Lung Infection Risk Increases with Drinking, Smoking

Drinkers Who Smoke at Greater Risk for Pneumonia

From LSU Health Sciences Center,
About.com Health's Disease and Condition content is reviewed by the Medical Review Board

Researchers have found that drinking alcohol increases the movement of harmful bacteria into the lung while smoking cigarettes exacerbates the alcohol-induced increase in the bacterial penetration. Streptococcus pneumoniae is a bacterium that can infect the upper respiratory tract and cause pneumonia, as well as infections in other parts of the body such as the bloodstream (bacteremia), lining of the brain and spinal cord (meningitis), bones (osteomyelitis), joints (arthritis), ears (otitis media) and sinuses (sinusitis). Alcoholics and cigarette smokers are particularly susceptible to pulmonary infections caused by S. pneumoniae. A rodent study in the May 2005 issue of Alcoholism: Clinical & Experimental Research has found that alcohol consumption increases movement of S. pneumoniae toward the lungs, and that smoke exposure exacerbates the alcohol-induced increase in bacterial penetration. "All of the infections caused by S. pneumoniae start with the bacterium colonizing or binding to cells in the upper part of the nose, which is called the nasopharynx," said Gentry-Nielsen, professor of microbiology and immunology at Creighton University School of Medicine, research microbiologist at the Omaha Veterans Affairs Medical Center, and corresponding author for the study. "The trachea that leads from the nasopharynx to the lungs is lined with cells that have hairlike projections called cilia. "These cilia beat in an upward direction to sweep mucus and microorganisms like S. pneumoniae upward and prevent their movement into the lungs. Disease normally occurs when the immune system is compromised or the person is colonized with a new or especially virulent strain of S. pneumoniae that is able to evade the action of the cilia and travel from the nasopharynx into the lungs." Gentry-Nielsen said that alcoholics are more susceptible to S. pneumoniae infections for several reasons. "They have a decreased gag reflex and an increased risk of movement of nasopharyngeal and gastric contents into their lungs, especially when they lose consciousness," she said. "Both of these defects provide additional opportunities for S. pneumoniae to enter their lungs. Host defences within the lungs of alcoholics are also compromised, so they are not well equipped to handle the infection once the organisms reach the lungs. 80 Percent of Alcoholics Smoke Cigarette smokers also have an increased susceptibility to pulmonary infections caused by S. pneumoniae. Smokers are much more likely to be colonized with the organism in their mouths and nasopharynx than non-smokers. Smoking also injures cilia and alters the efficiency of their beating so that bacteria entering the trachea have an increased likelihood of making their way into the lungs." "Clinical studies of this type are complicated because at least 80 percent of human alcoholics smoke," added Gregory J. Bagby, Kai and Earl Rozas professor of physiology at Louisiana State University Health Sciences Center. "Controlled studies in animals are therefore critically important in identifying interactive and separate effects of these two agents. This group is one of the first to study this interaction in a systematic way and the present study on the interactive effects of

cigarette smoke and alcohol on the mucociliary apparatus is the first study of its kind to my knowledge." More Bacteria in the Lungs For 12 weeks, researchers exposed Sprague-Dawley rats (n=64) twice daily to either smoke generated from 30 cigarettes or room air. For the last five weeks of exposure, rats were fed liquid diets that contained 0, 16, 26 or 36 percent of their calories as alcohol. The rats were then infected intranasally with S. pneumoniae, and movement of the organisms into the lower respiratory tract was followed. Results indicate that alcohol ingestion results in a dose-dependent increase in movement of S. pneumoniae into the rats' lungs, which is further exacerbated by concurrent smoke exposure. More Susceptible to Infections "Our study is the first to have reported showing that alcohol consumption in rats impairs the beating of their tracheal cilia, and that this correlates with increased movement of S. pneumoniae into their lungs," said Gentry-Nielsen. "This alcohol-induced defect was intensified in smokeexposed animals, although smoke exposure without ethanol ingestion did not increase movement of organisms into the lungs. These results point to alcohol- and smoke-induced defects in ciliary beating that are likely to make hosts more susceptible to infections caused by microorganisms that colonize their upper respiratory tracts." "This study points to the importance of understanding the potential combined adverse effects of alcoholism and cigarette smoking on lung defenses against pathogen infection," added Bagby. http://alcoholism.about.com/od/nicotine/a/bllsu050514.htm

Smoking and Lung Cancer

The Facts About Smoking and Lung Cancer
By Lynne Eldridge MD, About.com Guide
About.com Health's Disease and Condition content is reviewed by the Medical Review Board

Warning Label on Cigarettes Photo Courtesy of the National Cancer Institute, Bill Branson Photographer

By now, most people are aware of the connection between smoking and lung cancer. Yet I still hear the comments; "My uncle smoked for 60 years and never got lung cancer. My aunt never smoked, but got lung cancer anyway." What are the facts about cigarette smoking and lung cancer? Smoking and Lung Cancer The Statistics

Following the 1964 Surgeon Generals report on Smoking and Health, the public became widely aware of the risk of smoking. In that report, it was estimated that smokers had a nine- to ten-fold increased risk of developing lung cancer compared to non-smokers. But we suspected a link between smoking and lung cancer long before that time. Going through my grandparents belongings, I came across an article in Readers Digest, Cancer by the Carton. It was dated 1952. We now know that smoking is responsible for 87% of lung cancers in the United States. Men who smoke are 23 times more likely to develop lung cancer than those who dont smoke, and women smokers are 13 times more likely to develop the disease than their non-smoking counterparts. The risk of developing lung cancer is directly related to the number of cigarettes smoked, something we calculate using the term pack-years. That said, the majority of lung cancers (over 50%) now occur in former smokers that have quit, and roughly 10% of men and 20% of women with lung cancer have never smoked.

What Other Cancers are related to Smoking?

Smoking and Lung Cancer The Culprits There are more than 50 chemicals in tobacco smoke that are known to cause cancer. Some of the better known carcinogens (cancer causing chemicals) include arsenic, benzene, nickel, and vinyl chloride. Our About.com Guide to Smoking Cessation, Terry Martin, reviews these chemicals in depth in:

Harmful Chemicals in Cigarettes The List of Additives in Cigarettes Pesticides in Cigarette Smoke

Smoking and Lung Cancer Lung Cancer Types The lung cancer types found in people who smoke often differ from those in non-smokers. Small cell lung cancers, which account for roughly 20% of lung cancers, occur almost always in individuals who smoke or have smoked. Non-small cell lung cancers (NSCLC) are the type found more commonly in non-smokers, but the majority of cases still occur in people who have smoked. Historically, people who smoke were more likely to have a form of NSCLC called squamous cell lung cancer, and non-smokers a form called adenocarcinoma. With the switch from unfiltered to filtered cigarettes, adenocarcinomas have become more common in people who smoke. Smoking and Lung Cancer Does Quitting Help? It is never too late to quit smoking. If you quit smoking before the age of 30, you can lower your risk to nearly that of someone who has never smoked. Quitting by the age 50, halves your risk of developing the disease. But quitting at any age can reduce your risk of developing lung cancer. Smoking and Lung Cancer Smoking After a Diagnosis of Lung Cancer Even if someone has been diagnosed with lung cancer, quitting smoking can make a difference. Quitting smoking with lung cancer can make surgery more successful, treatment more effective, and lowers the risk of dying from another condition, such as another cancer or heart disease. Quitting smoking may also may also improve quality of life after a diagnosis of lung cancer, and studies suggest that individuals who continue to smoke have more moderate to severe pain, than those who are able to put cigarettes aside.

Why Should I Quit Smoking if I Have Lung Cancer?

Smoking and Lung Cancer Lung Cancer Screening In the past, it was thought that performing yearly x-rays might help detect lung cancer at an early stage in people who had smoked, but this is no longer recommended. Studies are now looking at CT screening as a way to detect lung cancer at the earliest stages. If you have a history of smoking, you may wish to discuss the issues about lung cancer screening with your doctor. Smoking and Lung Cancer The Stigma Since smoking is associated with the majority of lung cancers, there is a stigma associated with lung cancer. A stigma that somehow individuals have caused their disease and "deserve" to have cancer. This stigma is damaging and unfair. We dont confront people who are overweight or sedentary suggesting that they are responsible for illnesses they develop. Regardless of the cause of a cancer, or any condition for the matter, people who are struggling with a chronic illness need our unconditional caring and support.

http://lungcancer.about.com/od/causesoflungcance1/a/smokinglungcancer.htm

Chemicals in Cigarettes: What They Are and How They Harm Us

Harmful Chemicals in Cigarettes
By Terry Martin, About.com Guide
About.com Health's Disease and Condition content is reviewed by our Medical Review Board

Image Stockxpert

As smokers, we don't think about the chemicals in cigarettes. We think about how cigarettes help us cope with the stress of daily life, how they calm us down when we're angry, help us relax at the end of a long day, comfort us when we're sad or lonely. Harmful chemicals in cigarettes? No, we don't think much about that. The truth of the matter is that smoking does the opposite of just about everything we give it credit for. When the chemicals in cigarettes are inhaled, they put our bodies into a state of physical stress by sending literally thousands of poisons, toxic metals and carcinogens coursing through our bloodstream with every puff we take. And those chemicals affect everything from blood pressure and pulse rate to the health of our organs and immune system. While researchers are still working to uncover all of the hazards cigarettes present to human life, we do know that air tainted with cigarette smoke is dangerous for anyone who breathes it -smoker or not.

Let's take a closer look at some of the harmful chemicals in cigarettes and how they affect our health. Chemicals in Cigarettes: Carcinogens A carcinogen is defined as any substance that can cause or aggravate cancer. Approximately 60 of the chemicals in cigarettes are known to cause cancer. TSNAs Tobacco-specific N-nitrosamines (TSNAs) are known to be some of the most potent carcinogens present in smokeless tobacco, snuff and tobacco smoke. Benzene Benzene can be found in pesticides and gasoline. It is present in high levels in cigarette smoke and accounts for half of all human exposure to this hazardous chemical. Pesticides Pesticides are used on our lawns and gardens, and inhaled into our lungs via cigarette smoke. Formaldehyde Formaldehyde is a chemical used to preserve dead bodies, and is responsible for some of the nose, throat and eye irritation smokers experience when breathing in cigarette smoke. Chemicals in Cigarettes: Toxic Metals Toxic / heavy metals are metals and metal compounds that have the potential to harm our health when absorbed or inhaled. In very small amounts, some of these metals support life, but when taken in large amounts, can become toxic. Arsenic Commonly used in rat poison, arsenic finds its way into cigarette smoke through some of the pesticides that are used in tobacco farming. Cadmium Cadmium is a toxic heavy metal that is used in batteries. Smokers typically have twice as much cadmium in their bodies as nonsmokers. Chemicals in Cigarettes: Radioactive Toxic Metals There are a couple of toxic metals in cigarette smoke that carry an extra punch of danger for anyone breathing it in: they are radioactive. Radioactive Cigarette Smoke Lead-210 (Pb-210) and polonium-210 (Po-210) are poisonous, radioactive heavy metals that research has shown to be present in cigarette smoke. Chemicals in Cigarettes: Poisons Poison is defined as any substance that, when introduced to a living organism, causes severe physical distress or death. Science has discovered approximately 200 poisonous gases in cigarette smoke.

Ammonia Ammonia compounds are commonly used in cleaning products and fertilizers. Ammonia is also used to boost the impact of nicotine in manufactured cigarettes. Carbon Monoxide Carbon monoxide is present in car exhaust and is lethal in very large amounts. Cigarette smoke can contain high levels of carbon monoxide. Hydrogen Cyanide Hydrogen cyanide was used to kill people in the gas chambers in Nazi Germany during World War II. It can be found in cigarette smoke. Nicotine Nicotine is a poison used in pesticides and is the addictive element in cigarettes. A Word About Secondhand Smoke Also known as environmental tobacco smoke, secondhand smoke is a term used to describe cigarette smoke that comes from two sources: Smoke that is exhaled by the smoker (mainstream smoke) and smoke produced by a smouldering cigarette (sidestream smoke). Secondhand smoke is known to contain at least 250 toxic chemicals, including 50 cancer-causing chemicals. According to the U.S. Surgeon General, there is no risk-free level of exposure to secondhand smoke. That means if you can smell cigarette smoke in the air, it could be harming your health. http://quitsmoking.about.com/od/chemicalsinsmoke/a/chemicalshub.htm

What's in a cigarette?
The List of Additives A through C
By Terry Martin, About.com Guide
About.com Health's Disease and Condition content is reviewed by our Medical Review Board

The list of 599 additives approved by the US Government for use in the manufacture of cigarettes is something every smoker should see. Submitted by the five major American cigarette companies to the Dept. of Health and Human Services in April of 1994, this list of ingredients had long been kept a secret. Tobacco companies reporting this information were: American Tobacco Company Brown and Williamson Liggett Group, Inc. Philip Morris Inc. R.J. Reynolds Tobacco Company While these ingredients are approved as additives for foods, they were not tested by burning them, and it is the burning of many of these substances which changes their properties, often for the worse. Over 4000 chemical compounds are created by burning a cigarette, many of which are toxic and/or carcinogenic. Carbon monoxide, nitrogen oxides, hydrogen cyanide and ammonia are all present in cigarette smoke. Forty-three known carcinogens are in mainstream smoke, sidestream smoke, or both. It's chilling to think about not only how smokers poison themselves, but what others are exposed to by breathing in the secondhand smoke. The next time you're missing your old buddy, the

cigarette, take a good long look at this list and see them for what they are: a delivery system for toxic chemicals and carcinogens. http://quitsmoking.about.com/cs/nicotineinhaler/a/cigingredients.htm

Pesticides Discovered in Cigarette Smoke

By Terry Martin, About.com Guide
About.com Health's Disease and Condition content is reviewed by our Medical Review Board

A pesticide is defined as a chemical used to kill pests, usually insects. Pesticides are toxic, and if we use them on our lawns or gardens, we're careful to avoid direct contact if possible. We certainly wouldn't knowingly breathe pesticides into our lungs, yet that is exactly what smokers do every time they take a puff of a cigarette. Researchers at the Colorado School of Mines in Golden, Colorado, have recently identified three previously undetected pesticides in cigarette smoke. The pesticides are:

Flumetralin - This chemical is known to be toxic to humans, and is carcinogenic. It's an endocrine disruptor, and its use on tobacco plants has been banned in Europe. Pendimethalin - This is another endocrine disrupter that targets the thyroid specifically. Pendimethalin is carcinogenic and toxic to humans. Trifluralin - Like the other two pesticides mentioned, trifluralin is an endocrine disrupter, is toxic to humans and is carcinogenic.

These pesticides find their way into cigarettes because they're used on tobacco plants growing in the fields. Endocrine Disrupters Endocrine glands produce hormones which regulate reproduction, growth and development in humans and animals. Endocrine disrupters are chemicals that interfere with this natural process by mimicking or blocking normal hormone function. With the use of electron micrometer mass-spectrometry on a variety of smoke samples from both experimental and commercial cigarettes, the scientists were able to see the chemical makeup of the 3 substances and identify them as dinitroaniline pesticides. They also discovered that these 3 pesticides are present in both mainstream smoke and sidestream smoke, and survive the combustion process in levels as high as 10 percent of the original residue left on tobacco. "No information exists for long-term, low-level inhalation exposures to these compounds, and no data exists to establish the possible synergistic effect of these pesticides with each other, or with the other 4000-plus compounds that have been identified in tobacco smoke." said Kent Voorhees, researcher and co-author of the study The Detection of Nitro Pesticides in Mainstream and Sidestream Cigarette Smoke Using Electron Monochromator-Mass Spectrometry. http://quitsmoking.about.com/od/chemicalsinsmoke/a/pesticides.htm

Tar in Cigarettes
The Toxic Chemicals in Cigarettes
By Terry Martin, About.com Guide
About.com Health's Disease and Condition content is reviewed by our Medical Review Board

The term used to describe the toxic chemicals found in cigarettes. The concentration of tar in a cigarette determines its rating:

High-tar cigarettes contain at least 22 milligrams (mg) of tar Medium-tar cigarettes from 15 mg to 21 mg Low-tar cigarettes 7 mg or less of tar

Cigarette filters were first added to cigarettes in the 1950s when it was reported that the tar in cigarettes was associated with an increased risk of lung cancer. The idea was that the filter would trap harmful tars and nicotine, but the design never worked as well as hoped. Toxins still make it through and into the smoker's lungs, exposing them to the risks of smoking-related disease. In solid form, tar is the brown, tacky substance that is left behind on the end of the cigarette filter. It stains a smoker's teeth and fingers brown and coats everything it touches with a brownishyellow film. Imagine that settling into the delicate pink tissue of your lungs. Tar is present in all cigarettes and tends to increase as the cigarette is burnt down, which can mean that the last puffs on a cigarette may contain as much as twice the amount of tar as the first puffs. Tar in cigarette smoke paralyzes the cilia in the lungs, and contributes to lung diseases such as emphysema, chronic bronchitis, and lung cancer http://quitsmoking.about.com/od/chemicalsinsmoke/a/tar_in_cigs.htm

Lung cancer
From Wikipedia, the free encyclopedia Jump to: navigation, search

Lung cancer
Classification and external resources

Cross section of a human lung. The white area in the upper lobe is cancer; the black areas are discoloration due to smoking.

Lung cancer is a disease that consists of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are carcinomas, derived from epithelial cells. Lung cancer, the most common cause of cancer-related death in men and women, is responsible for 1.3 million deaths worldwide annually, as of 2004. The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss. The main types of lung cancer are small-cell lung carcinoma and non-small-cell lung carcinoma. Non-small-cell lung carcinoma (NSCLC) is sometimes treated with surgery,

while small-cell lung carcinoma (SCLC) usually responds better to chemotherapy and radiation. The most common cause of lung cancer is long-term exposure to tobacco smoke. Nonsmokers account for 15% of lung cancer cases, and these cases are often attributed to a combination of genetic factors, radon gas, asbestos, and air pollution including secondhand smoke.[13][14] Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed by bronchoscopy or CTguided biopsy. Treatment and prognosis depend on the histological type of cancer, the stage (degree of spread), and the patient's performance status. Possible treatments include surgery, chemotherapy, and radiotherapy. Survival depends on stage, overall health, and other factors, but overall only 14% of people diagnosed with lung cancer survive five years after the diagnosis.
Signs and symptoms

Symptoms that may suggest lung cancer include:[15]

dyspnea (shortness of breath) hemoptysis (coughing up blood) chronic coughing or change in regular coughing pattern wheezing chest pain or pain in the abdomen cachexia (weight loss), fatigue, and loss of appetite dysphonia (hoarse voice) clubbing of the fingernails (uncommon) dysphagia (difficulty swallowing).

If the cancer grows in the airway, it may obstruct airflow, causing breathing difficulties. The obstruction can lead to accumulation of secretions behind the blockage, and predispose to pneumonia. Many lung cancers have a rich blood supply. The surface of the cancer may be fragile, leading to bleeding from the cancer into the airway. This blood may subsequently be coughed up. Depending on the type of tumor, so-called paraneoplastic phenomena may initially attract attention to the disease.[16] In lung cancer, these phenomena may include Lambert-Eaton myasthenic syndrome (muscle weakness due to auto-antibodies), hypercalcemia, or syndrome of inappropriate antidiuretic hormone (SIADH). Tumors in the top (apex) of the lung, known as Pancoast tumors,[17] may invade the local part of the sympathetic nervous system, leading to changed sweating patterns and eye muscle problems (a combination known as Horner's syndrome) as well as muscle weakness in the hands due to invasion of the brachial plexus. Many of the symptoms of lung cancer (bone pain, fever, and weight loss) are nonspecific; in the elderly, these may be attributed to comorbid illness.[3] In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the brain, bone, adrenal glands, contralateral (opposite) lung, liver, pericardium, and kidneys.[18] About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph.[2]

[edit] Causes

The main causes of any cancer include carcinogens (such as those in tobacco smoke), ionizing radiation, and viral infection. This exposure causes cumulative changes to the DNA in the tissue lining the bronchi of the lungs (the bronchial epithelium). As more tissue becomes damaged, eventually a cancer develops.[3]
[edit] Smoking

NIH graph showing the correlation and time-lag between tobacco smoking and lung cancer rate in the U.S. male population.

Smoking, particularly of cigarettes, is by far the main contributor to lung cancer.[19] Cigarette smoke contains over 60 known carcinogens,[20] including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue.[21] Across the developed world, 91% of lung cancer deaths in men during the year 2000 were attributed to smoking (71% for women).[22] In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women).[23] Among male smokers, the lifetime risk of developing lung cancer is 17.2%; among female smokers, the risk is 11.6%. This risk is significantly lower in nonsmokers: 1.3% in men and 1.4% in women.[24] Women who smoke (former smokers and current smokers) and take hormone therapy are at a much higher risk of dying of lung cancer. In a study by Chlebowski et al. published in 2009, the women taking hormones were about 60% more likely to die of lung cancer than the women taking a placebo. Not surprisingly, the risk was highest for current smokers, followed by past smokers, and lowest for those who have never smoked. Among the women who smoked (former or current smokers), 3.4% of those taking hormone therapy died of lung cancer compared to 2.3% for women taking the placebo.[25] The time a person smokes (as well as rate of smoking) increases the person's chance of developing lung cancer. If a person stops smoking, this chance steadily decreases as damage to the lungs is repaired and contaminant particles are gradually removed.[26] In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers,[27] and that patients who smoke at the time of diagnosis have shorter survival times than those who have quit.[28]

Passive smokingthe inhalation of smoke from another's smokingis a cause of lung cancer in nonsmokers. A passive smoker can be classified as someone living or working with a smoker. Studies from the U.S.,[29] Europe,[30] the UK,[31] and Australia[32] have consistently shown a significant increase in relative risk among those exposed to passive smoke. Recent investigation of sidestream smoke suggests that it is more dangerous than direct smoke inhalation.[33] 1015% of lung cancer patients have never smoked.[34] That means between 20,000 to 30,000 never-smokers are diagnosed with lung cancer in the United States each year. Because of the five-year survival rate, each year in the U.S. more never-smokers die of lung cancer than do patients of leukemia, ovarian cancer, or AIDS.[35]
[edit] Radon gas

Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the Earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer in the general population, after smoking[8] with the risk increasing 816% for every 100 Bq/m increase in the radon concentration.[36] Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as Cornwall in the UK (which has granite as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The United States Environmental Protection Agency (EPA) estimates that one in 15 homes in the U.S. has radon levels above the recommended guideline of 4 picocuries per liter (pCi/L) (148 Bq/m).[37] Iowa has the highest average radon concentration in the United States; studies performed there have demonstrated a 50% increased lung cancer risk, with prolonged radon exposure above the EPA's action level of 4 pCi/L.[38][39]
[edit] Asbestos

Ferruginous bodies the histopathologic finding associated with asbestosis.

Asbestos can cause a variety of lung diseases, including lung cancer. There is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer.[9] In the UK,

asbestos accounts for 23% of male lung cancer deaths.[40] Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).
[edit] Viruses

Viruses are known to cause lung cancer in animals,[41][42] and recent evidence suggests similar potential in humans. Implicated viruses include human papillomavirus,[43] JC virus,[44] simian virus 40 (SV40), BK virus, and cytomegalovirus.[45] These viruses may affect the cell cycle and inhibit apoptosis, allowing uncontrolled cell division.
[edit] Particulate matter

Studies of the American Cancer Society cohort directly link the exposure to particulate matter with lung cancer. For example, if the concentration of particles in the air increases by only 1%, the risk of developing a lung cancer increases by 14%.[46][47] Further, it has been established that particle size matters, as ultrafine particles penetrate further into the lungs.[48]
[edit] Pathogenesis

Main article: Carcinogenesis

Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes.[49] Oncogenes are genes that are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens.[50] Mutations in the K-ras proto-oncogene are responsible for 1030% of lung adenocarcinomas.[51][52] The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion.[51] Mutations and amplification of EGFR are common in non-small-cell lung cancer and provide the basis for treatment with EGFR-inhibitors. Her2/neu is affected less frequently.[51] Chromosomal damage can lead to loss of heterozygosity. This can cause inactivation of tumor suppressor genes. Damage to chromosomes 3p, 5q, 13q, and 17p are particularly common in small-cell lung carcinoma. The p53 tumor suppressor gene, located on chromosome 17p, is affected in 60-75% of cases.[53] Other genes that are often mutated or amplified are c-MET, NKX2-1, LKB1, PIK3CA, and BRAF.[51] Several genetic polymorphisms are associated with lung cancer. These include polymorphisms in genes coding for interleukin-1,[54] cytochrome P450,[55] apoptosis promoters such as caspase-8,[56] and DNA repair molecules such as XRCC1.[57] People with these polymorphisms are more likely to develop lung cancer after exposure to carcinogens. A recent study suggested that the MDM2 309G allele is a low-penetrant risk factor for developing lung cancer in Asians.[58]
[edit] Diagnosis

Chest radiograph showing a cancerous tumor in the left lung.

Performing a chest radiograph is the first step if a patient reports symptoms that may suggest lung cancer. This may reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (pneumonia), or pleural effusion. If there are no radiographic findings but the suspicion is high (such as a heavy smoker with blood-stained sputum), bronchoscopy and/or a CT scan may provide the necessary information. Bronchoscopy or CT-guided biopsy is often used to identify the tumor type.[2] Abnormal findings in cells ("atypia") in sputum are associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may have a role in the early detection of lung cancer.[59]

CT scan showing a cancerous tumor in the left lung.

The differential diagnosis for patients who present with abnormalities on chest radiograph includes lung cancer as well as nonmalignant diseases. These include infectious causes such as tuberculosis or pneumonia, or inflammatory conditions such as sarcoidosis. These diseases can result in mediastinal lymphadenopathy or lung nodules, and sometimes mimic lung cancers.[3] Lung cancer can also be an incidental finding: a solitary pulmonary nodule (also called a coin lesion) on a chest radiograph or CT scan taken for an unrelated reason. The definitive diagnosis of lung cancer and its classification (described above) is based on examination of the suspicious tissue under the microscope.

[edit] Classification

Lung cancers are classified according to histological type. This classification has important implications for clinical management and prognosis of the disease. The vast majority of lung cancers are carcinomasmalignancies that arise from epithelial cells. The two most prevalent histological types of lung carcinoma, categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: non-small-cell and small-cell lung carcinoma.[60] The non-small-cell type is the most prevalent by far (see accompanying table).
Frequency of histological types of lung cancer[60]
Histological type Frequency (%)

Non-small-cell lung carcinoma Small-cell lung carcinoma Carcinoid[61] Sarcoma[62] Unspecified lung cancer

80.4 16.8 0.8 0.1 1.9

Cancer found outside of the lung may be determined to have arisen within the lung, as lung cancers that metastasize, i.e. spread, often retain a cell marker profile that allow a pathologist to say, with a good deal of certainty, that the tumor arose from the lung, i.e. is a primary lung cancer. Primary lung cancers of adenocarcinoma histology typically have nuclear immunostaining with TTF-1.[63][64] [edit] Non-small-cell lung carcinoma

Micrograph of squamous carcinoma, a type of non-small-cell carcinoma. FNA specimen. Pap stain.

The non-small-cell lung carcinomas (NSCLC) are grouped together because their prognosis and management are similar. There are three main sub-types: squamous cell lung carcinoma, adenocarcinoma, and large-cell lung carcinoma.

Sub-types of non-small-cell lung cancer in smokers and never-smokers[65] Frequency of non-small-cell lung cancers (%) Smokers 42 Neversmokers 33

Histological sub-type Squamous cell lung carcinoma Adenocarcinoma (not otherwise Adenocarcinoma specified) Bronchioloalveolar carcinoma Carcinoid Other

39

35

4 7 8

10 16 6

Pie chart of the incidence of lung cancer types in the Nurses' Health Study, sorted by histological subtypes, in turn sorted into how many are non-smokers versus smokers[66]

Accounting for 25% of lung cancers,[67] squamous cell lung carcinoma usually starts near a central bronchus. A hollow cavity and associated necrosis are commonly found at the center of the tumor. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types.[3] Adenocarcinoma accounts for 40% of non-small-cell lung cancers.[67] It usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have never smoked ("never-smokers"), adenocarcinoma is the most common form of lung cancer.[68] A subtype of adenocarcinoma, the bronchioloalveolar

carcinoma, is more common in female never-smokers, and may have different responses to treatment.[69] [edit] Small-cell lung carcinoma

Small-cell lung carcinoma (microscopic view of a core needle biopsy).

Small-cell lung carcinoma (SCLC) is less common. It was formerly referred to as "oat-cell" carcinoma.[70] Most cases arise in the larger airways (primary and secondary bronchi) and grow rapidly, becoming quite large.[71] The small cells contain dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this tumor an endocrine/paraneoplastic syndrome association.[72] While initially more sensitive to chemotherapy and radiation, it is often metastatic at presentation, and ultimately carries a worse prognosis. Small-cell lung cancers have long been dichotomously staged into limited and extensive stage disease. This type of lung cancer is strongly associated with smoking.[73] [edit] Others Lung cancers are highly heterogeneous malignancies, with tumors containing more than one subtype being very common.[74] Currently, the most widely recognized and utilized lung cancer classification system is the 4th revision of the Histological Typing of Lung and Pleural Tumours, published in 2004 as a cooperative effort by the World Health Organization and the International Association for the Study of Lung Cancer. It recognizes numerous other distinct histopathological entities of non-small-cell lung carcinoma, organized into several additional subtypes, including sarcomatoid carcinoma, salivary gland tumors, carcinoid tumor, and adenosquamous carcinoma. The latter subtype includes tumors containing at least 10% each of adenocarcinoma and squamous cell carcinoma. When a tumor is found to contain a mixture of both small-cell carcinoma and non-small-cell carcinoma, it is classified as a variant of small-cell carcinoma and called a combined small-cell carcinoma. Combined small-cell carcinoma is the only currently recognized variant of small-cell carcinoma. In infants and children, the most common primary lung cancers are pleuropulmonary blastoma and carcinoid tumor.[75] [edit] Metastasis

Micrograph of a lung lymph node biopsy showing metastatic colorectal adenocarcinoma. Field stain.

The lung is a common place for metastasis of tumors from other parts of the body. Secondary cancers are classified by the site of origin; e.g., breast cancer that has spread to the lung is called breast cancer. Metastases often have a characteristic round appearance on chest radiograph.[76] Solitary round lung nodules are not infrequently of an uncertain etiology and may prompt a lung biopsy. In children, the majority of lung cancers are secondary.[75] Primary lung cancers themselves most commonly metastasize to the adrenal glands, liver, brain, and bone.[3]
[edit] Staging See also: Lung cancer staging

Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. In most studies, it is the most important factor affecting the prognosis and potential treatment of lung cancer. Staging varies for the two major cell types of lung cancer (non-small cell lung carcinoma and small cell lung carcinoma). It is normally done prior to attempts at curative therapy, and usually consists of an extensive battery of tests, to include physical examination, laboratory tests, imaging studies, and/or biopsies and other invasive procedures (such as mediastinoscopy). Non-small cell lung carcinoma is usually staged from IA ("one A"; best prognosis) to IV ("four"; worst prognosis).[77] Small cell lung carcinoma has traditionally been classified as limited stage (confined to one half of the chest and within the scope of a single tolerable radiotherapy field) or extensive stage (more widespread disease). For both NSCLC and SCLC, there are two general types of staging evaluations: Clinical Staging: evaluated prior to definitive surgery, and typically based on the results of physical examination, imaging studies, and pertinent laboratory findings. Does not necessarily involve a pathologist. Pathological Staging: usually evaluated either intra- or post-operatively, and based on the combined results of surgical and clinical findings.[71]

[edit] Prevention

See also: Smoking ban

Prevention is the most cost-effective means of fighting lung cancer. While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventive tool in this process.[78] Of utmost importance are prevention programs that target the young. In 1998 the Master Settlement Agreement entitled 46 states in the USA to an annual payout from the tobacco companies.[79] Between the settlement money and tobacco taxes, each state's public health department funds their prevention programs, although none of the states are living up to the Center for Disease Control's recommended amount by spending 15 percent of tobacco taxes and settlement revenues on these prevention efforts.[79] Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries, with California taking a lead in banning smoking in public establishments in 1998. Ireland played a similar role in Europe in 2004, followed by Italy and Norway in 2005, Scotland as well as several others in 2006, England in 2007, France in 2008 and Turkey in 2009. New Zealand has banned smoking in public places as of 2004. The state of Bhutan has had a complete smoking ban since 2005.[80] In many countries, pressure groups are campaigning for similar bans. In 2007, Chandigarh became the first city in India to become smoke-free. India introduced a total ban on smoking at public places on Oct 2 2008. Arguments cited against such bans are criminalisation of smoking, increased risk of smuggling, and the risk that such a ban cannot be enforced.[81] The long-term use of supplemental multivitaminssuch as vitamin C, vitamin E, and folatedoes not reduce the risk of lung cancer. Indeed long-term intake of high doses of vitamin E supplements may even increase the risk of lung cancer.[82] The World Health Organization has called for governments to institute a total ban on tobacco advertising to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where already instituted.[83]
[edit] Screening Main article: Lung cancer screening

Screening refers to the use of medical tests to detect disease in asymptomatic people. Possible screening tests for lung cancer include chest radiograph or computed tomography (CT). As of December 2009, screening programs for lung cancer have not demonstrated any benefit.[84][85]
[edit] Treatment

Main article: Treatment of lung cancer

Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the patient's performance status. Common treatments include palliative care,[86] surgery, chemotherapy, and radiation therapy.[2][87]
[edit] Surgery Main article: Lung cancer surgery

Pneumonectomy specimen containing a squamous cell carcinoma, seen as a white area near the bronchi.

If investigations confirm lung cancer, CT scan and often positron emission tomography (PET) are used to determine whether the disease is localized and amenable to surgery or whether it has spread to the point where it cannot be cured surgically. Blood tests and spirometry (lung function testing) are also necessary to assess whether the patient is well enough to be operated on. If spirometry reveals poor respiratory reserve (often due to chronic obstructive pulmonary disease), surgery may be contraindicated. Surgery for lung cancer has an operative death rate of about 4.4%, depending on the patient's lung function and other risk factors.[88] In non-small-cell lung carcinoma, surgery is usually only an option if the cancer is limited to one lung, up to stage IIIA. This is assessed with medical imaging (computed tomography, positron emission tomography). A sufficient preoperative respiratory reserve must be present to allow adequate lung function after the tissue is removed.

Procedures include wedge resection (removal of part of a lobe), segmentectomy (removal of an anatomic division of a particular lobe of the lung), lobectomy (one lobe), bilobectomy (two lobes), or pneumonectomy (whole lung). In patients with adequate respiratory reserve, lobectomy is the preferred option, as this minimizes the chance of local recurrence. If the patient does not have enough functional lung for this, wedge resection may be performed.[89] Radioactive iodine brachytherapy at the margins of wedge excision may reduce recurrence to that of lobectomy.[90] Video-assisted thoracoscopic surgery and VATS lobectomy have allowed for minimally invasive approaches to lung cancer surgery that may have the advantages of quicker recovery, shorter hospital stay and diminished hospital costs.[91] Early studies suggested that small-cell lung carcinoma (SCLC) fared better when treated with chemotherapy and/or radiation than when treated surgically.[92][93] While this approach to treating SCLC remains the current standard of care,[94] the role of surgery in SCLC is being reconsidered, recent reviews indicating that surgery might improve outcomes when added to chemotherapy and radiation in early stage SCLC[95] and combined forms of SCLC and NSCLC.[96]
[edit] Radiotherapy

Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients with non-small-cell lung carcinoma who are not eligible for surgery. This form of high intensity radiotherapy is called radical radiotherapy.[97] A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), in which a high dose of radiotherapy is given in a short time period.[98] For small-cell lung carcinoma cases that are potentially curable, chest radiation is often recommended in addition to chemotherapy.[99] The use of adjuvant thoracic radiotherapy following curative intent surgery for non-small-cell lung carcinoma is not well established and is controversial. Benefits, if any, may only be limited to those in whom the tumor has spread to the mediastinal lymph nodes.[100][101] For both non-small-cell lung carcinoma and small-cell lung carcinoma patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy). Unlike other treatments, it is possible to deliver palliative radiotherapy without confirming the histological diagnosis of lung cancer. Brachytherapy (localized radiotherapy) may be given directly inside the airway when cancer affects a short section of bronchus.[102] It is used when inoperable lung cancer causes blockage of a large airway.[103] Patients with limited-stage small-cell lung carcinoma are usually given prophylactic cranial irradiation (PCI). This is a type of radiotherapy to the brain, used to reduce the risk of metastasis.[104] More recently, PCI has also been shown to be beneficial in those with extensive small-cell lung cancer. In patients whose cancer has improved following a course of chemotherapy, PCI has been shown to reduce the cumulative risk of brain metastases within one year from 40.4% to 14.6%.[105] Recent improvements in targeting and imaging have led to the development of extracranial stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiation

therapy, very high doses are delivered in a small number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities.[106]
[edit] Chemotherapy

The chemotherapy regimen depends on the tumor type. [edit] Small-cell lung carcinoma Even if relatively early stage, small-cell lung carcinoma is treated primarily with chemotherapy and radiation.[107] In small-cell lung carcinoma, cisplatin and etoposide are most commonly used.[108] Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also used.[109][110] Celecoxib showed a potential signal of response in a small study.[111] [edit] Non-small-cell lung carcinoma Primary chemotherapy is also given in advanced and metastatic non-small-cell lung carcinoma. Testing for the molecular genetic subtype of non-small-cell lung cancer may be of assistance in selecting the most appropriate initial therapy[112] For example, mutation of the epidermal growth factor receptor gene[113] may predict whether initial treatment with a specific inhibitor or with chemotherapy is more advantageous.[114] Advanced non-small-cell lung carcinoma is often treated with cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide, or vinorelbine.[115] Bevacizumab improves results in non-squamous cancers treated with paclitaxel and carboplatin in patients less than 70 years old who have reasonable general performance status.[116] Pemetrexed has been studied extensively in non-small-cell lung cancer, with numerous studies since 1995.[117] For adenocarcinoma and large-cell lung cancer, cisplatin with pemetrexed was more beneficial than cisplatin and gemcitabine; squamous cancer had the opposite results.[118] As a consequence, subtyping of non-small lung cancer histology has become more important.[119] Bronchoalveolar carcinoma is a subtype of non-small-cell lung carcinoma that may respond to gefitinib[120] and erlotinib.[121] [edit] Maintenance therapy In advanced non-small-cell lung cancer there are several approaches for continuing treatment after an initial response to therapy.[122] Switch maintenance changes to different medications than the initial therapy and can use pemetrexed,[123] erlotinib,[124] and docetaxel,[125] although pemetrexed is only used in non-squamous NSCLC.[126] [edit] Adjuvant chemotherapy

Adjuvant chemotherapy refers to the use of chemotherapy after apparently curative surgery to improve the outcome. In non-small-cell lung cancer, samples are taken during surgery of nearby lymph nodes. If these samples contain cancer, the patient has stage II or III disease. In this situation, adjuvant chemotherapy may improve survival by up to 15%.[127][128] Standard practice has often been to offer platinum-based chemotherapy (including either cisplatin or carboplatin).[129] However, the benefit of platinum-based adjuvant chemotherapy was confined to patients who had tumors with low ERCC1 (excision repair cross-complementing 1) activity.[130] Adjuvant chemotherapy for patients with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit.[131][132] Trials of preoperative chemotherapy (neoadjuvant chemotherapy) in resectable non-small-cell lung carcinoma have been inconclusive.[133]
[edit] Interventional radiology

Radiofrequency ablation should currently be considered an investigational technique in the treatment of bronchogenic carcinoma. It is done by inserting a small heat probe into the tumor to kill the tumor cells.[134]
[edit] Palliative care

In a 2010 study of patients with metastatic nonsmall-cell lung cancer, "early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival" (increased by 3 months).[86] Other studies in advanced cancer also found benefit from palliative care,[135] or found hospice involvement to be beneficial.[136] These approaches allow additional discussion of treatment options and provide opportunities to arrive at well-considered decisions[137][138] and may avoid unhelpful but expensive care at the end of life.[138] Chemotherapy may be combined with palliative care in the treatment of the non-small-cell lung cancer. In advanced NSCLC, a 1994 meta-analysis found that appropriate chemotherapy improved average survival over supportive care alone,[139] as well as improving quality of life.[140] With adequate physical fitness, maintaining chemotherapy during lung cancer palliation offers a 1.5 to 3 months prolongation of survival, symptomatic relief and an improvement in quality of life, with better results seen with modern agents.[141][142] Since 2008, the NSCLC Meta-Analyses Collaborative Group has recommended that if the recipient wants and can tolerate treatment then chemotherapy should be considered in advanced NSCLC.[143][144]
[edit] Prognosis

Main articles: Non-small-cell lung carcinoma staging and Manchester score

Prognostic factors in non-small-cell lung cancer include presence or absence of pulmonary symptoms, tumor size, cell type (histology), degree of spread (stage) and metastases to multiple lymph nodes, and vascular invasion. For patients with inoperable disease, prognosis

is adversely affected by poor performance status and weight loss of more than 10%.[145] Prognostic factors in small-cell lung cancer include performance status, gender, stage of disease, and involvement of the central nervous system or liver at the time of diagnosis.[146] For non-small-cell lung carcinoma (NSCLC), prognosis is generally poor. Following complete surgical resection of stage IA disease, five-year survival is 67%. With stage IB disease, five-year survival is 57%.[147] The five-year survival rate of patients with stage IV NSCLC is about 1%.[4] For small-cell lung carcinoma, prognosis is also generally poor. The overall five-year survival for patients with SCLC is about 5%.[2] Patients with extensive-stage SCLC have an average five-year survival rate of less than 1%. The median survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.[4] According to data provided by the National Cancer Institute, the median age at diagnosis of lung cancer in the United States is 70 years,[148] and the median age at death is 72 years.[149]
[edit] Epidemiology

Age-standardized death from tracheal, bronchial, and lung cancers per 100,000 inhabitants in 2004.[150] no data 5 5-10 10-15 15-20 20-25 25-30 30-35 35-40 40-45 45-50 50-55 55

Lung cancer distribution in the United States

Worldwide, lung cancer is the most common cancer in terms of both incidence and mortality (1.1 million new cases per year and 0.95 million deaths in males and 0.51 million new cases per year and 0.43 million deaths in females).[151] The highest rates are in Europe and North America.[152] The population segment most likely to develop lung cancer is over-fifties who have a history of smoking. Lung cancer is the second most commonly occurring form of cancer in most Western countries, and it is the leading cancer-related cause of death. In contrast to the mortality rate in men, which began declining more than 20 years ago, women's lung cancer mortality rates have been rising over the last decades, and are just recently beginning to stabilize.[153] The evolution of "Big Tobacco" plays a significant role in the smoking culture.[154] Tobacco companies have focused their efforts since the 1970s at marketing their product toward women and girls, especially with "light" and "low-tar" cigarettes.[155] Among lifetime nonsmokers, men have higher age-standardized lung cancer death rates than women. Not all cases of lung cancer are due to smoking, but the role of passive smoking is increasingly being recognized as a risk factor for lung cancerleading to policy interventions to decrease undesired exposure of nonsmokers to others' tobacco smoke. Emissions from automobiles, factories, and power plants also pose potential risks.[10][12][156] Eastern Europe has the highest lung cancer mortality among men, while northern Europe and the U.S. have the highest mortality among women. In the United States, black men and women have a higher incidence.[157] Lung cancer incidence is currently less common in developing countries.[158] With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China[159] and India.[160] Lung cancer incidence (by country) has an inverse correlation with sunlight and UVB exposure. One possible explanation is a preventive effect of vitamin D, which is produced in the skin on exposure to sunlight.[161] From the 1950s, the incidence of lung adenocarcinoma started to rise relative to other types of lung cancer.[162] This is partly due to the introduction of filter cigarettes. The use of filters removes larger particles from tobacco smoke, thus reducing deposition in larger airways. However the smoker has to inhale more deeply to receive the same amount of nicotine, increasing particle deposition in small airways where adenocarcinoma tends to arise.[163] The incidence of lung adenocarcinoma in the U.S. has fallen since 1999. This may be due to reduction in environmental air pollution.[162] However, in some developing countries like India, there has been little change in the epidemiology with squamous cell carcinoma

continuing to be the predominant histological type.[164][165][166] An absence of change in the type of tobacco smoking or the pattern of tobacco consumption in the population could be one of the possible reasons.
[edit] History

Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761.[167] Different aspects of lung cancer were described further in 1810.[168] Malignant lung tumors made up only 1% of all cancers seen at autopsy in 1878, but had risen to 1015% by the early 1900s.[169] Case reports in the medical literature numbered only 374 worldwide in 1912,[170] but a review of autopsies showed that the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952.[171] In Germany in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer,[169] which led to an aggressive antismoking campaign.[172] The British Doctors Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking.[173] As a result, in 1964 the Surgeon General of the United States recommended that smokers should stop smoking.[174] The connection with radon gas was first recognized among miners in the Ore Mountains near Schneeberg, Saxony. Silver has been mined there since 1470, and these mines are rich in uranium, with its accompanying radium and radon gas. Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s. An estimated 75% of former miners died from lung cancer.[175] Despite this discovery, mining continued into the 1950s, due to the USSR's demand for uranium.[176] The first successful pneumonectomy for lung cancer was performed in 1933.[177] Palliative radiotherapy has been used since the 1940s.[178] Radical radiotherapy, initially used in the 1950s, was an attempt to use larger radiation doses in patients with relatively early stage lung cancer but who were otherwise unfit for surgery.[179] In 1997, continuous hyperfractionated accelerated radiotherapy (CHART) was seen as an improvement over conventional radical radiotherapy.[98] With small-cell lung carcinoma, initial attempts in the 1960s at surgical resection[180] and radical radiotherapy[181] were unsuccessful. In the 1970s, successful chemotherapy regimens were developed.[182] http://en.wikipedia.org/wiki/Lung_cancer

Lung cancer
Reviewed by Dr Roger Henderson, GP
15Share
What is lung cancer?

Lung cancer is one of the largest killers in the Western world. The risk of developing lung cancer is increased 10-40 times if you smoke.

The cells of all living organisms normally divide and grow in a controlled manner. Cancer results when this control process is lost. A lump or tumour, known as the primary tumour can grow locally or spread to produce secondary tumours somewhere else in the body. This spreading process is called metastasis. About 40,000 people in the UK die every year from lung cancer. It is the most common form of cancer in the UK and the most common cause of death from cancer in both men and women although it affects more men than women.
What causes lung cancer?

Tobacco smoke is the primary cause of lung cancer. Although nonsmokers can get lung cancer, the risk is about 10 times greater for smokers and is also increased by the number of cigarettes smoked per day. If you are a heavy smoker consuming more than 20 cigarettes a day, the risk of developing lung cancer is about 30 to 40 times higher than if you don't smoke. The main reason for the substantial increase in the disease over the last 50 years has been the increase in the number of people who smoke cigarettes. This has resulted from the industrial production and marketing of tobacco. The risk of lung cancer in an ex-smoker falls to the same level as a nonsmoker after about 15 years.
What are the symptoms of lung cancer?

The symptoms of lung cancer include:

a chronic cough. worsening breathlessness. weight loss. excessive fatigue.

persistent pain in the chest or elsewhere, (possibly from the cancer spreading to a bone). symptoms can be due to the original tumour in the lung or to the effects of secondary tumours elsewhere in the body. one of the most significant symptoms of lung cancer is coughing up blood or haemoptysis. This can sometimes occur as an early warning sign of a cancer which may still be curable. Any person who coughs up blood should see their GP for advice urgently as lung cancer must be considered, particularly if the person is a smoker over the age of 40.

How is lung cancer diagnosed?

Sadly, most lung cancer is diagnosed too late for curative treatment to be possible. In over half of people with lung cancer the disease has already spread (metastasised) at the time of diagnosis. Early diagnosis is difficult because many of the common symptoms of lung cancer are similar to those of smokers' lung (chronic obstructive pulmonary disease or COPD). In addition to this, most lung cancer patients will also have COPD because both conditions are mainly caused by smoking. However, only 1 or 2 per cent of COPD patients will go on to develop lung cancer. The first investigation is a chest X-ray. If a lung tumour is present, it needs to be at least a centimetre in diameter to be detectable by an ordinary X-ray. However, by the time a tumour has reached this size the original cell which became cancerous has divided (or doubled) 36 times. As death usually results after 40 such cell divisions, it is clear that lung cancer is a disease that is usually detected late in its natural course. Some simple blood tests and further examinations may also be carried out. Bronchoscopy is direct inspection of the inside of the breathing tubes with a thin fibre-optic instrument using local anaesthetic and is the best test for tumours in the main bronchi (air passages) in the centre of the chest. Depending on the site of the cancer, a biopsy will be obtained either by a bronchoscopy or a needle biopsy. Needle biopsy is better for cancers near the periphery of the lungs (ie closer to the ribs than the centre of the chest), beyond the reach of the bronchoscope. Usually, a sample of sputum - the material coughed up from the respiratory tract - will also be examined for cancer cells and this can avoid the need for biopsy. A CT scan provides more information about how much the tumour may have spread. There are three main types of lung cancer, based on their appearance when examined under the microscope by a pathologist:

small cell carcinoma squamous cell carcinoma adenocarcinoma.

It is important to know which type of cancer a patient has because small cell cancers respond best to chemotherapy (anti-cancer medicines) whereas the other types (often referred to collectively as non-small cell cancer) are better treated with surgery or radiotherapy (X-ray treatment). The pathologist therefore needs a small tissue sample (biopsy) to examine. This will confirm that the diagnosis of suspected cancer is definitely correct and show which type of cell is involved.
How is lung cancer treated?

Surgery can cure lung cancer, but only one in five patients are suitable for this treatment. If the tumour has not spread outside the chest and does not involve vital structures such as the liver, then surgical removal may be possible, but only if the patient does not also have severe bronchitis, heart disease or other illnesses. These additional complications put too great a strain on the patient for them to be able to stand surgery. Small cell lung cancer is treated with chemotherapy. This is given either by an oncologist (a specialist in cancer treatment) or sometimes by a physician in chest diseases with special experience in chemotherapy. It is given in courses which means that the patient has to stay in hospital for about 48 hours approximately every three weeks. Popular misconceptions about chemotherapy are common and there is often concern about its perceived difficulties and usefulness. However, there is no doubt that chemotherapy is effective and that it both prolongs and improves the quality of survival in small cell lung cancer. The number of courses required will depend on how well the individual patient responds. Chemotherapy does have side-effects, particularly nausea, vomiting and hair loss. However there are very good drugs to control these side effects. Hair always grows again about three months after the chemotherapy courses have finished. There is scope for improving the results of chemotherapy and many research trials are going on. Patients who are asked for their consent to take part in a trial should not be frightened. Hundreds of patients take part in trials to detect any benefit between one treatment regime and another. This research must be done if cancer chemotherapy can continue to improve. Non-small cell cancer may be treated with radiotherapy, chemotherapy (as part of a research trial), or with supportive care. Radiotherapy is either 'radical' or 'palliative'. Radical is used in selected patients with localised tumours who are inoperable, and involves using high doses of radiation. Palliative radiotherapy is widely used. It involves using lower doses of radiation - often in just one or two doses. It is very good for relieving symptoms, such as blood in the sputum (haemoptysis), bone pain, and also for helping obstruction to the airway or large veins in the chest.
What is the outlook?

About 10 per cent of patients can expect to be 'cured' - that is alive five years after diagnosis with no evidence of the cancer having returned.

However, all patients can benefit from palliative treatment which can improve the quality of survival. The main improvement in the management of lung cancer in recent years relates to the palliative care services with an increased emphasis on symptom control and support to the family. The course of lung cancer may be very short. In the UK, Macmillan Cancer Support charity, the Hospice movement, the family doctor and their team provide invaluable support and information to patients and families affected by cancer. Based on a text by Dr Per Grinsted, GP http://www.netdoctor.co.uk/diseases/facts/lungcancer.htm