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Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected. No texting or chat messages, please. Ordinary e-mails are welcome.
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With one of four large boxes of "Pathguy" replies. |
I'm still doing my best to answer everybody. Sometimes I get backlogged, sometimes my E-mail crashes, and sometimes my literature search software crashes. If you've not heard from me in a week, post me again. I send my most challenging questions to the medical student pathology interest group, minus the name, but with your E-mail where you can receive a reply.
Numbers in {curly braces} are from the magnificent Slice of Life videodisk. No medical student should be without access to this wonderful resource.
I am presently adding clickable links to images in these notes. Let me know about good online sources in addition to these:
pathology.org -- my cyberfriends, great for current news and browsing for the general public
EnjoyPath -- a great resource for everyone, from beginning medical students to pathologists with years of experience
Medmark Pathology -- massive listing of pathology sites
Estimating the Time of Death -- computer program right on a webpage
Pathology Field Guide -- recognizing anatomic lesions, no pictures
Freely have you received, freely give. -- Matthew 10:8. My site receives an enormous amount of traffic, and I'm still handling dozens of requests for information weekly, all as a public service.
Pathology's modern founder, Rudolf Virchow M.D., left a legacy of realism and social conscience for the discipline. I am a mainstream Christian, a man of science, and a proponent of common sense and common kindness. I am an outspoken enemy of all the make-believe and bunk that interfere with peoples' health, reasonable freedom, and happiness. I talk and write straight, and without apology.
Throughout these notes, I am speaking only for myself, and not for any employer, organization, or associate.
Special thanks to my friend and colleague, Charles Wheeler M.D., pathologist and former Kansas City mayor. Thanks also to the real Patch Adams M.D., who wrote me encouragement when we were both beginning our unusual medical careers.
If you're a private individual who's enjoyed this site, and want to say, "Thank you, Ed!", then what I'd like best is a contribution to the Episcopalian home for abandoned, neglected, and abused kids in Nevada:
My home page
More of my notes
My medical students
Especially if you're looking for information on a disease with a name that you know, here are a couple of great places for you to go right now and use Medline, which will allow you to find every relevant current scientific publication. You owe it to yourself to learn to use this invaluable internet resource. Not only will you find some information immediately, but you'll have references to journal articles that you can obtain by interlibrary loan, plus the names of the world's foremost experts and their institutions.
Alternative (complementary) medicine has made real progress since my generally-unfavorable 1983 review. If you are interested in complementary medicine, then I would urge you to visit my new Alternative Medicine page. If you are looking for something on complementary medicine, please go first to the American Association of Naturopathic Physicians. And for your enjoyment... here are some of my old pathology exams for medical school undergraduates.
I cannot examine every claim that my correspondents
share with me. Sometimes the independent thinkers
prove to be correct, and paradigms shift as a result.
You also know that extraordinary claims require
extraordinary evidence. When a discovery proves to
square with the observable world, scientists make
reputations by confirming it, and corporations
are soon making profits from it. When a
decades-old claim by a "persecuted genius"
finds no acceptance from mainstream science,
it probably failed some basic experimental tests designed
to eliminate self-deception. If you ask me about
something like this, I will simply invite you to
do some tests yourself, perhaps as a high-school
science project. Who knows? Perhaps
it'll be you who makes the next great discovery!
Our world is full of people who have found peace, fulfillment, and friendship
by suspending their own reasoning and
simply accepting a single authority that seems wise and good.
I've learned that they leave the movements when, and only when, they
discover they have been maliciously deceived.
In the meantime, nothing that I can say or do will
convince such people that I am a decent human being. I no longer
answer my crank mail.
This site is my hobby, and I do not accept donations, though I appreciate those who have offered to help.
During the seventeen years my site has been online, it's proved to be one of the most popular of all internet sites for undergraduate physician and allied-health education. It is so well-known that I'm not worried about borrowers. I never refuse requests from colleagues for permission to adapt or duplicate it for their own courses... and many do. So, fellow-teachers, help yourselves. Don't sell it for a profit, don't use it for a bad purpose, and at some time in your course, mention me as author and William Carey as my institution. Drop me a note about your successes. And special thanks to everyone who's helped and encouraged me, and especially the people at William Carey for making it still possible, and my teaching assistants over the years.
Whatever you're looking for on the web, I hope you find it, here or elsewhere. Health and friendship!
KCUMB Students
"Big Robbins" -- Environmental / Nutritional
Lectures follow Textbook
QUIZBANK: Respiratory #'s 43-65, 150-169
LEARNING OBJECTIVES
Describe the origin, importance, and harmful effects of tobacco addiction. Describe factors that perpetuate it, and proposed remedies.
Describe what happens to particles of various shapes and sizes when they are inhaled.
Distinguish the inorganic and organic pneumoconioses. Distinguish harmful and innocuous inorganic dusts, and list some of each kind.
Describe groups at risk, gross and microscopic pathology, pathophysiology, clinical picture, and important complications of each of the following inorganic pneumoconioses:
coal worker's pneumoconiosis
silicosis
asbestosis
berylliosis
Describe medicolegal aspects of coal worker's pneumoconiosis and asbestosis. Explain why this subject is so complex.
Describe the typical clinical settings, pathophysiology, and means of diagnosis for the important organic pneumoconioses.
Sublime tobacco! which from east to west
Cheers the tar's labor or the Turkman's rest;...
Divine in hookas, glorious in a pipe,...
Yet thy true lovers more admire by far
Thy naked beauties -- Give me a cigar!
--Lord Byron (1788-1824) "The Island" II.19
... And for the vanities committed in this filthy custom, is it not both great vanity and uncleanness, that at the table, a place of respect, of cleanliness, of modesty, men should not be ashamed, to sit tossing of tobacco pipes, and puffing of the smoke of tobacco one to another, making the filthy smoke and stink thereof, to exhale across the dishes, and infect the air, when very often men that abhor it are at their repast?... It makes a kitchen also often-times in the inward parts of men, soiling and infecting them, with an ... oily kind of soot, as has been found in some great tobacco takers, that after their death were opened.... Have you not reason then to be ashamed and to forbear this filthy novelty ... a custom loathsome to the eye, hateful to the nose, harmful to the brain, dangerous to the lungs, and in the black stinking fume thereof, nearest resembling the horrible Stygian smoke of the Pit that is bottomless....?
-- King James I of England (1566-1625)
The incessant, witless repetition of advertisers' moron-fodder has become so much a part of life that if we are not careful, we forget to be insulted by it.
-- The Times of London
TOBACCO SMOKING: Med. Clin. N.A. 76: 355, 1992. Here are some facts you may find handy in talking with patients.
Tobacco was discovered by the American Indians, and has been described as their revenge. The addictive leaves were smoked in pipes, called "tobaccos", which gave the plant its European name. Columbus noticed the First Americans carrrying pipes through which they inhaled the smoke from the burning leaves. Early explorers introduced tobacco to the rest of the world. Today, the world has three billion tobacco addicts (Lancet 380: 668, 2012). No country has ever been able to rid itself of tobacco -- even when tobacco use has been a capital crime.
With widespread smoking of cigarets (your lecturer's preferred spelling of "cigarettes" -- they are not cute little things), previously-rare diseases such as lung cancer and emphysema became common. Even Hitler and his people recognized that smoking was highly addictive and explained the new epidemic of lung cancer, and as part of their "purity" campaign undertook a strong anti-tobacco campaign (Br. Med. J. 313: 1450, 1996); the German tobacco industry called this "unscientific". And by the 1930's, Americans recognized that smoking was bad for people, so much so that the tobacco industry ran many ads showing physicians smoking (Am. J. Pub. Health 96: 222, 2006). Cigaret smoking is now a major problem throughout the world. In Singapore, they're now caning anybody under 18 caught doing tobacco ("Good" says Ed; Br. Med. J. 313: 636, 1996).
Today, tobacco smoke is the most widespread of the known pollutants. In developed countries, ethanol and tobacco are the two principal causes of avoidable death. Surgeon General Koop called cigaret smoking "the chief, single, avoidable cause of death in our society and the most important public health problem of our time." (I'd have voted for alcoholism and mental illness as in a tie for first, with smoking third, but it's close....) Tobacco smoking kills around 1000 people in the US each day. Mortality rates for young and middle-aged cigaret smokers is 1.7 x that of nonsmokers. By taking up smoking, a person cuts his or her life expectancy by 15 years (JAMA 258: 2080, 1987); the estimate of "5 minutes of life lost for every cigaret" is probably low. |
Tobacco smoke is a complex mixture that contains nicotine (the major addictive component) and many other harmful substances, including carbon monoxide, benzopyrene (* mutates ras codon 12 G-->T; Cancer 72: 432, 1993), nickel, polonium, and radon. Strangely, the tobacco industry has at various times added each of at least 599 chemicals to their tobacco, and their reasons for introducing most of them are almost completely unknown (Am. J. Pub. Health 97: 1981, 2007). "Low-tar" and "low nicotine" cigarets are not measurably less dangerous than the regular kind (Am. J. Pub. Health 77: 546 & 685, 1987). Smoking without inhaling (pipes, cigars) is less addictive and easier on the lungs, but the risk of mouth and throat cancer is high.
"Smokeless tobacco" ("spit tobacco") is as addictive as cigarets; the blood nicotine levels can actually go higher than in smokers (Arch. Int. Med. 164: 1845, 2004). The average age at which an American begins "chewing tobacco" is now ten (JAMA 266: 3143, 1991). Tobacco companies make "starter" (low-nicotine, nice flavors) chewing tobacco products targeted at kids, who then graduate to the more familiar products. And every school kid knows that chewing tobacco and snuff are much safer in the long-term than smoking. (If anti-tobacco education really was concerned with telling the whole truth and saving lives, rather than "teaching values", we'd encourage teens who cannot quit using tobacco to switch to smokeless tobacco. But this is politics.) If snuff poses a cardiovascular risk, it's not obvious (Arch. Int. Med. 164: 1845, 2004). Even the venerable BMJ, doing a meta-analysis of whether smokeless tobacco increases risk of heart attack, could only come up with a "definite maybe" (BMJ 339: b3060, 2009). Snuff produces a trademark mutation in p53 (Int. J. Cancer 81: 527, 1999), and a variety of curious benign mucosal lesions (which often appear within a few days after beginning smokeless tobacco use), and occasionally causes a mouth cancer (same genes mutated as in smokers' mouth cancer: Cancer 83: 204, 1998... one has to wonder whether this really demonstrates cause and effect). The risk of getting cancer from chewing is much less than is generally supposed (Oral Surg Oral Path 86: 697, 1998); the Swedes cound demonstrate no link whatever from their national moist snuff (Lancet 369: 2015, 2007; another study did find a risk Int. J. Cancer 123: 168, 2008). No surprise. Apart from some nitrosamines, the noted carcinogens in tobacco smoke are products of combustion. Cardiovascular effects of snuff, at least in Sweden (Reg. Tox. Pharm. 28: 1, 1998; J. Am. Coll. Card. 34: 1784, 1999), are conspicuous by their absence: nor does Swedish snuff produce ANY measurable increased risk of cancer (Cancer 82: 1367, 1998). A study of baseball players, about half of whom were using smokeless tobacco, showed that it was bad for their gums and teeth (gee whiz) but produced no difference in athletic performance (ooh, Abstract 98185116; no cancers either). Smokeless tobacco does not impair middle-aged men's exercise abilities (Eur. J. Clin. Inv. 27: 427, 1997).
Here's the good news about smoking. There's been a 50% drop among teenaged males since the early 1990's (Am. J. Pub. Health 96: 897, 2006). Overall, the rate of smoking in the US is low. The British say it's not decreasing in the US (Lancet 376: 930, 2010); but in California many adults are quitting and many fewer kids are staring (JAMA 305: 1106, 2011 -- let's hope that "as California does, so the rest of the USA follows"). Adult US smokers who cannot quit tobacco altogether do tend to switch from cigarets to snuff (JAMA 299: 2629, 2008). But if you are not already physically addicted to nicotine, using smokeless tobacco has nothing to recommend it. Rates continue to drop for men and women in most of the developed world, but smoking is increasing tremendously in most of sub-Saharan Africa and in the Middle East (Lancet 385: 966, 2015), thanks largely to the political activity of tobacco companies. Among men, smokers outnumber non-smokers in Russia, most of the Middle East except for Israel and Iran (where it's very low), and Indonesia. In China and in most of the Muslim world, many men smoke but very few women smoke (Lancet 385: 1011, 1019 & 1029, 2015.)
What happens to tobacco smokers? You will learn about the anatomic lung pathology of uncomplicated cigaret smoking later in the course. After high serum cholesterol, cigaret smoking is the most important risk factor for CORNARY HEART DISEASE (heart attacks, sudden death, angina pectoris -- see Chest 94: 449, 1988) and other complications of atherosclerosis (including RUPTURED AORTIC ANEURYSMS and STROKES -- for the latter, see Lancet 2: 643, 1989). Smoking lowers HDL ("good") cholesterol; nobody knows how. CHRONIC BRONCHITIS and EMPHYSEMA (together, "chronic obstructive pulmonary disease") kill 150,000 people in the US each year. LUNG CANCER kills around 170,000 people in the US each year. Most patients who get the disease die of it. The vast majority of these cancers are caused by cigaret smoking. MOUTH CANCER, THROAT CANCER, LARYNX CANCER, and ESOPHAGEAL CANCER are all much more common in tobacco smokers. BLADDER CANCER rates are roughly tripled for cigaret smokers. PANCREATIC CANCER and KIDNEY CANCER rates are at least doubled for cigaret smokers. STOMACH CANCER, LEUKEMIA and PLASMA CELL MYELOMA are also probably increased in smokers. We are now zeroing in on the molecular biology on oncogenesis on these cancers, which seem to result, at least in part, from mutations that carcinogens in tobacco cause. Tobacco mutates p53 (no surprise NEJM 332: 712, 1995).
PEPTIC ULCER DISEASE is especially common in cigaret smokers. Cigaret smoking accounts for an extra 15,700 cases of STROKE among U.S. men each year (accelerated atherosclerosis and hypercoagulable blood: NEJM 316: 628, 1987; also Am. J. Med. 149: 2053, 1989). AGE-RELATED MACULAR DEGENERATION, the very common illness that blinds so many older folks, is clearly speeded by smoking. BUERGER'S DISEASE is a (fortunately rare) disease of young male smokers, who develop gangrene of their hands and feet. OSTEOPOROSIS in women is also exacerbated by smoking, and tobacco will rob a woman of 5-10% of her total bone mass over a lifetime (NEJM 330: 387, 1994). The relationship to rheumatoid arthritis is still unclear (Arth. Rheum. 56: 1745, 2007). The majority of HOUSEHOLD FIRES are caused by cigaret smoking; the technology to make cigarets that go out if you don't keep puffing (i.e., the paper is banded) has been available for many years, and now firemen are lobbying to make this the law (Tobacco Control 14: 338, 2005). In Cuban epidemic neuropathy (1991-1993), tobacco combined with malnutrition (Fidel's money from Russia had dried up) to cause a grisly disease, and tobacco amblyopia (i.e., going blind from it) is probably a sporadic variant. REAR-END AUTO COLLISIONS often result from "acts of smoking" (i.e., fumbling for your tobacco, lighting, flicking, etc.: JAMA 273: 1334, 1995). And smoking causes GUM DISEASE, BAD BREATH, and STAINED TEETH. (An unusually candid RJR dealer once acknowledged on TV that tobacco smoking "may" cause stained teeth "in predisposed individuals".) Smoking correlates very strongly with deformed sperms and white cells in the semen, which we may think is bad (Am. J. Clin. Path. 136: 247, 2011). In a study with an obvious flaw ("it's dumb to smoke, and being dumb could be hereditary"), mothers who smoked during pregnancy gave birth to kids with persistently far-lower IQ's (Pediatrics 93:221, 1994), but the "definite maybe" that this causes brain damage in the unborn child is still alarming. And we now know it greatly accelerates WRINKLING OF THE SKIN (Ann. Int. Med. 114: 840 & 900, 1991). Whether cigaret smoke truly "accelerates cellular senescence via Werner's syndrome protein down-regulation" / "makes you age faster" (Am. J. Resp. Crit. Care Med. 179: 279, 2009) I'll let you decide. (Werner's is a rare supposed "syndrome of accelerated aging.") A strong statistical relationship between parents' smoking and kids' tooth decay (JAMA 289: 1258, 2003) seems harder to believe; even though this is after controlling for frequency of dental visits and all the usual socioeconomic stuff, maybe parents who blow smoke on their kids also care less about their teeth-brushing and candy consumption.
Today, there is no longer any reasonable doubt that passive smoking (inhaling someone else's cigaret smoke) is dangerous. It is hard to know how many people die as a result of second-hand smoke, but histopathologists have reported some airway inflammation JAMA 268: 1697. 1992). Parents' smoking and children's health: Am. Rev. Resp. Dis. 133: 959, 1986; spouses' health: Am. J. Pub. Health 77: 548, 1987; smoking and children's asthma Chest 122: 409, 2002; one problem with this kind of work is controlling for the fact that any adult who'd smoke around his/her asthmatic kid probably doesn't take good care of the kid in general. More: Arch. Ped. Adol. Med. 151: 135, 1997. In New Zealand, they're monitoring nicotine levels in kids' hair to see whether the parents smoke around them (Arch. Env. Health 56: 117, 2001), while in the US (at least in Houstin, Texas), smoking parents tend to insist that their smoke doesn't make their child's asthma worse even when it obviously does (Chest 133: 1367, 2008). London's physicians found that if you send a nurse to the homes of asthmatic children "that are not doing well on their medication", the nurse is likely to discover the parents are lying and are still blowing smoke all over their sick child (Arch. Dis. Child. 94: 780, 2009), or otherwise sabotaging their child's health. In Scotland, the passage of smoke-free workplace legislation dramatically cut children's admissions for asthma -- because people got the idea that smoking was something you go outside to do (NEJM 363: 1139, 2010). Inhaling a lot of second-hand smoke can set your brain up to become nicontine-addicted (JAMA 305: 2510, 2011), with some people finding that they come to want it.
The impact of passive smoking on coronary disease (if real) is probably small: NEJM 340: 920, 1999 (the literature is full of people still trying to show an effect.) The EPA (Am. J. Med. 93(1A): 38-S, 1992) decided that second-hand smoke kills 53,000 Americans yearly (which is plain silly, as EPA pronouncements so often are). Philip Morris fought back with a campaign calling this "junk science" (and of course I agree), but ended up quietly admitting that environmental smoke could indeed cause lung cancer (Am. J. Pub. Health. 91: 1742, 2001). But the push to a smoke-free workplace is laudable.
The most effective way to reduce smoking is by sin taxes (Lancet 369: 1758, 2007). It is very difficult to quit, and people have done so deserve our congratulations. Quitting smoking greatly and quickly improves one's chance of a long and healthy life. The risk of sudden cardiac death drops almost to baseline immediately, while the risk of heart attack and lung cancer return to baseline over the next several years (NEJM 322: 213, 1990). Only the changes of emphysema are known to be irreversible.
Defenses of tobacco smoking are ingenious but flawed, and closely resemble other forms of junk science / pseudoscience. (See, for example, "Dr. Oat Cell"'s letter, JAMA 255: 1016, 1986.) Even the scientists who get their grant money from the tobacco companies ("The Council on Tobacco Research") are pretty much unanimous in agreeing that smoking obviously causes disease (Am. J. Pub. Health. 81: 894, 1991). To the credit of the tobacco companies, their strong financial backing was responsible for much of the historic work that actually identified the major cancer genes during the 1980's, and Philip Morris in particular is funding genuine, unbiased university science (Science 315: 901, 2007).
People don't smoke "because they like the taste" -- if they did, you could buy tobacco-flavored ice cream at "31 Flavors". People smoke because they are physically addicted to nicotine (see Chest 93(2S), 1988; the withdrawal syndrome is as severe as drugs that actually give pleasure, see JAMA 261: 898, 1989). Most addicts started smoking as teenagers or earlier, in order to assert their "independence" and as a sign of "maturity". The majority are never able to quit. In fact, the newest work (i.e., a family physician actually talked with yong smokers) shows that one can develop the typical nicotine withdrawal syndrome (cravings, irritability, inability to quit) after smoking only a few cigarets per week for a few weeks (Sci. Am. 298(5): 82, May 2008) -- even a few cigarets change the brain though at this level the "latency to withdrawal", i.e., how long it takes before you need another one, may be several days. Addicts cannot really exercise "freedom of choice". There is not a shred of evidence for "a gene to like cigarets" that also causes all cigaret-related diseases. There is no evidence, either, that smokers are self-medicating for a primary deficiency in certain neurotransmitters.
Our laws governing tobacco are "peculiar". The laws protecting US citizens from dangerous products all contain specific exemptions for tobacco. Before the 1997 compromise, the words ADDICTIVE and DEATH were kept off tobacco warning labels, as a compromise with dealers. We have banned heroin, cocaine, cyclamates, many useful drugs, lawn darts, and pet turtles, but we subsidize and advertise tobacco and use our political clout to keep the poor nations smoking. Some (not all) conservatives shout for more and tougher penalties for the recreational drugs, while sporting "Smokers' Rights" bumper stickers. Advertising by tobacco dealers is a multi-billion dollar industry (NEJM 311: 725, 1987). The Camel manufacturers actually sued the physician who did a study intended to show that Joe Camel appealed primarily to children (JAMA 266: 3143, 1991); of course in 1999, the Marlboro Man rode Joe into the sunset. The Minnesota Tobacco Trial documents are still a good read: JAMA 280: 1173, 1998; Mayo Clin. 84: 446, 2009. Today, tobacco advertisers are making a special effort to target minority youth, especially Hispanics, blacks, and gays (Am. J. Pub. Health 92: 1086, 2002; Pub. Health Rep. 122: 607, 2007), and to young people going to bars, where they are going to take up drinking and are most susceptible to taking up other "adult" habits as well (Am. J. Pub. Health 92: 75, 2002). U.S. tobacco companies presently give cigarets to minority youths in the US at sponsored "youth events" and to children in the poor nations as "gifts", i.e., to get them addicted. Perhaps there's some good news ... Mainland China was the heaviest-smoking country in the late 20th century, but if we're to believe the Beijing government (uh, sure), only 1 in 300 of their high school students are presently smokers (Am. J. Pub. Health 91: 1653, 2001). The cost to the U.S. of cigarets in terms of lost productivity is estimated at $53.7 billion per year (Onc. Times 9(9): 5, 1987). Of course, this ignores SAVINGS generated by cigarets -- specifically, in old-age care and pensions that smokers never use! (I suspect this is why tobacco is not more closely regulated!) Perhaps most disturbing of all, U.S. "fair trade" treaties with developing nations have restricted their attempts to prevent their citizens from smoking (Am. J. Pub. Health 80: 659, 1990). Despite the grandstanding of the 1997-8 settlement ("Protect children!"), don't expect this to change. Follow-up on the "settlement": Am. J. Pub. Health. 94: 218, 2004.
In spite of all this, however, most adults today know that tobacco is highly addictive and lethal. U.S. adults are smoking less, and the incidence of fatal lung cancer in men is starting to go down. Cigaret smoking, once macho, is now a teenaged girl's vice. The most successful stop-smoking campaigns are run by industry. Each smoking worker costs industry several hundred dollars extra per year. The most effective anti-smoking ads directed for young people are the ones that remind them "The tobacco companies are playing you for a fool" (JAMA 279: 772, 1998).
Health care professionals are natural leaders in the fight against tobacco. Today very few US physicians (and almost no US cardiologists: Am. J. Card. 97: 1093, 2006) are smokers. Fewer than one nurse in six smokes (Am. J. Pub. Health 88: 581, 1998). There are many packages to help your patients quit. The skin patch is now over-the-counter, and nicotine (though of course "evil") itself does not seem to be a problem for heart patients, who can use the patch safely (NEJM 337: 1230, 1997). Doxepin and clonidine both ease withdrawal, though they are not much used anymore. "Zyban" (bupripion: still works, update Arch. Int. Med. 167: 1791, 2007) became a sensation in 1998; it also seems to prevent the awful depression and awful weight gain on smoking cessation. There's also "Nicotrol" nicotine nasal spray (Mayo Clin. Proc. 73: 118, 1998; "the patch for 5 months and the spray for a year" BMJ 318: 285, 1999). Nowadays, folks use the patch for maintenance and gum/spray for "rescue" from nicotnine fits. Bupropion and/or patch: NEJM 340: 685, 1999. Varenicline binds to nicotine receptors as a partial agonist and seems to work (Clin. Ther. 29: 1027 & 1040, 2007; update JAMA 313: 687, 2015). Ask a clinician about whether you can give more than the recommended dose, and a psychiatrist about whether the drug actually can cause major mental illness or just make it worse (JAMA 299: 959, 2008) -- nowadays they're saying it probably doesn't cause the crazies after all (guide to smoking cessation JAMA 308: 1573, 2012; varenicline plus nicotine replacement JAMA 312: 155, 2014). Cytisine, a binder to a nicotine receptor, is very cheap and seems to work too NEJM 365: 1193, 2011. Or might reduced-nicotine cigarets be the answer: NEJM 373: 1340, 2015.
If you believe that a physician's job is to improve the health of his or her patients, you will want to talk to them about smoking. If you take two minutes to urge a patient to stop smoking, he or she is around 50% likely to eventually quit. (See also Am. J. Pub. Health 77: 313 & 782, 1987; JAMA 259: 2882 & 2883, 1988). To quantitate tobacco smoke exposure in your research, measure urinary cotinine (Thorax 45: 356, 1990). To measure oxidative damage to a person, measure serum F2-isoprostane: yes, cigarets greatly increase it (NEJM 332, 1995).
THE PNEUMOCONIOSES: A group of diseases, ancient and modern, resulting from dust inhalation. (* "Conios" means "dust" in Greek.) Occupational lung disease: Disease-A-Month 44: 41, 1998.
Pneumoconiosis Images
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Pneumoconiosis I
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Pneumoconiosis II
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Dust elimination by the respiratory tree:
Particles over 3 microns are usually caught in the upper airways and eliminated on the mucociliary elevator
Particles under 1 micron either are not deposited or are deposited diffusely on the alveolar surfaces
Particles 1-3 microns in size tend to be deposited at the level of the respiratory bronchioles because of the sudden decrease in air velocity at this level. (These particles are the most dangerous.)
The common pneumoconioses tend to involve the upper lobes more than the lower lobes, because more air goes to the upper lobes (why?)
Exception: long, thin fibers (i.e., asbestos) end up carried by the wind to alveolar duct bifurcations, where they penetrate the tissue and work their way through the lung parenchyma.
Mechanisms of dust removal from the respiratory bronchioles and alveoli include transport on surfactant and in lymphatics and/or phagocytosis by wandering macrophages.
INORGANIC PNEUMOCONIOSES:
Chronic diseases, typically with pulmonary fibrosis.
Silicosis, asbestosis, berylliosis, and complicated forms of coal workers' pneumoconiosis have caused widespread morbidity and mortality. They often appear and progress long after exposure to the dusts.
Except for trouble breathing, patients with the inorganic pneumoconioses usually have few or no physical signs.
Respiratory failure and/or cor pulmonale (right-sided heart failure from pulmonary hypertension) eventually kill the patients.
Most inorganic dust exposures are much less dangerous.
A variety of "dust diseases" -- including simple coal-worker's pneumoconiosis -- are caused by dust accumulation plus small amounts of fibrosis around the terminal (* "membranous") and respiratory bronchioles. These compromise respiration far less than do the fibrogenic dusts.
Traditionally included among the inorganic pneumoconioses are harmless accumulations of inert dusts -- iron oxide, barium, tin, welding fumes (NEJM 316: 631, 1987), etc.
* Exotic dusts (such as produced in grinding of "hard metal" -- a tungsten alloy used in the tool and die industry and infamously seen among diamond cutters) can occasionally cause disease (Eur. J. Resp. Dis. 69: 83, 1986). The chief culprit is probably cobalt (Chest 95: 2 & 29, 1989) with a contribution from nickel (Thorax 45: 267, 1990). αTNF is implicated as culprit in the pathophysiology: Am. Rev. Resp. Dis. 146: 1600, 1992. Giant cells without good granulomas are typical. Recreational or industrial inhalation of talc powder produces a picture overlapping silicosis and asbestosis (AJR 188: 326, 2007).
* "Muddy lung" caused the bizarre, prolonged death of a race-car driver who was submerged in muddy water after an accident. This may be the record for granulomas in the lung. Am. J. Clin. Path. 83: 240, 1985.
The inorganic pneumoconioses are often "mixed", depending on type of exposure and complications.
* For example, "dental technician's pneumoconiosis" is due to inhalation of a mixture of silica, asbestos, vitallium, and other curious substances.
"Black lung" changes its meaning as the laws change.
Like most diseases, the inorganic pneumoconioses are incurable.
Some of the coal dust may be lavaged from the lungs.
ORGANIC PNEUMOCONIOSES:
Allergic diseases caused by spores, fibers, etc. They are more important than their omission from certain pathology textbooks would indicate.
Type I (IgE-mediated, asthma) and/or type III (immune complexes, vasculitis) & IV (cell-mediated, granulomatous) reactions are the mechanisms of tissue injury. This is bad.
Usually patients recover, usually with little or no fibrosis, but repeated exposure causes the disease to recur. Treatment is directed against the hypersensitivity reaction.
{27639} bowling ball manufacture; rumors of dust disease
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COAL WORKER'S PNEUMOCONIOSIS (CSP, "black lung"): Path standards: Arch. Path. Lab. Med. 103(8), 375-432, 1979 (still the best); update for clinicians Am. J. Resp. Crit. Care Med. 187: 1178, 2013.
{27458} coal miner
{27514} coal workers
BOOP simulating coal dust disease |
A complex pneumoconiosis:
Lesions attributed to COAL DUST itself in the parenchyma ("simple CWP", i.e., the coal macule)
INDUSTRIAL BRONCHITIS caused by irritation of the airways by inhaled dust
Lesions of SILICOSIS (anthracite coal contains more silica, but bituminous coal workers get silicosis too, and any miner who cuts through rock and inhales the dust faces a terrible danger)
Lesions possibly due to AIR POLLUTION (miner's wives have historically also suffer severe respiratory symptoms)
Lesions of CIGARET SMOKING (much disabling "black lung" has resulted from cigaret smoking!)
Lesions of co-existing TUBERCULOSIS (thankfully, in the industrialized nations this seems to be disappearing among coal workers: Chest 126: 622, 2004)
Lesions resembling very large RHEUAMATOID NODULES ("Caplan's syndrome" generally the patient also has rheumatoid arthritis)
Lesions not easily accounted for by any of the above -- notably PROGRESSIVE MASSIVE FIBROSIS ("genuine black lung").
SIMPLE CWP: the coal macule (MACULE means "spot")
Focal accumulations of coal dust in the lung. Coal macules are considered practically harmless.
Patients with simple CWP rarely have serious respiratory problems unless there is additional pathology (silicosis, TB, Caplan's, progressive massive fibrosis, cigaret damage).
Coal macules do not grow after coal dust exposure ceases, though patients will cough up black dust ("melanoptysis") for years afterwards. This will impress the miner (and the politicians), who may believe this indicates serious disease.
Gross pathology:
You can feel the coal macules as ~1 mm, hard black bumps. These are located at the centers of pulmonary lobules (i.e., around respiratory bronchioles).
Microscopic pathology:
Aggregates of carbon-laden macrophages within a reticulin network. There is no dense fibrosis. There is mild focal stretching of air-spaces ("emphysema") around the bronchiole, but (in non-smokers!) this has traditionally not been held to impair respiratory function.
When there is progressive massive fibrosis, there's no question that it did.
When the patient has chronic bronchitis (i.e., a great deal of phlegm production, cough, and shortness of breath), does not have some mimic (i.e., adult-onset cystic fibrosis), has little or no tobacco smoking history, and spent a lot of time with heavy exposure to coal dust, you should feel comfortable attributing the illness to coal dust exposure. It helps if you see coal macules on x-ray.
In any other situation, you won't find things easy to sort out. There are many different levels of inhalable dust exposure in the coal industry. There are also different types of dust. Coal is ranked by carbon content. Even in a "soft coal" / "high rank" mine, where the coal itself contains very little silica, someone may be exposed to silica dust (which unlike coal is fibrogenic) while cutting through rock. "Low rank" coals containing huge amounts of silica.
Coal companies monitor their workers by chest x-ray and now offer retirement incentives to miners with heavy dust burdens. Workers' Comp claims usually want some radiographic evidence of dust exposure. In asbestosis cases, there's a fair correlation between abnormalities on chest x-ray and clinical disease, in silicosis less so, and in coal exposure the least. The Department of Labor has standards for reading x-rays of people making black lung claims, and a radiologist can get certification as a reader. The International Labor Organization uses the 12-point Liddell scale for simple pneumoconiosis. (For example, 0/1 means "I think it's normal, but I hesitated for a moment.") The ILO also defined "pneumoconiosis" as a profusion of opacities 1/0 or greater. "Simple pneumoconiosis" has opacities less than 1.0 cm. (Any larger is by definition "complicated"). The old work shows they're a fairly good measure of total lung coal burden.
"Chronic bronchitis" has the same definition in a coal worker as in a smoker -- defined clinically as cough, sputum production, shortness of breath, and wheezing.
The physical examination of the lungs may be normal, even in someone with obvious silicosis by history and x-ray. And there is still plenty of silicosis especially in older US coal miners who cut rock (Am. J. Ind. Med. 16: 605, 1989); in today's poor nations the problem is still terrible (Ann. Occup. Hyg. 50: 197, 2006 -- Tanzania).
The most troublesome situation is when a heavy-smoking coal-worker claims that part of the disability is due to coal dust exposure.
How do you sort this out? Here are facts and references you will find helpful.
Ordinary anthracosis of the lung |
Anthracosis
|
{08762} anthracosilicosis
In our polluted times, carbon pigment is present in the lungs of every adult. This is ordinarily called ANTHRACOSIS.
PROGRESSIVE MASSIVE FIBROSIS
PMF is variously defined to be many nodules 1 cm across or larger and/or one or more circumscribed areas of dense black scar-like tissue, usually in an upper lobe.
In the US, in the absence of silicosis, PMF is uncommon, affecting less than 1% of those exposed to coal dust. However, there is plenty of PMF in the poor nations (Chest 125: 1052, 2004) and it is as lethal as ever.
"Fibrosis" is a misnomer, as there is not nearly so much collagen in these lesions as you'd find in a scar or a silicotic nodule
Collagen: 20-30%
*Calcium phosphate: 1-30%
*Glycosaminoglycans: 10-20%
*IgA and IgG: several % (but no IgM)
Coal: up to 20%
*All the rest is "amorphous protein" including fibronectin
The etiology of PMF is still obscure, but is probably immune-mediated and caused by the carbon itself.
* Thinking about etiology focuses on rupture of carbon-filled hilar lymph nodes, with discharge of their contents into the air spaces. This makes the most sense.
* A PMF-like lesion can be induced in immunologically altered animals by giving coal dust, and PMF occurs in graphite and carbon electrode workers.
For whatever reason (reporting bias, changes in pattern of recognition, mystery factors), successful PMF claims increased tremendously in West Virginia during the first decade of the 21st century (Chest 139: 1458, 2011).
PMF is progressive and lethal. Death usually occurs within a few years. There is no treatment.
{49094} progressive massive fibrosis
{35063} progressive massive fibrosis
CAPLAN'S SYNDROME: very large rheumatoid nodules in coal workers who happen to have rheumatoid arthritis (or maybe lupus or scleroderma or polymyositis-dermatomyositis) with an inorganic pneumoconiosis.
Sometimes big rheumatoid nodules fill the lungs in these workers. In CWP with Caplan's, they are inky black, and they may be part of a continuum with PMF.
Coal dust and cancer: coal dust exposure places a worker at increased risk for stomach cancer, but not for any other common cancer.
Future pathologists: Crack cocaine smoking can impart considerable black pigment to the lungs. The blackest lungs in the world are probably seen in those who live in primitive housing with a great deal of smoke ("hut lung" -- Chest 144: 323, 2013). Some of these people suffer serious disability and there is a cancer risk.
SILICOSIS: Common and deadly; until recently the most serious occupational disease. All about silicosis: Lancet 379: 2008, 2012; Arch. Path. Lab. Med. 112: 673, 1988 (great pictures); historians see Science 256: 116, 1992.
The silicosis industries:
Sandblasting
Mining and tunneling (silicosis is still a major problem in third-world mines: Chest 113: 340, 1998;
Am. J. Resp. Crit. Care Med. 153: 706, 1996)
Foundries
Gun-flint industry
Sandstone industry
Granite industry
Pottery industry
Metal grinding
Manufacture of abrasive soaps
* Kaolin (china clay, mild because kaolin is really feldspar -- Thorax 41: 190, 1986; Am. Rev. Resp.
Dis. 138: 813, 1988; silicosis in a U.S. toilet factory: MMWR 41: 405, 1992)
* Manufacture of Japanese rush mats (who would have thought? -- Chest 125: 737, 2004).
* Contemporary "artificial stone"
{27461} sandblaster
{27462} sand mold lining
{34985} sandblaster
Mt. St. Helen's volcano survivors are not developing chronic silicosis (Am. Rev. Resp. Dis. 133: 526, 1986), but silicosis is common in areas of the world where sand-storms occur (Thorax 46: 334 & 341, 1991).
Tetrahedral crystals of silicon dioxide make up much of the earth's crust.
The tetrahedral configuration is essential to fibrogenicity; octahedral and other forms of silica, as well as other non-silica crystals with sharp edges (powdered diamonds, etc.) do not cause collagenization.
* Mixed rock dust disease ("silicatosis"; the term didn't catch on) is essentially silicosis.
Ideas about how silica causes fibrosis no longer emphasize death of macrophages. However they do their damage, tetrahedral silica crystals have potent effects in biologic membranes.
The hydroxyl groups on the surfaces of the crystals are arranged to interact efficiently with the -NH3 and -PO4 groups in lipids. (This is called "contact catalysis".)
* Free radical formation with peroxidation of membrane lipids is probably also involved. Interestingly, fresh-cut silica powder bears free radicals on its surface for several hours, and it is much more fibrogenic in the short-term than old-cut silica powder.
* Further, silica crystals directly activate C5a which attracts phagocytes.
The silica crystals seem mostly to affect macrophages. The steps leading to fibrosis are being worked out.
In the classic model of silica fibrogenesis, a macrophage (sometimes a neutrophil) ingests an inhaled silica particle, which is taken into phagolysosomes. The crystal disrupts the phagolysosome membrane, releasing the hydrolytic enzymes and killing the phagocyte. (The silica particle is then ready for phagocytosis by another phagocyte....) The breakdown products of macrophages are chemotactic for other phagocytes and finally promote collagen formation. This works in vitro, but is probably only a minor mechanism in vivo -- silica-laden macrophages washed from the lungs of workers usually seem quite healthy.
Current thinking focuses instead on inappropriate production of interleukin 1, inflammasomes (do you know about these?) and other factors by macrophages following contact with silica.
* A particular allele for α-TNF predisposes to much more severe silicosis (Am. J. Resp. Crit. Care Med. 165: 690, 2002).
Gross pathology of silicosis:
Pleural adhesions, silicotic nodules, eggshell calcifications (why?) in lung and lymph nodes, and silicotic nodules around the respiratory bronchioles ranging in diameter from 0.1 to 5 mm. (Several nodules may become confluent, and nodules may occur outside the lungs as crystals travel via lymphatics. See Hum. Path. 16: 393, 1985. Massively packed, expanding lymph nodes in the mediastinum can occlude the pulmonary artery (Br. J. Rad. 74: 859, 2001).
The lesions are most abundant in the middle lung fields, with some sparing of the bases; no one really knows why -- perhaps lymphatic clearance is better here, or more air and thus particulate matter reaches the mid-zones than the bases. Only in the most extreme cases do they become confluent ("conglomerate silicosis").
The silicotic nodule consists of:
{12437} silicotic nodules
{28760} silicosis
{28763} silicosis
{28766} silicosis
{28769} silicosis
{35000} silicosis
{49096} silicosis
{35057} anthracosilicosis
Silicosis and silicatosis |
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Variations:
SILICOTUBERCULOSIS: Silicosis with TB, a very common combination (because of poor macrophage function? poverty? probably both....)
CAPLAN'S SYNDROME: silicosis (or another inorganic pneumoconiosis) with autoimmune disease. (As in CWP, usually the autoimmune disease is rheumatoid arthritis or systemic lupus.
The active surface of the silica crystals possibly alter the patient's proteins to make them antigenic. Interleukins could be another problem.
ANTHRACOSILICOSIS: silicosis with coal worker's pneumoconiosis. Both simple coal macules (which most pathologists do not think will grow once exposure is stopped) and early silicotic nodules (which are infamous for growing after exposure stops) can look the same on x-ray. The diagnosis is made on biopsy, clinical history, or occupational history.
SIDERSILICOSIS: silicosis with iron oxide dust
ACUTE SILICOSIS ("alveolar silicoproteinosis"):
After a massive dose of silica particles, all the alveoli fill with proteinaceous fluid, surfactant, and necrotic mononuclear phagocytes. The patient dies in a few days to a few months.
The dose of silica overloads the periarteriolar lymphatics that go directly to the hilum. The silica is transported instead to the alveoli, where it is phagocytized by, and destroys, the type II pneumocytes.
Patients are usually sandblasters and rock drillers who fail to wear protective masks. Acute silicosis led to the World War II graffiti: "Join the Navy and see the world, become a sandblaster and see the next."
No joke; acute silicosis still exists. See Lancet 337: 344, 1991; Am. Rev. Resp. Dis. 143: 880, 1991 ("Ajax cleanser snorter"); AJR 189: 1402, 2007.
Alveolar proteinosis from silicosis
Lung pathology series
Dr. Warnock's Collection
Glucocorticoids for silicosis sufferers: Am. Rev. Resp. Dis. 143: 814, 1991.
* Interleukin 13 bound to pseudomonas immunotoxin seems to be a miracle-medicine for an animal model of silicosis, confirming that the havoc is mediated by macrophages factors and suggesting a possible treatment (J. Immuno. 191: 5220, 2013).
ASBESTOSIS: Update Chest 125: 744, 2004. The mineral Sci. Am. 272(1): July 1997. Counting asbestos fibers for pathologists: Arch. Path. Lab. Med. 134: 457, 2010.
Asbestos is a family of fibrous minerals, hydrated silicates of sodium, iron, calcium, magnesium. It is VERY dangerous stuff, and asbestos-related disease has been under-diagnosed. All types of asbestos are dangerous, * though chrysotile (serpentine, curved fibers) seldom reach the pleura.
Asbestosis follows heavy or prolonged exposure to airborne asbestos fibers, and progresses even if dust exposure ceases.
One million people in the US have industrial exposure (workers, neighbors). There are probably 70,000 cases of asbestosis here today. Spray-on asbestos was the worst. (See Postgrad. Med. 74: 93, Oct. 1983.)
Some of the heaviest exposure of the most people was in shipyards before 1970. (* Great historical article in CA 28: 87, 1978.)
* Asbestos is also used in insulation, fire-proofing, cement, water mains, brake linings, oven cloths, linoleum, ironing boards, gloves, fireman's suits, linings for chemical pans, theater curtains, acid-resistant filtering cloths, etc. etc. In Greece and nearby, asbestos is used for whitewash ("Metsovo Lung", Chest 99: 1158, 1991).
In the poor nations, workers enjoy no protections. A review of the asbestos "cancer epidemic", which we may reasonably think will cost 10 million lives worldwide: Env. Health Perspect. 112: 285, 2004. Update on asbestos exposure as a brutal fact of the workplace in "developing nations": Postgrad Med. 123(3): 116, May 2012.
If you, the physician, are asked about possible asbestosis, you must remember a notorious fact: the chest x-ray is neither sensitive (NEJM 298: 934, 1978, still good) nor specific (Chest 124: 1120, 2003) in determining whether someone with exposure has disease.
Thankfully, today in the US we seldom see the classic asbestosis cripple with obvious restrictive lung disease on spirometry, or obvious diffuse pulmonary fibrosis on imaging (Chest 125: 744, 2004). When we do, it looks the same as UIP/Hammman-Rich (Radiology 229: 731, 2003), just as on microscopy, and the old idea that asbestosis involved the upper lobes more was discredited.
See Science 247: 294, 1990 for the reasoning that ended the asbestos removal initiative. The Environmental Protection Agency (August 1990) reversed itself on the business of asbestos removal from schools and other public buildings, and now recommends removal only when buildings are to be demolished. This sensible action recognizes that undisturbed asbestos is no health threat, and that asbestos removal, (which re-introduces the material into the air) is dangerous. Perhaps the politicians also realized that asbestos removal would have cost the nation around $150,000,000,000; the whole episode is now discussed as a classic example of education finally overcoming hype and hysteria (JAMA 266: 696, 1991).
In 2001, the EPA told everybody not to worry about the tons of asbestos that went swirling through Manhattan from the World Trade Center collapse. Sensible -- but what a reversal from the old "one fiber is too many" ideology.
Asbestos fibers that remain in the lung are long (several microns) and slender (around 0.5 microns). The size and shape of the straight asbestos fiber appear to cause it to be carried preferentially to the pleural surfaces. Think about a needle, sharper at one end, moving through lung.
Gross pathology:
Marked pulmonary interstitial fibrosis (i.e., actual fibrosis of alveoli and collagenous thickening of the alveolar-capillary membrane.
Unlike silicosis, the fibrosis is diffuse rather than nodular, involving mostly the alveolar septa. It tends to be worst at the bases; no one knows why -- perhaps the particles (which are much heavier than silica particles) tend to end up in the dependent areas just from the effects of gravity during inhalation.
Future pathologists: Here's how to grade the lesions!
Most cases have 10,000 to 100,000 fibers per gram of wet lung, which means you'll see maybe 3-4 fibers in a section if you look hard.
Pleural and subpleural fibrosis develop before there is much pulmonary fibrosis. Large, dense fibrous plaques form on both parietal and visceral pleura. They may calcify and are occasionally visible on chest x-ray. These may be accompanied by chronic bleeding into the pleural spaces. Asbestos pleural disease: Chest 99: 191, 1991).
Microscopic pathology:
Marked peribronchiolar and (later) alveolar interstitial fibrosis and many asbestos bodies. Often whole alveoli are obliterated. Granulomas form early in involved areas, but have undergone fibrosis by the time the patient comes to autopsy (Exp. Mol. Path. 44: 207, 1986).
Asbestos bodies ("ferruginous bodies") are characteristic. They are 10-200 microns long, 1-6 microns wide; golden-yellow beaded rods formed when asbestos (or talc, or other) fibers are coated by protein in the body. They are most plentiful beneath the pleural surfaces.
{27472} asbestos on the pipes
{36190} ferruginous body
{39685} ferruginous body
{09834} ferruginous body, special preparation (darkfield?)
Ferruginous body |
Fibrous pleural plaque |
Asbestosis
Lung pathology series
Dr. Warnock's Collection
Only a few of the fibers get coated, and in symptomatic asbestosis, a gram of dry lung tissue may contain more than a million asbestos fibers. Today's standard seems to be 1000 perticles per gram of dry lung as an indicator of occupational disease (Am. J. Clin. Path. 117: 90, 2002).
Chrysotile -- white asbestos, the commonest form -- is seldom coated, is less likely to reach the pleura, and dissolves more readily than the other forms. Nevertheless, it's dangerous and is clearly linked to mesothelioma (Cancer 67: 1912, 1991).
The finding of an asbestos body in sputum or pulmonary lavage fluid is not diagnostic of clinical asbestosis. Most city-dwellers have a few in their lungs and solid particles of all sorts tend to be released during episodes of pulmonary edema. However, the more you have in your lavage fluid, the more likely you are to have serious asbestosis (big study Chest 126: 966, 2004).
* Standards for pulmonary pathology of asbestosis: Arch. Path. Lab. Med. 106: 544, 1982 (still good).
The mechanism of fibrogenesis in asbestosis is probably similar to that in silicosis.
Magnesium atoms spaced along the surface of a fiber react electrostatically with sialic acid residues on surface glycoproteins of cells, immobilizing them. (See Lab Invest. 49: 468, 1984; Chest 89(S3): 156 S.) Asbestos fibers also activate complement, attracting phagocytes.
As in silicosis and PMF, there is much discussion of altered immunity, but little is known (Chest 91: 110, 1987). * Like silica, asbestos is a potent activator of C5a.
Even in the absence of pulmonary fibrosis, asbestos-exposed people are at special risk for several forms of cancer.
No one knows exactly how asbestos does its mischief in causing cancer. Asbestos fibers tangle chromosomes -- Am. J. Path. 126: 343, 1987. Or perhaps it works by altering surface EGFR (Am. J. Path. 152: 333, 1998). Or it simply causes apoptosis of cells that it contacts (Am. J. Path. 174: 2324, 2009).
Asbestos is the principal risk factor for MESOTHELIOMA ("Steve McQueen's cancer" -- he worked on his own motorcycle, including the asbestos-lined brakes, and inhaled huge quantities of asbestos while working in a military brig).
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The mechanism is still unknown (old work Am. J. Path. 128: 410, 1987; Env. Health Perspect. 81: 81, 1989; Br. J. Ind. Med. 50: 673, 1993). It is not generally considered a mutagen (a few obscure papers mention a possible effect), but scrambles chromosomes when cells containing an asbestos fiber divide. Of course, it causes epithelial cell death and replacement, making it a promoter. Concurrent cigaret smoking does not increase the risk.
Most mesotheliomas involve the pleura or, less often, the peritoneum.
One of the most infamous trick questions in medical-school pathology is, "Asbestosis most often causes which cancer?" The answer is "common bronchogenic carcinoma" rather than "mesothelioma".
Mesothelioma Information Group
Resources and advocacy
Also asbestosis and bronchogenic CA
Mesothelioma Group
Support community
"Mesothelioma Symptoms"
Resources and advocacy
I liked the frank talk about mesothelioma quackery
Pleural Mesothelioma . com
Internet friend
A high mortality rate (20%, up to 50% for smokers) due to the common types of lung cancer has been reported in U.S. asbestos workers, even those with fairly low exposure and without clinical asbestosis. For common lung cancers ("bronchogenic carcinoma"), cigaret smoke and asbestos are obviously synergistic, perhaps because tobacco carcinogens adsorb onto the asbestos fibers.
It's taken until 2013 to prove with statistics, but non-smoking asbestos workers actually are at increased risk for the common lung cancers (Am. J. Resp. Crit. Care Med. 188: 90, 2013.)
Asbestos exposure also clearly increases the risks of laryngeal and GI cancer, and perhaps malignant lymphomas.
Other carcinogenic dusts:
Chromium: cancer of the nasopharynx and/or lung
Nickel: cancer of the lung
* Your lecturer does not believe that silica is a carcinogen, but it is currently classified as such by some government agencies. Stay tuned.
{27494} asbestos and lung cancer
However, the majority of asbestos workers seeking compensation have breathing problems still due primarily to heart disease or cigaret smoking (Am. Rev. Resp. Dis. 135: 812, 1987).
* Tobacco smoking greatly increases the amount of peribronchiolar fibrosis -- which was surprising when it was discovered (JAMA 259: 370, 1988); more recently, we've come to recognize that some, but not most, smokers get this "obliterative bronchiolitis", and probably asbestos exposure is part of the explanation (your lecturer's prediction... stay tuned.)
The asbestos companies knew the dangers long, long ago: JAMA 265: 898, 1991.
* You may enjoy visiting the informational site of mesothelioma lawyers
here or here
or here
or here
(not endorsements, but an instructive read for young doctors -- Ed).
* It takes almost no time or effort to make up and publish a shameless
lie. If the lie is ugly or stupid enough, some people will choose to believe
and act on it, simply to feel "moral" / "spiritual".
And refuting the lies of others is a hard, thankless task.
In 1999, an e-mail campaign
warned about big commercial tampon
manufacturers putting asbestos in cotton tampons to make women
bleed heavier and longer. Of course this was simply made up.
I traced it as
far as I could, and found a culture warrior (left-wing)
who linked her endorsement
and promotion of the
claim with her mail-order "natural" tampon company. She also
mentioned that she founded this company
"to get herself off welfare". I am not making this up. Although
I do not understand why tampon cotton needs to be bleached, the
business about the bleaching process generating agent orange
and causing toxic shock syndrome wasn't true, either. And the persons
cited as the authors of the e-mail vociferously denied having written
it.
BERYLLIOSIS (Chest 109(3S): 40-S, 1996)
Due to inhaled beryllium, which activates macrophages and T-helper cells (NEJM 320: 1103, 1989). Thanks to public health measures, there are fewer opportunities to get berylliosis today -- but the Rocky Flats epidemic of the 1980's and the Toledo epidemic of the 1990's should reminded us that powdered beryllium is still dangerous.
In the past, the greatest peril was in the rocket and fluorescent bulb industries.
The typical lesion of chronic berylliosis is granulomas and interstitial fibrosis of the lung. You may or may not see necrosis. Sensitization takes a while but tends to progress (Am. J. Resp. CCM. 171: 54, 2005); thankfully the vast majority of those exposed never get sick (J. Clin. Inv. 110: 1473, 2002; the key is the immunology).
Cutaneous berylliosis also showed the non-necrotizing granulomas. These patients had scratched themselves on old fluorescent light bulbs.
The lesions are practically identical to those of sarcoidosis. If you need to distinguish the two diseases using the lab, we can check for berylliosis.
* Only a minority of exposed people are vulnerable to this disease (i.e., most people are non-reactive to beryllium). Those who can get it had glutamate in position 69 of the HLA-DPβ1 chain (Science 262: 197, 1993; a robust finding now J. Imm. 163: 1647, 1999; update on the molecules J. Immuno. 189: 4014, 2012).
* The Rocky Flats fiasco: Allied Occup. Env. Hy. 16: 405, 2001; Env. Health Perspect. 104 (S5): 981, 1996. Some folks got sick, notably about 10% of the beryllium machinists, but it was not a massive disaster as it has been portrayed. Probably the neighbors were not endangered (Env. Health Perspect. 107: 731, 1999). However, neighbors to the old (1950's-1960's) beryllium foundries are still showing up with newly-diagnosed berylliosis (AMRCCM 177: 1012, 2008).
{27503} berylliosis
Beryllium lung and sarcoid
Lung pathology series
Dr. Warnock's Collection
* There was also an acute, "irritant" pneumoconiosis.
* Zirconium dust produces the same picture; "deodorant granulomas" were from zirconium.
* PAINT-SPRAYER'S LUNG resulted when poor workers were forced to inhale spray-paint in a Spanish factory, the bosses falsely reassuring them that the respiratory distress was harmless. The histopathology was that of a cryptogenic organizing pneumonia (Arch. Bronch. 31: 89, 1995).
HYPERSENSITIVITY PNEUMONITIS / EXTRINSIC ALVEOLAR PNEUMONITIS (FARMER'S LUNG and variants)
Hypersensitivity pneumonitis
Lung pathology series
Dr. Warnock's Collection
In classic farmer's lung, victims are sensitive to spores from moldy hay, etc. (Micropolysporum, Thermoactinomyces -- these "molds" include allergenic bacteria). Both farmers and their animals are susceptible.
{27489} farmers in moldy hay
Non-farmers can get a similar disease from heat-loving bacterial spores in air-conditioners ("humidifier fever", etc.), cardboard, etc. (See JAMA 258: 1210, 1987).
Clinically, an exposed farmer can present either with asthma (usually not serious) or genuine farmer's lung (often VERY serious). Don't be surprised if the illness is biphasic.
Asthma ("early phase"): transient IgE-mediated syndrome with bronchoconstriction (wheezing, etc.)
Real farmer's lung ("late phase"): IgG-mediated type III-injury vasculitis ("extrinsic allergic alveolitis"; "hypersensitivity alveolitis") which may be serious. It can be acute, subacute, or chronic. In really bad cases, there may be granuloma formation, tissue necrosis, fibrosis (Am. Rev. Resp. Dis. 133: 88, 1986), etc.
Precipitating IgG antibodies against the offending mold can be demonstrated in the patient's serum (and in the serum of many asymptomatic farmers, too; Thorax 44: 469, 1989). For a review of the diagnostic immunology of the organic pneumoconioses, see Clin. Lab. Med. 4: 523, 1984.
BAGASSOSIS: farmer's lung caused by molds in dry sugar cane.
* Other forms of "extrinsic allergic alveolitis":
"Animal house lung": fraternity party with straw (JAMA 258: 1219, 1987)
Woodworker's pneumoconiosis (including "sequoiosis" from redwood mold)
Mushroom worker's lung (Chest 122: 1080, 2002)
Cheese worker's disease
Grain handler's pneumoconiosis (Can. Med. Assoc. J. 133: 969, 1985)
Malt worker's pneumoconiosis
Pigeon keeper's lung ("bird-fancier's lung"), from pigeon proteins
Pituitary snuff taker's lung (diabetes insipidus victims)
Portuguese cork-worker's lung (suberosis)
Sisal-worker's disease
Hungarian paprika-splitter's disease
Tea-maker's asthma
Coffee bean dust disease
Furrier's lung
Sudanese bat-guano asthma (Lancet 1: 316, 1987)
Leather waterproofer's lung (Br. Med. J. 292: 727, 1986)
Zimbabwe ivory-carver's lung (Thorax 43: 342, 1988); save the elephants
Silkworm dropping lung (Thorax 45: 233, 1990)
You can benefit many of these people by installing electrostatic dust filters (Ann. Int. Med. 110: 115, 1989). A face mask for hay-time: Chest 95: 100, 1989. Some organic pneumoconiosis patients have poor T-cell responses (Thorax 44: 132, 1989); this has never gotten sorted out.
Now this is serious.... Without a history, you will probably not be able to tell chronic hypersensitivity pneumonia from "usual interstitial pneumonia" / "idiopathic pulmonary fibrosis". Even with a history, you may need a biopsy. Again, the keys are (1) fibrosis in chronic hypersensitivity pneumonitis centers around the bronchioles, and (2) chronic hypersensitivity pneumonitis usually has granulomas, which are generally loose unlike those in sarcoidosis. Despite the term "hypersensitivity", you will not see eosinophils in the chronic form. Review Chest 134: 126, 2008.
BYSSINOSIS / "COTTON DUST LUNG DISEASE" (cotton, flax, hemp processing; update Curr. Op. Pulm. Med. 13: 137, 2007)
Cotton dust disease is thankfully becoming much less common, at least in the US. This is good; the most recent autopsy series was Thorax 30: 612, 1975.
Nobody questions that fibers from vegetable textiles are noxious and irritating. Type III hypersensitivity to Enterobacter agglomerans contaminating the cotton is often blamed.
Traditional pathology texts describe "monday morning asthma". This is the only organic pneumoconiosis in which there is prolonged wheezing.
Here's the familiar story. On Monday, lots of guys at the cotton mill report not feeling well, particularly with tightness in the chest. This may be in the morning, but is often delayed until afternoon. On the following days, there's much less discomfort.
Old discussions of "sufficient mediators accumulating only over the weekend, and being consumed during the episode" make sense, but leave unanswered the question "Which mediator(s)?" Certainly not histamine, and leukotrienes aren't even stored.
About a third of cotton workers get symptoms, and after many years, these tend to become more lasting.
"Brown lung" is claimed by some textile workers to be a major cause of chronic respiratory disability, and the autopsy series shows thickening of the muscle of the large airways, mucous gland hyperplasia, and these correlated with obstructive patterns on pulmonary function testing even considering concurrent emphysema.
Much of the problem, of course, is due to cigaret smoking. However, there's more respiratory disease than in other factory workers, and the airway narrowing is cumulative with what one would expect just from smoking (though smoking generally does more overall damage to individual workers.)
A Japanese group described a granulomatous interstitial disease with cotton fibers in giant cells (Thorax 59: 1095, 2004).
WORLD TRADE CENTER LUNG (WTC-SLGPD, or "sarcoid-like granulomatous pulmonary disease"): Chest 131: 1414, 2007
There is also extensive granulomatous change, both in the lungs and often outside, just as in sarcoidosis.
There is also considerable wheezing as in asthma, with airway hyper-reactivity. Stay tuned on this challenging disease in this heroic population.
BIBLIOGRAPHY / FURTHER READING
I urge anyone interested in learning more about the pneumoconioses to consult these standard textbooks.
In my notes, the most helpful current journal references are embedded in the text. Students using these during lecture strongly prefer this. And because the site is constantly being updated, numbered endnotes would be unmanageable. What's available online, and for whom, is always changing. Most public libraries will be happy to help you get an article that you need. Good luck on your own searches, and again, if there is any way in which I can help you, please contact me at scalpel_blade@yahoo.com. No texting or chat messages, please. Ordinary e-mails are welcome. Health and friendship!
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