مواجهه با رادون به عنوان یک مسئله بهداشت عمومی- یک بازنگری

Exposure to Radon as a Public Health Issue- A Review

Abstract

Radon (222Rn) is a noble gas formed from the decay of radium (226Ra), which is a decay product of Uranium (238U). Radon is an inert noble gas, having a half-life of 3.8 days emanating from rocks and soils and tending to concentrate in enclosed spaces like underground mines or houses. Radon was classified as a human carcinogen by the International Agency for Research on Cancer in 1988, a review of the major studies of underground miners exposed to radon that were available in the 1990s and case-control study of residential radon exposure confirmed radon as a carcinogen. This paper reviews the publications of the World Health Organization, the International Atomic Energy Agency and other relevant publications specifically on sources and historical perspectives of radon, the association between lung cancer and radon, health effects and radon risk communication.

2- RADON HISTORICAL PERSPECTIVE

High mortality rate from respiratory diseases among miners in Central Europe had been identified before the seventeen century. In the nineteen century, it was confirmed that the disease was lung cancer. Radon was first suspected as the primary cause of these cancers. As early as in the 1950s, domestic and drinking water from drilled wells were observed to have high concentrations of radon. By the mid1970s, building materials was recognized to emanate radon in some areas due to the use of alum shale with enhanced levels of radium. In 1978, soil gas infiltration became recognized as the most important source of radon as indoor radon concentration were found not to be associated with well water transport or emanation from building materials [3]. Radon has been classified as a human carcinogen [6,7] based on the epidemiological studies of High mortality rate from respiratory diseases among miners in Central Europe had been identified before the seventeen century. In the nineteen century, it was confirmed that the disease was lung cancer. Radon was first suspected as the primary cause of these cancers. As early as in the 1950s, domestic and drinking water from drilled wells were observed to have high concentrations of radon. By the mid1970s, building materials was recognized to emanate radon in some areas due to the use of alum shale with enhanced levels of radium. In 1978, soil gas infiltration became recognized as the most important source of radon as indoor radon concentration were found not to be associated with well water transport or emanation from building materials [3]. Radon has been classified as a human carcinogen [6,7] based on the epidemiological studies of underground miners exposed to high radon concentrations in their workplaces.

A large number of studies have examined the relationship between indoor radon and lung cancer since then. The three pooled-analyses from the major studies in Europe, North America and China present very similar pictures of the risks of lung cancer from residential exposure to radon. Together, they provide overwhelming evidence that radon is causing a substantial number of lung cancers in the general population and they provided a direct estimate of the magnitude of the risk. They also suggested that an increased risk of lung cancer cannot be excluded even below 200 Bq/m3 , which is the radon concentration at which action is currently advocated in many countries [3]. Radon is now recognized as the second most important cause of lung cancer after smoking in the general population [3].

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فهرست مقاله:

چکیده
مقدمه
روشها و مورد موردنیاز
روش آزمایشگاهی
آزمایشات شستشو
نتایج تست شستشوی زباله های خطرناک
نتایج TCLP مطالعه ی اولیه
نتایج شستشوی TCLP و WET
تجزیه و تحلیل زباله های خطرناک
طبقه بندی زباله های خطرناک
نقش نیکوتین در دسته بندی زباله های خطرناک
مفاهیم مدیریت سیگار الکترونیکی دور انداخته شده
نتیجه گیری

بخشی از ترجمه فارسی مقاله:

چکیده
در این مطالعه سیگارهای الکترونیکی دور انداخته شده را از این جهت بررسی میکنیم که آیا میشود آنها را بعنوان زباله های خطرناک تلقی کرد یا نه. چهار سیگار الکترونیکی برای تجزیه و تحلیل انتخاب شدند. بر اساس نتایج برخی انواع سیگارهای الکترونیکی به لحاظ سمیت خطرناک و بقیه نیستند. وقتی به شکل استفاده نشده دفع میشوند در ایالات متحده تحت زباله های خطرناک دسته بندی میشوند. اگرچه زباله های خانگی از مقررات مشمول زباله های خطرناک مستثی هستند با این وجود مواردی هست که تحت این مقررات میتوانند قرار گیرند. تولید کننده ها یا فروشنده های سیگارهای الکترونیکی یا محلول نیکوتین تاریخ مصرف گذشته یا استفاده نشده را بایستی جزء زباله های خطرناک بدانند. سیگارهای الکترونیکی یکبار مصرف استفاده شده و سریعتر از وسایل الکترونیکی معمول دور ریخته میشوند که به احتمال برای مسئولان زباله تبدیل به یک معضل شود.
1. مقدمه
با معرفی و عرضه ی محصولات جدید تولید کننده ها و نهادهای قانونگذار با چالشی دیگر برای تعیین وضعیت آنها بعد از مصرف مواجه اند. مثلا وسایل الکترونیکی دور انداخته شده اغلب تحت زباله های خطرناک دسته بندی میشوند. سیگارهای الکترونیکی محصولاتی هستند که در سالهای اخیر افزایش مصرف زیادی داشته اند. برخی از این سیگارها یکبار مصرف هستند و برخی دیگر تا یکسال کار میکنند. توزیع کننده ها در تبلیغاتشان از آنها تحت عنوان جایگزین سیگارهای معمولی یاد میکنند. در برخی کشورها آنها را تحت داروها دسته بندی میکنند درحالیکه در برخی کشورهای دیگر وارد کردن یا فروش سیگارهای الکترونیکی ممنوع است. طرفداران این سیگارهای الکترونیکی آنها را جایگزین سالم تری برای سیگارهای معمول تبلیغ میکنند.
سیگارهای الکترونیکی یکبار مصرف معمولا تکی دور انداخته میشوند البته اجزای زیادی دارند: باطری، محتوی مایع و افشانگ. این سیگارها به لحاظ شکل و اندازه یکسان هستند و انواع مختلف این محصولات اجزای یکسانی دارند.
هیچ گزارشی در رابطه با مسائل و مشکلات پیرامون دفع سیگارهای الکترونیکی ارائه نشده است، البته مطالعاتی درباره ی محتوای شیمیایی آنها انجام شده است. مایع نیکوتین سیگارهای الکترونیکی پیشتر مورد تجزیه و تحلیل واقع شده است.
سازمان محافظت از محیط زیست ایالات متحده روشی تحلیلی دارد که برای تعیین اینکه یک زباله ی جامد تحت زباله های خطرناک تقسیم بندی میشود یا نه استفاده میشود. همچنین مقررات دولت فدرال ایالات متحده لیستی از مواد شیمیایی ارائه کرده است که در تقسیم بندی محصولات شیمیایی دور انداخته شده تحت زباله های خطرناک میتوانند تاثیر بگذارند. در اکثر ایالات آمریکا مقررات زباله ها مشابه با مقررات فدارال است ولی در برخی مقرراتی تا حدی متفاوت وجود دارد.
با توجه به اینکه سیگارهای الکترونیکی بعنوان جایگزین سالم تر سیگارهای معمول جا افتاده اند مشتریهای گسترده ای بدست آورده اند درحالیکه تاثیر آنها در سیستم های مدیریت زباله هنوز بدرستی شناخته نشده است.
2. روشها و مورد موردنیاز
2.1 روش آزمایشگاهی
هدف از آزمایش این بود که بفهمیم آیا این سیگارها را میشود بعنوان زباله های خطرناک در ایالات متحده قلمداد کرد یا نه. سیگارهای الکترونیکی مورد آزمایش از فروشگاههای معمولی در گینسویل فلوریدا و نیز از فروشنده های آنلاین خریداری شدند.
چهار محصول برای آزمایش انتخاب شدند. جدای از فلزات سنگین آرسنیک، باریم، کادیم، کرمیوم، سرب، جیوه، سلنیوم، نقره مقدار فلزات مس، آهن و نیکل و روی نیز اندازه گیری شد. طبق مقررات کالیفرنیا مس، نیکل و روی بعنوان فلزات سمّی تلقی میشوند درحالیکه در لیست فلزات TC ایالات متحده وارد نشده اند.
2.2 آزمایشات شستشو
نتایج TCLP بررسی اولیه برای انتخاب 4 محصول اولیه جهت تست تکرارپذیری آزمایشات شستشو و مقایسه با دو تست شستشوی مواد زائد خطرناک انتخاب شدند. با شستشوی دو محصول مقادیر سرب اندازه گیری شد. این محصولات برای تعیین تکرارپذیری آزمایشات در سیگارهای الکترونیکی انتخاب شدند و نیز برای اینکه با نتایج حاصله از دو روش شستشوی مواد زائد خطرناک مقایسه شوند. TCLP بر چهار محصول سیگار الکترونیکی یکبار مصرف انجام شد.

بخشی از مقاله انگلیسی:

Abstract

The potential for disposable electronic cigarettes (e-cigarettes) to be classified as hazardous waste was investigated. The Toxicity Characteristic Leaching Procedure (TCLP) was performed on 23 disposable e-cigarettes in a preliminary survey of metal leaching. Based on these results, four e-cigarette products were selected for replicate analysis by TCLP and the California Waste Extraction Test (WET). Lead was measured in leachate as high as 50 mg/L by WET and 40 mg/L by TCLP. Regulatory thresholds were exceeded by two of 15 products tested in total. Therefore, some e-cigarettes would be toxicity characteristic (TC) hazardous waste but a majority would not. When disposed in the unused form, e-cigarettes containing nicotine juice would be commercial chemical products (CCP) and would, in the United States (US), be considered a listed hazardous waste (P075). While household waste is exempt from hazardous waste regulation, there are many instances in which such waste would be subject to regulation. Manufactures and retailers with unused or expired e-cigarettes or nicotine juice solution would be required to manage these as hazardous waste upon disposal. Current regulations and policies regarding the availability of nicotine-containing e-cigarettes worldwide were reviewed. Despite their small size, disposable e-cigarettes are consumed and discarded much more quickly than typical electronics, which may become a growing concern for waste managers.

1. Introduction

As new products are introduced and marketed, generators and regulatory agencies face the challenge of determining appropriate end-of-life regulatory status. For example, discarded electronic devices are often classified as regulated hazardous waste (Townsend, 2011). Electronic cigarettes (e-cigarettes) represent one type of an electronic product that has seen a great increase in use in recent years (Benowitz and Goniewicz, 2013). The units are shaped like a cigarette and contain a battery that heats a filament to vaporize liquid nicotine in a cartridge (Grana et al., 2014). Some devices are disposable, meant for a single use, while others may last as long as one year with nicotine solution (called ‘‘juice’’) refills. Distributors advertise them as an alternative to conventional cigarettes, as opposed to smoking cessation tools which in the US avoids more stringent regulation by the Food and Drug Administration (FDA) (Sottera, Inc. vs. FDA, 2010). Some countries classify them as medicines, while others prohibit the importation or sale of these electronic nicotine delivery systems (ENDS) (Baker, 2013). Proponents promote e-cigarettes as a safer alternative to conventional cigarettes, but their emergence and widespread popularity has outpaced understanding of the scientific and regulatory impacts of these new electronic products. Disposable e-cigarettes are generally discarded as a single item, but they contain multiple components: the battery, liquid container, and atomizer (Franck et al., 2014). They are uniform in shape and size, and the various products contain essentially the same configuration of components (Grana et al., 2014). E-cigarettes are similar to other small, battery-powered devices such as digital watches or medical devices currently classified as waste electrical and electronic equipment (WEEE) in the European Union (EU) (European Parliament, 2012). It is the intention of regulations such as the Restriction of Hazardous Substances (RoHS) Directive to cause fewer devices to trigger hazardous waste classification based on current regulatory criteria (European Parliament, 2011). While no data have been reported regarding the disposal issues surrounding e-cigarettes, some research on chemical content and exposure during use has been conducted. Because an e-cigarette user inhales vaporized nicotine juice, concerns regarding the chemicals contained within the products and the quality of the manufacturing process have been raised. E-cigarette nicotine juice has been previously analyzed for impurities (Bahl et al., 2012; Etter et al., 2013; Trehy et al., 2011; Westenberger, 2009), as has the composition of the emitted vapor (Goniewicz et al., 2014a; Ingebrethsen et al., 2012; McAuley et al., 2012; Williams et al., 2013). Goniewicz et al. (2014a) measured 0.03–0.57 lg of lead per e-cigarette in emitted vapor. Williams et al. (2013) found metals (e.g. lead, nickel, and silver), silicate beads, and nanoparticles in e-cigarette aerosol. The US Environmental Protection Agency (EPA) Toxicity Characteristic Leaching Procedure (TCLP, EPA Method 1311) is the analytical method used to determine whether a solid waste meets the definition of hazardous waste based on the toxicity characteristic (TC; i.e. target constituents leach at concentrations above specified thresholds) (US EPA, 1992). US federal regulations also provide a list of chemicals that can cause discarded commercial chemical products (CCPs) to be classified as hazardous waste if that unused chemical is the sole active ingredient; nicotine is included on this list (US Congress, 1980a). While most US states regulate waste in an identical manner as the federal rules, some states have adopted additional, more stringent standards. California, for example, requires a separate leaching experiment known as the California Waste Extraction Test (WET) as part of hazardous waste determination (California Code of Regulations, 1985). E-cigarettes have fast gained a wide audience because of their perception as a safer alternative to conventional cigarettes, but their impact on waste management systems is unknown. In this study, the potential for e-cigarettes to exceed regulatory thresholds for hazardous waste when discarded was examined using toxicity hazardous waste determinants TCLP and WET. Discarded e-cigarettes would be much smaller by mass than most other WEEE; however, it can be assumed their frequency of consumption and disposal would be much greater as well. Therefore, knowledge of leaching behavior and the potential for hazardous waste generation is needed at the local and national level. While the test results presented here specifically address US regulatory classification, the results will provide benefit to those in other regulatory agencies facing a similar question. An added regulatory complication encountered with e-cigarettes not seen in other WEEE is the presence of the liquid nicotine juice, and this issue is discussed within the context of current regulation and policies worldwide.

2. Materials and methods

2.1. Experimental strategy

A total of 51 e-cigarettes were examined by TCLP and WET in two phases of research. The purpose of the testing was to provide a broad indication of whether these devices had the potential to be hazardous waste in the US (and thus merit additional testing or evaluation), not to assess the hazardous waste status of any one product. E-cigarettes were purchased from convenience stores in the vicinity of Gainesville, FL, USA, as well as through online vendors to test a variety of manufacturers with a range of nicotine strengths (e.g. 1.6 mg nicotine, 2.4% nicotine, etc.) and flavors (e.g. tobacco, menthol, blueberry, etc.). TCLP was performed on 23 e-cigarette samples in a preliminary survey of disposable e-cigarette products, representing 15 unique products from eight national and regional manufacturers or distributors (as labeled on the packaging). Four products were selected for further testing based on the results of the preliminary survey of e-cigarette leaching. Replicates of the four products were used to examine repeatability of the WET and TCLP on individual e-cigarettes and to compare the results of the two leaching methods. Along with the heavy metals arsenic, barium, cadmium, chromium, lead, mercury, selenium, and silver, the presence of copper, iron, nickel, and zinc were measured. California regulations include copper, nickel, and zinc as additional metals with a toxicity characteristic concentration; they are not included on the US federal list of TC metals (California Code of Regulations, 1985; US EPA, 1992). While the TCLP typically requires 100 g of material (50 g for WET), the batch-leaching process was scaled down to examine each of the products individually. E-cigarette samples weighed an average of 10 grams. A 20:1 liquid:solid (L:S) ratio was maintained based on each individual sample weight (i.e. 200 mL solution:10 g e-cigarette). Other researchers have scaled TCLP sample size and extraction vessel in a similar manner to maintain a 20:1 L:S ratio (Musson et al., 2006; Vann et al., 2006b).

2.2. Leaching experiments: TCLP and WET

TCLP results from the preliminary survey were used to select 4 products to test the repeatability of the leaching experiments and compare the results of two hazardous waste leaching tests. Two products leaching elevated (x > 1 mg/L) amounts of lead and two products leaching undetectable (x < 0.004 mg/L) amounts of lead were selected for replicate analysis by TCLP and WET. These products were selected to determine the repeatability of the experiments on e-cigarettes, as well as to compare results from two hazardous waste leaching methods, which has not been documented previously. The TCLP and California WET were performed on the four disposable e-cigarette products (Samples A, B, C, and D) in triplicate (TCLP) and quadruplicate (WET). All samples were consumed of their nicotine juice and milled (Fritsch Pulverisette 25) to pass a 9.5 mm (TCLP) or 2 mm sieve (WET). Because of the small particle size required by WET and due to the design of the samples and the mill, some portions of each sample could not be further size-reduced. The mass of the non-reduced portions were noted for each applicable sample and the entire e-cigarette was used in the leaching experiment. For all products leached by TCLP, extraction solution #1 was used in the experiment. Samples were rotated for 18 ± 2 h in high-density polyethylene extraction vessels (Fisher), then vacuum filtered with acid-washed glass fiber filters (Whatman). Control blanks were also digested. Final extract pH ranged from 4.79 to 6.16. Extracts were digested and acidified below pH 2.0 with nitric acid for sample preservation. Samples were stored at 4 C until analysis. Samples were analyzed by Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES, iCAP 6000 Thermo Scientific). WET extraction solution and samples were placed in high-density polyethylene bottles in a 10:1 (L:S) ratio and the solutions were purged with nitrogen gas for 15 min before extraction. WET samples were rotated for 48 h. Final liquid extraction pH ranged from 5.85 to 9.91. Samples were filtered with a 0.45 lm membrane filter and acidified to 5% nitric acid by volume. Extract samples were analyzed by ICP-AES. WET is generally regarded as a more aggressive test than TCLP because of the properties of the citric acid reagent, the lower liquid to solid ratio (10:1), the smaller particle size (<2 mm), and the longer extraction time (48 h). The Soluble Threshold Limit Concentration (STLC) are the regulatory limits that WET extract concentrations are compared to determine hazardous waste status. Values that exceed the STLC are considered hazardous waste in California (California Code of Regulations, 1985).

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مقدمه:
مواجهه با دود سیگار با پیامدهای زیان آور برای سلامتی افراد غیر سیگاری همراه شده است. در سال 1992 ، آژانس حفاظت محیط زیست(EPA) ، مواجهه با دود سیگار را به عنوان عامل سرطان زای شناخته شده دسته بندی کرد.
اثرات بر روی سیستم قلبی-عروقی افراد غیر سیگاری مهم برآورد شد؛ به طور متوسط 80-90 درصد به اندازه ی افراد سیگاری (میانگینی از اثرات مکانیکی ، مانند عملکرد غیرمعمول اندوتلیال ، سفتی شریان ها). مواجهه با دود سیگار در محیط های مختلفی نظیر خانه، محل کار و محیط های عمومی رخ می دهد. مواجهه در خانه و محل کار ممکن است به طور ویژه ای زیان آور باشد؛ چون بسیاری از مردم بیشتر زمان خود را در خانه و محل کارشان می گذرانند.
مواجهه با دود سیگار در محل کار سابقاً در نتایج مرگهای سالانه ناشی از بیماری قلبی کم خونی در بیش از 1710 نفر از کارگران غیر سیگاری آمریکایی بین سنین 36-69 ارزیابی شده بود. یک تحلیل آماری meta از 17 مطالعه، یک خطر نسبی برای رویدادهای عروقی از 1.25 (95% CI=1.17-1.33) بین افراد غیر سیگاری که با همسران سیگاری ازدواج کرده اند، در مقایسه با آنهایی که همسران غیر سیگاری دارند.
در چند دهه اخیر، افزایش آگاهی نسبت به مضرات دود سیگار منجر به تلاش در جهت کاهش یا اجتناب از مواجهه شده و برخی مطالعات مقطعی مبتنی جمعیت، به دلیل انجام یک مطالعه طولی که زنان را مستثنی کرد، روند زمانی رو به کاهش را گزارش داده اند.
ما تصمیم گرفتیم تا تغییرات مواجهه با دود سیگار را بین شرکت کنندگان غیر سیگاری مسن تر در یک مطالعه طولی بر پایه جمعیت طی دوره پنج ساله بین دو بررسی: 1998-2000 و 2003-2005 را تعیین کنیم. ما بویژه پس از محاسبه تغییرات جسمانی مهم شامل سن افراد، بازنشستگی و مرگ همسر؛ ارتباط دوره زمانی اخیر را با مواجهه با دود سیگار در محیط های مختلف، بررسی کردیم.
روش ها:
جمعیت مورد مطالعه
اپیدمیولوژی مطالعه کاهش شنوایی (EHLS) یک مطالعه طولی مبتنی بر جمعیت از کاهش حواس و افزایش سن در شهر Beaver Damاز سال 1993تا به امروز می باشد. یک سرشماری خصوصی طی سالهای 1987-1988 انجام شد که ساکنین 43 تا 84 ساله از شهر یا شهرستان بیور دم ( 5924نقر) را تعیین هویت کرد. در طی سالهای 1988-1990 ، 4926 نفر از 5924 نفر از افراد واجد شرایط (83%) در بخش اول بررسی، معاینه چشم Beaver Dam (BDES)، شرکت کردند.
افرادی که در سنجش BDES شرکت کردند و در یک مارس سال 1993 ( 4541نفر) در قید حیات بودند، برای اپیدمیولوژی مطالعه کاهش شنوایی (EHLS) واجد شرایط بودند و 3753نفر (82.6%)طی سالهای 1993-1995 در بخش سنجش EHLS شرکت کردند. بررسی های پنج ساله و پیگیرانه EHLS طی سالهای 1998-2000 انجام شده و از 3407 نفر از افراد در قید حیات شرکت کننده در EHLS در مارس سال 1998 ، 2800 نفر (82.2%) شرکت کردند.
در طی بررسی ده ساله و پیگیرانه در طی سالهای 2003-2005 ، 2395 نفر از بازماندگان (82.5%) شرکت کردند. شرکت کنندگانی که اطلاعات پرسشنامه ETS در هردو مصاحبه پیگیرانه ، پنج ساله (1998-2000) و ده ساله (2003-2005) را عرضه کردند شامل این مطالعه بودند ( 2231نفر). بررسی ها محدود به شرکت کنندگان غیر سیگاری در هردو نقطه زمانی (1898 نفر) ، به ترتیب 87.1% و 89% از کل شرکت کنندگان بررسی پیگیرانه پنج ساله و ده ساله بود. این مطالعه توسط هیئت بررسی نهادی علوم بهداشتی دانشگاه ویسکانسین تائید و از هریک از شرکت کنندگان رضایت نامه گرفته شد.

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Introduction

Exposure to environmental tobacco smoke (ETS) has been associated with adverse health outcomes in nonsmokers. In 1992, the Environmental Protection Agency (EPA) classified ETS as a known human carcinogen.1 The effects on the cardiovascular system are estimated to be substantial, on average 80–90% as large as that from active smoking (averaged across mechanistic effects, e.g., endothelial dysfunction, arterial stiffness).2 ETS exposure occurs in a variety of settings, including home, work, and social settings. Exposure in the home and workplace may be particularly harmful, as many people spend much of their time at home and in their workplaces. ETS exposure in the workplace was previously estimated to result in about 1710 excess ischemic heart disease deaths per year among 35–69 year old nonsmoking U.S. workers.3 A meta-analysis of 17 studies estimated a relative risk for coronary events of 1.25 (95% CI = 1.17–1.33) among never smoking spouses married to smokers, compared to those with nonsmoking spouses.4 In recent decades, increasing awareness of the harms of ETS has led to attempts to reduce or avoid exposure, and some cross-sectional population-based studies have reported declining temporal trends, as did one longitudinal study which excluded women.5–8 We aimed to determine if ETS exposure changed among non-smoking older adult participants in a longitudinal population-based study during the five-year period between two examinations: 1998–2000 and 2003–2005. In particular, we investigated whether later time period was associated with ETS exposure in a variety of settings, after taking into account important temporal changes including age of the participants, retirement, and spousal death.

Methods

Study population

The Epidemiology of Hearing Loss Study (EHLS) is a population-based longitudinal study of sensory loss and aging in Beaver Dam, WI (1993-present). A private census was conducted in 1987–1988 which identified 43 to 84 year old residents of the city or township of Beaver Dam, WI (n=5924). In 1988–1990, 4926 of the 5925 eligible (83%) participated in the first examination phase of the Beaver Dam Eye Study (BDES).9 Those who participated in the baseline BDES and were alive on March 1, 1993 (n=4541) were eligible for the EHLS, and 3753 (82.6%) participated in the baseline EHLS examination phase from 1993–1995.10 The EHLS five-year follow-up examinations took place from 1998–2000 and, of the 3407 EHLS participants alive as of March 1998, 2800 (82.2%) participated.11 During the 10-year follow-up examination phase in 2003–2005, 2395 (82.5% of survivors) participated.12 Participants who provided ETS questionnaire data at both the 5-year (1998–2000) and the 10-year (2003–2005) follow-up interviews were included in this study (n=2231). Analyses were limited to participants who were nonsmokers at both time points (n=1898), 87.1% and 89% of all participants at the 5- and 10-year follow-up examinations, respectively. This study was approved by the Health Sciences Institutional Review Board of the University of Wisconsin and informed consent was obtained from each participant.