What is influenza?

Influenza is a respiratory infection caused by a number of airborne RNA viruses that enter the body through the nose or mouth. Influenza viruses bind to epithelial cells in the nose, throat and lungs. Cells than absorb the virus. Once inside, the virus replicates using a cellular enzyme called an RNA-dependent RNA polymerase. The polymerase enzyme lacks proofreading capability and makes a spontaneous mutation at a rate of 1 per genome per replication [2]. Thus, essentially every influenza virus replicated contains a mutation. This is the reason why influenza viruses continually change over time and are able to evade the host immune system.

Symptoms of the flu present quickly and are worse than the common cold. Flu symptoms include body or muscle aches, chills, cough, high fever lasting 3-4 days, headache, sore throat, stuffy nose, extreme tiredness and stomach symptoms (more common in children), including nausea, vomiting and diarrhea. The incubation period between acquiring the infection and becoming ill is 1-4 days. Most heathy adults are able to infect other people 1 day before symptoms develop and up to 5 days after becoming sick [3]. Viral shedding, the period during which a person can infect others, usually peaks on the second day of symptoms. Children can infect others for several days prior to developing symptoms and can be infectious for more than 10 days. Since children can shed the greatest amounts of virus, they pose the greatest risk for viral transmission.

The flu vaccine: your options

The best way to prevent seasonal flu is to get vaccinated. Hospitalization and death from flu complications pose real risks; every year, on average, more than 200,000 people are hospitalized from flu complications and approximately 36,000 people die from the flu [3]. Immunizing children against influenza is perhaps the best method to reduce the occurrence of the flu in the community. If children receive the flu shot but the rest of the family abstains, the influenza attack rate drops by 40%; if parents also get the flu shot, the influenza attack rate drops by 80% [4].

The flu vaccine is available in two forms, a shot and a nasal spray (FluMist). The flu shot, which is approved for use in children 6 months and older, contains an inactivated flu virus. Although you may develop a slight reaction to the shot, including soreness at the injection site, muscle ache or fever, you won’t get the flu because the viruses in the vaccine have been inactivated. The nasal spray flu vaccine (FluMist), which is approved for use in children 2 years and older, contains a low dose of live but weakened flu virus. Similar to the flu shot, the nasal spray doesn’t cause the flu, but prompts an immune response so that your body develops antibodies necessary to fight influenza infection. A review of 48 reports on influenza vaccine efficacy over the past four decades found that the flu shot was 80% efficacious against influenza in healthy adults when the vaccine matched the circulating strain and the circulation was high [5]. If the circulating strain didn’t match the vaccine, efficacy was reduced to 50%. The flu vaccine was 30% effective against influenza-like illness. FluMist efficacy has been reported to be higher in both children and adults [6-8].

What else can you do?

In addition to the flu vaccine, one of the best ways to avoid getting sick and stay healthy is to simply wash your hands. Even something as simple as coughing or sneezing can spread cold and flu germs; hand washing is the single most important thing you can do to prevent the spread of infection and to stay healthy. Some scientists estimate that as much as 80% of all infections are transmitted by unwashed hands [9]. Nevertheless, a dab of soap and a quick rinse isn’t effective. The key is to wash your hands for at least 20 seconds to ensure that you’ve removed the microbes (here’s a trick: sing the ABC’s to yourself). By rubbing your hands with soapy water, you pull dirt and oil from your skin. The soap lather suspends any germs trapped inside and are then washed away when rinsing. If soap and water aren’t available, use an alcohol-based hand sanitizer. However, while alcohol-based hand sanitizers reduce the number of germs on skin, they aren’t necessarily more effective at reducing the flu virus on human hands. Studies have found that hand washing with soap and water is superior to all alcohol-based treatments.

References

1. Evans M. Flu shot. Can Fam Physician. 2005 Nov;51:1511-2, 1515-6.
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2. Drake JW. Rates of spontaneous mutation among RNA viruses. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4171-5.
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3. Key Facts About Seasonal Influenza (Flu). Centers for Disease Control and Prevention. Updated 2007, Sep 17.
4. Hurwitz et al. Effectiveness of influenza vaccination of day care children in reducing influenza-related morbidity among household contacts. JAMA. 2000 Oct 4;284(13):1677-82.
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5. Jefferson et al. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD001269.
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6. Belshe et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. N Engl J Med. 1998 May 14;338(20):1405-12.
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7. Belshe et al. Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine. J Pediatr. 2000 Feb;136(2):168-75.
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8. Treanor et al. Evaluation of trivalent, live, cold-adapted (CAIV-T) and inactivated (TIV) influenza vaccines in prevention of virus infection and illness following challenge of adults with wild-type influenza A (H1N1), A (H3N2), and B viruses. Vaccine. 1999 Dec 10;18(9-10):899-906.
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9. Put Your Hands Together. National Center for Preparedness, Detection, and Control of Infectious Diseases (NCPDCID) and National Center for Zoonotic, Vector-Borne, and Enteric Diseases (NCZVED). 2008 Oct 13.

Shore delivered powerful closing arguments in the case as only the incomparable James Spader could present. Throughout his closing, he cited research findings and statistics that seemed “made for TV” but are, in fact, very real. In quintessential Highlight HEALTH fashion, I have referenced the studies throughout his closing arguments below. There will only be 12 episodes in this, the fifth and final season of Boston Legal. Enjoy it while you can.

Closing arguments

Michael Rhodes smoked cigarettes for 50 years, got lung cancer and died; we all know what happened here. We also all know this death. Everybody in this room knows somebody who has fought this same battle and dies … agonizing, brutal, excruciating …

But … emotion has no play here. Michael Rhodes was eleven years old when he started smoking, it was 1948. At that time, there was no known risk, and even if there were, at eleven he certainly lacked the capacity to assume it. And after that, he was addicted. They manufacture them to be addictive.

In just the last few years, they’ve increased the amount of nicotine in the average cigarette by 11.6% to make them even more addictive [1]. Recently, we learned that tobacco companies have been adding an ammonia-based compound to cigarettes for years to increase absorption of nicotine [2]. It’s basically the same principle used in crack cocaine.

And let’s look at the obscene strategy they’ve employed here. Smoking may cause cancer, but it didn’t cause this particular cancer. It wasn’t our cigarettes, or it was genetic, or asbestos or a paper mill. Never do they take responsibility ever. And God forbid, if you sue them, they’ll bury you and your lawyer. They might even depose your doctor to death, for good measure. All their insidious methods and cunning corporate tactics aren’t just history, it’s what they continue to do now, today. Because the tobacco industry is like a nest of cockroaches, they will always find a way to survive.

They still go after kids with one strategy after another. They put up brightly colored ads at kid’s eye level in convenience stores. They hire gorgeous twenty-somethings to frequent popular venues and seduce young adults into attending lavish corporate-sponsored parties. Cockroaches will always find a way.

They can’t advertise on TV but they’ve hired PR agencies to hook them up with the film industry. And it’s worked. Researchers estimate that smoking in movies delivers nearly 400,000 adolescent smokers every year [3]. Every time you try to kill the cockroach, it finds another way. It has to, because when you make a product that kills off your consumers, you have to find a way to recruit new customers.

They’ve now got a new feminized version of the macho Camel brand using slogans like “lite” and “luscious” with hot pink packaging. Virginia Slims advertised their “thin cigarette”. Allure Magazine did a whole spread on the cigarette diet [4]. They use social and psychological profiling [5], targeting potential smokers by gender, ethnicity, sexual preference, socioeconomic groups … cockroaches don’t discriminate.

Their CEO comes into this courtroom gloating over their anti-smoking campaign, which is designed to get kids to smoke. In 2003, they spent more than 15 billion on advertising and promotion [6]. That’s a 225% increase from 1998, and they have the audacity to declare they’re trying to discourage smoking. This is not how corporations with a conscience behave.

How in God’s name are cigarettes even legal, can anybody tell me that? They are a deadly concoction of carcinogens that damage every single organ in your body. Why do we not ban them? Because it’s a free country, because freedom of choice is an American ideal worth somebody dying every six seconds? How can any company, especially one with such a conscience no less, knowingly manufacture a product that poisons its users? … and make that product look cool and hip and sexy and fun, so they can get children. How can any attorney defend a company that would do such a thing and how could any society tolerate it, but we do.

There is no conscience at big tobacco. There is no conscience in Washington, which has been bought and paid for by this industry. Conscience has to come from you, the jury. If real regulation is to happen, it has to come from you. People are smoking day after day after day and dying and dying and dying and the tobacco companies keep getting richer and richer. Last year alone, they made 12 billion dollars in profits [7]. How can that be?

How can that be?

References

1. Connolly et al. Trends in nicotine yield in smoke and its relationship with design characteristics among popular US cigarette brands, 1997-2005. Tob Control. 2007 Oct;16(5):e5.
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2. How an Unregulated Industry Experiments on America’s Kids and Consumers. American Cancer Society Cancer Action Network, American Heart Association, American Lung Association and Campaign for Tobacco-Free Kids. 2008 Feb 20.
3. Sargent, J. AAP Handout, October 2006. News release, American Academy of Pediatrics.
4. Morris, L. “The Cigarette Diet.” Allure Magazine. 2000 Mar.
5. Ling and Glantz. Using tobacco-industry marketing research to design more effective tobacco-control campaigns. JAMA. 2002 Jun 12;287(22):2983-9.
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6. Federal Trade Commission Cigarette Report For 2004 and 2005. United States Federal Trade Commission. 2007
7. Fortune Global 500 2007: Altria Group.

The ACS has just wrapped up their first ever video contest on YouTube, where they asked people to create videos – one minute or less – to discourage smoking. You can check out the contest winners at the American Cancer Society.

You can also read more about the harmful effects of smoking and tobacco smoke in these articles here at Highlight HEALTH:

• Smoking Duration vs. Intensity and the Impact on Lung Cancer Risk
• Irreversible Gene Expression Changes From Smoking
• Smoking Cessation Timeline: What Happens When You Quit
• Second-hand Smoke Exposure Linked to Psychological Problems in Children

Accept the Great American Smokeout Challenge.
Quit for one day, or quit for good.

References

1. Cigarette smoking among adults–United States, 2006. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep. 2007 Nov 9;56(44):1157-61.
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• Smoking Cessation Timeline: What Happens When You Quit
• Irreversible Gene Expression Changes From Smoking

One of our readers asked a question I’m sure many have us have wondered about at one time or another:

Which is worse for the development of lung cancer — smoking heavily over a short period of time or smoking fewer cigarettes over many years?

Here’s what the research has to say:

In 2003, researchers at Memorial Sloan-Kettering Cancer Center created a prediction tool that can assess a long-term smoker’s absolute risk of developing lung cancer within 10 years. How long and how much people have smoked, as well as how long it’s been since their last puff, affect the risk of getting lung cancer.

The formula for the study was published in the Journal of the National Cancer Institute. I’ve linked to the full article since it’s publicly available. The study uses a number of predictors, including age, duration of smoking, average amount smoked per day while smoking and duration of abstinence from smoking (for former smokers) [1]. These predictors are not only identifiable from a clinical history but they are established or strongly suspected risk factors for lung cancer. Additionally, they are also risk factors for all-cause mortality.

Figure 1 models multivariable relations between 1-year lung cancer risk and (A) duration of smoking, (B) average number of cigarettes smoked per day, (C) duration of abstinence and (D) age. In panel A, the relative risk of lung cancer increases exponentially with duration of smoking. In contrast, panel B shows that the relative risk of lung cancer tends to level off between 30 and 60 cigarettes smoked per day.

What does this mean? It means that the relative risk of tobacco-attributable lung cancer sharply increases with increasing duration of smoking, much more so than smoking intensity (i.e. the number of cigarettes smoked per day).

The model for the prediction tool was derived from data collected during CARET, a multicenter, randomized, controlled study that evaluated the impact of beta-carotene and vitamin A supplementation on lung cancer incidence and mortality [2]. Unfortunately, the prediction tool only works for people age 50 and older who smoked at least 10 cigarettes a day for at least 25 years, since those were the people tracked for cancer development in the study.

Further research found that the model described above slightly underestimated the observed risk of lung cancer over 10 years [3]. I choose to write about this particular study because of the accessibility of the online prediction tool. However, other risk models have been developed [4-6].

Additional studies have also suggested that smoking duration has a stronger effect in the prediction of lung cancer risk than number of cigarettes smoked per day [7-10]. These models are consistent with the results from epidemiologic studies, which indicate that risks of lung cancer, as well as bladder cancer, tend to level off with increased smoking intensity [11].

Smoking cessation at any age is beneficial. Nevertheless, lower lung cancer death risk is observed for people who quit at younger ages [12]. Indeed, cessation of smoking prior to middle age is associated with a more than 90% reduction in cancer risk attributed to tobacco [13].

This isn’t to say that smoking intensity isn’t a major contributor to tobacco-attributable cancer risk. However, the take-home message is that long-term smoking clearly impacts lung cancer risk to a greater extent. That’s why it’s more important than ever to quit smoking now.

References

1. Bach et al. Variations in lung cancer risk among smokers. J Natl Cancer Inst. 2003 Mar 19;95(6):470-8.
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2. Omenn et al. The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers. Cancer Res. 1994 Apr 1;54(7 Suppl):2038s-2043s.
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3. Cronin et al. Validation of a model of lung cancer risk prediction among smokers. J Natl Cancer Inst. 2006 May 3;98(9):637-40.
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4. Peto et al. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. BMJ. 2000 Aug 5;321(7257):323-9.
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5. Prindiville et al. Sputum cytological atypia as a predictor of incident lung cancer in a cohort of heavy smokers with airflow obstruction. Cancer Epidemiol Biomarkers Prev. 2003 Oct;12:987-93.
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6. Cassidy et al. Defining high-risk individuals in a population-based molecular-epidemiological study of lung cancer. Int J Oncol. 2006 May;28(5):1295-301.
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7. Doll and Peto. Cigarette smoking and bronchial carcinoma: dose and time relationships among regular smokers and lifelong non-smokers. J Epidemiol Community Health. 1978 Dec;32(4):303-13.
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8. Peto, R Influence of dose and duration of smoking on lung cancer rates. Zaridze, D Peto, R eds. Tobacco: a major international health hazard; proceedings of an international meeting Moscow, USSR, June 4-6, 1985. 1986 World Health Organization, International Agency for Research on Cancer Lyon, France. International Agency for Research on Cancer Science Publication No. 74, 23-33.
9. Flanders et al. Lung cancer mortality in relation to age, duration of smoking, and daily cigarette consumption: results from Cancer Prevention Study II. Cancer Res. 2003 Oct 1;63(19):6556-62.
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10. Lubin and Caporaso. Cigarette smoking and lung cancer: modeling total exposure and intensity. Cancer Epidemiol Biomarkers Prev. 2006 Mar;15(3):517-23.
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11. Vineis et al. Levelling-off of the risk of lung and bladder cancer in heavy smokers: an analysis based on multicentric case-control studies and a metabolic interpretation. Mutat Res. 2000 Jul;463(1):103-10.
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12. Halpern et al. Patterns of absolute risk of lung cancer mortality in former smokers. J Natl Cancer Inst. 1993 Mar 17;85(6):457-64.
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13. Peto et al. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. BMJ. 2000;321:323-329.
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Xenobiotics

A xenobiotic is a chemical found in an organism that is not normally produced or expected to be present in that organism. For example, antibiotics are considered to be xenobiotics in humans because the human body does not produce them and they would not be expected to be present in the body. Other xenobiotics include chemical carcinogens, insecticides, petroleum products and other environmental pollutants. In the body, xenobiotic metabolism is responsible for the removal of xenobiotics. Xenobiotics are metabolized in a two-phase process that typically occurs in the liver. Phase I reactions involve the addition or unmasking of a functional polar group (meaning that one end of the molecule is more positively charged while the other is more negatively charged) on the xenobiotic. In the second phase, glutathione, glucuronic acid or sulphuric acid is conjugated (meaning the union of a substance with a normal constituent of the body) to the xenobiotic and facilitates excretion. The cytochrome P450 enzymes, a superfamily of more than 160 known proteins, catalyze many reactions involved in drug metabolism and are important Phase 1 enzymes.

Gene Expression Changes

Genes associated with airway mucosal response were found to be strongly involved with airway epithelium repair and regeneration. Many of the genes involved in airway repair and regeneration have varying degrees of reversibility. Following smoking cessation, reversible gene expression changes included Trefoil factor 3 (gene symbol TFF3), a structural component of mucus that is elevated in inflammatory response, Ectonucleoside triphosphate diphosphohydrolase 8 (gene symbol ENTPD8), an enzyme involved in nucleic acid metabolism that may play a role in the chemical formation of DNA adducts and Calcium binding tyrosine-(Y) phosphorylation regulated (gene symbol CABYR), a newly discovered bronchial protein that may be involved in ciliary function associated with muco-ciliary clearance response within the lungs.

Gene expression changes that were partially reversible included Mucin 5 (gene symbol MUC5AC), a mucin gene and extracellular matrix structural constituent.

Gene expression changes that were irreversible consisted of functionally diverse genes but included a small number related to the cell cycle and DNA repair. The expression of P21/Cdc42/Rac1-activated kinase 1 (gene symbol PAK1), a protein that regulates cell motility and morphology, and Cyclins D1 (gene symbol CCND1) and G2 (gene symbol CCNG2), proteins that function as regulatory subunits for cell cycle progression, all appeared to be irreversibly lower in both current and former smokers relative to those who had never smoked. Additionally, APEX nuclease (multifunctional DNA repair enzyme) 1 (gene symbol APEX1), High-mobility group box 1 (gene symbol HMGB1), REV1-like (gene symbol REV1) and Tumor suppressor candidate 4 (gene symbol TUSC4) are DNA repair genes that were found to be irreversibly under-expressed in both current and former smokers.

Although CABYR gene expression was found to be reversible, one of its few known interactions occurs with another gene called Glycogen synthase kinase 3 beta (gene symbol GSK3B). Although GSK3B was not identified in the primary analysis, it too is irreversibly reduced in current and former smokers. GSK3B has been shown to negatively interact with Cyclooxygenase 2 (gene symbol COX2), an enzyme responsible for inflammation and pain [1]. The authors suggest that its reduced expression may account for the exaggerated inflammatory response despite smoking cessation and may contribute to the development of lung cancer [2].

According to the first author [3] of the study:

Those genes and functions which do not revert to normal levels upon smoking cessation may provide insight into why former smokers still maintain a risk of developing lung cancer.

Indeed, until recently, many smoking cessation timelines showed that, after 10 years of not smoking, the risk of cancer was that of people who had never previously smoked. However, statistics show an increased risk of lung cancer, even after a decade of not smoking. Age at cessation has a major impact on subsequent lung cancer risk. Although the risk of lung cancer is higher for former smokers than for those who have never smoked, lower lung cancer death is observed for people that quit earlier in life [4].

Your best bet? Don’t start smoking in the first place. If you do smoke, now is the time to quit.

References

1. Thiel et al. Expression of cyclooxygenase-2 is regulated by glycogen synthase kinase-3beta in gastric cancer cells. J Biol Chem. 2006 Feb 24;281(8):4564-9. Epub 2005 Dec 21.
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2. Chari et al. Effect of active smoking on the human bronchial epithelium transcriptome. BMC Genomics. 2007 Aug 29;8(1):297 [Epub ahead of print]
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3. Smoking Turns On Genes — Permanently. Science Daily. 2007 Aug 30.
4. Halpern et al. Patterns of absolute risk of lung cancer mortality in former smokers. J Natl Cancer Inst. 1993 Mar 17;85(6):457-64.
   View abstract

How’s this for bad odds: tobacco kills 50% of its regular users. One out of every two regular smokers will die from smoking [2].

In addition, an estimated 200,000 people die every year due to second-hand smoke exposure at work. The United States Environmental Protection Agency estimates that second-hand smoke is responsible for approximately 3000 lung cancer deaths annually among non-smokers [2]. Additionally, new research has linked second-hand smoke exposure to psychological problems in children, including attention deficit disorder (ADHD) and conduct disorder.

The best time to quit smoking is RIGHT NOW. And while quitting is tough, you can start counting the benefits of not smoking in as little as 20 minutes. Here’s what happens to your body when you quit smoking [3-5]:

Why is it so difficult to quit smoking?

In one word … nicotine.

Nicotine is an organic compound known as an alkoloid (meaning a nitrogen-containing ring compound, usually water-insoluble and alcohol soluble) found in the leaves of several species of plants, predominantly tobacco, as well as in lower quantities in several frequently consumed vegetables from the nightshade or Solanaceae family, including tomatoes, potatoes, aubergines (eggplant) and peppers [6]. Nicotine by itself is not carcinogenic [7]. However, it does inhibit UV-induced activation of cell death (a process known as apoptosis) [8], interfering with the body’s ability to destroy potentially cancerous cells.

Nicotine activates a specific type of neurotransmitter receptor – the acetylcholine receptor – an integral membrane protein widely distributed in the brain and neuromuscular junctions that normally responds to the binding of the neurotransmitter acetylcholine. This is nicotine’s addictive property: activation of acetylcholine receptors leads to an increased flow of adrenaline (epinephrine), which increases the heart rate, blood pressure, respiration and glucose levels in the blood.

When smokers try to cut back or quit smoking, they experience nicotine withdrawal. A regular smoker will have nicotine or its by-products present in their body for 3 to 4 days after quitting [9]. Withdrawal symptoms appear within a few hours and peak 24 to 48 hours after quitting [10]. Withdrawal symptoms include tobacco craving, a desire for sweets, increased coughing and impaired performance on tasks that require concentration [10-11]. Most symptoms last an average of one month, but hunger (due to the lack of increased blood glucose) and craving can last 6 months or more [10].

Did you ever smoke? How hard was it for you to quit? How did you do it?

References

1. 2005 National Survey on Drug Use & Health Results. U.S. Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Office of Applied Studies. 2005.
2. 10 Facts About Tobacco and Second-hand Smoke. World Health Organization.
3. Quitting Smoking: Why To Quit and How To Get Help. National Cancer Institute.
4. Quit Smoking – Smoking Cessation Support – Benefits. American Lung Association.
5. When Smokers Quit – The Health Benefits Over Time. American Cancer Society. Revised 10/25/2006.
6. Siegmund et al. Determination of the nicotine content of various edible nightshades (Solanaceae) and their products and estimation of the associated dietary nicotine intake. J Agric Food Chem. 1999 Aug;47(8):3113-20.
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7. Dasgupta and Chellappan. Nicotine-mediated cell proliferation and angiogenesis: new twists to an old story. Cell Cycle. 2006 Oct;5(20):2324-8. Epub 2006 Oct 16.
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8. Sugano et al. Nicotine inhibits UV-induced activation of the apoptotic pathway. Toxicol Lett. 2001 Dec 15;125(1-3):61-5.
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9. Guide to Quitting Smoking. American Cancer Society. Revised 10/27/2006.
10. Hughes and Hatsumkami. The nicotine withdrawal syndrome: A brief review and update. International Journal of Smoking Cessation. 1992 1:21-26.
11. Hughes, Higgins and Hatsukami. Effects of abstinence from tobacco: a critical review, in Research Advances in Alcohol and Drug Problems, vol 10. Edited by Kozlowski LT, Annis HM, Cappell HD, Glaser FB, Goodstadt MS, Israel Y, Kalant H, Sellers EM, Vingilis ER. New York, Plenum, 1990, pp 317-398.