Selected annotated bibliography. (Featured CME Topic: Adverse Effects of Smoking).

EDITOR'S NOTE: There is overwhelming evidence that smoking is associated with a number of adverse effects. The literature is saturated with original and review articles documenting these adverse effects. Rather than having yet more reviews on this topic, we decided to select from the published literature a few select papers that adequately summarize the state of knowledge about specific adverse effects. We tended to avoid original research articles as these are too numerous, and we felt were too focused and could not be abstracted in a few sentences. A proper evaluation of these papers would require a critical evaluation of the methodology used and the results obtained. Instead, we decided to include in this bibliography selected review articles, most of which refer to and evaluate original research articles. Readers who need more detailed information may either read the papers cited in this bibliography or may use these papers to launch their own discovery about the adverse effects of smoking. We hope this compendium will help health care professionals convince patients under their care to stop smoking.

Next month's Special CME Feature will be devoted to smoking cessation.

Ronald C. Hamdy, MD, FRCP, FACP Editor

BACK PAIN

* Eriksen W, Natvig B, Bruusgaard D: Smoking, heavy physical work and low back pain: a four-year prospective study. Occup Med 1999; 49:155-160.

Smoking increases the risk of low back pain in persons involved in heavy lifting and standing for long periods of time. The odds ratio for low back pain in those engaged in heavy physical work and standing was 5.53 (95% CI, 1.93-15.84) in smokers and 1.12 (95% CI, 0.48-2.59) in nonsmokers (P<.01). This increased risk was after adjusting for several possible confounding factors such as age, gender, and body weight. Smoking may inhibit healing of injuries, bring about reduced perfusion and malnutrition of spinal tissues, and reduce resistance to stress. Exercising at least once a week reduces the risk for low back pain. Results are based on a four-year prospective study in Norway on 708 subjects who responded to a questionnaire and had not experienced low back pain 1 year prior to the study.

* Feldman DE, Rossignol M, Shrier I, et al: Smoking: a risk factor for development of low back pain in adolescents. Spine 1999; 24:2492-2496.

Adolescents who smoke are twice as likely to experience low back pain as nonsmokers (OR=2.4; 95% CI, 1.3-6.0). There is a dose-response relationship between cigarette smoking and low back pain. These results are based on a cohort study of 502 high school students followed prospectively over 12 months.

CANCER

Bladder Cancer 

* Pirastu R, Iavarone I, Comba P: Bladder cancer: a selected review of the epidemiological literature. Ann 1st Super Sanita 1996; 32:3-20.

About half of all bladder cancers in western countries are attributed to smoking. Some studies indicate a higher risk for bladder cancer in association with fats and cholesterol and chlorination in drinking water. These conclusions are based on a review of the literature.

Cervical Cancer 

* Reid J: Women's knowledge of Pap smears, risk factors for cervical cancer, and cervical cancer. J Obstet Gyne Neonatal Nurs 2001; 30:299-305.

Smoking cigarettes places women at greater risk for developing cervical cancer. Early sexual activity, multiple sexual partners, failure to use condoms, and papillomavirus infection are other factors associated with cervical cancer. This is a 10-year review of the published literature.

* Murthy NS, Mathew A: Risk factors for pre-cancerous lesions of the cervix. Eur J Cancer Prev 2000; 9:5-14.

Cigarette smoking is a risk factor for pre-cancerous lesions of the cervix, although studies do not confirm that it is independent of human papilloma virus (HPV), the major infectious aetiological agent associated with the condition. Other risk factors include contraceptive use, nutritional deficiencies, and poor personal hygiene. Risks for pre-cancerous lesions of the cervix are similar to risks for cervical cancer.

Colorectal Cancer 

* Giovannucci E: An updated review of the epidemiological evidence that cigarette smoking increases risk of colorectal cancer. Cancer Epidemiology, Biomarkers & Prevention 2001; 10:725-731.

The effect of tobacco may be irreversible. Smoking one pack of cigarettes a day for 30 to 40 years increases the risk of recurrent colon adenomas 2-3 times and persists 10 years after smoking has stopped, according to a study of 186 recurrent polyp cases and 330 individuals with no adenomas at follow-up. There is a possibility that since colorectal adenomas are precursors for cancer, risk factors for adenomas increase the risk for colorectal cancer. Evidence suggests that as many as 20% of colorectal cancers in the U.S. are linked to tobacco use. Beginning smoking at a younger age and at heavy doses increases lifetime risks. This is a review of data through March 2001 concerning the association between colorectal cancer and smoking.

General Cancer

* Tominaga S: Major avoidable risk factors of cancer. Cancer Lett 1999; 143 (suppl 1):S19-S23.

Tobacco is responsible for 20%-30% of cancers. Although occupation, environmental pollution, sunlight, radiation, food additives, pesticides, and drugs may increase risks for various types of cancer, tobacco is the primary avoidable risk in a number of cancers. Oral cavity, larynx, lung, pharynx, esophagus, stomach, liver, pancreas, kidney (pelvis), ureter, bladder, and cervix are types of cancer for which tobacco increases risk. These conclusions are based on a review of the published literature.

Larynx Cancer

* Koufman JA, Burke AJ: The etiology and pathogenesis of laryngeal carcinoma. Otolaryngol Clin North Am 1997; 30:1-19.

Tobacco use significantly increases the risk of laryngeal carcinoma. This multifactorial model of laryngeal mucosal carcinogenesis looks at influential environmental and lifestyle factors, including smoking, ethanol consumption, toxic substance exposure, diet, irradiation, papilloma virus infection, and laryngopharyngeal reflux. Data are compiled from the published literature.

* Szyfter K, Szmeja Z, Szyfter W, et al: Molecular and cellular alterations in tobacco smoke-associated larynx cancer. Mutat Res 1999; 445:259-274.

Carcinogens in tobacco smoke are linked to the development of laryngeal cancer, and the mortality rate among males with larynx cancer is increasing. Cancers in the head and neck are the most common of all cancers worldwide. The molecular and cellular events from carcinogenic exposure, DNA adduct formation, p53 gene mutation, and other biological discussions are found in this review of the published literature.

Liver Cancer 

* Yu MC, Yuan JM, Govindarajan S, et al: Epidemiology of hepatocellular carcinoma. Can J Gastroenterol 2000; 14:703-709.

Cigarette smoking is a risk factor for hepato-cellular carcinoma (HCC), the eighth most common cancer in the world. Although this type of malignancy is rare in North America, rates of HCC in the U.S. have increased by 70% in the last 20 years. Chronic infection by the hepatitis B virus is the most important association for HCC worldwide, and hepatitis C virus is a risk factor in HCC cases in the U.S. Results are from a review of the published literature.

* Chen CJ, Yu MW, Liaw YF: Epidemiological characteristics and risk factors of hepatocellular carcinoma. J Gastroenterol Hepatol 1997; 12:5294-5308.

Cigarette smoking increases the risk for hepatocellular carcinoma (HCC), and exposure to risk factors such as this accounts for the variance in HCC incidence rates between countries. Men are twice as likely to have HCC as women, and risks vary among different ethnic groups living in the same area and among the same ethnic groups living in different areas. Hepatitis B and C viruses are risk factors for HCC, along with aflatoxin exposure, heavy alcohol consumption, low vegetable intake, inorganic arsenic ingestion, radioactive thorium dioxide exposure, iron overload, oral contraceptives, and anabolic steroids. Results from this review of the published literature confirm that hepatocarcinogenesis is a multistage process involving a number of factors.

* Bosch FX, Ribes J, Borras J: Epidemiology of primary liver cancer. Semin Liver Dis 1999; 19:271-285.

Men are twice as likely to have liver cancer (LC) as women, although Caucasian populations in North America are generally at lowest risk. Incidence rates vary between and within countries, from 27.6-36.6 per 100,000 men in Eastern Asia to fewer than 5 cases per 100,000 men in North America. Exposure to risk factors accounts for the variance, and cigarette smoking is a documented risk factor for LC. Hepatitis B and hepatitis C viruses account for more than 80% of LC cases worldwide. Researchers are investigating the possibility of interactions between risk factors; new laboratory techniques may yield quantitative estimates of risks for LC such as smoking, alcohol consumption, oral contraceptives, and aflatoxin in diets. Results are obtained from a review of the published literature.

Lung Cancer 

* Ernster VL: Female lung cancer. Annu Rev Public Health 1996; 17:97-114.

Lung cancer is the leading cause of death of women in the U.S. who have cancer, and cigarette smoking is responsible for about 80% of those lung cancers. Women may be more susceptible than men to developing lung cancer when exposed to cigarette smoke. Other factors increasing the risk of lung cancer include a positive family history; personal history of lung disease such as asthma, chronic bronchitis, pneumonia, and tuberculosis; and status post-radiation therapy. Passive smoking increases the risk of lung cancer in nonsmoking women. Consuming large amounts of fruits and vegetables may lower the risk, although results from clinical trials do not support a beneficial effect of beta-carotene supplementation. These conclusions are based on a review of the published literature.

* Vineis P, Caporaso N: Tobacco and cancer: epidemiology and the laboratory. Environ Health Perspect 1995; 103:156-160.

Evidence indicates an association between smoking and cancer apart from genetic predisposition. Studies were consistent with oncogene/tumor-suppressor gene mutations in smokers' lung cancer and other tobacco-related cancers. Time sequence between exposure, gene mutation, and cancer onset is still unclear. These conclusions are based on a review of published literature.

* Almand B, Carbone DP: Biological considerations in lung cancer. Cancer Treat Res 2001; 105:1-30.

Most lung cancers are caused by environmental risk factors, a large number of which are due to genetic alterations from exposure to carcinogens. This knowledge is important for the understanding and development of new methods for treating this refractory disease. The body's immune system will be the basis of improved treatment approaches. This article is a review of the published literature.

* Christiani DC: Smoking and the molecular epidemiology of lung cancer. Clin Chest Med 2000; 21:87-93,viii.

This is a review of literature on lung cancer and carcinogenesis. Tobacco smoking poses the greatest risk of lung cancer worldwide; other environmental agents such as radioactive compounds, asbestos, heavy metals, and petrochemicals are additional sources of lung carcinogens.

* Osann KE: Epidemiology of lung cancer. Curr Opin Pulm Med 1998; 4:198-204.

The number of women in the U.S. who have lung cancer is increasing, but lung cancer in men is decreasing. Cigarette smoking is the number one cause of lung cancer, but factors such as gender, race, and age are also influences. Radon exposure in the home, occupational exposures, diet, and family history are risk factors for lung cancer independent of cigarette smoking. Results are from a review of the published literature.

Further Reading

1. Boyle P: Cancer, cigarette smoking and premature death in Europe: a review including the recommendations of European cancer Experts Consensus Meeting, Helsinki, October 1996. Lung Cancer 1997; 17:1-60

2. Leonard CT, Sachs DP: Environmental tobacco smoke and lung cancer incidence. Curr Opin Pulm Med 1999; 5:189-193

3. Pandey M, Mathew A, Nair MK: Global perspective of tobacco habits and lung cancer: a lesson for third world countries. Eur J Cancer Prev 1999; 8:271-279

4. Bepler G: Lung cancer epidemiology and genetics. J Thorac Imaging 1999; 14:228-234

5. Hecht SS: Tobacco smoke carcinogens and lung cancer. J Nail Cancer Inst 1999; 91:1194-1210

Oral Cancer

* Allard R, Angelopoulos A, Ainamo A, et al: Tobacco and oral diseases - Report of EU Working Group, 1999. J Irish Dental Assoc 2000; 46:12-19, 22.

Bad breath, yellow teeth and periodontal disease are just a few minor side effects associated with smoking. Oral cancer and precancer are more prevalent and serious in smokers than in never-smokers. Dental implant failure is linked to smoking. Discoloration of dentures and teeth is more common and unsightly in smokers than nonsmokers. Recent studies indicate more chronic gingivitis, dental plaque and calculus in smokers. There is also a clear association between cigarette smoking and acute necrotizing ulcerative gingivitis. Adult periodontitis and smoking show a strong correlation. In a large population study it was found that smokers have an increased occurrence of periodontitis with more severity when compared to never-smokers. This is noted in cases where smokers displayed severe attachment loss and a greater marginal bone loss as opposed to nonsmokers. In implant failures, smoking was the most detrimental factor. Failure rates were 11.3 in smokers compared to 4.8 in nonsmokers. Cigarette smoking adversely affects the oral mucous membranes. Symptoms include reversible lesions, such as smoker's palate, to oral cancer. It is interesting to note that alcohol consumption increases the risk of oral cancer in smokers by 6-15 times greater than nonsmokers/non-drinkers. Oral cancer risks diminish within 5-10 years after smoking cessation.

Further Reading

1. Rassekh C: Tobacco cancer of the oral cavity and pharynx. WV Med J 2001; 97:8-12

Pancreatic Cancer

* Chiu BC, Lynch CF, Cerhan JR, et al: Cigarette smoking and risk of bladder, pancreas, kidney, and colorectal cancers in Iowa. Ann Epidemiol 2001; 11:28-37.

Cigarette smoking doubles the risk of pancreatic cancer in both sexes. The odds ratio (OR) of cancer of the pancreas in men smoking cigarettes is 1.8 (95% CI, 1.2-2.8). In women the OR is higher: 2.1 (95% CI, 1.43.1). Cigarette smoking also increases the risk of bladder, kidney and colorectal cancers.

* Chowdry P, Rayford PL: Smoking and pancreatic disorders. Eur J Gastroenterol Hepatol 2000; 12:869-877.

Cigarette smoking predisposes to pancreatitis and cancer of the pancreas. In this review article, the authors discuss the role of cigarette smoking as a risk factor for both pancreatitis and cancer of the pancreas.

* Li D: Molecular epidemiology of pancreatic cancer. Cancer J 2001; 7:259-265.

Cigarette smoking is a risk factor for pancreatic cancer. Some of the mechanisms by which cigarette smoking may induce pancreatic cancer are discussed in this review article.

* Simon B, Printz H: Epidemiological trends in pancreatic neoplasia. Dig Dis 2001; 19:6-14.

Cigarette smoking is the most consistent environmental risk factor predisposing to cancer of the pancreas.

* Harnack LJ, Anderson KE, Zheng W, et al: Smoking, alcohol, coffee, and tea intake and incidence of cancer of the exocrine pancreas: the Iowa Women's Health Study. Cancer Epidemiol Biomarkers Prey 1997; 6:1081-1086.

Cigarette smoking doubles the risk of cancer of the pancreas. Alcohol further increases this risk.

* Boyle P, Maisonneuve P, Bueno de Mesquita B, et al: Cigarette smoking and pancreas cancer: a case control study of the search programme of the IARC. Int J Cancer 1996; 67:63-71.

Cigarette smoking increases the risk of cancer of the pancreas. The increased risk is proportional to the total exposure to tobacco smoke: quantity of cigarette smoked and number of years smoked. The relative risk in the highest cigarette smokers was 2.70 (95% CI, 1.95-3.74). Smoking cessation is associated with a reduced risk, but it may take up to 15 years for this risk in heavy smokers to return to a level similar to never-smokers.

Further Reading

1. Lowenfels AB, Maisonneuve P: Pancreatico-biliary malignancy: prevalence and risk factors. Ann Oncol 1999; 10(suppl 4):1-3

2. Weiderpass E, Partanen T, Kaaks R, et al: Occurrence, trends and environment etiology of pancreatic cancer. Scand J Work Environ Health 1998; 24:161-164

3. Partanen TJ, Vaino HU, Ojajarvi IA, et al: Pancreas cancer, tobacco smoking and consumption of alcoholic beverages: a case-control study. Cancer Lett 1997; 116:27-32

Renal Cancer

* Van Poppel H, Nilsson S, Algaba F, et al: Precancerous lesions in the kidney. Scand J Urol Nephrol 2000; 205:S136-S165.

Renal cell carcinoma (RCC) is not as common as prostate or bladder cancer, but it kills more than 35% of affected patients. Cigarette smoking, as well as obesity, hypertension, diet, and asbestos exposure, is an established risk for RCC. Health care providers should focus on identifying and screening risk groups in order to detect RCC at its earliest stage. This is a review of the published literature.

* Godley PA, Ataga KI: Renal cell carcinoma. Curr Opin Oncol 2000; 12:260-264.

Smoking is a risk factor for renal cell carcinoma, which has an unexplained increase in incidence rate. Other risk factors are hypertension, diet (especially increased red meat intake), and heightened body mass index. Immunotherapy has a response rate of 5%-20% and is the basis for systemic treatment. Pathologic stage, nuclear grade, microscopic vascular invasion, DNA content, nuclear morphometry, and histologic pattern are survival determinants. Results are obtained from a review of the literature.

* McLaughlin JK, Lipworth L: Epidemiologic aspects of renal cell cancer. Semin Oncol 2000; 27:115-123.

Smoking cigarettes increases the risk for renal cell cancer, which account for about 2% of all cancers. African-Americans have the highest rate of renal cell cancer in the U.S., with the overall rate increasing at 3% per year. Patients now have a 50%-60% chance of survival, compared with 30%-40% in the 1960s. Causal factors include obesity (especially among women), high blood pressure, and genetics. Fruits and vegetables in the diet are beneficial in lowering risk for this type of cancer. Research should focus on the reasons behind the risk factors and the cause of an increase in renal cell cancer among blacks in the U.S. This is a review of the published literature.

Further Reading

1. Orth SR: Smoking: a renal risk factor. Nephron 2000; 86:12-26

2. Zeegers MP, Tan FE, Dorant E, et al: The impact of characteristics of cigarette smoking on urinary tract cancer risk: a meta-analysis of epidemiologic studies. Cancer 2000; 89:630-639

CARDIOVASCULAR SYSTEM (CVS)

* Villablanca AC, McDonald JM, Rutledge JC: Smoking and cardiovascular disease. Clin Chest Med 2000; 21:159-172.

Cardiovascular disease accounts for the largest number of smoking-related deaths, smokers die nearly 7 years earlier than nonsmokers, and 20% of teenagers aged 12-17 smoke. The authors present a comprehensive review of the effects of mainstream smoke, environmental tobacco smoke, and nicotine on the cardiovascular system. While no single factor determines patterns of tobacco use among racial/ethnic minority groups, smoking rates are associated with educational level: Only 17% of college graduates smoke, but 37% of Americans with less than 12 years' education are smokers. Figures are based on 1995 U.S. government statistics.

* Prescott E, Hippe M, Schnohr P, et al: Smoking and risk of myocardial infarction in women and men: longitudinal population study. BMJ 1998; 316:1043-1047.

Risks associated with smoking are consistently higher in women than in men. Compared with nonsmokers, female smokers have a myocardial infarction risk of 2.24 and male smokers 1.43. Ex-smokers reduce this risk by as much as 50% within the first year after quitting. Results are based on a multiplicative model in a study of more than 24,000 subjects in Copenhagen 1976-1987, ages 20-93.

* Keil U: Coronary artery disease: the role of lipids, hypertension and smoking. Basic Res Cardiol 2000; 95(suppl 1):S152-S158.

Although a number of factors affect the risk of CHD, smokers with high cholesterol have a much greater risk for developing CHD. Those who stop smoking lower their risk for CHD by 50%-70 % within 1-5 years. These conclusions are based on a review of published literature.

* UK Small Aneurysm Trial Participants: Smoking, lung function, and the prognosis of abdominal aortic aneurysm. Eur J Vasc Endovasc Surg 2000; 19:636-642.

The abdominal aortic aneurysm rupture rate is nearly four times higher for smokers than for nonsmokers (1.9% and 0.5%, respectively). Smokers also have poorer long-term survival rates. Findings are based on a study of 1,090 male and female patients with a mean age of 69.3 years, mean follow-up of 4.6 years, and principal outcome measures of all-cause mortality and aneurysm rupture.

* Olin JW: Thromboangiitis obliterans (Buerger's Disease). N Engl J Med 2000; 343:864.869.

Although its cause is unknown, there is an association between Buerger's disease and tobacco use, with typical onset in male smokers 40-45 years of age. This is a review of selected literature on Buerger's disease, which is a nonatherosclerotic segmental inflammatory disease affecting small- and medium-sized arteries, veins, and nerves of the arms and legs. Research indicates an increasing prevalence (11%-23%) of thromboangiitis obliterans in women, although the prevalence in Japanese and other Asian women remains low despite increased smoking. One study involved 112 patients evaluated and treated at the Cleveland Clinic Foundation from 1970-1987.

* Shigematsu H, Shigematsu K: Factors affecting the long-term outcome of Buerger's disease (thromboangiitis obliterans). International Angiology 1999; 18:58-64.

Most studies find smoking cessation the key factor in the prevention of amputation with Buerger's disease patients. Data suggests that the natural history of the limbs in this disease is not as discouraging if anti-platelet agents or vasodilators are given and smoking is stopped. Results are based on a study of 682 patients with Buerger's disease treated from 1965 to 1980 in Tokyo, with follow-up 15 years after date of onset. Ages ranged from 17 to 60, and 92.7% were male, 7.3% female.

Further Reading

1. Wang XL, Mahaney MC: Genotype-specific effects of smoking on risk of CHD. Lancet 2001; 358:115-119

2. Feron VJ, Arts JH, Kuper CF, et al: Health risks associated with inhaled nasal toxicants. Crit Rev Toxicol 2001; 31:313-347

3. Zhu BQ Parmley WW: Hemodynamic and vascular effects of active and passive smoking. Am Heart J 1995; 130:1270-1275

4. Cross CE, Traber M, Eiserich J, et al: Micronutrient antioxidants and smoking. Br Med Bull 1999; 55:691-704

5. Nilsson 5, Carstensen JM, Pershagen G: Mortality among male and female smokers in Sweden: a 33-year follow-up. J Epidemiol Community Health 2001; 55:825-830

6. Bottcher M, Falk E: Pathology of the coronary arteries in smokers and nonsmokers. J Cardiovasc Risk 1999; 6:299-302

7. Havranek EP: Primary prevention of CHD: nine ways to reduce risk. Am Fam Physician 1999; 59:1455-1463, 1466

8. Milionis HJ, Rizos E, Mikhailidis DP: Smoking diminishes the beneficial effect of statins: observations from the landmark trials. Angiology 2001; 52:575-587

CIGAR SMOKING

* Shapiro J, Jacobs E, Thun M: Cigar smoking in men and risk of death from tobacco-related cancers. J Natl Cancer Inst 2000; 920:333-337.

Cigar smoke goes from debonair to deadly. Between 1993 and 1998 cigar consumption has increased by approximately 50% in the U.S. This increase is striking and deadly. Researchers have found that there is a strong correlation between cigar smoking and mortality from cancers of the esophagus, pharynx, larynx, lung and oral cavity. Findings indicate that these risks are independent from the use of other tobacco and alcohol products. Of the 137,243 men included in the final analysis, there was found an increased risk of death by lung cancer (RR = 5.1; 95% confidence interval [CI], = 4.0-6.6), oral cavity/pharynx (RR = 4.0; 95% CI = 1.5-10.3), larynx (RR = 10.3; 95% CI 2.6-41.0), and esophagus (RR = 1.8; 95% CI = 0.9-3.7). The data indicated an increased risk of pancreas and bladder cancers for those who inhaled the cigar smoke. Study data was extrapolated using information from the American Cancer Society's Cancer Prevention Study II cohort.

* Iribarren C, Tekawa IS, Sidney S, et al: Effect of cigar smoking on the risk of cardiovascular disease, chronic obstructive pulmonary disease, and cancer in men. N Engl J Med 1999; 340:1773-1780.

Cigar smokers had a higher risk of coronary heart disease (RR = 1.27; 95% CI, 1.12-1.45) and chronic obstructive pulmonary disease (RR = 1.45; 95% CI, 1.10-1.91), had twice the risk of cancer of the upper aerodigestive tract (RR = 2.02; 95% CI, 1.01-4.06), or lung (RR = 2.14; 95% CI, 1.12-4.11), and about 1 1/2 times the risk of all smoking-related cancers considered together as compared with nonsmokers. There is evidence of a dose-response effect. There seems to be a synergistic correlation between alcohol consumption ([greater than or equal to]3 drinks/day) and cigar smoking with respect to oropharyngeal cancer and upper aerodigestive tract cancers. These results are based on a cohort study of 17,774 men, ages 30-85, enrolled in the Kaiser Permanente health plan who never smoked cigarettes and did not currently smoke a pipe. Of these, 1,546 reported currently smoking cigars and the rest, 16,228, reported not currently smoking cigars.

DIABETES MELLITUS

* Wannamethee SG, Shaper AG, Perry IJ: Smoking as a modifiable risk factor for type 2 diabetes in middle-aged men. Diabetes Care 2001; 24:1590-1595.

Risk of diabetes decreases after 5 years of smoking cessation and reverts to that of nonsmokers after 20 years. Although smoking cessation is associated with weight gain, long-term benefits outweigh the risks for diabetes. Switching from cigarettes to pipes or cigars does not lower diabetes risk. Results are based on a 16-year study of 7,735 men, aged 40-59 years, from 24 towns in England, Wales, and Scotland.

* Uchimoto S, Tsumura K, Hayashit T, et al: Impact of cigarette smoking on the incidence of type 2 diabetes mellitus in middle-aged Japanese men: the Osaka Health Survey. Diabetic Medicine 1999; 16:951-955.

The more cigarettes smoked, the higher the risk for type 2 diabetes mellitus; smokers are about 1 1/2 times more likely to develop the disease than nonsmokers. The increased relative risk of 1.47 (95% CI, 1.14-1.92) was observed after adjustment for many variables including age, body mass index, alcohol consumption, physical activity, and parental history of diabetes. The mechanism of how smoking increases the risk may be related to a decrease in the blood flow in muscles due to nicotine or carbon monoxide, leading to insulin-mediated glucose uptake, or increased counter-regulatory hormone levels causing insulin resistance. Results are from a 1981 study in Osaka, Japan, examining 450 middle-aged men with type 2 diabetes mellitus during a 4- to 16-year observation period.

Further Reading

1. Ritz E, Ogata H, Orth SR: Smoking: a factor promoting onset and progression of diabetic nephropathy. Diabetes Metab 2000; 26(suppl 4):54-63

EAR DISEASES

* Kitchens GG: Relationship of environmental tobacco smoke to otitis media in young children. Laryngoscope 1995; 105(suppl 69):1-13.

Children exposed to environmental tobacco smoke (ETS) are more susceptible to otitis media (OM) requiring tympanostomy tubes. This conclusion is based on a prospective study of 175 children with recurrent OM who required tympanostomy tubes (case group) and 175 demographically similar children (controls). The case group had the most exposure to ETS (35.4% in the case group and 24.8% in the control group, P = .04). No significant difference existed in the clinical course of the children exposed to ETS than those who were not on follow-up.

* Gulya AJ: Environmental tobacco smoke and otitis media. Otolaryngol Head Neck Surg 1994; 111:6-8.

Parental smoking, particularly maternal, increases the risk for otitis in children, and reducing cigarette smoke exposure decreases the severity of asthma. These conclusions were based on a review of data regarding environmental tobacco smoke (ETS) and its effect on the ears and eustachian tube. In one study of 96 children with bilateral myringotomy and tympanostomy tube insertion, exposure to two or more household smokers increased the risk for persistent middle ear effusion nearly threefold; with exposure to smoke from more than three packs per day, the risk increased fourfold. While other studies cite similar results, some researchers dispute the relationship between ETS and serious otitis media or acute otitis media.

* Blakley BW, Blakley JE: Smoking and middle ear disease: are they related? a review article. Otolaryngol Head Neck Surg 1995; 112:441-446.

The authors question whether the literature supports the claim that secondhand smoke causes ear diseases, especially in children. They cite errors in studies such as design flaws including inaccurate data analysis, unusual statistical techniques, and no control group identification. The factor most consistently associated with middle ear disease in children was daycare attendance. The authors suggest that exposure to smoke irritants would be greater and a higher risk to the smoker than to the nonsmoker, and they found no literature suggesting that smoking causes middle ear disease in actual smokers.

ERECTILE DYSFUNCTION

* McVary KT, Carrier 5, Wessells H: Smoking and erectile dysfunction: evidence-based analysis. J Urol 2001; 166:1624-1632.

Cigarette smoking may double the risk of moderate-to-complete erectile dysfunction (ED) and enhances the association between ED and coronary artery disease/atherosclerosis. The adverse effect that smoking has on ED may be due to impairment of endothehum dependent smooth muscle relaxation. Smoking cessation possibly reduces the risk of ED. These conclusions are based on a review of the literature.

* Tengs TO, Osgood ND: The link between smoking and impotence: two decades of evidence. Prey Med 2001; 32:447-452.

Risks of heart disease and cancer are not as disturbing to smokers as they once were, and impotence is the new weapon in the war on tobacco use. Advertisements which feature impotence as a risk for smokers are grounded in scientific facts. In 84% of studies conducted over two decades, smoking rate among impotent men in the U.S., ages 17-85, was 12.4% greater than that of the general male population. Smoking is thought to be an independent risk factor for erectile dysfunction and may also contribute to other forms of impotence. These results are collected from 19 studies involving 3,819 impotent men.

* Ledda A: Cigarette smoking, hypertension and erectile dysfunction. Curr Med Res Opin 2000; 16(suppl 1):S13-S16.

The risk of erectile dysfunction is increased in cigarette smokers if other risk factors exist, such as hypertension, diabetes, dyslipidaemia, or aging. Smoking causes impaired penile flow and interferes with intracavernous papaverine and prostaglandin El effectiveness. Smoking cessation is important for the prevention of atherosclerosis and is the first treatment step in reversing erectile dysfunction.

* McVary KT, Carrier 5, Wessels H, et al: Smoking and erectile dysfunction: evidence-based analysis. J Urol 2001; 166:1624-1632.

Strong indirect evidence suggests that an association exists between smoking and erectile dysfunction due to endothelium dependent smooth muscle relaxation. The risk for erectile dysfunction increases when associated with other risk factors such as coronary artery disease and hypertension. Smokers are two times more likely than nonsmokers to have moderate or complete erectile dysfunction. Smoking cessation decreases the risk of erectile dysfunction. These conclusions are based on an evidence-based analysis of the literature.

EYE DISEASES

* Cheng AC, Pang CP, Leung AT: The association between cigarette smoking and ocular diseases. Hong Kong Med J 2000; 6:195-202.

Smoking is linked to ocular damage and permanent blindness. Current literature indicates smoking causes morphological and functional changes to the ocular lens and retina. Studies show more smokers than nonsmokers develop a number of common eye diseases which include age-related macular degeneration (ARMD), cataract, glaucoma and Graves' ophthalmopathy.

ARMD risk with visual loss was lowered to 1.76 (95% CI, 1.23-2.53) for heavy smokers who had quit in the past 20 years. The duration of heavy smoking (40%; P = .07) still carried a significant risk for ARMD with visual loss in smokers who had quit over 20 years before the study (OR = 1.40; 95% CI, 0.972.03). Cigarette smoking risk association with ARMD is dose-related.

* A careful review of the current literature indicates that ARMD cigarette related risks are estimated at 2.4 (95% CI, 1.44.0) for female heavy smokers when compared to same sex never-smokers.

* There is a two-fold increased risk for women who have quit smoking (RR = 2.0; 95% CI, 1.2-3.4). Men are statistically more at risk (OR= 2.6; 95% CI, 1.155.75) than women (OR = 0.84; 95% CI, 0.48-1.47) indicating a sex difference.

There are conflicting reports on the effects of smoking in regard to the non-exudative form of ARMD. For example, the Blue Mountains Eye Study from Australia, which included 3,654 subjects, indicated a marked increase of ARMD among current smokers in comparison to never-smokers (OR = 4.46; 95% CI, 2.20-9.30). In contrast, the Rotterdam Study (n = 36) conducted in the Netherlands indicates no correlation between cigarette smoking and non-exudative ARMD.

Several mechanisms come into play in regard to the causal relationship between ARMD and cigarette smoking.

1. Subretinal vessels leading to the manifestation of a tubular capillary network from choriocapillaries may be promoted by smoking with disciform macular degeneration as the end result.

2. Cigarette smoking may cause atherosclerotic and hypoxic injury to the choroidal disposition of blood vessels in the eye. HDL-cholesterol plasma levels decrease with smoking. In contrast, total cholesterol, LDL cholesterol, fibrinogen levels and platelet adhesiveness increase. This in turn promotes hypoxia, microinfarction and ischaemia in the macula. Greater levels of carboxyhaemoglobin decrease choroidal blood flow. As a result, neovascular growth is stimulated and degenerative changes are accelerated in the macula.

3. Oxidative stress in the retina is increased by oxidants in tobacco smoke and/or generated by the activation of phagocytic cells. Peroxidation of polyunsaturated fatty acids is enhanced by the increased oxidative stress, a precursor to AIRMD.

4. Plasma concentrations of antioxidants are reduced thereby lowering the antioxidant level in the retina. A reduced level of carotenoid concentrations in the blood and retina is directly related to cigarette smoking. The adverse effects of smoking negatively impact the accommodation of oxidative stress and the body's ability to maintain retinal structures against free radicals produced during light exposure. There remains overwhelming evidence that smoking is an independent risk for ARMD (especially the exudative form).

Cataract

Worldwide, cataract is the leading cause of blindness. Half of the 23 million people who have a corrected visual acuity of 3/60 or less have lost their vision as a result of cataract. Several case controlled, prospective and cross-sectional studies confirm the epidemiological relationship between smoking and cataracts. The development of nuclear cataract is directly related to the cumulative amount of cigarettes smoked, signifying a dose-response relationship.

* A 30-year prospective study has shown that heavy smokers (those who smoke more than 20 cigarettes per day) have a substantially higher risk of developing nuclear opacity than nonsmokers (OR = 2.84; 95% CI, 1.46-5.51). Among smokers who have quit 10 or more years ago, the risk for nuclear opacity decreases (OR = 0.67; 95% CI, 0.49-0.92). Pipe smoking is more strongly associated with nuclear cataract (OR =3.1; 95% CI, 1.58.2) than cigarette smoking (OR = 1.5; 95% CI, 1.1-2.1).

* Excess smoke may cause harm to the lens either by continually raising the temperature of the lens or by direct entry of the combustion and condensation products of tobacco into the eyes. Smoking reduces the levels of nutrients with antioxidative capabilities in the eye thus indirectly imposing additional oxidative stress on the lens.

* By-products of cigarettes, such as cadmium or isocyanate, may cause direct and structural injury to the lens. Lens damage by in vivo exposure to cigarette smoke has been substantiated by direct evidence from these studies.

Glaucoma

Smoking is associated with an elevation in intraocular pressure according to a population based study involving 3,752 non-glaucoma subjects aged 40 to 84 (P < .05). Research indicates that cigarette smoke may be a secondary causative factor in open-angle glaucoma. Risks for developing glaucoma may be related to the effects of environmental tobacco smoke (ETS) on the optic nerve. There is a strong correlation between cigarette smoke and increased intraocular pressure. A recent physiological study of the dynamics of aqueous humour revealed that intraocular pressure rises by 5 mm Hg immediately after smoking. The outflow tract is impeded by a rise in the episcleral venous pressure due to selective vasoconstriction. Conflicting data exist among studies on the correlation of smoking and the risk of developing glaucoma. One population-based study showed no relationship between the two. In contrast, a recent case control study indicated that cigarette smokers are more likely to develop glaucoma than never-smokers ( OR= 2.9; 95% CI, 1.3-6.6).

Graves' Ophthalmapathy

A review of the current literature indicates that Graves' ophthalmopathy occurs more frequently in smokers than in nonsmokers. The risk for Graves' ophthalmopathy with hyperthyroidism is greatly increased by smoking cigarettes according to a case control study involving 400 subjects (odds ratio [OR] = 6.5; 95% confidence interval [CI], 3.8-11.2). Thyroid-stimulating hormone levels are slightly lower and thyroglobulin levels are elevated in chronic smokers. Additionally, people who smoke have a higher occurrence of goiters than never-smokers. Overall, smoking significantly increases the risk of developing Graves' ophthalmopathy and negatively affects the response to treatment. It is recommended that patients--particularly those at risk--give up smoking. A causal relationship between smoking and several common eye diseases exists including age-related macular degeneration, cataract, glaucoma, and Graves' ophthalmopathy. There are conflicting evidence and inconclusive results from different studies in relation to the risk of developing an ocular disease due to smoking. For instance, interactive susceptibility factors, both environmental and oenetic, may have exaggerated or suppressed the adverse effects of smoking. Inconclusive findings resulting from small sample sizes in some studies have led to insignificant statistics. The temporal relationship is hard to see due to the extensive use in assessing smoking as a risk factor and the nature of cross-sectional and case control studies. Due to selection bias, recalling subjects especially in cohort studies remains a problem to be addressed. Considering the overwhelming evidence that links smoking to ocular diseases, it is wise advice to cease smoking and avoid passive smoke. Data were extrapolated from a Medline search of literature from 1966 to 1999.

Age-related Macular Degeneration

* A study involving 421 patients, 56 years of age and older, who were diagnosed with neovascular age-related macular degeneration (ARMD), and an age- and sexmatched control group of 615 patients, showed overwhelming evidence that smokers are at a greater risk of developing exudative ARMD than nonsmokers. Smokers (risk ratio [RR] = 2.2; 95% CI, 1.4-3.5) and past smokers (RR = 1.5; 95% CI, 1.2-2.1) had a statistically higher risk for ARMD than never-smokers.

A study was done of 21,157 U.S. male physicians. Researchers found that heavy current smokers (more than 20 cigarettes a day) had a two- to three-fold increased risk for ARMD accompanied with visual loss when compared to never-smokers.

GASTROINTESTINAL SYSTEM

* Ashley MJ: Smoking and diseases of the gastrointestinal system: an epidemiological review with special reference to sex differences. Can J Gastroenterol 1997; 11:345-352.

Risk of death from peptic ulcer disease is increased by cigarette smoking. The risk of recurrence is also augmented in subjects who smoke. Peptic ulcers heal more slowly in patients who smoke than in nonsmokers. Studies indicate women confront a particular risk for Crohn's disease (CD) that may be linked with oral contraceptives. When men and women were compared, women showed a greater affinity for this disease. The clinical course of CD was negatively affected both in men and women smokers, but more so in women. Cigarette consumption is not a risk factor for cirrhosis of the liver. More studies are needed to assess the risk of smoking while controlling for alcohol consumption.

* Thomas GA, Rhodes J, Green JT, et al: Role of smoking in inflammatory bowel disease: implications for therapy. Postgrad Med J 2000; 76:273-279.

Because of its opposite effects on Crohn's disease and ulcerative colitis, there is some confusion about the relationship of smoking and inflammatory bowel disease. One study found that current smokers have twice the risk of nonsmokers for Crohn's disease (95% CI, 1.65-2.47), but the relative risks of colitis in ex-smokers, nonsmokers, and smokers were 2.5, 1.0, and 0.6 respectively, with the highest risk (4.4) for ex-smokers who had smoked <11 cigarettes per day. Although there are conflicting results in the literature, a study of 51 patients with ulcerative colitis revealed that males who continued to smoke had fewer bowel complaints than nonsmokers. Among 17,032 women in another study, colitis sufferers were primarily nonsmokers. However, 70% of 138 patients in another study developed colitis within one year after they stopped smoking. Nicotine may be of some advantage in ulcerative colitis, but further research is needed to confirm its role.

Further Reading

1. Ahlgren JD: Epidemiology and risk factors in pancreatic cancer. Semin Oncol 1996; 23:241-250

2. Sercombe J: Inflammatory bowel disease and smoking. Prof Nurse 2000; 15:439-442

3. Thomas GA, Rhodes J, Green JT: Inflammatory bowel disease and smoking: a review. Am J Gastroenterol 1998; 93:144-149

4. Pandolfino JE, Kahrilas PJ: Smoking and gastro-oesophageal reflux disease. Eur J Gastroenterol Hepatol 2000; 12:837-842

5. Logan RFA, Skelly MM: Smoking and hepato-biliary disease. Eur J Gastroenterol Hepatol 2000; 12:863-867

6. Rubin DT, Hanauer SB: Smoking and inflammatory bowel disease. Eur J Gastroenterol Hepatol 2000; 12:855-862

7. Chowdhury P, Rayford PL: Smoking and pancreatic disorders. Eur J Gastroenterol Hepatol 2000; 12:869-877

8. Parasher G, Eastwood GL: Smoking and peptic ulcer in the Helicobacler pylori era. Eur J Gastroenterol Hepatol 2000; 12:843-853

9. Karlinger K, Gyorke T, Mako E, et al: The epidemiology and the pathogenesis of inflammatory bowel disease. Eur J Radiol 2000; 35:154-167

10. Birtwistle J: The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis. Postgrad Med J 1996; 72:714-718

IMPACT/HEALTH CARE COSTS

* Halpern MT, Shikiar R, Rentz AM, et al: Impact of smoking status on workplace absenteeism and productivity. Tob Control 2001; 10:233-238.

Productivity in the workplace increased and absenteeism decreased among former smokers compared to current smokers. The mean percentage increase in objective productivity measures for former smokers was 4.5% compared to current smokers. Objective productivity measures decreased the first year compared to current smokers but then exceeded the values of current smokers by 1-4 years. These findings are based on a prospective cohort study of 300 U.S. airline employees, 100 each of former, current and never-smokers.

* Leistikow BN, Martin DC, Milano CE: Fire injuries, disasters, and costs from cigarettes and cigarette lights: a global overview. Prey Med 2000; 31:91-99.

Cigarette smoking tops out as leading cause of total fire deaths in eight countries. Denmark, Holland, Hungary, Israel, Japan, New Zealand, United Kingdom and the United States all claim cigarette smoking and lights (lighter and match ignitions) are the cause of residential fire deaths in their respective countries. U.S. statistics indicate that cigarette materials are the perpetrator in an estimated 30% of all fire deaths. Subsequently, this takes a toll on the American public at an estimated $110 billion per year in damages. Worldwide, there are 200,000 cigarettes lit every second, each of which must be extinguished to avoid fires. In 1995, cigarettes, cigars, and pipes caused 3,789 injuries, 1,122 civilian deaths, and $500 million in property damage. Cigarettes are believed to be the cause in 27,000 residence, 8,000 other building, 8,000 vehicle, and 110,000 outdoor reported fires in the U.S. Tragically, children who play with smoking material will start an estimated one million fires globally this year. I nternational anti-smoking educational and legislative platforms are needed to combat the burdens of cigarette fire related injury, death and property damage. Results are based on smoking-related fire and disaster tolls from documents published primarily between 1984 and 2000 in the U.S. and extrapolated globally.

* Leistikow BN: The human and financial costs of smoking. Clin Chest Med 2000; 21:189-197, x-xi.

Health costs of smoking in the U.S. total more than $100 billion per year directly and indirectly. In this article, the author addresses costs of smoking by category, such as individual, societal, medical, and family costs. Studies from 1978 to 1999 suggest that approximately 8% of U.S. health care costs are attributable to smoking. Smoking may reduce average wages by 4%-8%. Smoking caused more than 140,000 fires in 1995 with 2,600 injuries and 1,000 deaths. Intangible medical costs of lung cancer were estimated at $39.2 billion in 1995, 84% of which was attributed to smoking.

* Nair AK, Brandt EN Jr: Effects of smoking on health care costs. J Okla State Med Assoc 2000; 93:245-250.

Smokers pay premium price for a bad habit. In 1993, health care costs for all smokers in the U.S. were estimated at $50 billion. These expenditures include hospital, physician, nursing home, home health care and prescription drugs. Estimated health care fees rose sharply to $205 billion in 1985. When compared to never-smokers, the average health care expenditure over a lifetime for smokers is 32% higher for males ($35,914 versus $27,276) and 24% for females ($52,902 versus $42,783). Among heavy smokers health care expenditures escalated: 47% higher for males and 41% for females. Intensive educational programs and legislation are needed to prevent the initiation of smoking, encourage cessation of smoking, and protect nonsmokers.

MISCELLANEOUS

* Giovino GA, Henningfield JE, Tomar SL, et al: Epidemiology of tobacco use and dependence. Epidemiol Rev 1995; 17:48-65.

Highest smoking rates are found among individuals who live in poverty, are blue-collar workers, are separated or divorced, and are on active military duty. Only 3% of U.S. physicians are smokers. This summary of the epidemiology of tobacco use in the U.S. primarily focuses on cigarettes and cigarette smoking, although chewing tobacco, snuff, cigars, and pipes are also discussed. The rate of smoking among U.S. males peaked at 67% in the 1940s and 1950s; smoking prevalence in U.S. females was at its highest in the 1960s at 44%. Cessation increased 26% from 1965 to 1993 at about the same rate for men as for women and in all educational categories. By 1993 the 42% rate of U.S. adult smokers in 1965 had fallen to 25%. Most smokers begin the habit before the age of 18.

* Bang KM, Kim JH: Prevalence of cigarette smoking by occupation and industry in the United States. Am J Ind Med 2001; 40:233-239.

Blue-collar laborers outsmoke American workforce. Researchers declare white-collar workers take a back seat when it comes to cigarette smoking prevalence by occupation in the U.S. In 1994, 24.2% of white-collar workers smoked as opposed to 39.2% of blue-collar workers. Current literature indicates that smoking among blue-collar laborers has declined over the past few years from 43.7% between 1978-1980 to 39.2% during 1987-1990. According to the U.S. Department of Health and Human Services, this figure still remains high for the blue-collar worker. From a pool of 40 occupational groups and 44 industry groups during the 1988-1994 period, cigarette smoking prevalence was assessed to be 28.3% (95% CI, 26.9-29.8) overall. Men smokers topped the ladies at 31.7% (95% CI, 29.9-33.5) to 25.1% (95% CI, 23.5-26.7), respectively. Of those in varying occupations and industries, material moving occupations came in first at 45.9% (95% CI, 35.7-56.1). Construction workers were second at 41.9% (95% CI, 31.5-52.3). Vehicle mec hanics and repairers were not far behind at 41.7% (95% CI, 31.3-52.1). Teachers and sales representatives had the lowest prevalence of smoking, 12.2% (95% CI, 8.5-15.9), 18.5% (95% CI, 13.6-23.4), respectively. This study was conducted by using data obtained from the third National Health and Nutrition Examination Survey (NHANES III).

* Schrand JR: Is sleep apnea a predisposing factor for tobacco use? Med Hypotheses 1996; 47:443-448.

Sleep apnea, the periodic lapses in breathing during sleep, may complicate illnesses related to tobacco use and passive smoking. Nicotine reduces somnolence and obesity, the main symptoms of sleep apnea. Since the natural response of the human body is to continue that which improves life, an addiction for nicotine is the result. Understanding and adequately treating sleep apnea may be a prerequisite for the success of smoking cessation and smoking prevention programs.

* Straten M, Carrasco D, Paterson M, et al: Tobacco use and skin disease. South Med J 2001; 94:621-634.

Physicians may find it helpful to use the argument that smoking affects attractiveness and will cause those who use tobacco to appear older than their chronological age when counseling patients not to smoke. A study of recent literature indicates a number of skin disorders and diseases are directly and indirectly related to tobacco use. Dermatologic effects include facial wrinkling, facial gauntness, complexion color changes, decreased skin moisture, yellowed nails, harlequin nails, halitosis, nicotine stomatitis, and skin burns. Some indirect effects of smoking are poor wound healing, psoriasis, atherosclerotic peripheral vascular disease, Buerger's disease, Raynaud's disease, diabetic foot disease, oral yeast infections, Condyloma acuminatum, cutaneous findings in HTV and AIDS, Crohn's disease and malignancies.

* Rodrigo C: The effects of cigarette smoking on anesthesia. Anesth Prog 2000; 47:143-150.

The over 4,000 substances in cigarette smoke can cause a multitude of problems during and after surgery. Nicotine increases blood pressure, heart rate, and systemic vascular resistance, which leads to a decrease in the coronary blood flow. Higher levels of carbon monoxide (6%) have caused ventricular arrhythmias during anesthesia. Other components interfere with oxygen uptake, transport, and delivery. The risk of perioperative events occurring during anesthesia was 1.8 times that of nonsmokers. Postoperative pulmonary complications are 4 times more likely to occur in smokers than in nonsmokers. Those who stopped smoking less than 8 weeks compared with more than 8 weeks before surgery had a 4 times higher incidence of postoperative pulmonary complications. Patients should be encouraged to stop smoking at least 8 weeks before surgery to reduce the risk of complications, eliminate carbon dioxide and nicotine, and improve immune functions.

* Krueger JK, Rohrich RJ: Clearing the smoke: the scientific rationale for tobacco abstention with plastic surgery. Plast Reconstr Surg 2001; 108:1063-1077.

Tobacco smoke interferes with wound healing. Smokers are 12.5 times more likely to develop skin necrosis than nonsmokers and have a 19.5% incidence of superficial necrosis compared with 5% in nonsmokers. The incidence of abdominoplasty flap necrosis was 27.5% in smokers and 5.9% in nonsmokers who had breast reconstruction surgery involving transverse rectus abdominis muscle. The presence of umbilical necrosis in smokers was 27.5% and 11.8% in nonsmokers. Eighty percent of smoking patients with bone grafting and dental implant placement had intraoral wound dehiscence and/or infection, whereas only 10% of nonsmokers had wound complications. Smoking one cigarette can reduce blood flow to the thumb by 24%. This article discusses tobacco smoke effects on wound healing, reviews the data on tobacco use and plastic surgery complications, and recommends treatment options for patients who use tobacco products.

* Hoffmann D, Hoffmann I: The changing cigarette, 1950-1995. J Toxicol Environ Health 1997;50:307-364.

Nicotine is the principal addictive ingredient in tobacco, and since 1954 U.S. cigarette manufacturers have reduced the amounts of tar from 38 mg to 12 mg and nicotine from 2.7 mg to 0.95 mg. However, higher nitrate levels in air-cured (burley) tobacco, which is used in the U.S., enhances tobacco combustion. The increased nitrogen oxides result in more tobacco-specific N-nitrosamines in the smoke and are of special cancer-causing significance. Cigarette smoking is associated with increased health risks, including chronic obstructive lung disease and myeloid leukemia, as well as cancer of the lung and upper aerodigestive system, pancreas, renal pelvis, urinary bladder, liver, uterine cervix, and nasal cavity. There is a problem in that smoke component measurements are based on standards of 1 puff per minute over a 2-second period with a volume of 35 mL. These parameters are not realistic today, especially for smokers of cigarettes with low nicotine yield who puff 2-4 times per minute with volumes up to 55 mL. Nicotine content should be reduced so that it does not create a dependence on tobacco.

Further Reading

1. Sherman CB: Health effects of cigarette smoking. Clin Chest Med 1991;12:643-658

2. Doll R: Cancers weakly related to smoking. Br Med Bull 1996;52:35-49

MUSCULOSKELETAL SYSTEM

* Leino-Arjas P: Smoking and musculoskeletal disorders in the metal industry: a prospective study. Occup Environ Med 1998; 55:828-833.

A strong association exists between pack-years of smoking and musculoskeletal symptoms over a 10-year period. A dose-response association exists where, compared to never-smokers, [greater than or equal to]1 pack/day smokers show a higher risk of musculoskeletal symptoms (odds ratio, 2.1) whereas those smoking <1 pack/day show no increased risk. These findings are based on a 10-year longitudinal study of 604 employees of a manufacturing plant.

* Albano SA, Santana-Sahagun E, Weisman MH: Cigarette smoking and rheumatoid arthritis. Semin Arthritis Rheum 2001;31:146-159.

The discovery of p53, a suppressor gene that regulates cell growth, in cigarette smokers and patients with cancers and rheumatoid arthritis (RA) may be an important step in understanding the link between environmental factors and chronic illness. Smoking cigarettes increases the risk for onset and severity of RA, especially in seropositive men. The downward trend in tobacco use worldwide has resulted in decreased extra-articular symptoms of RA and overall improved mortality. This is a review of the medical literature from 1985 to 2001.

Further Reading

1. Eriksen W, Natvig B, Bruusgaard D: Smoking, heavy physical work and low back pain: a four-year prospective study. Occup Med 1999;49:155-160 [Please see Back Pain]

2. Feldman DE, Rossignol M, Shrier I, et al: Smoking: a risk factor for development of low back pain in adolescents. Spine 1999; 24:2492-2496 [Please see Back Pain]

3. Spangler JG, Quandt S, Bell RA: Smokeless tobacco and osteoporosis: a new relationship? Med Hypotheses 2001;56:553-557

4. Porter SE, Hanley EN Jr: The musculoskeletal effects of smoking. J Am Acad Orthop Surg 2001;9:9-17

5. Hadley MN, Reddy Sv: Smoking and the human vertebral column: a review of the impact of cigarette use on vertebral bone metabolism and spinal fusion. Neurosurgery 1997;41:116-124

NEUROLOGICAL SYSTEM

* Hankey GJ: Smoking and risk of stroke. J Cardiovasc Risk 1999;6:207-211.

Cigarette smoking causes one-fourth of all strokes and independently triples the relative risk equally in men and women. Middle age is the time when smokers are most likely to have a stroke, and the risk factor decreases with age. Relative risk among smokers declines as follows: ages <55, 2.9 (95% CI, 2.4 - 3.6); ages 55-74, 1.8 (95% CI, 1.6-2.0); age [greater than or equal to]75, 1.1 (95% CI, 0.96-1.28). Smokers' relative risk of ischemic stroke declines similarly from 3.6 at age 55 to no effect at age 90 (95% CI). There is a direct correlation between relative risk of stroke and the number of cigarettes smoked, ie, doubling the number of cigarettes smoked per day from 10 to 20 increases the relative risk of stroke from 2.5 to 4. Overall, smokers are at risk for stroke 1.5 to 4 times more than nonsmokers. For those who smoke more than 20 cigarettes a day, the risk of subarachnoid hemorrhage is 8.3 when compared with nonsmokers and the risk of cerebral infarction or intracerebral hemorrhage is 3.5. Smoking p ipes or cigars doubles the risk, and switching from cigarettes to pipe or cigar smoking lowers the risk to 2-3 times that of nonsmokers. The combination of smoking cigarettes and pipes or cigars increases stroke risk to 6 times that of nonsmokers. Environmental tobacco smoke or passive smoking caused a 20% increase in the progression of atherosclerosis in a study of 10,914 middle-aged adults over a 3-year period. Earlier studies indicated a 50% increase in the progression of the disease among smokers, with 25% increase for past smokers.

* Tegos T, Kalodiki E, Daskalopoulou S, et al: Stroke: epidemiology, clinical picture, and risk factors. Part I of III. Angiology 2000; 51:793-808.

Stroke risk is increased for smokers. A recent meta-analysis of 32 studies indicated that the relative risk of stroke for current smokers is 1.5 times greater for smokers than never-smokers. There is a dose-response association between cigarette consumption and the risk of stroke. In the U.S. white male population, it is estimated that there are approximately 16,000 strokes per year solely attributable to cigarette smoking. Since smoking is a modifiable risk for all types of stroke, physicians should inform their patients of this imminent threat associated with smoking.

* Sacco RL, Wolf PA, Gorelick PB: Risk factors and their management for stroke prevention: outlook for 1999 and beyond. Neurology 1999; 53(suppl 4) :S15-S24.

Stroke is the third leading cause of death in the United States and smoking increases risk of stroke about 50%. In this review of the published literature, the authors examine risk factors for stroke, including smoking, hypertension, physical inactivity, and diabetes. Some populations have a higher stroke risk that is directly linked to smoking prevalence, such as in East Germany where the increase in stroke rate parallels an increase in cigarette smoking. African-Americans, who have a higher rate of smoking, are at twice the risk for having a stroke or dying from stroke than are white Americans. Stroke frequency doubles with each decade for those >55. Within 2-4 years after cessation, stroke rates decrease to that of never-smokers for men and women of all ages. If all smokers in the U.S. stop smoking, about 350,000 strokes (50%) may be prevented each year.

* Fratiglioni L, Wang HX: Smoking and Parkinson's and Alzheimer's disease: review of the epidemiological studies. Behav Brain Res 2000; 113:117-120.

A review of the published literature confirms that cigarette smokers are about 50% less likely to develop Parkinson's disease than age and gender matched nonsmokers and that smoking has a protective, as yet not fully determined, effect in Parkinson's disease. Although cigarette smoking is also associated with a reduced risk of developing Alzheimer's disease, this association is controversial, as it may be affected by a number of biases such as survival and the known association between smoking and dementia.

* Waters AJ, Sutton SR: Direct and indirect effects of nicotine/smoking on cognition in humans. Addict Behav 2000; 25:29-43.

Are the cognitive effects of nicotine direct effects, or are they mediated by nicotine's effects on mood and arousal? Nicotine has a direct effect on cognition if a certain dose increases cognition but shows no change on mood and arousal. Nicotine has similar effects on smokers and nonsmokers but very different effects on mood and arousal. Further research is required to fully address this question. These findings are based on a review of the literature.

* Kassel JD: Smoking and attention: a review and reformulation of the stimulus-filter hypothesis. Clin Psychol Rev 1997; 17:451-478.

Nicotine does enhance sustained, divided, and focused attention, but the stimulus-filter model does not explain this finding. An attention, allocation model of nicotine reinforcement explains that nicotine heightens attention due to its tendency to cause attentional narrowing and increase perceptual processing capacity. These conclusions are based on a review of the literature.

* Roy K, Parker G, Mitchell P, et al: Depression and smoking: examining correlates in a subset of depressed patients. Aust N ZJ Psychiatry 2001; 35:329-335.

Cigarette smoking and depression are not causally related; rather, they are linked by shared early deprivational variables. Compared with nonsmokers, smokers were more likely to have negative childhood experiences, use illicit drugs and alcohol, and attempt suicide. The most significant predictor set, determined through logistic regression, includes dysfunctional personality "domains," physical violence in childhood, long-term anxiolytic use and illicit drug use. These findings are based on a sample of 92 smokers with depression compared to 92 controls of nonsmokers with depression.

* Quattrocki E, Baird A, Yurgelun-Todd D:m Biological aspects of the link between smoking and depression. Harvard Rev Psychiatry 2000; 8:99-110.

The prevalence of smoking is higher among individuals with depression or a psychotic disorder than in the general population. Smoking affects neurotransmitter pathways that regulate mood and cognition. Nicotine, an addictive substance and a psychoactive component of cigarette smoke, binds to nicotinic receptors in the brain causing modulation of neurotransmitters including dopamine, serotonin, norepinephrine, acetyicholine, [gamma]-aminobutyric acid, and glutamate. Another psychoactive property of cigarette smoke is its ability to inhibit monoamine oxidase, an enzyme that breaks down catecholamine neurotransmitters. Replacing the psychoactive chemicals of cigarette smoke with antidepressants that act on similar neurotransmitter pathways may increase smoking cessation rates. Understanding the neurobiological mechanisms underlying the link between smoking and depression may enhance a physician's ability to assist smokers in their efforts to quit.

Further Reading

1. Wolf PA, D'Agostino RB, Kannel WB, et al: cigarette smoking as a risk factor for stroke: The Framingham Study. JAMA 1988; 259:1025-1029

2. Boden-Albala B, Sacco RL: Lifestyle factors and stroke risk: exercise, alcohol, diet, obesity, smoking, drug use, and stress. Curr Atheroscler Rep 2000; 2:160-166

3. Shinton R, Beevers C: Meta-analysis of relation between cigarette smoking and stroke. BMJ 1989; 298:789-794

4. Gorelick PB, Erkinjuntti T, Hofman A, et al: Prevention of vascular dementia. Alzheimer Dis Assoc Disord 1999; 13(suppl 3):S131-S139

5. Benson RT, Sacco RL: Stroke prevention: hypertension, diabetes, tobacco, and lipids. Neurol Clin 2000; 18:309-319

ORAL DISEASES

* Fried JL: Women and tobacco: oral health issues. J Dent Hyg 2000; 74:49-55.

Tobacco use is a key risk factor for periodontal disease, and an association between periodontal infection due to smoking and coronary heart disease is suspected. Tobacco use during pregnancy can result in oral clefting, fluctuating dental asymmetry, and tooth morphologic variants in children. The occurrence of cleft lip increases 25% with maternal smoking. Women who smoke may experience earlier onset of oral changes caused by menopause. Tobacco use raises different health issues for women than for men, and cessation efforts should be gender specific.

Further Reading

1. Johnson GK, Slach NA: Impact of tobacco use on periodontal status. J Dent Educ 2001; 65:313-321

2. Johnson GK: Position paper: tobacco use and the periodontal patient. J Periodontol 1999; 70:1419-1427

3. Winn D: Tobacco use and oral disease. J Dent Educ 2001; 65:306-312

PASSIVE SMOKING

* Fennell A: Secondhand smoke and statistical analysis. CMAJ1999; 160:180.

Many of the "facts" about environmental (secondhand) tobacco smoke may have been exaggerated. Studies with negative correlations, in foreign languages, or with no statistically significant associations are often ignored. In addition, relative risks of less than 2.0 are reported as positive although they are small and difficult to interpret.

* Nelson E: The miseries of passive smoking. Hum Exp Toxicol 2001; 20:61-83.

There is a positive correlation between cardiovascular disease and passive smoking. In 10 nonsmokers who were asked to sit for 20 minutes beside smokers, the plasma nicotine concentration increased from 0 to 2.8 ng/mL, carboxyhemoglobin level went from 0.9% to 1.3%, platelet aggregate ratio decreased from 0.87 to 0.78, and endothelial cell count increased from 2.8 to 3.7 per counting chamber. Nonsmoker exposure is determined by the physical conditions of the environment, lung volume and breathing frequency, age and individual health condition, in addition to the amount of smoke generated. A recent WHO report suggests that unless current smoking trends are reversed, the death rate will increase by 10 million per year by the 2020s. Cancer, allergies, neurotoxicity, cardiovascular effects, genotoxicity, pregnancy, reproduction, and prevention are among the topics addressed in this review of random independent research which demonstrates the toxic effects of passive smoking.

* Lejeune HB, Cote DN: Passive smoking. J La State Med Soc 1995; 147:444-447.

In 698 healthy children monitored from birth to age 2, the amount of environmental tobacco smoke (ETS) exposure (none, <1.5 packs per day, and >1.5 packs per day) increased the time in the second year spent with otitis media with effusion respectively, 26.6%, 31.3%, and 35.4%. In another study involving 892 children, one-third of middle ear effusion cases were statistically attributable to ETS exposure. The author reviews pertinent literature regarding ETS and its association with otologic disease, tonsil and adenoid disease, sore throats, snoring, coughing, and other benign diseases. Adenoidectomy or tonsillectomy-and-adenoidectomy frequencies were 28%, 42%, and 51% in children with two nonsmoking parents, one smoking parent, and two smoking parents, respectively. Similarly, children undergoing a tonsillectomy were almost twice as likely to have at least one parental smoker. In a survey of more than 15,000 children 8-19 years of age, parental smoking was the second most significant factor affecting children 's coughs. Other research indicates a 4.9-fold increase in prevalence of hearing defects in babies exposed to cigarette smoke.

* Glueck CJ, Freiberg PA, Crawford A, et al: Secondhand smoke, hypofibrinolysis, and Legg-Perthes disease. Clin Orthop 1998; 352:159-167.

Cessation of parental smoking may prevent or reduce the risk of osteonecrosis development in children. Cigarette smoking is associated with low tissue plasminogen activator activity (the major stimulator of fibrinolysis) and high tissue plasminogen activator antigen and plasminogen activator inhibitor activity (the major inhibitor of fibrinolysis). Children with Legg-Perthes disease who are chronically exposed to secondhand smoke are more likely (48%) to have low simulated tissue plasminogen activator activity ([s-tPA-Fx [<2.19]3) than are those not exposed (7%, P = .010). Results are based on a study of 39 children with LeggPerthes disease, 15 of whom had no secondhand smoke exposure and 24 of whom had secondhand smoke exposure before diagnosis.

* Lam T, Leung GM, Ho LM: The effects of environmental tobacco smoke on health services utilization in the first eighteen months of life. Pediatrics 2001; 107:E91.

Environmental tobacco smoke (ETS) increases health service use and cost during the first 18 months of life. Odds for inpatient surgeries are 6%-21 % higher in children with respiratory and febrile illness who are exposed to ETS. This may be due to fetal lung development and functioning having been affected by ETS. Data are based on a sample of 8,327 mother-infant pairs in Hong Kong in 1997-1998.

* Ellis R: Smoking out the tobacco connection. CMAJ 1999; 160:180-181.

In this letter to the editor, the author notes that affiliation with the tobacco industry is the major factor in research concluding that passive smoking is not harmful.

* Glantz SA, Parmley WW: Passive smoking and heart disease: mechanisms and risk. JAMA 1995; 273:1047-1053.

Environmental tobacco smoke (ETS) reduces oxygen delivery to the heart and the ability of the myocardium to convert oxygen into adenosine triphosphate resulting in lower exercise capability. Nonsmokers have greater responses to the toxins in ETS smoke than do smokers. After 20 minutes of exposure to secondhand smoke, nonsmokers had platelet activity similar to habitual smokers. Increased amounts of blood platelets increases the likelihood of the formation of a thrombus and of damage to the lining of the coronary arteries which can lead to the development of atherosclerosis. Free radicals in ETS increase tissue damage after ischemia or myocardial infarction. Lastly, passive smoking increases the risk for fatal and nonfatal cardiac events. These conclusions are based on a literature review.

* Valkonen M, Kuusi T: Passive smoking induces atherogenic changes in low-density lipoprotein. Circulation 1998; 97:2012-2016.

Data on the results of passive smoking provides background information about the increased risk of coronary heart disease among passive smokers. Passive smoking results in a one-third decrease in serum ascorbic acid (P < .001), a. significant decrease in serum antioxidant defense (P < .001), a 19% decrease in the resistance of LDL to oxidation (P < .01), and 1.5 times the amount of lipid peroxidation end products in serum (P< .01), and an increase in the uptake of LDL. These results are based on blood samples taken from 10 healthy, nonsmoking subjects aged 23 to 39 years during 2 ordinary working days before and up to 5.5 hours after spending half-anhour in a smoke-free area or in a room for smokers.

* Valkonen MM, Kuusi T: Vitamin C prevents the acute atherogenic effects of passive smoking. Free Radic Biol Med 2000; 28:428436.

Vitamin C, an effective free radical scavenger, reduces the proatherogenic effects of secondhand smoke. Vitamin C supplementation prior to passive smoke exposure prevents the smoke-induced failure in serum antioxidant defense (TRAP, P < .001), the decrease in the resistance of LDL to oxidation (P < .05) and the accelerated formation of serum thiobarbituric acid reactive substances (TBARS, P < .05). These results are based on a study of blood samples taken from 10 healthy, nonsmoking subjects aged 23-48 years during 4 separate days as they were exposed to normal air or cigarette smoke.

* Glatz SA, Parmley WW: Passive smoking and heart disease: epidemiology, physiology, and biochemistry. Circulation 1991; 83:1-12.

Passive smoking is the third leading cause of preventable death in the U.S. following smoking and alcohol. According to recent epidemiological studies, there is a 30% added risk of mortality from myocardial infarction and ischemic heart disease among nonsmokers who cohabit with smokers. Mounting biochemical and physiological data indicate that environmental tobacco smoke (ETS) impairs exposed nonsmokers' exercise capability by stunting the body's oxygen delivery capabilities. Furthermore, there is increasing evidence that passive smoke damages arterial endothelium, which can lead to an increased risk of heart disease. This risk increases incrementally by dose. There are approximately 10 times as many deaths from ETS-induced heart disease as lung cancer. A projected 53,000 people die in one year due to passive smoking. Information for this study was derived from a review of current literature and 10 epidemiological studies.

* Larsson ML, Frisk M, Hallstrom J, et al: Environmental tobacco smoke exposure during childhood is associated with increased prevalence of asthma in adults. Chest 200l; 120:711-717.

Exposure to environmental tobacco smoke (ETS) during childhood was a risk factor for physician-diagnosed asthma during adulthood, with a prevalence of 7.6% in exposed subjects as compared to 5.9% in nonexposed subjects (P = .036). The prevalence of physician-diagnosed asthma among never-smokers with no family history of asthma was 6.8% for subjects exposed to ETS compared with 3.8% for nonexposed subjects (P < .001). These results are based on the study of 8,008 randomly selected people aged 15 to 69 years from a city population.

* Janson C, Chinn S, Jarvis D, et al: Effect of passive smoking on respiratory symptoms, bronchial responsiveness, lung function, and total serum IgE in the European Community Respiratory Health Survey: a cross-sectional study. Lancet 2001; 358:2103-2109.

Eliminating tobacco smoke in the workplace improves respiratory health. In addition to causing nocturnal chest tightness, nocturnal breathlessness, breathlessness after activity, and increased bronchial responsiveness, passive smoking is associated with asthma and all types of respiratory symptoms (odds ratio, 1.90; 95% CI, 0.90 - 2.88). Prevalence of community smoking/passive smoking is closely related to passive smoking in the home. This 1990-1994 study included 7,882 European adults ages 20-48 from 16 countries, and researchers used logistic regression to calculate odds ratio on the effect of environmental tobacco smoke on asthma, respiratory symptoms, and allergic rhinitis. In one-third of centres reporting results, more than half the respondents were exposed to passive tobacco smoke.

* Dezateux C, Stocks J, Wade AM, et al: Airway function at one year: association with premorbid airway function, wheezing, and maternal smoking. Thorax 2001; 56:680-686.

Maternal smoking during the first year of life in an infant causes diminished respiratory function and is a precursor to wheezing in early childhood. Plethysmographic measurements of airway resistance (Raw) and conductance (Gaw) were used to determine airway function in this London health centre study. Children of mothers who smoked had urinary cotinine levels of 157.8 ng/mg creatinine, as opposed to 30.0 in infants of nonsmoking mothers. Specific conductance end expiration was significantly less in infants of mothers who smoked. Results were obtained from a study of 118 healthy, white, term infants in which respiratory function was measured at age 1-3 months and again at age 1 year.

* Adlkofer F: Lung cancer due to passive smoking: a review. Int Arch Occup Environ Health 2001; 74:231-241.

Passive smoking only slightly increases the risk of lung cancer. Small amounts of genotoxic compounds are found in people after exposure to environmental tobacco smoke (ETS), and the average intake of those substances is so low that it is difficult to link them to lung cancer. The differences in ETS and mainstream smoke are discussed. Mainstream smoke, which is inhaled by the smoker, is different to ETS in its physical, chemical, and toxicological makeup and changes with conditions in the air, dilution, and aging. This is a review of the scientific literature.

Further Reading

1. American Academy of Pediatrics Committee on Environmental Health: Environmental tobacco smoke: a hazard to children. Pediatrics 1997; 99:639-642

PREGNANCY

* Wang X, Zuckerman B, Pearson C, et al: Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. JAMA 2002; 287:195-202.

Low-birth-weight (LBW) is recorded in 7.6% of live-born babies in the U.S. and nearly two-thirds of infant mortality is due to LBW. Although maternal smoking increases risk of LBW, not all women who smoke during pregnancy have LBW babies, suggesting that there may be other predisposing factors. In this case control study, smoking during pregnancy resulted in a mean weight reduction of 377 g when genotype was not considered. However, the mean weight reduction in the offspring of women who smoked and had the Aa/aa CYP1A1 genotype was 520 g (SE, 126 g), whereas the mean weight reduction in those with the AA genotype was 252 g (SE, 111 g). Similarly, women with GSTT1 genotype had a mean weight reduction in their offspring of 642 g (SE, 142 g) compared to 285 g (SE, 99 g) in those without this genotype. Data were obtained from a 1998-2000 study of 741 mothers at Boston Medical Center.

* Day NL, Richardson GA, Goldschmidt L, et al: Effects of prenatal tobacco exposure on preschoolers' behavior. J Dev Behav Pediatr 2000; 21:180-188.

Prenatal and postpartum tobacco exposure is directly related to preschool behavioral problems. Using the Toddler Behavior Checklist (TBC) to find a correlation between prenatal/postpartum smoking and the development of behavior problems in preschoolers, researchers found that third trimester maternal smoking was directly associated with an increase of 6 points in the total problem behavior score. Hyperactivity, attention problems, impulsivity and peer problems were associated with both current and prenatal cigarette smoking. Attention problems were only associated with current tobacco smoke exposure. Data was obtained from a longitudinal study using 672 children at the age of 3 years and information obtained from the TBC. The TBC measured the mother's perception of her child at age 3 in the areas of opposition, immaturity, emotional instability, and physical aggression.

* Miller DP, Villa KF, Hogue SL, et al: Birth and first-year costs for mothers and infants attributable to maternal smoking. Nicotine Tob Res 2001; 3:25-35.

Maternal smoking results in rocketing health care costs for mother and infant. A review of published articles and recent metaanalysis indicate maternal smoking is associated with at least 11 infant and maternal conditions. These include low birth weight, upper respiratory infections, lower respiratory infections, abruptio placenta, otitis media, respiratory distress syndrome, sudden infant death syndrome, pre-eclampsia, placenta previa, and premature rupture of membranes. Low birth weight and lower respiratory infections are more common, and abruptio placenta and respiratory distress syndrome are more expensive in regard to health care cost than the other conditions. Most of these additional expenses are to treat the infant (90%). This information was extrapolated from a claims database of 7,784 mothers and 7,901 infants delivered during 1996 and from ICD-9 codes. Researchers sought to find a correlation between maternal smoking and high health care cost during the infant's first year of life.

* Wisborg K, Kesmodel U, Henriksen TB, et al: Exposure to tobacco smoke in utero and the risk of stillbirth and death in the first year of life. Am J Epidemiol 2001; 154:322-327.

Exposure to tobacco smoke increases the risk of stillbirth (odds ratio = 2.0; 95% CI, 1.4-2.9) and infant death (odds ratio = 1.8; 95% CI, 1.3-2.6). Compared to nonsmokers, smokers had about twice the risk of stillbirth and of infant death. Women who stopped smoking in the first trimester reduced the risk for stillbirth and infant death to percentages comparable to nonsmokers. If all pregnant smokers in a population of 30% pregnant smokers stopped smoking by the sixteenth week, approximately 25% of all stillbirths and 20% of all infant deaths could be avoided. These conclusions are based on a cohort of 25,102 pregnant women scheduled for delivery at Aarhus University Hospital in Denmark from September 1989 to August 1996.

* Ernst M, Moolchan ET, Robinson ML: Behavioral and neural consequences of prenatal exposure to nicotine. J Am Acad Child Adolesc Psychiatry 2001; 40:630-641.

There is a dose-response relationship between maternal smoking rates and low birth weight, spontaneous abortion, and impaired cognitive development, as well as increased incidence of attention deficit hyperactivity disorder, conduct disorder, and substance abuse in adolescents and young adults whose mothers smoked during pregnancy. Reduced auditory acuity, decreased motor scores and verbal comprehension, attention deficits, response inhibition, memory, impulsivity, cognitive function, and receptive language ability are also affected by maternal smoking.

* Zenzes MT: Smoking and reproduction: gene damage to human gametes and embryos. Hum Reprod Update 2000; 6:122-131.

Smoke-altered genes transmit codes with serious consequences. Research indicates that smoking alters the DNA in preimplantation embryos. Smoke-related chromosome errors increase the risk of childhood cancer. By-products of smoking were found in ovarian granulosa-lutein cells, spermatozoa, oocytes and preimplantation embryos. Spermatozoa and oocytes are altered by tobacco smoke leading to chromosome errors that affect zygotes.

* Matthews TJ: Smoking during pregnancy in the 1990s. National Vital Statistics Report 2001; 49:1-15.

Women born outside the U.S. are less likely to smoke during pregnancy than those born inside the U.S. (2.3%/14.6%). Maternal smoking declined in the decade of the 1990s. The smoking rate for pregnant women 15-19 years of age decreased between 1990 and 1994, but since 1996 the rate for teenagers has been the highest. In 1999, Chinese and Central/South American women had the lowest smoking rates; American Indian, non-Hispanic white, and Hawaiian women had the highest. Results are based on 1990 data on 75% of all live births, 1994-1998 data on 79%-81% of all births, and 1999 data on 87% of all births. Trend analysis is based on a reporting area of 46 states, Washington, DC, and New York City (California, Indiana, New York, and South Dakota excluded due to changes in reporting areas).

* Fried P, Watkinson B: Visuoperceptual functioning differs in 9-12-year-olds prenatally exposed to cigarettes and marijuana. Neurotoxicol Teratol 2000; 22:11-20.

Visuoperceptual functioning was examined in 9-12 year olds who were exposed to marijuana and cigarettes in utero. There was a negative correlation between prenatal tobacco smoke exposure and a total score showing fundamental visuoperceptual performance. By contrast, the children who were exposed to marijuana prenatally did not show an association with visuoperceptual performance. However, there was a negative association with implementation in visual problem solving situations. This study was part of the Ottawa Prenatal Prospective Study on 146 subjects.

Further Reading

1. Leonard CT, Sachs DP: Environmental tobacco smoke and lung cancer incidence. Curr Opin Pulm Med 1999; 5:189-193

2. Murin S, Bilello KS, Matthay R: Other smoking-affected pulmonary diseases. Olin Chest Med 2000; 21:121-137

RESPIRATORY SYSTEM

* Floreani AA, Rennard SI: The role of cigarette smoke in the pathogenesis of asthma and as a trigger for acute symptoms. Curr Opin Pulm Med 1999; 5:38-46.

Smoking amplifies airway inflammation already present in asthmatics by many mechanisms such as increasing numbers of inflammatory cells, altering cell subtypes, and, in vitro, promoting neurogenic inflammation, increasing oxidative stress, and elevating cysteinyl leukotrienes.

* Langhammer A, Johnsen R, Holmen J, et al: Cigarette smoking gives more respiratory symptoms among women than among men: The Nord-Trondelag Health Study (HUNT). J Epidemiol Community Health 2000; 54:917-922.

Women experience the impact of smoking significantly more than men. A recent cross-sectional population study (questionnaire) conducted in Norway indicates that men who smoke show fewer respiratory symptoms than women smokers. Symptoms reported include persistent cough, current asthma, wheezing, and breathlessness. When compared to previous and current smokers, the prevalence of respiratory symptoms doubled that of never-smokers. Symptoms augmented as smoking burden increased (P < .001). The study was part of the BONT (bronchial obstruction in Nord-Trondelag) which encompassed all inhabitants (65, 717 subjects) 20 years and older. A total of 71.3% of the participants completed the main questionnaire.

* Wise RA: Changing smoking patterns and mortality from chronic obstructive pulmonary disease. Prey Med 1997; 26:418-421.

Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in the United States, has shown no rate of decline for the past 20 years but rather an increase in mortality trends among women, African-Americans, and the elderly. Smoking cessation and the early identification of individuals with respiratory problems can stop the progression of COPD. These conclusions are based on a review of the published literature.

* Nuorti JP, Butler JC, Farley MM, et al: Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team. N Engl J Med 2000; 342:681-689.

Cigarette smoking greatly increases the risk for invasive pneumococcal disease among immunocompetent, non-elderly adults, attributing to 51% of the disease burden. The risk decreased by 14% per year after subjects quit smoking, returning to levels similar to those who have never smoked in about 13 years. A dose-response relationship exists for the current number of daily cigarettes smoked, pack-years of smoking, and time since quitting. These results are based on a population-based case-control study of 228 immunocompetent patients who were aged 18 to 64 years and had invasive pneumococcal disease.

* Rahman I, MacNee W: Role of oxidants/antioxidants in smoking-induced lung diseases. Free Radic Biol Med 1996; 21:669-681.

Smokers and individuals with chronic obstructive pulmonary disease have increased neutrophil sequestration and activation in the microvessels of the lungs, capable of releasing reactive oxygen species (ROS). ROS increases the oxidant burden and may be a factor in causing epithelial damage. The effects of this burden are countered by the lung antioxidant defenses. These conclusions are based on a review of the published literature.

* Shields PG: Epidemiology of tobacco carcinogenesis. Curr Oncol Rep 2000; 2:257-262.

Although the level of tar and nicotine in cigarettes has decreased, the level of some of its carcinogens (tobacco-specific nitrosamines [TSNs]) has increased. A smaller amount of nicotine can lead to increased smoking so that blood nicotine levels are maintained. This is a discussion of tobacco smoke, tobacco addiction, carcinogen-DNA adduct formation, tumor specific mutations, and additional factors influencing lung cancer, including genetics, gender, and race.

* Fitzpatrick TM, Blair EA: Upper airway complications of smoking. Clin Chest Med 2000; 21:147-157.

Tobacco smoke causes a range of problems in the upper airway, from inflammatory reactions to life-threatening malignancies. Early diagnosis and treatment, including cessation counseling, are key steps in resolving upper airway ailments. This is a review of the published literature.

Further Reading

1. Shiota Y, Kawai T, Matsumoto H, et al: Acute eosinophilic pneumonia following cigarette smoking. Intern Med 2000; 39:759-760

2. Murin S, Bilello KS, Matthay R: Other smoking-affected pulmonary diseases. Clin Chest Med 2000; 21:121-137

3. Seagrave J: Oxidative mechanisms in tobacco smoke-induced emphysema. J Toxicol Environ Health A 2000; 61:69-78

4. Patel DR, Homnick DN: Pulmonary effects of smoking. Adolesc Med 2000; 11:567-576

5. Ryu JH, Colby TV, Hartman TE, et al: Smoking-related interstitial lung diseases: a concise review. Eur Respir J 2001; 17:122-132

6. Sockrider M: The respiratory effects of passive tobacco smoking. Curr Opin Pulm Med 1996; 2:129-133

TEENS AND ADOLESCENTS

* Unger JB, Rohrbach LS, Cruz TB, et al: Ethnic variation in peer influences on adolescent smoking. Nicotine Tob Res 2001; 3:167-176.

Cultural differences may play a role in peer influence on smoking initiation. Recent literature shows that white adolescents are more prone to begin smoking as a result of peer pressure than are teens from other ethnic groups. Informational peer pressure (best friend smoking) affected white teens more than adolescents from other ethnic groups. Due in part to a collectivist culture (differing values and norms) African-Americans, Hispanics, Asian-Americans, Pacific Islanders and many other multi-ethnic groups are not as likely to be influenced by friends who smoke. The data for this study was derived from a representative sample of California eighth-graders (n = 5,870). The study encompassed 68 schools in 18 California counties and took place during the 1996-1997 school year. It was a part of the Independent Evaluation of the California Tobacco Control, Prevention, and Education Program (Independent Evaluation Consortium, 1998).

* Ellickson PL, Tucker JS, Klein DJ: High-risk behaviors associated with early smoking: results from a 5-year follow-up. J Adolesc Health 2001; 28:465-473.

Adolescent smokers in grade 7, compared with nonsmokers, were almost 4 times more likely to skip class or to be sent out of class; 2-3 times more likely to have academic problems, such as frequent absences, poor grades, and failures; 82 times more likely to use marijuana and 36 times more likely to use hard drugs; 8-11 times more likely to drink; and 7 times more likely to steal. Early smokers were 3 times more likely by grade 12 to use tobacco/marijuana/hard drugs, sell drugs, have drug problems, drop out of school, and experience early pregnancy than nonsmokers. This study used logistic regression based on longitudinal self-reported data to develop weighted estimates of academic difficulties, substance use, and delinquent behavior in 4,327 nonsmokers, experimenters, and smokers in grades 7 and 12. Sample subgroups included 10.2% African-American, 9.8% Hispanic, 8.2% Asian, and 4.2% other. Females comprised 48% of the sample group. Boys classified as "experimenters" outnumbered girls 37% to 27%, while 24% of girls compared to 19.4% of boys were likely to be smokers.

* Sargent JD, Beach ML, Dalton MA, et al: Effect of seeing tobacco use in films on trying smoking among adolescents: cross sectional study. BMJ 2001; 323:1394-1397.

Adolescents who frequently see tobacco use in films are more likely to try smoking, the odds depending on number of viewing occurrences. Incidences of having tried smoking increase with on-screen exposure, from 4.9% for 0-50 observances to 31.3% for >150. After adjustment for other factors such as age, school performance, and parents' educational level, the odds ratios remain significant (1.7, 2.4, and 2.7, in the three categories <50). An average of about 800 smoking scenes occur in every 150 films, and videotapes have made viewing more accessible to all ages. Studies suggest that the influence of film stars on adolescents' behavior is as great as that of their siblings or parents. Children whose parents smoke were not as likely to imitate film stars, however, perhaps due to experiencing firsthand the negative aspects of smoking. These results are based on a cross-sectional survey of 4,919 school children ages 9-15 and assessment of 601 films.

* Loule D: The effects of cigarette smoking on cardiopulmonary function and exercise tolerance in teenagers. Can Respir J 2001; 8:289-291.

Cigarette smoking has strong adverse effects on cardiopulmonary function and exercise performance in teenagers. Nonsmokers finished a one-mile run significantly faster than smokers; smokers had a sharp decline in peak expiratory flow from pre- to postrun. Nonsmokers had a mean expired carbon monoxide concentration of 1.9 [+ or -] 0.9 compared to 14.3 [+ or -] 2.5 for smokers. The dose-response relationship shows that baseline peak flow rate decreases with an increase in the number of cigarettes smoked per day. Results are based on a group of 27 students from grade 10.

URINARY SYSTEM

* Righetti M, Sessa A: Cigarette smoking and kidney involvement. J Nephrol 2001; 14:3-6.

Cigarette smoke is a key risk factor for several kidney diseases. These include primary glomerular diseases, diabetic nephropathy, and primary hypertension. Smoke is also to blame for adverse effects on renal outcome in systemic diseases involving the kidney, and in patients on chronic hemodialysis, or following renal transplantation. The good news is there is overwhelming evidence that cessation of smoking will improve chronic renal disease outcomes.

A review of study data indicates renal plasma flow is impaired by cigarette smoking and may suppress endothelial nitric oxide synthase. This in turn upsets the relations between endothelial nitric oxide's polymorphism and vascular disease. Furthermore, structural alterations to the vessels in vascular smooth muscle cell proliferation are adversely affected by smoke-induced inhibition of nitric oxide production. Renal plasma flow is also affected by cigarette smoke. Thanks to compensatory adaptation of spared glomeruli, renal function encumbrance is delayed for a certain period of time. However, when the compensatory stage, is overwhelmed, progressive azotemia may become apparent.

* In patients with primary hypertension smoking is a major predictor of renal failure.

* Studies show that smoking is strongly linked to the development and progression of diabetic glomerulopathy.

* Extensive population studies indicate a strong correlation between smoking and development of microalbuminuria in patients with type 1 or 2 diabetes.

* A fall in creatinine clearance and an increase in proteinuria in subjects with diabetic glomerulopathy is directly associated with cigarette smoking.

* It is not yet known whether cessation of smoking leads to the regression of diabetic kidney disease.

* In non-diabetic nephropathies, cigarette smoking is believed to be an adverse prognostic factor.

* Cigarette smoking was found to be a dose-dependent risk factor in the progression and eventual renal failure of patients with IgA glomerulonephritis and autosomal dominant polycystic kidney disease.

* In lupus nephritis, smoking was found to be an important prognostic risk factor.

* An increased graft failure was noted in kidney transplant patients who currently smoke.

There is overwhelming evidence that cessation of smoking greatly increases the health of renal patients. In light of this, physicians and especially nephrologists should make a determined effort to exhort their patients to stop smoking.

* Mikhailidis DP, Ganotakis ES, Papadakis JA, et al: Smoking and urological disease. J R Soc Health 1998; 118:210-212.

Smoking, which may increase risk of prostatic and renal cancer, adversely affects nearly every part of the human body and is the most preventable cause of urinary bladder cancer. Smoking also affects sperm motility and count, and smoking cessation is recommended for men with marginal semen quality wishing to start a family.

* Ritz E, Ogata H, Orth SR: Smoking: a factor promoting onset and progression of diabetic nephropathy. Diabetes Metab 2000; 4(suppl 1):54-63.

Smoking contributes to nephropathy onset and progression in diabetic patients, and recent studies show that smoking adversely affects renal function in people without renal disease. Cessation of smoking delays renal failure.

* Orth SR: Smoking: a renal risk factor. Nephron 2000; 86:12-26.

Smoking increases the risk of nephropathy development, and the progression rate to end-stage renal failure is nearly doubled in both type 1 and type 2 diabetes. Smoking is an independent risk factor for end-stage renal failure in patients with inflammatory and noninflammatory renal disease. Renal damage may be due to the intermittent increase in blood pressure during smoking. This review article presents current knowledge about smoking and renal impairment.

* Platz EA, Rimm EB, Kawachi I, et al: Alcohol consumption, cigarette smoking, and risk of benign prostatic hyperplasia. Am J Epidemiol 1999; 149:106-115.

Smoking 35 or more cigarettes daily is associated with a greater risk of benign prostatic hyperplasia (BPH) (OR = 1.33; 95% CI, 1.07-1.97). Moderate alcohol consumption and abstinence from smoking may reduce the risk of BPH. A strong inverse relationship exists between moderate alcohol consumption and total BPH (30.1-50.0 g/day vs 0; OR = 0.59; 95% CI, 0.51-0.70; P < .0001), but the relationship becomes attenuated with greater alcohol consumption (>50.1 g/day vs 0; OR = 0.72; 95% CI, 0.57-0.90). These findings are based on the results of the Health Professionals follow-up study where a subset of 29,386 men, ages 40-75, were followed for incidence of BPH surgery between 1986 and 1994.