Tobacco

TOBACCO

Neal L. Benowitz -

DEFINITION

Harmful Constituents of Tobacco

Tobacco smoke is an aerosol of droplets (particulates) containing water, nicotine and other alkaloids, and tar. Tobacco smoke contains several thousand different chemicals, many of which may contribute to human disease. Major toxic chemicals in the particulate phase of tobacco include nicotine, benzo(a)pyrene and other polycyclic hydrocarbons, N′-nitrosonornicotine, β-naphthylamine, polonium 210, nickel, cadmium, arsenic, and lead. The gaseous phase contains carbon monoxide, acetaldehyde, acetone, methanol, nitrogen oxides, hydrogen cyanide, acrolein, ammonia, benzene, formaldehyde, nitrosamines, and vinyl chloride. Tobacco smoke may produce illness by way of systemic absorption of toxins or cause local pulmonary injury by oxidant gases.

Tobacco Addiction

Tobacco use is motivated primarily by the desire for nicotine. Drug addiction is defined as compulsive use of a psychoactive substance, the consequences of which are detrimental to the individual or society. Understanding addiction is useful in providing effective smoking cessation therapy. Nicotine is absorbed rapidly from tobacco smoke into the pulmonary circulation; it then moves quickly to the brain, where it acts on nicotinic cholinergic receptors to produce its gratifying effects, which occur within 10 to 15 seconds after a puff. Smokeless tobacco is absorbed more slowly and results in less intense pharmacologic effects. With long-term use of tobacco, physical dependence develops in association with an increased number of nicotinic cholinergic receptors in the brain. When tobacco is unavailable, even for only a few hours, withdrawal symptoms often occur, including anxiety, irritability, difficulty concentrating, restlessness, hunger, craving for tobacco, disturbed sleep, and, in some people, depression.

EPIDEMIOLOGY

Currently, about 46 million individuals in the United States are cigarette smokers, including 26% of men and 21% of women. People who are less well educated or have unskilled occupations are more likely to smoke. Smoking is responsible for about 430,000 preventable U.S. deaths annually. A lifelong smoker has about a one in three chance of dying prematurely of a complication of smoking. Smoking is the major preventable cause of death in developed countries.

Other forms of tobacco use include pipes and cigars (used by 8.7% of men and 0.3% of women) and smokeless tobacco (5.5% of men and 1% of women). Smokeless tobacco use in the United States is primarily oral snuff and chewing tobacco, whereas nasal snuff is used to a greater extent in the United Kingdom. Oral snuff (snus) is widely used by men in Sweden.

Addiction to tobacco is multifactorial, including a desire for the direct pharmacologic actions of nicotine, relief of withdrawal symptoms, and learned associations. Smokers report a variety of reasons for smoking, including pleasure, arousal, enhanced vigilance, improved performance, relief of anxiety or depression, reduced hunger, and control of body weight. Environmental cues, such as a meal, a cup of coffee, talking on the phone, an alcoholic beverage, or friends who smoke, often trigger an urge to smoke. Smoking and depression are strongly linked. Smokers are more likely to have a history of major depression than are nonsmokers. Smokers with a history of depression are also likely to be more highly dependent on nicotine and to have a lower likelihood of quitting. When they do quit, depression is more likely to be a prominent withdrawal symptom. Cigarette smoking is also more common in alcoholics and other substance abusers and in people with schizophrenia and attention-deficit disorder.

Most tobacco use begins in childhood or adolescence. Risk factors for youth smoking include peer and parental influences; behavioral problems (e.g., poor school performance); personality characteristics, such as rebelliousness or risk taking, depression, and anxiety; and genetic influences. Adolescent desire to appear older and more sophisticated, such as emulating more mature role models, is another strong motivator. Environmental influences such as advertising also are thought to contribute. Approaches to prevention of tobacco addiction in youth include educational activities in schools, aggressive anti-tobacco media campaigns, taxation, changing the social and environmental norms, and deglamorizing smoking (restricting indoor smoking, educating parents not to smoke around children).

PATHOBIOLOGY

Health Hazards of Tobacco

Tobacco use is a major cause of death from cancer, cardiovascular disease, and pulmonary disease ( Table 1 ). Smoking is also a major risk factor for osteoporosis, reproductive disorders, and fire-related and trauma-related injuries.

TABLE 1 -- HEALTH HAZARDS OF TOBACCO USE (RISKS INCREASED BY SMOKING)

CANCER

See Table 2

CARDIOVASCULAR DISEASE

Sudden death

Acute myocardial infarction

Unstable angina

Stroke

Peripheral arterial occlusive disease (including thromboangiitis obliterans)

Aortic aneurysm

PULMONARY DISEASE

Lung cancer

Chronic bronchitis

Emphysema

Asthma

Increased susceptibility to pneumonia

Increased susceptibility to pulmonary tuberculosis and

desquamative interstitial pneumonitis

Increased morbidity from viral respiratory infection

GASTROINTESTINAL DISEASE

Peptic ulcer

Gastroesophageal reflux

Crohn's disease

REPRODUCTIVE DISTURBANCES

Reduced fertility

Premature birth

Lower birth weight

Spontaneous abortion

Abruptio placentae

Premature rupture of membranes

Increased perinatal mortality

ORAL DISEASE

Oral cancer

Leukoplakia

Gingivitis

Gingival recession

Tooth staining

OTHER

Non–insulin-dependent diabetes mellitus

Earlier menopause

Osteoporosis

Cataract

Tobacco amblyopia

Age-related macular degeneration

Premature skin wrinkling

Graves' disease, including ophthalmopathy

Aggravation of hypothyroidism

Altered drug metabolism or effects

Cancer

Although it is the largest preventable cause of cancer ( Table 2 ), smoking is responsible for about 30% of cancer deaths. Many chemicals in tobacco smoke may contribute to carcinogenesis as tumor initiators, cocarcinogens, tumor promoters, or complete carcinogens. Cigarette smoking induces specific patterns of p53 mutations that are associated with squamous cell carcinomas of the lung, head, and neck. Lung cancer is the leading cause of cancer deaths in the United States and is predominantly attributable to cigarette smoking. The risk of lung and other cancers is proportional to how many cigarettes are smoked per day and the duration of smoking. Exposure in the workplace to asbestos or of uranium miners to α-radiation synergistically increases the risk of lung cancer in cigarette smokers. Alcohol use interacts synergistically with tobacco in causing oral, laryngeal, and esophageal cancer. The mechanism of interaction may involve alcohol-solubilizing tobacco carcinogens or alcohol-related induction of liver or gastrointestinal enzymes that metabolize and activate tobacco carcinogens. The tobacco-related risks of bladder and kidney cancer are enhanced by occupational exposure to aromatic amines, such as in the dye industry. Cervical cancer is more common in women who smoke, presumably the result of exposure to carcinogens in cervical secretions. Smoking seems to be involved in 20 to 30% of leukemia cases in adults, including lymphoid and myeloid leukemia, and in 20% of colorectal cancers.

TABLE 2 -- SMOKING AND CANCER MORTALITY

		Relative Risk among Smokers		Mortality Attributable to Smoking
Type of Cancer		Current	Former	Percentage	Number
Lung
	Male	22.4	9.4	90	82,800
	Female	11.9	4.7	79	40,300
Larynx
	Male	10.5	5.2	81	2400
	Female	17.8	11.9	87	700
Oral cavity
	Male	27.5	8.8	92	4900
	Female	5.6	2.9	61	1800
Esophagus
	Male	7.6	5.8	78	5700
	Female	10.3	3.2	75	1900
Pancreas
	Male	2.1	1.1	29	3500
	Female	2.3	1.8	34	4500
Bladder
	Male	2.9	1.9	47	3000
	Female	2.6	1.9	37	1200
Kidney
	Male	3.0	2.0	48	3000
	Female	1.4	1.2	12	500
Stomach
	Male	1.5	?	17	1400
	Female	1.5	?	25	1300
Leukemia
	Male	2.0	?	20	2000
	Female	2.0	?	20	1600
Cervix
	Female	2.1	1.9	31	1400

Modified from Newcomb PA, Carbone PP: The health consequences of smoking: Cancer. Med Clin North Am 1992;76:305–331.

Cardiovascular Disease

Cigarette smoking accounts for about 20% of cardiovascular deaths in the United States. Risks are increased for coronary heart disease, sudden death, cerebrovascular disease, and peripheral vascular disease, including aortic aneurysm. Cigarette smoking accelerates atherosclerosis and promotes acute ischemic events. The mechanisms of the effects of smoking are not fully elucidated but are believed to include (1) hemodynamic stress (nicotine increases the heart rate and transiently increases blood pressure), (2) endothelial injury and dysfunction (nitric oxide release and resultant vasodilation are impaired), (3) development of an atherogenic lipid profile (smokers have on average higher low-density lipoprotein, more oxidized low-density lipoprotein, and lower high-density lipoprotein cholesterol than nonsmokers do), (4) enhanced coagulability, (5) arrhythmogenesis, and (6) relative hypoxemia because of the effects of carbon monoxide. Carbon monoxide reduces the capacity of hemoglobin to carry oxygen and impairs the release of oxygen from hemoglobin to body tissues, both of which combine to result in a state of relative hypoxemia. To compensate for this hypoxemic state, polycythemia develops in smokers, with hematocrits often 50% or more. The polycythemia and the increased fibrinogen levels that are found in cigarette smokers also increase blood viscosity, which adds to the risk of thrombotic events. Cigarette smoking also induces a chronic inflammatory state, as evidenced by increased levels of C-reactive protein and other inflammatory markers in the blood of smokers. Chronic inflammation is thought to contribute to atherogenesis.

Cigarette smoking acts synergistically with other cardiac risk factors to increase the risk of ischemic heart disease. Although the risk of cardiovascular disease is roughly proportional to cigarette consumption, the risk persists even at low levels of smoking (e.g., one or two cigarettes per day). Cigarette smoking reduces exercise tolerance in patients with angina pectoris and intermittent claudication. Vasospastic angina is more common, and the response to vasodilator medication is impaired in patients who smoke. The number of episodes and total duration of ischemic episodes as assessed by ambulatory electrocardiographic monitoring in patients with coronary heart disease are substantially increased by cigarette smoking. The increase in relative risk of coronary heart disease because of cigarette smoking is greatest in young adults, who in the absence of cigarette smoking would have a relatively low risk. Women who use oral contraceptives and smoke have a synergistically increased risk of myocardial infarction and stroke.

After acute myocardial infarction, the risk of recurrent myocardial infarction is higher and survival is half during the next 12 years in persistent smokers compared with quitters. Smoking also interferes with revascularization therapy for acute myocardial infarction. After thrombolysis, the reocclusion rate is four-fold higher in smokers who continue than in quitters. The risk of reocclusion of a coronary artery after angioplasty or occlusion of a bypass graft is increased in smokers. Cigarette smoking is not a risk factor for hypertension but does increase the risk of complications, including the development of nephrosclerosis and progression to malignant hypertension. Cigarette smoking has been shown to be a substantial contributor to morbidity and mortality in patients with left ventricular dysfunction. The mortality benefit of stopping smoking in such patients is equal to or greater than the benefit of therapy with angiotensin-converting enzyme inhibitors, β-blockers, or spironolactone.

Pulmonary Disease

More than 80% of chronic obstructive lung disease in the United States is attributable to cigarette smoking. Pulmonary disease from smoking includes the overlapping syndromes of chronic bronchitis (cough and mucus hypersecretion), emphysema, and airway obstruction. The pathologic changes produced in the lung by cigarette smoking include loss of cilia, mucous gland hyperplasia, increased number of goblet cells in the central airways, inflammation, goblet cell metaplasia, squamous metaplasia, mucus plugging of small airways, destruction of alveoli, and reduced number of small arteries. The mechanism of injury is complex and seems to include direct injury by oxidant gases, increased elastase activity (a protein that breaks down elastin and other connective tissue), and decreased antiprotease activity. A genetic deficiency of α₁-antiprotease activity produces a similar imbalance between pulmonary protease and antiprotease activity and is a risk factor for early and severe smoking-induced pulmonary disease. Cigarette smoking is associated with an increased risk of desquamative interstitial pneumonitis.

Cigarette smoking also increases the risk of respiratory infection, including pneumonia, and results in greater disability from viral respiratory tract infections. Smoking is a substantial risk factor for pneumococcal pneumonia and in particular with invasive pneumococcal disease. Cigarette smoking increases the risk for development of and the severity of viral infections including the common cold, influenza, and varicella. Tuberculosis is perhaps the most important smoking-associated infection. Smoking is a substantial risk factor for tuberculin skin test reactivity, skin test conversion, and development of active tuberculosis. A case-control study from India found a prevalence risk ratio of 2.9 and a mortality risk ratio of 4.2 to 4.5 (for rural and urban residents, respectively) for ever-smokers compared with never-smokers.^[1] Thus, smoking contributes substantially to the worldwide disease burden of tuberculosis.

Other Complications Ulcer

Cigarette smoking increases the risk of duodenal and gastric ulcers, delays the rate of ulcer healing, and increases the risk of relapse after ulcer treatment. Smoking also is associated with esophageal reflux symptoms. Smoking produces ulcer disease by increasing acid and pepsinogen secretion, reducing pancreatic bicarbonate secretion, impairing the gastric mucosal barrier (related to decreased gastric mucosal blood flow and inhibition of prostaglandin synthesis), and reducing pyloric sphincter tone.

Diabetes Mellitus

Cigarette smoking is an independent risk factor for the development of non–insulin-dependent diabetes mellitus, which is a consequence of development of resistance to the effects of insulin. The effects of nicotine seem to contribute at least in part to insulin resistance, and insulin resistance has been described in users of smokeless tobacco, who are not exposed to tobacco combustion products.

Osteoporosis

Cigarette smoking is a risk factor for osteoporosis in that it reduces the peak bone mass attained in early adulthood and increases the rate of bone loss in later adulthood. Smoking antagonizes the protective effect of estrogen replacement therapy on the risk of osteoporosis in postmenopausal women.

Reproductive Problems

Cigarette smoking is a major cause of reproductive problems and results in approximately 4600 U.S. infant deaths annually. Growth retardation from cigarette smoking has been termed the fetal tobacco syndrome. Cigarette smoking causes reproductive complications by causing placental ischemia mediated by the vasoconstricting effects of nicotine, the hypoxic effects of chronic carbon monoxide exposure, and the general increase in coagulability produced by smoking.

Other Adverse Effects

Other adverse effects of cigarette smoking include premature facial wrinkling, increased risk of cataracts, olfactory dysfunction, and fire-related injuries; the last-mentioned contribute significantly to the economic costs of tobacco use. Smoking is associated with Graves' disease and especially increases the risk of more severe ophthalmopathy. Smoking also reduces the secretion of thyroid hormone in women with subclinical hypothyroidism and increases the severity of clinical symptoms of hypothyroidism in women with subclinical or overt hypothyroidism, the latter effect reflecting antagonism of thyroid hormone action. Cigarette smoking also potentially interacts with a variety of drugs by accelerating drug metabolism or by the antagonistic pharmacologic actions that nicotine and other constituents of tobacco have with other drugs ( Table 3 ).

TABLE 3 -- INTERACTION BETWEEN CIGARETTE SMOKING AND DRUGS

Drug		Interaction (Effects Compared with Nonsmokers)	Significance
Antipyrine	Imipramine	Accelerated metabolism	May require higher doses in smokers, reduced doses after quitting
Caffeine	Lidocaine
Chlorpromazine	Olanzapine
Clozapine	Oxazepam
Desmethyldiazepam	Pentazocine
Estradiol	Phenacetin
Estrone	Phenylbutazone
Flecainide	Propranolol
Fluvoxamine	Tacrine
Haloperidol	Theophylline
Oral contraceptives		Enhanced thrombosis, increased risk of stroke and myocardial infarction	Do not prescribe to smokers, especially if older than 35 years
Cimetidine and other H2-blockers		Lower rate of ulcer healing, higher ulcer recurrence rates	Consider the use of proton pump inhibitors
Propranolol		Less antihypertensive effect, less antianginal efficacy; more effective in reducing mortality after myocardial infarction	Consider the use of cardioselective β-blockers
Nifedipine (and probably other calcium blockers)		Less antianginal effect	May require higher doses or multiple-drug antianginal therapy
Diazepam, chlordiazepoxide (and possibly other sedative-hypnotics)		Less sedation	Smokers may need higher doses
Chlorpromazine (and possibly other neuroleptics)		Less sedation, possibly reduced efficacy	Smokers may need higher doses
Propoxyphene		Reduced analgesia	Smokers may need higher doses

Health Hazards of Smokeless Tobacco

Smokeless tobacco refers to snuff and chewing tobacco. Oral snuff is placed (as a “pinch”) between the lip and gum or under the tongue; chewing tobacco is actively chewed and generates saliva that is spit out (“spit tobacco”). Smokeless tobacco products are usually flavored, many with licorice, and also contain sodium bicarbonate to keep the local pH alkaline to facilitate buccal absorption of nicotine. Nicotine absorption from smokeless tobacco is similar in magnitude to that from cigarette smoking. Other chemicals, including sodium, glycyrrhizinic acid (from licorice), and potentially carcinogenic chemicals such as nitrosamines also are absorbed systemically.

Smokeless tobacco is addictive and is associated with an increased risk of oral cancer at the site where the tobacco is usually placed (inside the lip, under the cheek or tongue) or nasal cancer in nasal snuff users. Other oral diseases also associated with smokeless tobacco include leukoplakia, gingivitis, gingival recession, and staining of the teeth. Cardiovascular effects of smokeless tobacco include acute aggravation of hypertension or angina pectoris as a result of the sympathomimetic effects of nicotine, hypokalemia and hypertension secondary to the effects of glycyrrhizinic acid (a potent mineralocorticoid, and excessive sodium absorption resulting in aggravated hypertension or sodium-retaining disorders.

Health Hazards of Secondhand Smoke

Considerable evidence indicates that exposure to secondhand smoke is harmful to the health of nonsmokers ( Table 4 ). The U.S. Environmental Protection Agency classifies secondhand smoke as a class A carcinogen, which means that it has been shown to cause cancer in humans.

TABLE 4 -- HEALTH HAZARDS OF ENVIRONMENTAL TOBACCO SMOKE IN NONSMOKERS

Children	Adults
Hospitalization for respiratory tract infection in first year of life Wheezing Middle ear effusion Asthma Sudden infant death syndrome	Lung cancer Myocardial infarction Reduced pulmonary function Aggravation of asthma and chronic obstructive pulmonary disease Irritation of eyes, nasal congestion, headache Cough

Secondhand smoke consists of smoke that is generated while the cigarette is smoldering and mainstream smoke that has been exhaled by the smoker. Of the total combustion product from a cigarette, 75% or more enters the air. The constituents of environmental tobacco smoke are qualitatively similar to those of mainstream smoke. However, some toxins, such as ammonia, formaldehyde, and nitrosamines, are present in much higher concentrations in secondhand smoke than in mainstream smoke. The Environmental Protection Agency has estimated that secondhand smoke is responsible for approximately 3000 lung cancer deaths annually in nonsmokers in the United States, is causally associated with 150,000 to 300,000 cases of lower respiratory tract infection in infants and young children up to 18 months of age, and is causally associated with the aggravation of asthma in 200,000 to 1 million children. Secondhand smoke exposure is also responsible for about 40,000 cardiovascular deaths per year. An appreciation of the hazards of secondhand smoke is important to the physician because it provides a basis for advising parents not to smoke when children are in the home, for insisting that child care facilities be smoke free, and for recommending smoking restrictions in work sites and other public places

TREATMENT

Cessation Intervention

Of cigarette smokers, 70% would like to quit, and 46% try to quit each year. Spontaneous quit rates are about 1% per year. Simple advice from the physician to quit increases the quit rate to 3%. Minimal-intervention programs increase quit rates to 5 to 10%, whereas more intensive treatments, including smoking cessation clinics, can yield quit rates of 25 to 30%. A practical office smoking cessation program developed by the U.S. Public Health Service consists of 5 As: (1) ask about smoking at every opportunity, (2) advise all smokers to stop, (3) assess willingness to make a quit attempt, (4) assist the patient in stopping and maintaining abstinence, and (5) arrange follow-up to reinforce nonsmoking. Assistance in quitting should include providing self-help material or quit kits, which are widely available from governmental health agencies, professional societies, and local organizations such as cancer, heart, and lung associations. The physician may offer additional education and counseling through the office (most efficiently provided by office staff and by teaching aids such as videotapes) or through referral to community smoking cessation programs. Telephone counseling is effective in promoting smoking cessation.^[2] Telephone quitlines are available at no cost in most states in the United States. Thus, the busiest physician can easily refer patients to telephone quitlines for counseling if personal counseling time is not available. Smokers who are interested should be offered nicotine replacement or other pharmacologic therapy.

Medical Therapy

Currently, three medications have been approved for smoking cessation: nicotine, bupropion, and varenicline. All types of smoking cessation medications, if used properly, double smoking cessation rates compared with placebo treatments.

Nicotine Replacement

Nicotine replacement medications include 2- and 4-mg nicotine polacrilex gum, 2- and 4-mg nicotine buccal lozenges, transdermal nicotine patches, nicotine nasal spray, and nicotine inhalers. All seem to have comparable efficacy, but in a randomized study, compliance was greatest for the patch, lower for gum, and very low for the spray and the inhaler. A smoker should be instructed to quit smoking entirely before beginning nicotine replacement therapies. Optimal use of nicotine gum includes instructions not to chew too rapidly, to chew 8 to 10 pieces per day for 20 to 30 minutes each, and to use it for an adequate period for the smoker to learn a lifestyle without cigarettes, usually 3 months or longer. Side effects of nicotine gum are primarily local and include jaw fatigue, sore mouth and throat, upset stomach, and hiccups. Nicotine lozenges have recently been marketed over-the-counter. The lozenges are placed in the buccal cavity where they are slowly absorbed for 30 minutes. Smokers are instructed to choose their dose according to how long after awakening in the morning they smoke their first cigarette (a measure of the level of nicotine dependence). Those who smoke within 30 minutes are advised to use the 4-mg lozenge, whereas those who smoke their first cigarette at 30 minutes or more are advised to use 2-mg lozenges. Use is recommended every 1 to 2 hours.

Several different transdermal nicotine preparations are marketed; three deliver 21 or 22 mg during a 24-hour period, and one delivers 15 mg during 16 hours. Most have lower dose patches for tapering. Patches are applied in the morning and removed either the next morning or at bedtime, depending on the patch. Full-dose patches are recommended for most smokers for the first 1 to 3 months, followed by one or two tapering doses for 2 to 4 weeks each. Nicotine nasal spray, one spray into each nostril, delivers about 0.5 mg of nicotine systemically and can be used every 30 to 60 minutes. Local irritation of the nose commonly produces burning, sneezing, and watery eyes during initial treatment, but tolerance develops to these effects in 1 or 2 days. The nicotine inhaler delivers nicotine to the throat and upper airway, from where it is absorbed similarly to nicotine from gum. It is marketed as a cigarette-like plastic device and can be used ad libitum.

Nicotine medications seem to be safe in patients with cardiovascular disease and should be offered to cardiovascular patients. Although smoking cessation medications are recommended by the manufacturer for relatively short-term use (generally 3 to 6 months), the use of these medications for 6 months or longer is safe and may be helpful in smokers who fear relapse without medications. Combination therapy—combining bupropion and nicotine or combining slow-release nicotine patches with preparations with more rapid release, such as gum, inhaler, or nasal spray—increases the likelihood of cessation compared with single-drug therapy.

Buproprion

Bupropion, also marketed as an antidepressant drug, is dosed at 150 to 300 mg/day (150 mg BID) for 7 days before stopping smoking, then at 300 mg/day (150 mg BID) for the next 6 to 12 weeks; the sustained-release preparation should be used. Bupropion also can be used in combination with a nicotine patch.^[3] Bupropion in excessive doses can cause seizures and should not be used in individuals with a history of seizures or with eating disorders (bulimia or anorexia). On average, nicotine medications or bupropion treatment doubles the cessation rates found with placebo treatment, and absolute rates of smoking cessation have increased from 12% (placebo) to 24% (active medication) in clinical trials.

Varenicline

Varenicline is an α4 β2 nicotinic acetylcholine receptor partial agonist. Thus, varenicline both stimulates the receptor and blocks actions of nicotine on the receptor. The α4 β2 receptor subtype is believed to mediate the rewarding properties of nicotine. Varenicline appears both to reduce craving and other withdrawal symptoms after stopping smoking and to block the nicotine satisfaction if a person lapses to smoking. Clinical trials find cessation rates for varenicline treatment to be greater than either placebo (odds ratio 2.82) or bupropion (odds ratio 1.56).^[4] The main side effects are nausea and abnormal dreams. Treatment is started 1 week before the target quit date. Dose escalation is recommended to reduce the risk of nausea: 0.5 mg per day for 3 days; 0.5 mg twice daily for 4 days; then 1 mg twice daily for 12 weeks. For those who have quit successfully at 12 weeks but would like futher pharmacologic support, treatment for an additional 12 weeks has been shown to sustain higher quit rates.

Follow-up

Follow-up office visits or telephone calls during and after active treatment increase long-term smoking cessation rates. Even in the best treatment circumstances, 70% or more of smokers relapse. Most smokers go through a quitting process three or four times before they finally succeed. When a quit attempt fails, the health care provider should encourage patients to try again as soon as they are ready. Cost-effectiveness studies find average costs per year of life saved of $400 to $900 for brief counseling by a physician alone and an incremental cost for adding a course of nicotine patch therapy of $2000 to $4000, depending on the individual's gender and age, to aid cessation. Smoking cessation treatment is much less costly per year of life saved than are other widely accepted preventive therapies, including treatment of mild to moderate hypertension or hypercholesterolemia.

Benefits of Quitting Smoking

The benefits of quitting smoking are substantial for smokers of any age. A person who quits smoking before the age of 50 years has half the risk of dying in the next 15 years compared with a continuing smoker. Smoking cessation reduces the risks for development of lung cancer, with the risk falling to half that of a continuing smoker by 10 years and one sixth that of a smoker after 15 years' cessation. Quitting smoking in middle age substantially reduces lung cancer risk, with a 50% reduction in risk if a lifelong smoker quits at 55 years of age compared with 75 years. The risk of acute myocardial infarction falls rapidly after quitting smoking and approaches nonsmoking levels within a few years of abstinence. Cigarette smoking produces a progressive loss of airway function over time that is characterized by an accelerated loss of forced expiratory volume in 1 second (FEV₁) with increasing age. FEV₁ loss to cigarette smoking cannot be regained by cessation, but the rate of decline slows after smoking cessation and returns to that of nonsmokers. Women who stop smoking during the first 3 to 4 months of pregnancy reduce the risk of having a low-birth-weight infant to that of a woman who has never smoked.

After quitting, smokers gain an average of 5 to 7 pounds, which is perceived as undesirable and a reason not to quit by some smokers. Smokers tend to be thinner because of the effects of nicotine to increase energy expenditure and reduce compensatory increases in food consumption. After they quit smoking, ex-smokers tend to reach the weight expected had they never smoked. On balance, the benefits of quitting far outweigh the risks associated with weight gain, and patients should be counseled accordingly.

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Cataract

Cataract
Vaughan & Asbury's General Ophthalmology 17th Edition

A cataract is any opacity in the lens. Aging is the most common cause of cataract, but many other factors can be involved, including trauma, toxins, systemic disease (such as diabetes), smoking, and heredity. Age-related cataract is a common cause of visual impairment. Cross-sectional studies place the prevalence of cataracts at 50% in individuals aged 65-74; the prevalence increases to about 70% for those over 75.

The pathogenesis of cataracts is not completely understood. However, cataractous lenses are characterized by protein aggregates that scatter light rays and reduce transparency. Other protein alterations result in yellow or brown discoloration. Additional findings may include vesicles between lens fibers or migration and aberrant enlargement of epithelial cells. Factors thought to contribute to cataract formation include oxidative damage (from free radical reactions), ultraviolet light damage, and malnutrition. No medical treatment has been found that will retard or reverse the underlying chemical changes that occur in cataract formation. However, some recent evidence suggests a protective effect from dietary carotenoids (lutein), but studies evaluating the protective effect of multivitamins have yielded conflicting results.

A mature cataract is one in which all of the lens protein is opaque; the immature cataract has some transparent protein. If the lens takes up water, it may become intumescent. In the hypermature cataract, cortical proteins have become liquid. This liquid may escape through the intact capsule, leaving a shrunken lens with a wrinkled capsule. A hypermature cataract in which the lens nucleus floats freely in the capsular bag is called a morgagnian cataract.

Most cataracts are not visible to the casual observer until they become dense enough to cause severe vision loss. The ocular fundus becomes increasingly more difficult to visualize as the lens opacity becomes denser, until the fundus reflection is completely absent. At this stage, the cataract is usually mature, and the pupil may be white.

The clinical degree of cataract formation, assuming that no other eye disease is present, is judged primarily by the Snellen visual acuity test. Generally speaking, the decrease in visual acuity is directly proportionate to the density of the cataract. However, some individuals who have clinically significant cataracts when examined with the ophthalmoscope or slitlamp see well enough to carry on with normal activities. Others have a decrease in visual acuity out of proportion to the degree of lens opacification. This is due to distortion of the image by the partially opaque lens. The Cataract Management Guideline Panel recommends reliance on clinical judgment combined with Snellen acuity as the best guide to the appropriateness of surgery but recognizes the need for flexibility, with due regard to a patient's particular functional and visual needs, the environment, and other risks, all of which may vary widely.

AGE-RELATED CATARACT

(Figures 1, and 2)

The normal condensation process in the lens nucleus results in nuclear sclerosis after middle age. The earliest symptom may be improved near vision without glasses ("second sight"). This occurs from an increase in the focus power of the central lens, creating a myopic (near-sighted) shift in refraction. Other symptoms may include poor hue discrimination or monocular diplopia. Most nuclear cataracts are bilateral but may be asymmetric.

Figure 1. Age-related cataract. A and B: "Coronary" type cortical cataract (frontal and cross-sectional views): club-shaped peripheral opacities with clear central lens; slowly progressive. C: "Cuneiform" type cortical cataract: peripheral spicules and central clear lens; slowly progressive. D: Nuclear sclerotic cataract: diffuse opacity principally affecting nucleus; slowly progressive. E: Posterior subcapsular cataract: plaque of granular opacity on posterior capsule; may be rapidly progressive. F: "Morgagnian" type (hypermature lens): the entire lens is opaque, and the lens nucleus has fallen inferiorly.

Figure 2. Age-related cataract. In the photo at right the scene shown at left is reproduced as if seen by a person with a moderately advanced senile cataract (opacity denser centrally).

Cortical cataracts are opacities in the lens cortex. Changes in the hydration of lens fibers create clefts in a radial pattern around the equatorial region. They also tend to be bilateral, but they are often asymmetric. Visual function is variably affected, depending on how near the opacities are to the visual axis.

Posterior subcapsular cataracts are located in the cortex near the central posterior capsule. They tend to cause visual symptoms earlier in their development owing to involvement of the visual axis. Common symptoms include glare and reduced vision under bright lighting conditions. This lens opacity can result also from trauma, corticosteroid use (topical or systemic), inflammation, or exposure to ionizing radiation.

Age-related cataract is usually slowly progressive over years, and death may occur before surgery becomes necessary. If surgery is indicated, lens extraction definitely improves visual acuity in over 90% of cases. The remainder of patients either have preexisting retinal damage or develop serious postsurgical complications that prevent significant visual improvement, eg, glaucoma, retinal detachment, intraocular hemorrhage, or infection. Intraocular lenses have made adjustment following cataract operation much easier than when only thick cataract glasses or aphakic contact lenses were available.

CHILDHOOD CATARACT

(Figures 3 and 4)

Childhood cataracts are divided into two groups: congenital (infantile) cataracts, which are present at birth or appear shortly thereafter, and acquired cataracts, which occur later and are usually related to a specific cause. Either type may be unilateral or bilateral.

Figure 3. Congenital cataract.

Figure 4. Congenital cataract, zonular type. One zone of lens involved. The cortex is relatively clear.

About one-third of cataracts are hereditary, while another third are secondary to metabolic or infectious diseases or associated with a variety of syndromes. The final one-third result from undetermined causes. Acquired cataracts arise most commonly from trauma, either blunt or penetrating. Other causes include uveitis, acquired ocular infections, diabetes, and drugs.

Clinical Findings

Congenital Cataract

Congenital lens opacities are common and often visually insignificant. A partial opacification or one out of the visual axis—or not dense enough to interfere significantly with light transmission—requires no treatment other than observation for progression. Dense central congenital cataracts require surgery.

Congenital cataracts that cause significant visual loss must be detected early, preferably in the newborn nursery by the pediatrician or family physician. Large, dense white cataracts may present as leukocoria (white pupil), noticeable by the parents, but many dense cataracts cannot be seen by the parents. Unilateral infantile cataracts that are dense, central, and larger than 2 mm in diameter will cause permanent deprivation amblyopia if not treated within the first 2 months of life and thus require surgical management on an urgent basis. Even then there must be careful attention to avoidance of amblyopia related to postoperative anisometropia. Symmetric (equally dense) bilateral cataracts may require less urgent management, although bilateral deprivation amblyopia can result from unwarranted delay. When surgery is undertaken, there must be as short an interval as is reasonably possible between surgery on the two eyes.

Acquired Cataract

Acquired cataracts do not require the same urgent care (aimed at preventing amblyopia) as infantile cataracts because the children are older and the visual system more mature. Surgical assessment is based on the location, size, and density of the cataract, but a period of observation along with subjective visual acuity testing can be part of the decision-making process. Because unilateral cataracts in children will not produce any symptoms or signs parents would routinely notice, screening programs are important for case finding.

Treatment

Surgical treatment of infantile and early childhood cataracts involves lens extraction through a small limbal incision utilizing a mechanical irrigation-aspiration handpiece. Phacoemulsification is rarely required. In contrast to the procedure used for adult lens extraction, the posterior capsule and anterior vitreous are removed by many surgeons using a mechanical vitreous suction-cutting instrument. This prevents formation of secondary capsular opacification or after-cataract (see below). Primary removal of the posterior capsule thus avoids the necessity for secondary surgery and enhances early optical correction.

Using today's sophisticated surgical techniques, operative and postoperative complications are similar to those reported with adult cataract procedures. Optical correction can consist of spectacles in older bilaterally aphakic children, but most childhood cataract operations are followed by contact lens correction. The use of intraocular lenses in early childhood is becoming increasingly frequent. It may lessen the difficulty of optical rehabilitation associated with contact lenses in children, but there are difficulties calculating the appropriate power of intraocular lens, which may need to be changed as the eye develops.

Prognosis

The visual prognosis for childhood cataract patients requiring surgery is not as good as that for patients with age-related cataract. The associated amblyopia and occasional anomalies of the optic nerve or retina limit the degree of useful vision that can be achieved in this group of patients. The prognosis for improvement of visual acuity is worst following surgery for unilateral congenital cataracts and best for incomplete bilateral congenital cataracts that are slowly progressive.

TRAUMATIC CATARACT

Traumatic cataract (Figures 5) is most commonly due to a foreign body injury to the lens or blunt trauma to the eyeball. Air rifle pellets and fireworks are a frequent cause; less-frequent causes include arrows, rocks, contusions, overexposure to heat ("glassblower's cataract"), and ionizing radiation. Most traumatic cataracts are preventable. In industry, the best safety measure is a good pair of safety goggles.

Figure 5. A. Traumatic "star-shaped" cataract in the posterior lens. This is usually due to ocular contusion and is only detectable through a well-dilated pupil. B. Traumatic cataract with wrinkled anterior capsule. C. Imprint of iris pigment on anterior surface of lens.

The lens becomes white soon after the entry of a foreign body, since interruption of the lens capsule allows aqueous and sometimes vitreous to penetrate into the lens structure. The patient is often an industrial worker who gives a history of striking steel upon steel. A minute fragment of a steel hammer, for example, may pass through the cornea and lens at a tremendous rate of speed and lodge in the vitreous or retina.

CATACARACT SECONDARY TO INTRAOCULAR DISEASE ("COMPLICATED CATARACT ")

Cataract may develop as a direct effect of intraocular disease upon the physiology of the lens (eg, severe recurrent uveitis). The cataract usually begins in the posterior subcapsular area and eventually involves the entire lens structure. Intraocular diseases commonly associated with the development of cataracts are chronic or recurrent uveitis, glaucoma, retinitis pigmentosa, and retinal detachment. These cataracts are usually unilateral. The visual prognosis is not as good as in ordinary age-related cataract.

CATARACT ASSOCIATED WITH SYSTEMIC DISEASE

Bilateral cataracts may occur in association with the following systemic disorders: diabetes mellitus (Figure 6), hypocalcemia (of any cause), myotonic dystrophy, atopic dermatitis, galactosemia, and Lowe's, Werner's, and Down's syndromes.

Figure 6. Punctate dot cataract. This type of cataract is sometimes seen as an ocular complication of diabetes mellitus. It may also be congenital.

AFTER-CATARACT (SECONDARY MEMBRANE)

After-cataract (Figure 7) denotes opacification of the posterior capsule following extracapsular cataract extraction. Persistent subcapsular lens epithelium may favor regeneration of lens fibers, giving the posterior capsule a "fish egg" appearance (Elschnig's pearls). The proliferating epithelium may produce multiple layers, leading to frank opacification. These cells may also undergo myofibroblastic differentiation. Their contraction produces numerous tiny wrinkles in the posterior capsule, resulting in visual distortion. All of these factors may lead to reduced visual acuity following extracapsular cataract extraction.

Figure 7. After-cataract.

After-cataract is a significant problem in almost all pediatric patients unless the posterior capsule and anterior vitreous are removed at the time of surgery. In the past, up to one-half of all adult patients developed an opacified posterior capsule after extracapsular cataract extraction. However, improved surgical techniques and new intraocular lens materials have significantly reduced the incidence of posterior capsule opacity.

The neodymium:YAG laser provides a noninvasive method for discission of the posterior capsule. Pulses of laser energy cause small "explosions" in target tissue, creating a small hole in the posterior capsule in the pupillary axis. Complications of this technique include a transient rise in intraocular pressure, damage to the intraocular lens, and rupture of the anterior hyaloid face with forward displacement of vitreous into the anterior chamber, potentially leading to rhegmatogenous retinal detachment or cystoid macular edema. The rise in intraocular pressure is usually detectable within 3 hours after treatment and resolves within a few days with treatment. Rarely, the pressure does not return to normal for several weeks. Small pits or cracks may occur on the intraocular lens but usually have no effect on visual acuity. No significant damage seems to be done to corneal endothelium with the neodymium:YAG laser.

Cataract Surgery

Cataract surgery has undergone dramatic change during the past 30 years with the introduction of the operating microscope and microsurgical instruments, the development of intraocular lenses, and alterations in techniques for local anesthesia. Further refinements continue to occur, with automated instrumentation and modifications of intraocular lenses allowing surgery through small incisions.

The generally preferred method of cataract surgery in adults and older children preserves the posterior portion of the lens capsule and thus is known as extracapsular cataract extraction. Intraocular lens implantation is part of this procedure. An incision is made at the limbus or in the peripheral cornea, either superiorly or temporally. An opening is formed in the anterior capsule, and the nucleus and cortex of the lens are removed. The intraocular lens is then placed in the empty "capsular bag," supported by the intact posterior capsule. In the nuclear expression form of extracapsular cataract extraction, the nucleus is removed intact, but this requires a relatively large incision. The cortex is removed by manual or automated aspiration. The technique of phacoemulsification is now the most common form of extracapsular cataract extraction. It utilizes a handheld ultrasonic vibrator to disintegrate the hard nucleus such that the nuclear material and cortex can be aspirated through an incision of approximately 3 mm. This same incision size is then adequate for insertion of foldable intraocular lenses. If a rigid intraocular lens is used, the wound needs to be extended to approximately 5 mm. The advantages of small-incision surgery are more controlled operating conditions, avoidance of suturing, rapid wound healing with lesser degrees of corneal distortion, and reduced postoperative intraocular inflammation—all contributing to more rapid visual rehabilitation. The phacoemulsification technique does, however, entail a higher risk of posterior displacement of nuclear material through a posterior capsular tear, which generally necessitates complex vitreoretinal surgery. After all forms of extracapsular cataract surgery, there may be secondary opacification of the posterior capsule that requires discission using the neodymium:YAG laser (see After-Cataract, above). Lens extraction through the pars plana during posterior vitrectomy is called pars plana lensectomy or phacofragmentation. This type of cataract removal is usually performed in conjunction with the removal of an opaque or scarred vitreous.

Intracapsular cataract extraction, consisting of removal of the entire lens together with its capsule, is rarely performed today. The incidence of postoperative retinal detachment and cystoid macular edema is significantly higher than after extracapsular surgery, but intracapsular surgery is still a useful procedure, particularly when facilities for extracapsular surgery are not available.

Intraocular Lens

There are many styles of intraocular lenses, but most designs consist of a central biconvex optic and two legs (or haptics) to maintain the optic in position. The optimal intraocular lens position is within the capsular bag following an extracapsular procedure. This is associated with the lowest incidence of postoperative complications, such as pseudophakic bullous keratopathy, glaucoma, iris damage, hyphema, and lens decentration. The newest posterior chamber lenses are made of flexible materials such as silicone and acrylic polymers. This flexibility allows the lens implant to be folded, thus decreasing the required incision size. Lens designs that incorporate multifocal optics have also been produced. The goal of this design is to provide the patient with good vision for both near and distance without glasses, which current monofocal designs are unable to do.

After intracapsular surgery—or if there is inadvertent damage to the posterior capsule during extracapsular surgery—intraocular lenses can be placed in the anterior chamber or sometimes fixated in the ciliary sulcus.

Methods of calculating the correct dioptric power of an intraocular lens are discussed in other chapter. If an intraocular lens cannot be safely placed or is contraindicated, postoperative refractive correction generally requires a contact lens or aphakic spectacles.

Postoperative Care

If a small-incision technique is used, the postoperative recovery period is usually shortened. The patient is usually ambulatory on the day of surgery but is advised to move cautiously and avoid straining or heavy lifting for about a month. The eye may be patched on the day of surgery. Protection at night by a metal shield is often suggested for several days after surgery. Temporary glasses can be used a few days after surgery, but in most cases the patient sees well enough through the intraocular lens to wait for permanent glasses (usually provided 4-8 weeks after surgery).

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