Smoking Cessation and E n v i ro n m e n t a l H y g i e n e Cheryl Pirozzi,

MD,

Mary Beth Scholand,

MD*

KEYWORDS  Smoking cessation  Air pollution  Occupational exposure  Environmental hygiene  COPD KEY POINTS  Modifiable risk factors for chronic obstructive pulmonary disease (COPD) include tobacco smoking, secondhand smoke (SHS), outdoor air pollution, biomass smoke, and occupational exposures.  Tobacco cigarette smoking is the most important risk factor for development of COPD and is the single most preventable cause of death worldwide.  SHS contains the same respiratory irritants encountered in personal smoking and may lead to development of COPD in unaffected individuals and produce adverse health effects in persons with COPD.

Chronic obstructive pulmonary disease (COPD) represents an important public health challenge that is both preventable and treatable.1,2 Tobacco smoking is the most important risk factor for COPD. However, a significant proportion of COPD cases cannot be fully attributed to tobacco smoke. Individual variations in the development and progression of COPD occur as a result of both host factors and environmental risks.3 There are several nonmodifiable risk factors that likely alter a person’s susceptibility to the development of COPD. Genetic susceptibility is among the most important of these. The most well documented of these genetics factors is the hereditary deficiency of a1-antitrypsin.4 Family aggregation studies and multiple genetic association studies have yielded several potential genes that likely contribute to the susceptibility of COPD development or progression.5 These genetic relationships are complex and COPD susceptibility likely involves multiple genes as well as epigenetic factors.6–8 Gender also likely affects susceptibility to COPD. Women may be more susceptible to the effects of tobacco smoke than are men.9,10 Despite these intrinsic susceptibilities, most known risk factors for development of COPD are modifiable. Reduction of these risk factors is critical to the prevention and management of COPD.2 Modifiable risk factors include tobacco smoking, secondhand

Pulmonary Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA * Corresponding author. E-mail address: [email protected] Med Clin N Am 96 (2012) 849–867 doi:10.1016/j.mcna.2012.04.014 medical.theclinics.com 0025-7125/12/$ – see front matter Ó 2012 Elsevier Inc. All rights reserved.

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smoke (SHS), outdoor air pollution, biomass smoke, and occupational exposures. By identifying and understanding these factors, action can be taken to improve the environment and mitigate risks for COPD. CIGARETTE SMOKING AND SMOKING CESSATION

Tobacco cigarette smoking is the most important risk factor for development of COPD and is the single most preventable cause of death worldwide.11 Smoking cessation may prevent the development of COPD by reducing the accelerated rate of decline associated with smoking to the normal age-related decline rate.12 In the setting of COPD, smoking cessation remains the only intervention proven to meaningfully reduce the rate of decline of forced expiratory volume in 1 second (FEV1) in patients with COPD.13 In a series of studies, smoking cessation showed improvements in respiratory symptoms,14 FEV1,13 and health-related quality of life measures in smokers both with and without COPD.15,16 The Lung Health Study was a landmark study that defined many of the benefits of smoking cessation. This study examined the effects of smoking cessation and inhaled bronchodilators in 5887 smokers with mild-to-moderate COPD. Smoking cessation significantly reduced decline in lung function.13 At 11-year follow-up, sustained quitters had a mean FEV1 decline of less than 27 mL/y, compared with an FEV1 decline of 60 mL/y in continuing smokers.17 Sustained quitters also had less severe airway obstruction compared with continuing smokers, In sustained quitters, only 3.3% of the subjects showed an FEV1 value less than 50% of predicted, versus 18% of the subjects who continued to smoke.17 Further, subjects showed improvement in respiratory symptoms of chronic cough, sputum production, wheezing, and shortness of breath after 5 years of smoking cessation, with the greatest improvement seen within the first year after smoking cessation.14 Sustained quitters also had fewer lower respiratory illnesses than continuing smokers.18 The number of COPD exacerbations also decline after smoking cessation.19 Although smoking cessation mitigates the impact of COPD, sustained quitters persist with residual negative health effects. In smokers with mild-to-moderate COPD, smoking cessation improves the FEV1 and decreases the rate of FEV1 decline back to the age-related decline seen in nonsmokers; however, the FEV1 does not fully recover to that predicted for nonsmokers. After smoking cessation, mortalities are less than in those who continue to smoke, but ex-smokers continue to have a higher mortality risk than never-smokers, even many years after smoking cessation.20 Despite clear evidence linking smoking with morbidity and mortality in COPD, a third or more of patients with moderate and severe COPD continue to smoke.21 It is possible that patients with COPD are more resistant to smoking cessation interventions. Smokers with COPD have higher nicotine dependence scores than those without COPD.22 Educating patients with COPD about their disease state is important. Smokers who are diagnosed with COPD and subsequently counseled regarding their lung disease have higher rates of successful smoking cessation than smokers without COPD.23,24 SMOKING CESSATION TECHNIQUES

Multiple pharmacologic and nonpharmacologic interventions are effective for smoking cessation. Physician advice to quit smoking during an office visit improves quit rates from 1% to 3%.25 Telephone quitlines and mobile text messaging increase the likelihood of continuous absence.26,27 Several studies have shown the effectiveness of group and individual counseling programs.13,28 However, the composition of the

Smoking Cessation and Environmental Hygiene

group has a significant impact on the effectiveness of this approach.29 Two reviews of smoking cessation strategies in patients with COPD concluded that the most effective intervention for prolonged smoking cessation is the combination of pharmacologic interventions and psychosocial interventions.30,31 Nicotine replacement therapy is effective for smoking cessation. Silagy and colleagues32 reviewed 123 randomized trials and concluded that the composite odds ratio (OR) for abstinence from smoking of at least 6 months is 1.77 for nicotine replacement therapy compared with control. All forms of nicotine replacement (gum, transdermal patch, nasal spray, inhaler, and sublingual tablets/lozenges) were equally effective.32 Bupropion was the first non-nicotine pharmacologic agent approved for smoking cessation. It is thought to work by inhibiting uptake of dopamine and norepinephrine, which may help reduce craving and withdrawal symptoms.33 Bupropion as much as doubles the rates of smoking cessation compared with placebo in smokers34,35 and is particularly effective in patients with COPD.28,36,37 Side effects include insomnia and lowering of the seizure threshold, and a black box warning was issued by the US Food and Drug Administration (FDA) in 2009 about risk of serious neuropsychiatric symptoms of depression, agitation, and suicidal thoughts and behavior (www.fda.gov). Nortriptyline, another antidepressant, has also been used effectively for smoking cessation.37 Varenicline is a partial agonist for the a4b2 nicotinic acetylcholine receptor. Use of varenicline generates 1-year abstinence rates of 22% to 23%, compared with 8.4% to 10.3% for placebo and 14.6% to 16.1% for bupropion.38,39 In patients with COPD, abstinence rates were higher for the varenicline group compared with placebo at 12 weeks (42.3% vs 8.8%, respectively) and at 52 weeks (18.6% vs 5.6%, respectively).40 A black box warning for varenicline was issued by the FDA in 2009 about the risk of serious neuropsychiatric symptoms of depression, agitation, and suicidal thoughts and behavior. Combination pharmacotherapy may be more effective than monotherapy for smoking cessation in the general smoking population. Nicotine replacement has been shown to be more effective when it is used in combination with another agent, including another form of nicotine replacement therapy or bupropion.41 Among patients with COPD, a meta-analysis concluded that the most effective smoking cessation strategy to achieve sustained abstinence is the combination of smoking cessation counseling and nicotine replacement therapy. Less effective strategies are smoking cessation counseling combined with an antidepressant or counseling alone.42 An encouraging new approach to smoking cessation is with immunization against nicotine. Nicotine conjugate vaccines work by stimulating production of nicotinespecific antibodies that bind to nicotine molecules, resulting in nicotine-antibody complexes that are too large to cross the blood-brain barrier, thus preventing nicotine from entering the brain and lowering the reinforcing effects of nicotine.21,43 Three nicotine vaccines are currently in advanced stages of clinical development and early studies are promising but not conclusive.43,44 In one study, the higher dose created a higher antibody response to the vaccine and was associated with increased 8-week abstinence rates compared with placebo (24.6% vs 12.0%),43 suggesting that the antinicotine antibodies are important components to smoking cessation. Nonpharmacologic therapies are widely used as an aid for smoking cessation. Hypnotherapy is designed to weaken the desire to smoke and strengthen the will to quit. A randomized trial of 286 smokers did not show significantly higher rates of smoking cessation when hypnosis was combined with nicotine patch compared with behavioral counseling and nicotine patch.45 A meta-analysis of randomized controlled trials failed to show effectiveness for hypnotherapy based on insufficient evidence.46

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Acupuncture, acupressure, laser therapy, and electrostimulation have all been used to reduce nicotine withdrawal symptoms. Acupuncture was superior to sham acupuncture immediately after the intervention, but the effect was not sustained at long-term follow-up and the evidence was limited by bias.47 Electrostimulation was not more effective than placebo, and there is insufficient evidence to support effectiveness of acupressure or laser therapy for smoking cessation.47 Exercise may be helpful for smoking cessation by decreasing nicotine cravings and helping manage weight gain. One randomized controlled trial comparing a cognitivebehavioral smoking cessation program with and without vigorous exercise in 281 women showed improved continuous abstinence in the exercise group persisting to 12 months after treatment (11.9% vs 5.4% P 5 .05).48 A meta-analysis concluded that exercise is valuable in reducing tobacco withdrawal cravings, but there is insufficient evidence to recommend exercise as a specific aid to smoking cessation.49 NONSMOKING RISK FACTORS IN COPD

In the United States, it is estimated that as many as 30% of people with COPD were never-smokers.50 There may be even more in developing countries, where up to 50% of the COPD population has never smoked.51–53 Nonsmoking risk factors that contribute to the development of COPD include secondhand smoke, outdoor air pollution, biomass smoke, and occupational exposures. SHS

SHS contains the same respiratory irritants encountered in personal smoking and may lead to development of COPD in unaffected individuals and produce adverse health effects in persons with COPD. Although the levels of tobacco smoke encountered through passive smoking are lower than those in personal smoking, exposure to tobacco smoke in the environment likely leads to respiratory disease by the same mechanisms.3 Homes with smokers living in them have higher levels of ambient nitrogen dioxide, endotoxin, and particles less than 2.5 mm in diameter (particulate matter 2.5 mm [PM2.5] levels).54 Epidemiologic studies performed throughout the world support an association between exposure to environmental tobacco smoke and COPD.55–61 Among nonsmoking housewives in Turkey, those who had lived with a smoker for greater than 30 years had an almost 5-times greater risk for developing COPD.62 A meta-analysis of 12 studies calculated a summary OR of 1.56 for SHS exposure and risk of COPD.3 Among patients with COPD, exposure to SHS is associated with poorer health status, including increased respiratory symptoms and more COPD exacerbations. Persons with COPD living in smoking areas report increased respiratory symptoms.54 Higher levels of SHS exposure levels are associated with more serious clinical effects including worse COPD severity, greater dyspnea, and reduced disease-specific quality of life.63 Exposure to passive smoking increases the risk of emergency department visits and hospitalization for COPD exacerbations.64 Following admission for COPD exacerbations, exposure to environmental tobacco smoke was a risk factor for readmission for COPD.65 Much of our knowledge of SHS risks comes from high-risk groups such as airline attendants and hospitality workers who have been exposed to high levels of environmental tobacco smoke. Airliner cabin air quality before smoking bans on planes was abysmal. Levels of respirable suspended particles on smoking flights was 3 times higher than federal air quality standards for PM2.5 and 10 to 100 times greater than the irritation thresholds.66 Studies of urinary cotinine concentration revealed flight

Smoking Cessation and Environmental Hygiene

attendants’ exposure to SHS in aircraft cabins to be approximately 6-fold that of the average US worker and 14-fold that of the average person.66–68 This SHS exposure was associated with diagnosis of respiratory disease, airway obstruction, and decreased diffusing capacity,69 with 69.7% diagnosed with at least 1 respiratory disease, including 2% who developed COPD.70 Hospitality workers in restaurants and bars are also exposed to high levels of environmental tobacco smoke. Before smoking bans, 74% of a cohort of bartenders in California reported respiratory symptoms and 77% had sensory irritation symptoms.71 Among casino workers in London, 84% reported respiratory symptoms. Exposure to high levels of SHS at work was associated with the presence of respiratory symptoms (OR 2.24).72 To protect the public and employees from the harmful effects of SHS, smoking bans have been implemented in many settings. A series of regulations were imposed to make airplanes a smoke-free environment. In 1973, the US Civil Aeronautics Board established nonsmoking sections on airplanes. In 1988, the US Congress mandated a smoking ban on domestic airline flights scheduled for 2 hours or less, which was extended to 6 hours the following year. By 1999, 97% of flights to and from the United States were smoke free.66 In 1998, California became the first state in the United States to enact a comprehensive state-wide smoking ban prohibiting smoking in all workplaces including restaurants and bars. Since then, similar legislation has been implemented in most American states. In 2004, Ireland was the first European country to ban tobacco smoking in all workplaces and, since that time, many other countries have passed national workplace smoking bans.73 In a systematic review of 50 studies evaluating effects of legislative smoking bans, the investigators found consistent evidence that smoking bans reduced exposure to environmental tobacco smoke in public places and improved health outcomes.73 Following the bans, bar workers in California, New York, Scotland, and Ireland showed decreased serum cotinine levels and reported fewer respiratory symptoms. Moreover, physiologic testing revealed improvements in FEV1 and forced expiratory vital capacity.71,74–76 In a 2006 report, the Surgeon General reported that policies prohibiting smoking in the workplace have also reduced tobacco use by smokers and changed general public attitudes about tobacco use. Despite the significant progress that has been made, SHS exposure remains an important public health problem, and further protection of nonsmokers is needed through restriction of smoking in public places and workplaces as well as voluntary restriction of smoking at home. These restrictions are particularly necessary for vulnerable populations such as children and people with respiratory disease. OUTDOOR AIR POLLUTION

Outdoor air pollutants originate from fuel combustion produced by motor vehicles, power stations, factories, heating, and other sources. Many pollutants contribute to outdoor air pollution, including gaseous pollutants such as nitrogen dioxide (NO2), ozone (O3), sulfur dioxide (SO2), and carbon monoxide (CO), as well as particulate matter.77 Particulate matter is categorized by aerodynamic diameter, such as less than 10 mm (PM10) or less than 2.5 mm (PM2.5). The smaller particles are particularly concerning because these can be inhaled deeply into the lungs and deposited in the alveoli.78 The role of ultrafine particles, which are less than 0.25 mm (PM.25) has recently attracted attention. These particles are usually not reflected in standard measures of air pollution, which reflect total mass, but may be particularly toxic. Long-term exposure to outdoor air pollution likely contributes to the development of COPD. Increased levels of outdoor air pollution is associated with a population level

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reduction in pulmonary function and increased prevalence of COPD.3 Studies in multiple countries, including Germany, Switzerland, and the United States, indicate that high levels of both gaseous and PM10 exposures are associated with an increased risk for COPD and a decreased FEV1, forced vital capacity (FVC), and FEV1/FVC.79–81 The Swiss study showed an FVC decrease of 3.4% for every 10 mg/m3 increase in PM10.81 Long-term exposure to traffic-related air pollution has been associated with increased incidence of COPD,82,83 and higher traffic density was associated with decreased FEV1 and FVC in women.84,85 COPD is 1.6 to 1.8 times more likely in those living less than 100 m from a major road.79,86 Outdoor air pollution has also been associated with decreased growth of pulmonary function among children and adolescents.87,88 Outdoor air pollution affects patients with COPD adversely. Increased levels of outdoor air pollution are associated with increased respiratory symptoms in patients with COPD.83 Short-term increases in pollution are also associated with decreased FEV1 and FVC in adults with COPD.89 Among patients with COPD in the Lung Health Study, acute increases in PM10 of 100 mg/m3 were associated with an approximately 2% decline in FEV1.90 Many epidemiologic studies have shown an association between air pollution and COPD exacerbations. Throughout the world, increased ambient concentrations of SO2, NO2, O3, PM10, and PM2.5 are consistently associated with increased emergency department visits and hospital admissions for COPD or respiratory disease.77,91–99 Among 8 European cities, every 10 mg/m3 increase in PM10 was associated with an approximately 1% increase in mean number of daily admissions for COPD.100 Outdoor air pollution is also associated with increased mortality, both in the general population and among people with COPD.101 Long-term exposure to traffic-related air pollution, including black smoke, NO2, and PM2.5, is associated with increased naturalcause and respiratory mortality in the general population.102–104 Long-term exposure to ozone has also been associated with increased risk of death from respiratory causes.105 Among patients with COPD in Spain, levels of particulate pollutants, but not gaseous pollutants, were associated with increased all-cause mortality (OR 1.11) and mortality from respiratory causes.106,107 Increased PM10 has been associated with increased mortality among patients with COPD following hospital discharge.108 The global impact of outdoor air pollution is significant. The World Health Organization (WHO) estimates that approximately 1.4% of all deaths and 0.8% of disabilityadjusted life-years can be attributed to particulate air pollution. Given the large global impact of outdoor air pollution, efforts have been underway for many years to decrease levels of air pollutants, with some success. Governments worldwide have introduced air quality guidelines. The Clean Air Act of 1970 requires the US Environmental Protection Agency administrator to set National Ambient Air Quality Standards (NAAQS) for what are now known as criteria pollutants (particulate matter, ozone, carbon monoxide, nitrogen dioxide, sulfur dioxide, and lead), and regulates emissions of major polluting sectors. Worldwide, the Convention on Long-range Transboundary Air Pollution was established in 1979 and includes 51 countries in Europe, Asia, and North America (United Nations Economic Commission for Europe, www.unece.org). Aggressive air quality standards exist in Europe and other developed countries. With these efforts to reduce emissions, ambient air pollution concentrations in the United States and other developed countries have been declining in recent decades.109 Health outcome improvements have mirrored these changes. In an 11-year prospective study in Switzerland, improved air pollution was associated with improved lung function. For every 10 mg/m3 reduction in PM10, the rate of FEV1 decline was decreased by 3 mL/y or approximately 9%.110 In Germany, improvements in air quality were

Smoking Cessation and Environmental Hygiene

associated with improved lung function in children, and attenuated age-related increase in chronic respiratory diseases and symptoms in elderly women.111–113 Decreasing fine particulate air pollution in the United States during the 1980s and 1990s correlated with improvements in life expectancy, with an estimated increase in life expectancy of 0.77 years associated with every 10-mg/m3 decrease in PM2.5 concentration.114 However, cities in developing countries suffer from disproportionately high levels of outdoor air pollution because of many factors, including weak governance, geographic vulnerability, low income, and increasing populations, and have not experienced these same recent improvements. BIOMASS SMOKE

Biomass fuels are used extensively for domestic cooking and home heating in developing countries throughout the world. Biomass fuel includes wood, animal dung, and crop residues. Biomass stoves emit high levels of many pollutants, most of which are in the inhalable size range (