of the disease burden and breadth of tobacco-alternative exposures. Finally, the NHIS data lacks the granularity to assess how the frequency or duration of our studied exposures may affect the prevalence and severity of AMD.

E-cigarette and smokeless tobacco use are important public health policy concerns and have significant implications for vision health. Based on our findings, we recommend that public health efforts be aimed at raising awareness about the increased risk of developing vision-threatening diseases such as AMD that may be conferred with tobacco use, and that the message include use of not only cigarettes but also tobacco-alternative products as well. Similarly, we recommend that exposure to tobacco-alternative products be considered when taking patient histories and when counseling patients about AMD risk-mitigation measures. Future studies are warranted to further elucidate our findings in other populations and to provide long-term data on e-cigarette use, which would allow a better understanding of its impact on AMD.