Thursday, January 05, 2012

1957: The invention of the rescue inhaler x

When Americans unite and put their minds and imaginations together in a quest to obtain a united goal, anything can be accomplished.  This was what occurred during WWII.  While war is bad, it can bring about many good things.  In this way, the metered dose inhaler -- the rescue inhaler you have in your pocket right now -- is a byproduct of war.

A 1957 ad for the Riker inhaler (a)
Allied troops fighting in the fields of Europe were often infested with bugs that caused Malaria.  This was impeding the war effort.

To remedy this problem the U.S. Government hired researchers to come up with a bug repellent that would help allied soldiers attack bugs.

Lyle Goodhue and William Sullivans must have first looked to the past to find a solution.  They would have learned that in 1790 pressurized aerosols were introduced in France to create carbonated beverages.

They would have learned that in 1837 the first spray can was made of heavy steal in Perpigna.  The can had a valve in it that allowed it to create the spray.  Several prototypes were tested in 1862, although nothing ever came of it. (1)

They would have learned that in 1927 a Norwegian man named Erik Rotheim patented the first spray can that was capable of holding pressurized contents and spraying them.  It's now considered the forerunner of modern spray cans.

Goodhue and Sullivans then took these old ideas and combined them with ideas of their own and came up with a design capable of carrying a pressurized propellant called flurocarbon.  The bug spray was added to the propellent and the spray can allowed for the bugs to be sprayed and killed.

So while the first spray cans were used to hold bug sprays during the war, the concept soon evolved to other products, such as paint and perfume.  It was the perfume market that Riker Laboratories (a subsidiary of what is now 3M Pharmaceuticals) was thinking of when it started tinkering with this product.  They wanted to create a spray perfume. (2)

Yet Riker researchers soon realized there was a demand by asthmatics for a convenient to use and portable spray can for asthma medicine.  This was how the first inhaler came to fruition.  In 1956 Riker inventors created the asthma inhaler market with a Medihaler-Epi that contained epinepherine and medihaler Iso that contained Isophrenaline.

The Riker inhaler was a major breakthrough.  This product was incorporated with the first ever actuator with a one-way valve that allowed for the medicine and propellant to be sprayed in a uniform dose (a metered dose), and soon became known as the metered dose inhaler (MDI).  The Medi-Iso delivered a metered dose of 0.15 mg and the Medi-Epi delivered a dose of 0.06 mg.  The inhalers were  easy to use, provided fast relief, and were easy to lug around. (2)

The design of this original inhaler was very similar to many of the inhalers we lug around today, such as the Ventolin inhaler.  It could easily fit into a boy's front pocket or a mom's purse, and using it was as as easy as squeezing the actuator.

Electric nebulizers in the 1950s were large, bulky and made of glass.  They were also expensive, so many asthmatics had less expensive nebulizers that required them to squeeze a bulb to aerosolize the medicine.  Many asthmatics continued to smoke asthma cigarettes, insents, or other palliative asthma remedies.

So getting asthma relief was inconvenient when the medihaler was introduuced, and the relief given wasn't very good. So this was the market advertisers for Riker Laboratories aimed for when they started their first advertising campaign.

1956 ad for the Medihaler (b)
An old advertisement for the Medihaler (see image) used the inconvenience of these other devices as a marketing ploy:
Medihaler with your favorite bronchodilator:
  • No rubber bulbs to deteriorate
  • No breakage of costly glass nebulizers
  • No spilling of solution in pocket or purse
The Medihaler became an instant hit.  It, coupled with the discovery of theophylline, caused the market for asthma medicines to boom.

Gregg Mitman, in his book "Breathing Space: How allergies shape our lives and landscapes," explained that between 1972 and 1985 prescription drugs in the United States showed a modest 7 percent increase in the number of prescriptions filled.

During the same period, prescriptions for asthma drugs increased 200 percent."  The market for asthma inhalers was so bullish that other pharmaceutical companies raced to make their asthma remedies available as an inhaler.  (3)

Mitman further explained that the sale of asthma inhalers alone (both beta adrenergics and others), accounted for "25 percent of all prescriptions dispensed for the treatment of asthma in 1985."

So it didn't take long at all for pharmaceuticals, doctors and asthmatics to catch on to the convenience of the rescue inhaler.  Life for asthmatics changed forever, and for the better.


Click here for more asthma history.

References:
  1.  About.com, "History of spray cans,"  http://inventors.about.com/od/astartinventions/a/aerosol.htm (provides a good history of the spray can)
  2. Brenner, Barry E, ed., "Emergency Medicine," 1998, from chapter one "Where have we been?  A history of acute asthma," page 23
  3.  Mitmann, Gregg, "Breathing Space:  How allergies shape our lives and landscape, 2007,  page 237 (a great read if you want to learn more about the history of asthma/ allergies)
Pictures:
  1. (a)  Deco Dog, http://www.decodog.com/inven/medical2.html, you can purchase or check out old asthma inhaler ads here 
  2. (b)  Deco Dog, ibid

Wednesday, January 04, 2012

1933-1957: Research leads to asthma rescue medicine

So hormonal therapy was first used therapeutically in the late 19th century, and by 1901 epinephrine was isolated.  This set off a series of experiments to synthesize and learn about the actions of epinephrine on the body.

It was soon learned that the hormone adrenaline was a neurotransmitter.  It was released by the adrenal gland in response to stress, and attached to receptors that lined smooth muscles and vessels throughout the body.  This results in vasoconstriction that resulted in increased rate and force of the heart, increased cardiac output and blood pressure.  It also caused smooth muscle dilation, including dilation of bronchioles to make breathing easier.

This theory was basically rejected by the medical and scientific community and considered a speculative theory.  Yet in the year 1933 the theory was proven and validated, and slowly but surely these theories were accepted, and interest peaked so much that the two of the researchers responsible for this theory were given the noble prize.

This knowledge was extremely important for asthmatics, because the more scientists, pharmacists and physicians knew about how these medicines worked, the better medicine they could create. Once the theory was accepted, scientific progress continued.

1936: Iseotharene was synthesized as the first successful modification of epinephrine. (1)

1940s: Iseotharine was marketed as Aleudrin in Germany

1946:  Swedish physiologist and pharmacologist Ulf von Euler (1905-1983) discovered that norepinephrine (noradrenaline) not adrenaline (epinephrine), was the sympathetic transmitte responsible for sympathetic messages to be sent from the nerve ending to the effector site (smooth muscle, heart or vessel).  This is yet another method by which the sympathetic nervous system works. The idea that neurotransmitters worked in this was was postulated in 1905, only to be proved by von Euler.  He won the Noble prize with fellow scientists working with chemical transmitters Julius Axelrod and Bernard Katz.  (2,4,5)

1948:  Working with the research of van euler, Raymond Ahlquis (1914-1983) discovered that there are various types of receptor cells used by the sympathetic nervous system.   Beta 2 adrenergic receptors (B2) were discovered to line smooth muscles that wrap around air passages in the lungs.  When these receptors were stimulated these smooth muscles relaxed, and this dilated the air passages to make breathing easeir  Since this discovery, rescue medicine is sometimes referred to as beta-2 agonists, beta adrenergic agonist, or simply beta agonists. (2)

Alquist also discovered the following: (2)
  • Alpha Affect:  noradrenaline is stronger than adrenaline is stronger than isoprenaline
  • Beta Affect:  isoprenaline is stornger than adrenaline is stronger than noradrenaline (3)(4)
The idea here is that the "flight or fight" response initiates the adrenal gland to release epinephrine, which attaches to B2 adrenergic receptors and causes the bronchioles to dilate.  Beta adrenergic medicine (such as epinephrine) can mimic this response.  So such medicine that mimic the sympathetic system in this way are called sympathomimetic agents.  . 

The terms Beta 1 Adrenergic (B1) and alpha-1 adrenergics (A1) are also described by Raymond Ahlquis.  A1 and B1 receptors line smooth muscles in the heart and that wrap around vessels, and when stimulated the heart rate increases in rate and force.  Epinephrine was found to be attracted to B1, B2 and A1 receptors.  So this explained why the instant breathing relief came with cardiac side effects.  The quest was now on to create a drug that had a strong B2 effect without the B1 and A1 effect.

Isopretoronol was learned by Raymond Ahlquist to have a stronger B2 effect than epinephrine, yet it also had a strong B1 effect that caused the heart to speed up "even when administered via inhalation."  So Isopretoronol still had to be used with discretion. (2)

1951: Iseotharine was approved by the FDA and marketed as Bronkosol.   It became yet another option via the nebulizer route, although, like epinepherine, it only lasted one and a half to two hours. It was the first B2 specific rescue medicine to hit the market.   It had a stronger beta effect and less of an alpha effect.  It was marketed as the first B2 specific inhaled aerosolized bronchodilator.  Bronkosol had less of a B2 effect than Isopretoronol, yet it was more desirable because of the decreased cardiac affect.  The medicine still only lasted one and a half to two hours.  (2)

1954:   It should be noted here that Alquists experiments were initially rejected by many of his peers.  It wasn't until 1954, when he was invited by Victor Drill to write a chapter in Pharmacoloy in Medicine, that his ideas were accepted.  So, thankfully, "Ahlquist took advantage of the opportunity to promote his theory, which ultimately enabled it to gain general acceptance. The concept not only prompted fresh thinking about adrenergic receptor pharmacology, it also vaulted scientific research into new directions that would guide future drug development." (4)

1957:  The first metered dose inhaler hits the market.  Riker Pharmaceuticals introduced the Medihaler-Epi and the Medihaler-Iso which had epinephrine and isoprotoronol respectively.  For the first time ever asthmatics had a handy little inhaler to carry with them wherever they went.  The medicine provided instant relief from an asthma attack without the hassle of hunting down a doctor, or dealing with fragile and complicated nebulizers, solutions and hand held squeeze bulbs.  I wrote about this in more detail here.

Further reading:
Click here for more asthma history.

References:
  1. Brenner, Barry E, ed., "Emergency Medicine," 1998, from chapter one "Where have we been?  A history of acute asthma," page 23
  2. Rau, Joseph L., "Inhaled Adrenergic Bronchodilators: Historical Development and Clinical Application," at AARC.org (American Association of Respiratory Care, July, 2000, Vol. 45, number 7),
  3. Pang, Humphrey P., Maureen M. Dale, James M. Ritter, Rod J. Flower, Graeme Henderson, "Rand and Dale's Pharmacology," 2012, Esevier Churchill Livingstone
  4. Rubin, Ronald P., "A Brief History of Great Discoveries in Pharmacology: In Celebration of teh Centennial Anniversary of the Founding of the American Socieity of Pharmacology and Experimental Therapeutics," Pharmacological Reviews, December, 2007, vol. 59, no. 4, pages 289-359 (This article provides a good history of the discoveries of the sympathetic nervous system, the neuromuscular synapse, and how hormones such as adrenaline work)
  5. "Ulf on euler Biography (1905-1983)," faqs.org, http://www.faqs.org/health/bios/15/Ulf-von-Euler.html, acessed 3/9/13

1858-1929: History of nebulizers x

While we asthmatics should consider epinephrine the greatest discovery in the history of medicine, the greatest invention may be that of the nebulizer and inhaler.

Ancient doctors as far back as 10,000 B.C had access to various herbal remedies for asthma-like symptoms, and as early as 5,000 B.C. they learned the best mode of delivery was inhalation.  Yet the only methods they knew of were steam and smoke.

The Ancient Egyptians inhaled smoke from dried and crushed belladona burned on bricks.  Ancient Indians burned cigarettes with dried and crushed strammonium.  Insents were ultimately used as well.

As we travel forward to the mid 19th century not much has changed.  Enter any random home and you'll quickly be able to tell if an asthmatic lives there by the bittersweet smell of smoke wafting through the doorway  

Surely there were a few devices called nebulizers and inhalers at this time, yet they were large, bulky, fragile, hard to operate and very expensive.  Operating them was often difficult and time consuming, and the medicine available wasn't much good anyway.
Sales-Giron and his portable nebuliser (1858)*

The first nebulizer was actually produced in 1858 by a French inventor named Dr. Sales-Girons.   His nebulizer was unique in that it had a pedal that acted like a bicycle pump, and when pulled up air was forced through an atomizer and a mist was created to be inhaled.  (1)

(A picture and good description of this first nebulizer can be seen here at Inhalatorium.)

One thing to note as we delve into the past here is that nebulizers of old came by varying names.  Some were called atomizers, some nebulizers, and some inhalers.

The idea is that an atomizer refers to any device that converts a liquid to a fine spray.  Likewise, nebulizers and inhalers create an aerosolized mist to be inhaled.

So sometimes atomizers were referred to as atomizers, sometimes nebulizers, and sometimes inhalers.  Which name was used was left to the discretion of the inventor or marketer of the device.  And while some were called inhalers, they were nothing like the inhalers we use today.

Dr. Siegel inhaler (1872)
In 1864 Dr. Siegel invented Siegle’s steam spray inhaler that used the force of steam through a small tube to draw up the medicine and turn it into a vapour that is inhaled through a glass mouthpiece.  The principle used here is similar to modern nebulizers, only now we use air instead of steam. (2)

Siegel's invention is often considered the beginning of nebulizer therapy.

There were various attempts at copying Siegel's nebulizer, yet neither Siegel's nor any of the others were effective enough to become popular among asthmatics.  Again, the medicine available back then provided only minimal relief, and this fact probably made efforts to use these devices fruitless, and perhaps too expensive to make them worthwhile investments.

So the evolution of such devices was left at a standstill until the discovery of epinephrine in 1900. Now, for the first time ever, there was a medicine available that could end an asthma attack.   The only problem now was the asthmatic in need had to seek out a doctor and have the medicine injected into a vein.

Silbe hand-held rubber bulb nebulizer (1940)*
Doctors also quickly learned that the systemic delivery in this way of epinephrine into your body caused significant side effects, such as full and bounding heart rate, increased blood pressure, and hyperactivity.  The medicine also took several minutes to take effect.  Entrepreneurs sensed an opening to a new market, and searched for a device to help asthmatics better deliver this medicine.

By 1910 epinephrine was available as a solution to be nebulized, yet nebulizers continued to be too expensive and too difficult to operate to be of much use.  However, for those willing asthmatics, there were a few nebulizers available such as the:
  •  Silbe Atomizer:  A hand held nebulizer with a bulb syringe that had to be squeezed
  •  Colossol Nebulizer:   A glass nebulizer with a rubber squeeze ball
  • Glass Collosol Nebulator with rubber bulb*
  •  Volatilizer Inhaler:  Dr. Coulter's vaporizer and inhaler was called the champion Volatizer.  It was steam powered and made of copper, brass and nickel plate. (2)
In 1929 various bulb syringe nebulizers (like this one) were available.  The asthmatic would draw up some of the epinephrine from a small vial and mix it with some water in the nebulizer cup and then squeeze the bulb to create a fine mist that could be inhaled.

As you can guess, this took a lot of time, coordination, and even muscle strength to get an adequate amount of medicine aerosolized to do any good.  I had a bulb to connect to my nebulizer cup back in 1985 to use in case of a power outage, and I tried it once just for kicks.  It took forever just to get minimal results

1892 ad for Dr. Couilter's vaporizer & inhaler*
However, I suppose if that's all you had available, you'd squeeze that bulb as long as you had to.  Yet we asthmatics yearned for something better, simpler, cheaper and easier to use.  Aware of the possibility of a new market, many investors and inventors worked overtime searching for the ideal device.

By the 1930s asthmatics finally got what they yearned for when the first electric nebulizers hit the market.  These nebulizers were a reasonable size, generally inexpensive and easy to operate.  Asthmatics could now have access to epinephrine in the comfort of their own home right away when they needed it.

Aerosolized epinephrine worked faster, almost immediately giving the asthmatic relief from an asthma attack.  Since it was inhaled instead of injected into a vein, side effects were significantly diminished.  In this way, the invention of the electric, mass producible nebulizer was a godsend to asthmatics.

Adrenalin Inhaler used to nebulize epinephrine (1930s)*
Nebulizers have continued to evolve since then, yet the general concept has not changed.

Click here for more asthma history.

References:
  1. Rau, Joseph L., "Inhaled Adrenergic Bronchodilators: Historical Development and Clinical Application," at AARC.org (American Association of Respiratory Care, July, 2000, Vol. 45, number 7),
  2. Inhalatorium.com provides pictures and descriptions of antique nebulizers and inhalers
  3. * Pictures used with permission from Inhalatorium.com.  Check out the site for more antique nebulizers and inhalers.

Thursday, December 29, 2011

1200-1600: Asthma in ancient Korea

If you were an asthmatic living in Ancient Korea you would have had to wait until the 13th century before you had any options available to you other than folk medicine.  

Folk medicine was basic philosophies and treatments of various disease processes handed down from generation to generation to anyone interested in learning them.  Remedies usually consisted of simple things such as concocting herbal remedies, applying ointments, drinking teas, or soothing massages.  (1)

It was around the 12th and 13th centuries when medical philosophies of Traditional Chinese Medicine started to influence Korean physicians, which were recorded in various Chinese texts.  Yet the first medical texts in Korea simply consisted of compilations of folk medicine, which up to this time was passed on only by word of mouth

It was in 1236 that all the folk medicine of the day was compiled into one treaties called "Hyang-yak kugup  pang" or "Emergency Remedies of Folk Medicine."  It's the oldest medical texts written by a Korean. (2)

At about the same time several other such treaties were compiled, including "Samhwaja hyangyak pang," or "Folk Remedies of Samhwaja."This was mainly a diagnostic guide.  (3)

All the medical wisdom from these books were compiled in 1433 into "Hyangyak chipsong pang," or "Compilations of Native Korean Prescriptions."  (4) Two centuries later, in 1610,  Korean philosopher Ho Chun compiled all the medical wisdom up to his time in "Tongui pogam," or "Exemplar of Korean Medicine."  (5)

Mark Jackson, in his book "On Asthma:  The Biography," explains that Korean physicians believed asthma-like symptoms or coughing were caused by excessive eating, fear and shock.  While folk medicine was the original treatment for any ailment, various remedies from Chinese medical texts worked their way into Korean medicine. (6)

While Traditional Chinese Medicine influenced Korean medicine, Korean texts were likewise respected in China.  It wasn't until the 18th century that Eastern and Western civilizations shared medical wisdom.  
  1. WebMD,  http://dictionary.webmd.com/terms/folk-medicine
  2. Lee, Ki-baik, "A New History of Korea," 1984, Korea, page 171
  3. Lee, ibid, page 171
  4. Lee, ibid, page 171
  5. Jackson, Mark, "Asthma: The Biography," 2006, New York, page 43
  6. Jackson, ibid, page page 43

Tuesday, December 27, 2011

500 A.D. Asthma in Ancient Japan

Fuiwara no teika ( (1162-1241)
If you lived with asthma in ancient Korea and Japan your asthma may have been recognized, yet treatment would have been mainly supportive.  It wasn't until the 6th century A.D. that Chinese medical ideals -- mainly in the form of the Nei Ching -- spread to these nations.

Chinese medicine was referred to as canpo in Japan, and asthma-like symptoms were referred to as zensoku as early as 700 A.D.  (1)

The most famous asthmatic in Ancient Japan was Fujiwara no Teika who is considered one of the most famous poets in Japanese history.  Legend has it that his poems became well read due to his cordial relationship with the Emporor Go-Toba (1180-1239).

Japanese children learned early that there were 404 different kinds of illnesses, and they learned of the various herbal formulas used as remedies, most of them indigenous to the region.  One interesting remedy for asthma was by eating a potion containing earthworms dried under the sun, cooled and then boiled.

Most asthma remedies were similar to what was recommended by Traditional Chinese Medicine.  So prior to the 6th century Japanese asthmatics would have been recognized although there wasn't much anyone could do other than offer support.

Yet if you were afflicted with breathing difficulties in the 6th century you would have had available to you many of the same treatments available to Chinese asthmatics, including Ma Huang, a very efficient bronchodilator.

Click here for more asthma history.

References:
  1. Jackson, Mark, "Asthma: A biography," 2006, New York, page...

Monday, December 26, 2011

25 BC-50 AD: Celcus spearheads quest to define asthma

So what would life be like for the asthmatic when Jesus and Caesar walked the earth? From my investigations into this era I'd imagine the best remedy might simply be to tough it out, as many of the recommended remedies seem like they'd be worse than the disease. Of course this was true of most medicine prior to the 20th century.



Aurelius Cornelius Celsus was a voluminous writer. While
most of his works have been lost to history, his medical treaties
became one of the most read books during the Renaissance.
The second century A.D. was a very "fruitful era of literature and philosophy." (1, pages xxi, xxii) It is for this reason we have resources available to help us learn what was known about asthma at that time and the remedies to treat it. Among those influential to medicine in this era are Pliny the Elder, Seneca the Younger and Aurelius Cornelius Celsus.

The contributions of Pliney and Seneca will be expounded upon in a separate post. In this post I will shine the light on Celsus.
Although, we must be sure we are shining the light on the right Celsus, for this name was among the most popular of that time. The name Celsus in 2nd century Rome was akin to names like Bob or John in 21st century Europe or the United States of America. (5, pages 32-33)

Our Celsus can be seen as we enter the courtyard of one of the homes, reclining back comfortably on a couch with the tablets set firmly upon his knee. With a pen he writes about asthma today, a symptom he learned about during his philosophic studies. (5, pages 32-33)

Already in his repertoire were treaties on philosophy, architecture, rhetoric, agriculture and war. He also wrote a book called "The True Word," in which he attacked Christianity, the newest philosophy of his era.

Yet all those treaties would eventually be lost to history. The only remaining treaties that we have of his is his Treaties Medicina, of which he wrote about medicine and surgery. The first eight books were on medicine, the first four of which treated internal diseases with diet and regimen. The fifth and sixth dealt with pharmacology, or the drugs used to treat diseases. The seventh and eighth dealt with surgery. (5, page 32-33)(3, page 74)

He was born Aurelius Cornelius Celsus in 25 A.D. to respectable parents in Greece. He was a stoic, meaning he did not believe in an after life. He was also well learned, meaning that he was educated in all the knowledge of the day. His specialty became pharmaceutics, medicine, surgery, war, and architecture, all of which he, as noted above, wrote voluminously about.

His writings were later described as "diligent" and "attentive." (2, pages 425-5) Yet while some say that his skills as a surgeon were "second to none," (1, page xvii) others suspect he may not have practiced what he preached, that he was neither a physician nor a surgeon. (2, pages 425-5)

He rose above his peers by paying attention to all aspects of medicine, rather than just one. For instance, prior to his time medicine was divided into three parts: (9, page 33)
  • Dietetic: Curing by diet
  • Pharmaceutic:  Curing by medicine
  • Chirurgic: Curing by manual operations (knife, cupping, etc.)(5, page 33)
Celsus became the first to preach the importance of all three. (5, page 33)
Perhaps it was for these reason that his medical writings were "ignored by Roman practitioners of his day, and his name is mentioned only four times by the medieval commentators," said medical historian Fielding Hudson Garrison in the 1913 edition of his book "An introduction to the history of medicine." (3, page 74)

Not until 1478 would he get his revenge. In this year his book, De Re Medicina, would become the first medical treaties printed on the Gutenberg Printing Press. The treaties would then pass " through more separate editions than almost any other scientific treaties," said Garrison (3, page 74)
This was partly due to the fact it was a medical treaties, but more due to the fact of the way it was written. "It was due largely to the purity and precision of his literary style, his elegant Latinity assured him the title of 'Cicero medicorum,'" said Garrison. (3, page 74)

Medical historian Thomas Lindsley Bradford, in his 1898 book “Quiz questions on the history of medicine said that his medical treaties was a "test of Latin scholarship, and of a liberal education, for if the student was familiar with Celsus he received the purest Latin of the Augustinian Age." (5, page 33)

Along with his writings on medicine and surgery, he also described the history of medicine, giving descriptions of over 72 medical authors, although all have been lost except for the works of Hippocrates. He likewise provides us with the most precise account of medicine at the time of Jesus, describing both the Dogmatic and the Empiric Schools of medicine. (3, page 74)(5, page 33)

Celsus defended the idea that anatomy was important in medicine, so he was definitely not an Empiric, who, as we will learn later, did not support the notion that anatomy was important to medicine. Despite this, "his knowledge of anatomy was somewhat superficial." (5, page 33)
Regardless of how he was perceived in the past, Celsus remains an important figure in our history of asthma. It is thanks to him that we learn what physicians knew about asthma during the time of Jesus.

As a medical writer Celsus emulated Hippocrates, and parts of his books are word per word transcriptions from the "Hippocratic Corpus."  In fact, Celsus did this so often that one later author, Nicholas Mondaris, referred to him as the "Ape of Hippocrates." (1, pages 259-61)

The Treaties on Medicine written by Celsus would become the first
medical treaties printed on the Gutenberg Printing Press.
 It would go on to pass through more editions than
any other scientific treaties.  
Yet he incorporated into his treaties the latest wisdom of his day, plus some of his own ideas.  This is clearly evident in his writings on asthma.

When asthma was first defined by Hippocrates in 400 B.C., it was often difficult to distinguish between the causes of dyspnea, and therefore they were grouped under the umbrella term asthma. Thus, all that caused dyspnea were referred to as asthma.

Celsus, on the other hand, believed asthma was more than just dyspnea, and for this reason he provided us with our first description of asthma as more than simply a blanket term.

Celsus wrote the following:
Est etiam circa fauces malum, quod apud Gracos aliud aliudque nomen habet. Orane in difflcultate spirandi consistit; sed haec dum modica est, neque ex toto strangulat, appellator. Cum vehementior est, ut spirare aeger sine sono et anhelatione non possit; cum accessit id quoque, ne nisi recta cervice spiritus trahatur. (4, page 10)
By the above, which is taken from John Charles Thorowgood 1890 book "Asthma and Chronic Bronchitis," we learn that Celsus believed there were three thoracic disorders that resulted in difficulty of breathing, and they varied by their "degree of violence":
  1. Dyspnea:  Moderate, unsuffocative breathing without a wheeze; it's chronic
  2. Asthma:  Vehement breathing that is sonorous and wheezing; it's acute
  3. Orthopnea:  Breathing only takes place in an erect position; it's acute (1, pages 259-61) (4, page 10)
By the order above, Celsus implies that asthma is the "mean" level of difficulty of breathing, with dyspnea being less severe than asthma, and orthopnea being more severe than asthma. (4, page 10)

He was also the first to describe asthma as a specific condition involving constriction of the air passages in the lungs, and he was likewise the first to describe a wheeze. He described an attack of asthma this way:
The symptoms common to these are, that on account of the constriction of the respiratory passage, the breath is emitted with a sibilous noise (whistle or wheeze), there is pain in the chest and precordia (over the heart), sometimes also in the shoulder; and that sometimes departs, sometimes returns; in addition to these a slight cough accedes. (1, pages 260)
His remedy for asthma included any of the following:
  1. Blood letting (common remedy for just about any ailment)
  2. Milk (to relax the bowels)
  3. Purging of the bowels with enemas (clysters) or injections if necessary
  4. Hydromel (honey diluted in water
  5. Head must be kept high in bed
  6. Thorax relieved by fomentations (warm, moist medicincal compress)
  7. Thorax relieved by hot cataplasms (a heated medical dressing, either dry or moist)
  8. Malagma (lotion or salve) or iris ointment after fomentations and cataplasms (these act as emollients to soften skin to make chest movements easier)
  9. Hydromel as a drink (mixture of water and honey)
  10. Bruised root of capers has been boiled
  11. Nitre or white cresses fried, bruised, then mixed up with honey and given as electuary (oral, by mouth)
  12. Honey, galbanum, and turpentine resin boiled together and, when they are coalesced to the size of a bean, dissolved under the tongue daily
  13. Impure sulfur or southernwood triturated together in a glass of wine and sipped warm
  14. Fox's liver dried, hardened and pounded into a powder and sprinkled on a drink (such as wine)
  15. Eating the fresh, roasted lungs of a fox (but you can't cook it with iron utensils)
  16. Gruels (watery porridge) and mild food
  17. Light austere wine
  18. Sometimes a vomit (Emetics)
  19. Anything that promotes urine (diuretics make you pee, but they probably believed they were full of poisons that caused the humors to be imbalanced)
  20. Gentle walking (nothing more) 
  21. Massage (he referred to it as friction; it's done to move poisons around the body to balance the humors and to make breathing easier) (1, pages 259-61)
While some of these were later proven to have medical significance, most were simply palliative, and some were downright barbaric.  Still, his ideas were studied and followed for many years after his death.

We asthmatics should be thankful to Celsus for spearheading -- although he didn't know it at the time -- a 3,000 year effort to define asthma as a disease of its own. You can decide for yourself if you'd have been satisfied with his remedies for your asthma,  or if you would rather have just stayed home and suffered.

References:
  1. Celsus, Aurelius Cornelius, "De Medicina," translated by L. Targa, London, pages xiiv-xxiii, "The Life of Cornelius Aurelius Celsus," by J. Rhodius and translated from Almeloveen's Lugduni Batavorum
  2. Parr, Bartholomew Par, M.D., "The London Medical Dictionary," 1809, London, Vol. 1, pages 425-5 
  3. Garrison, Fielding Hudson, "An introduction to the history of medicine: with medical chronology, Bibliographic data and test questions," 1913, Philadelphia and London, W.B. Saunders company
  4. Thorowgood, John C., "Asthma and Chronic Bronchitis: A New Edition of Notes on Asthma and Bronchial Asthma," 1894, London, Bailliere, Tyndall, & Cox
  5. Bradford, Thomas Lindsley, writer, Robert Ray Roth, editor, “Quiz questions on the history of medicine from the lectures of Thomas Lindley Bradford M.D.,” 1898, Philadelphia, Hohn Joseph McVey

Saturday, December 24, 2011

62 B.C.: Seneca the asthma philosopherx

"What in fact makes people who are morally unenlightened by the experience of physical distress is their failure to acquire the habit of contentment with the spirit.  They have instead been preoccupied by the body.. so do not go out of your way to make your troubles any more tiresome than they are and burden yourself with fretting."  Seneca
Like the writings of Pliney the Elder, Seneca's writings became well read, and Seneca became one of the most well known philosophers.  In one of his letters to Lucilius, a friend and correspondent of Seneca's, Seneca provided a description of asthma, although he doesn't use the term asthma.

 Sculpture of Seneca by Puerta de Almodóvar in Córdoba, Spain
From his 54th letter to his friend Lucius (who also had asthma and catarrh), we get Seneca's description of asthma from "On Asthma and Death" as translated by Richard M. Gummere:
My ill health had allowed me a long furlough, when suddenly it resumed the attack.  "what kind of ill-health?" you say.  And you surely have a right to ask; for it is true that no kind is unknown to me.  But I have been consigned, so to speak, to one special ailment.  I do not know why I should call it by its Greek name; for it is well enough described as "shortness of breath."  It's attack is of very brief duration, like that of a squall at sea; it usually ends within an hour.  Who indeed could breathe his last for long?  I have passed through all the ills and dangers of the flesh; but nothing seems to me more troublesome than this.  And naturally so; for anything else may be called illness; but this is a sort of continued 'last gasp.'  Hence physicians call it 'practising how to die."  For some day the breath will succeed in doing what it has so often essayed (breath will succeed in doing what it is supposed to do). 
In letter 65 he wrote about his and his friend Lucius's catarrh*:
"I am all the more sorry to hear about your constant catarrh, and the spells of feverishness that go with it when it becomes protracted to the point of being chronic, because this kind of ill health is something I have experienced myself.  In its early stages I refused to let it bother me, being still young enough to adapt a defiant attitude to sickness and put up with hardships, but eventually I succumbed to it altogether.  Reduced to a state of complete emaciation, I had arrived at a point where the catahhral discharges were virtually carrying me away with them altogether.  On many an occasion I felt the urge to cut my life short there and then, and was only held back by the thoughts of my father who had been the kindest of fathers to me and was then in his old age.  Having in mind now how bravely I was capable of bearing the loss, I commanded myself to live.  There are times when even to live an act of bravery."
This was probably saying a lot back then, because I can imagine living in a state of shortness of breath.  And I can imagine this coupled with the misery of allergies on top of that.

Yet I cannot imagine what those two ailments would be like when there was no cure and no remedy that really provided any relief.  It must have been pure hell to live like that.  I can understand how he might be compelled to think about just ending the misery right "there and then."

Yet life is special, and there are few who get to enjoy this special gift.  Seneca realized this.  He used his father to provide himself the courage to go on. 

In letter 65 he described to his friend Lucius and what he did to survive the attacks of asthma and catarrh*. 

"Let me tell you the things that provided me consolation in those days, telling you to begin with that the thoughts which brought me this peace of mind had all the effects of medical treatment.  Comforting thoughts contribute to a person's cure; anything which raises his spirit benefits him physically as well.  It was my Stoic studies that really saved me.  For the fact I was able to leave my bed and was restored to health I give the credit to philosophy.  I owe her -- and it is the least of my obligations to her -- my life.  But my friends also made a considerable contribution to my health.  I found a great deal of relief in their cheering remarks, in the hours they spent at my bedside and in their conversations with me.  There is nothing, my good Lucius, quite like the devotion of one's friends for supporting one in illness and restoring one to health, and for dispelling one's anticipation of dread and death.  I even came to feel that I could not really die when these were the people I would leave surviving me, or perhaps I should say I came to think I would continue to live because of them, if not among them; for it seemed to me that in death I would not be passing on my spirit to them.  These things gave me the willingness to help my own recovery and endure all the pain.  It is quite pathetic, after all, if one has put the will to die behind one, to be without the will to life.
Another remedy he later adds "is to turn your mind to other thoughts and in that way get away from your suffering.  Call to mind things which you have done that have been upright and courteous; run over in your mind the finest parts that have been played.  And cast your memory over the things you have most admired."

No potions.  No magic.  No herbs.  Seneca might have been one of the first asthma experts to recommend, mainly due to his own experiences, the importance of relaxing to control your asthma.

Click here for more asthma history.

*Campbell, Robin, Lucius Annaeus Seneca, "Letters from a Stoic: Epistulae morales ad Lucilium, " Penguin, 1969, letter LXXVII.
"There then are your remedies."