Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in adults older than 40 years in the United States.1 The prevalence of advanced AMD is estimated to increase from 0.05% for those aged 40 to 49 years to almost 12% for those older than 80 years.1 Smoking (all forms of combustible tobacco) has been identified as a major modifiable risk factor for AMD. Most, but not all, studies of smoking and macular degeneration have noted an excess risk, with some studies reporting 100% increases among active smokers.2 Studies of AMD and smoking have relied on self-report of smoking status. Smoking deception, or failing to self-report as a smoker, is a recognized concern in studies involving reports of active smoking status.3 Studies specifically investigating the underreporting of active smoking have noted rates from a low of 1% to as high as 79%.3–5 There is concern that as social mores related to smoking have changed, this number may be higher.3 While active smoking is the principal method of nicotine delivery, other methods of tobacco exposure including the use of smokeless tobacco and environmental exposure occur. Environmental tobacco exposure (ETS) or passive smoking is exposure to tobacco smoke due to inhalation of the sidestream vapor of an active smoker. The restriction of smoking in public places in the United States has reduced ETS exposure; despite this, environmental ETS remains common. Similar to self-reported active smoking, self-report of exposure to environmental smoke has been shown to underestimate true exposure rates.6
Nicotine is the primary agent of addiction in tobacco use.7 Cotinine is the principal first-order metabolite of nicotine after hepatic cytochrome P450 oxidation and is found in blood, urine, and saliva rapidly after nicotine exposure.8 It is the most commonly used biomarker of nicotine and smoking exposure and has been used to identify both active nicotine intake and environmental exposure. As a biomarker of nicotine exposure, cotinine has the advantage of having a much longer half-life in serum than nicotine itself. Serum cotinine levels are generally thought to be a reflection of nicotine exposure over the previous 3 to 4 days.8 Cotinine level has a bimodal population distribution. The majority of persons not actively smoking have levels near the minimum detection threshold, whereas smokers have levels consistent with active intake that vary substantially based on ethnicity.9 The purpose of this study was to develop estimates of smoking deception within the US population among those with macular degeneration and those at risk of advanced macular degeneration.
This study uses data from the National Health and Nutrition Examination Survey (NHANES).10 NHANES is one of the major data collection instruments used in the United States to track health trends for children and adults. The NHANES has been administered since the 1960s by the National Center for Health Statistics (NCHS) under the direction of the Centers for Disease Control and Prevention. It is a nationally representative sample of the US population that enrolls about 5000 persons each year. There are two main components of the NHANES: a household interview and a medical examination. The household interviews are conducted by trained health care interviewers in participant’s homes and includes socioeconomic, demographic, and health risk factor information. A subset population participates in the medical evaluation, which consists of interview, medical and dental evaluation, physiological measurements, and laboratory tests.11 The medical examination is conducted in mobile clinics that travel to sites throughout the country by physicians and other trained health personnel.
Smoking-related questions within the NHANES are asked in both the household interview and during the medical clinic examination. Participants older than 20 years were asked in the household survey if they had smoked at least 100 cigarettes in their life and if they currently smoke cigarettes every day, some days, or never. At the mobile medical clinic examination, participants older than 12 years were asked if they had used any products containing nicotine in the last 5 days. Further questions delineate the forms of tobacco used.
As part of the medical examination, ophthalmic photography was done for participants older than 40 years. Ophthalmic photography consisted of two 45° nonmydriatic digital fundus photographs of each eye with a Canon CR6-45NM system. Digital video disc images were compiled and sent to the University of Wisconsin for grading.12 A more detailed overview of fundus photography methods and quality control can be found through the NCHS.12 A three-level grading scheme for AMD is used.13 No AMD is defined as gradable images with no evidence of lesions associated with AMD. Early AMD is defined as either soft drusen present with a grid area of greater than a 500-μ circle and a pigmentary abnormality present (increased pigment or depigmentation in the grid) or soft drusen present in the center grading circle and a pigmentary abnormality is present (increased pigment or depigmentation) in the grid. Late AMD is defined as the presence of any late lesions, such as geographic atrophy, pigment epithelium or retinal detachments, subretinal hemorrhage, subretinal fibrous scar, subretinal new vessels, or laser treatment and/or photodynamic therapy for AMD.
All participants in the medical examination older than 3 years were eligible for serum cotinine determination. Whole blood specimens and urine are processed, stored, and shipped to the Division of Laboratory Sciences, National Center for Environmental Health, and Centers for Disease Control and Prevention for analysis. Serum cotinine is measured by an isotope dilution-high performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry method.14 Using this method, the detection threshold for serum cotinine is 0.05 ng/mL.
Data Methods and Variable Definitions
Data from the 2005 to 2008 NHANES were obtained from the NCHS. The data were pooled according to the methods suggested by the NCHS. Data of Whites, African Americans, and Mexican Americans aged 40 years and older were included in this analysis. Because of oversampling of non-Mexican Hispanics in the 2007 to 2008 but not in the 2005 to 2006 survey, it is recommended that only data from these three racial groups be pooled.11 Participation rates in the study components are found in Fig. 1.
Responses to questions during the in home interview were used to classify subjects as a current cigarette smoker, former smoker, and never smoker. Persons who reported smoking cigarettes during the in-home interview on at least some days were considered active cigarette smokers. Participants who reported nicotine use in the last 5 days at the medical clinic interview were considered active tobacco users. For those who responded positively to the nicotine question, a three-level categorical variable was created, combining those who reported smoking cigarettes, pipes, and cigars to encompass all forms of combustible tobacco use, those using various forms of oral tobacco, and a third category for those using nicotine patches or gum. Serum cotinine level from laboratory data was sorted into a three-level categorical variable of no measurable serum cotinine (<0.05 ng/mL all ethnicities), environmental exposure level, and active nicotine exposure. Active smoking levels were defined based on race-adjusted cotinine levels as suggested by Benowitz et al.9 using the NHANES population (Mexican American = 0.84 ng/mL, Whites = 5.2 ng/mL, and African American = 4.8 ng/mL).
Only subjects who had gradable photographs in both eyes were used. Macular degeneration was considered present if early or late AMD as defined by the NHANES system was present in either eye. A variable approximating the Age-Related Eye Disease Study categories 3 and 4 was created to encompass those at risk of late-stage disease.15 This variable excluded persons with late-stage AMD in both eyes and included persons with late-stage disease in one eye with any stage less than late in the other, early AMD in at least one eye, drusen greater than 125 μ in diameter in at least one eye, and pigment abnormalities in at least one eye.
Descriptive statistics were generated for all major variables. Univariate analyses evaluating the association of AMD and at-risk late AMD to serum cotinine level in former smokers, never smokers, and either group were explored. Rao-Scott χ2 results are reported for cross tabulations. Possible smoking deception was evaluated by comparing self-reported smoking behavior in the home and at the medical clinic interview to serum cotinine levels adjusted for ethnicity. Deception was considered possible if there were inconsistencies between the report of cigarette use in the home interview, and cigarettes were not identified as the type of nicotine product used in the medical interview. Since the in-home interview asked specifically about cigarettes, if other nicotine products were identified at the medical interview, deception was not considered present. For those with concordant reports between the home and medical interview, cotinine levels were evaluated for those with no reported nicotine or cigarette use. Levels above the threshold for active use were used to assess possible deception in this group. Care was taken to take into account alternative forms of nicotine delivery, which could cause elevated cotinine levels. All analyses were weighted to the US population accounting for the complex sampling frame of the NHANES.
The study population consisted of 6063 adults older than 40 years, with a mean age of 57.2 years and a range of 40 to 85 years. This cohort is representative of more than 121 million Mexican American, White, and African American adults. The demographic characteristics follow the current US population older than 40 years, with more than 80% of subjects White and with a slightly higher proportion being female. Detectable serum cotinine levels were found in 48.0% (95% confidence interval [CI] = 44.7% to 51.3%; Table 1). Levels were split almost evenly between those consistent with ETS (24.2%, 95% CI = 22.0% to 26.3%) and those consistent with active smoking (23.8%, 95% CI = 21.5% to 26.2%). Tobacco products use in the last 5 days (nicotine user) was reported at the mobile clinic interview by 23.9% (95% CI = 21.4% to 26.5%). This rate was higher in comparison to individuals reporting that they smoked cigarettes on at least some days in the household interview 20.2% (95% CI = 18.0% to 22.5%).
Any-level AMD was found to be present in 6.7% (95% CI = 5.6% to 7.8%) of this cohort. Excluding those with late AMD, slightly less than 10% of adults had at-risk disease consisting of early AMD in one eye or AMD-associated findings, which would put them at risk of late-stage disease in both eyes. This equates to an estimated 9.5 million persons at risk of bilateral late disease. Owing to the substantial overlap in each group, usage of cigarettes and nicotine products was similar among those at risk of late AMD and those currently having any level AMD (Table 2). Among both groups, self-reported cigarette usage was slightly less than that seen in the general US population without either characteristic. The unadjusted differences were only significant for those with AMD (p = 0.04). This is not surprising given cigarette smoking rates are well known to decline with aging and, among this cohort, decreased from 26.5% (95% CI = 22.5% to 30.6%) among those 40 to 50 years to 3.4% (95% CI = 1.8% to 4.9%) for those older than 80 years. Combustion products represented the overwhelming majority of tobacco products used among both the AMD and at-risk groups. Rates of self-reported nicotine usage and environmental and active exposure based on cotinine levels were similar between those at risk of AMD, those with AMD, and the general US population. No group differences were statistically significant.
Among all respondents from the household interview with a cotinine level consistent with active tobacco use, 14.4% (95% CI = 12.0% to 16.8%) were self-reported former cigarette smokers and 7.7% (95% CI = 5.6% to 9.7%) were self-reported never cigarette smokers. Among all former cigarette smokers at the household survey, 10.9% (95% CI = 8.7% to 13.1%) had cotinine levels consistent with active nicotine use, while among reported never cigarette smokers 3.8% (95%CI 2.8, 4.8) had cotinine at levels consistent with active use. For those with AMD, about 16% of former smokers and 2% of reported never cigarette smokers had serum cotinine levels consistent with active nicotine exposure (Table 3). Together, former and never cigarette smokers accounted for one-third (33.4%, 95% CI = 18.8% to 48.0%) of all persons with AMD who had cotinine levels consistent with active use. The bulk of this group was accounted for by self-reported former cigarette smokers. A similar prevalence pattern was seen among the at-risk group. Former cigarette smokers were much more likely than never smokers to have serum cotinine at levels consistent with active use. In both those with AMD and those at risk of late AMD, about 9% of self-reported noncigarette smokers had cotinine levels at active use levels. The likelihood of having elevated serum cotinine for former cigarette smokers, never smokers, or either was not significantly higher than that of the general population without AMD or the at-risk population.
As would be expected, the reporting rates of nicotine exposure were higher within the medical clinic interview than self-reports of cigarette use in the home interview. Among those reporting no nicotine exposure at the medical clinic, approximately 2% of both the population with AMD and the at-risk population had cotinine levels consistent with active exposure. After taking into account discordance in direct reporting of cigarette use between the two interviews, the use of alternative nicotine-containing products, and serum cotinine levels, 5.4% (95% CI = 2.1% to 8.6%) of subjects with any-level AMD were potential smoking deceivers. A similar rate was seen among those at risk of late-stage disease at 5.0% (95% CI = 2.3% to 7.6%).
The relative aging of the US population and other societies is expected to result in large increases in age-related eye diseases that are associated with smoking. In recognition of this, tobacco use assessment and cessation counseling have become a quality-of-care measure for AMD in the United States.16 Counseling for smoking cessation by health care providers has been shown to have a positive effect on quit rates.17 Less than 3 minutes of counseling by health care providers has been shown to increase quit rates by 30%.17 Cessation counseling rates specifically by eye care providers are not known in the United States, but research in the United Kingdom has suggested that rates are lower among optometrists than among ophthalmologists.18 To provide the best possible counseling, understanding the factors related to tobacco use among individuals with AMD is of paramount importance.
Self-report has been the mainstay of studies linking smoking to macular degeneration. To date, no studies have evaluated the validity of the relationship of self-reported smoking to smoking status assessed by biochemical assay in persons with macular degeneration. This study suggests that, for both any-level AMD, and those at risk for late AMD, the rate of misclassification is approximately 5%. Most research studies of smoking and macular degeneration have shown robust increases in risk. Smoking deception would likely cause underestimation of the true excess risk. The rate of smoking deception identified in this study is relatively small at the individual level and is likely to be close to that seen in the clinical setting. The NHANES methodology uses a face-to-face interview system similar to the clinical setting. Face-to-face interview has been shown to reduce deception rates.3
Smoking is the leading cause of preventable disease and death in the US population.19 Given this, it is not surprising that the validity of self-reported smoking has been the subject of tremendous scrutiny. The reported rate of misclassification in these studies has varied substantially, with investigations outside the US reporting rates as high as 79%.5 A variety of authors have identified social desirability as a major reason for failing to self-report as a smoker.3 There is concern among some researchers that the tobacco companies’ global settlement with the US government and enacted legislation to reduce smoking may have increased social pressure to not self-report as a smoker.3 Studies specifically evaluating the social desirability hypothesis using the Bogus Pipeline method have shown that adults seem to feel no particular pressure to deny smoking.20
Smoking deception has been studied directly within the NHANES itself on a number of occasions. Klein et al.21 evaluated the 2001 to 2002 NHANES and concluded that 4.5% of respondents were possible deceivers. Yeager and Krosnick3 evaluated data from the 2001 to 2008 NHANES and found a relatively small rate of deception of between 0.89% and 1.25%. The much higher rates seen in this study than in either of those studies is likely a reflection of methodological differences. The most important being the level of cotinine chosen to be considered positive for active nicotine exposure. In the studies of Klein et al. and Yeager et al., 15 ng/mL was used as the cut point for active nicotine exposure. This cut point was used across all ethnic groups. The rationale for using the lower cut points in the current study was the 2009 study of Benowitz et al.,9 indicating a substantial racial variation in nicotine metabolism. The study of Benowitz et al. further showed that lower cut points optimized the area under the receiver operator curve for the classification of smoking status. In addition, the age of the population in this study is much older. Both studies of Klein et al. and Yeager et al. used adults older than 19 years, whereas this study includes only subjects older than 40 years. The effect of limiting age is uncertain. The effect of age on smoking deception has had little study. Pell et al.22 evaluated smoking deception in acute coronary syndrome, a tobacco-related disorder similar to macular degeneration, and found higher rates of smoking deception among patients with coronary disease. The higher rates in coronary syndrome were, however, modified by advanced age, with age reducing the deception rate. In that study, no age effect on deception was found among controls.
The NHANES has been used in other studies to describe the prevalence of macular degeneration in the US population.23 It has many advantages, including a large racially diverse population. Few studies collect data on tobacco exposure in the detail that NHANES does. Caution should be used in interpretation of the results. Despite the large sample size of the NHANES, actual sample sizes for AMD and at-risk subpopulations within the tobacco subcategories are small.
Cigarettes are the principal form of nicotine delivery in the United States.24 Among self-reported former cigarette smokers with AMD or at risk of late AMD, a relatively high percentage have cotinine levels consistent with active tobacco exposure. The majority of this exposure seems to due to the use of tobacco products other than cigarettes, including other forms of combustible tobacco. For both individuals with AMD and at risk for late AMD, about 5% are potential smoking deceivers. This is not a large prevalence at the individual level; however, given the approximate 9.5 million people at risk for late AMD, this equates to more than 450,000 persons within the US population who may misidentify themselves as a nonsmokers.
School of Optometry
University of Alabama at Birmingham
1716 University Blvd
Birmingham, AL 35294-0010
Received December 16, 2013; accepted February 26, 2014.
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