1772-1832: Napolian's army surgeon recommended leaches for asthma

Napoleon Bonaparte (1769-1821)

When the American colonists fought for their independence from Britain, the general feeling among most Europeans at the time was that there was no way a disconnected military was going to defeat the greatest military in the world.  Yet it happened.

Perhaps inspired by this, the French began a revolution of their own.

Napoleon Bonaparte was the brilliant politician who became Emperor of France in 1804, thus gaining control of the French military during the later portions of this revolution.  

In order to obtain money to pay for his wars, which were his attempt to gain power for France, but mainly for himself, in 1803 he sold French lands in the Americas to the United States in what would become known as the Louisiana Purchase.  The purchase became known as a brilliant move by President Thomas Jefferson. However, the only reason Bonaparte made the sale was because he had all the intent on taking over the world, which included the United States. So France would end up with the land back anyway.

Broussais was army surgeon under Napoleon,
and he believed the best remedy for all diseases,
including asthma I'm sure, was to cover the entire
body of the patient with leeches.  (1, page 426)

Of course, after his ill fated conquest into Russia, Napoleon, the greatest military general of his time, was defeated and then ousted as Emperor in shame. The French Revolution had failed.

In retrospect, some surmise it failed because, while the founding fathers in the United States fought for the rights of individual men, the French fought for the rights of man, or of the collective.  While fighting for their individual natural and inalienable rights, the American colonists were more inspired to fight.  Whether this was the case may be forever debated.

Regardless, our quest is to determine what life would be like if you had asthma during the Napoleonic Wars?  Well, thanks to his army surgeon Francois Joseph Victor Broussais (1772-1838) chances are pretty good you'd be treated with leeches, and lots of them.

Broussais expounded upon an older doctrine called the "Doctrine of Irritation."  The doctrine stated that "life depends on irritation -- in particular heat -- which excises the channel processes of the body.  Disease, however, depends on localized irritation of some viscus organ, i.e. the heart, or , above all, the stomach and intestines." 

Prior to Broussais disease were often referred to as fevers.  This was no more once Brousais's theory was accepted by society, as he replaced the idea of fevers with the idea of diseases organs.  There were no longer diseases like syphilis,  you simply had a diseased organ instead. 

Pierre-Charles-Alexandre Louis (1787-1872).

He came to the conclusion that there were better

remedies for diseases than leeches.  His analysis

pretty much put an end to bleeding, at least for

pneumonia patients (1, page 428-429)

Instead of trying to find a remedy for specific diseases, such as asthma, the sick, which more than likely would have included the asthmatic, would undergo a "powerful antiphlogistic regime*" which included:

1. Depriving the person of the proper food
2. Leeching him all over the body

His remedy was used to such an extent in 1833 alone that some 41,500,000 leeches were imported into France.

His ideas started to fade when Pierre-Charles-Alexandre Louis (1787-1872) realized that the remedy of Broussais failed the many victims of an epidemic of diphtheria, and realized the "necessity of deeper study." 

Perhaps based on the all the blood letting performed as a result of the theories of Broussais, Louis came to the realization that blood letting wasn't as useful as once thought, and he proved that blood letting was of little value in cased of pneumonia.  This pretty much did away with its use for that disease.

Louis was also the first physician since Sir John Floyer to use the pulse watch (invented by Floyer) to monitor the pulse rate of his patients.  He also performed research on pthisis in 1825, based his observations on over 358 dissections and observing 1460 clinical cases.  He thus concluded "good statistics could do away with old theories like Broussais."

The ideas of Broussais, however, faded as "good sense and temperate judgement took over."  Could you imagine if you went to your doctor because you couldn't breathe, only to end up with leeches covering your body? 

*Phlogistic is Greek for inflammation and fevers, according to Merriam-Webster, so the remedies of Broussais were basically to reduce inflammation in a particular organ.

References:

1. Garrison, Fielding Hudson, "An introduction to the history of medicine," 1913, 1st edition, Philadelphia and London, W.B. Saunders and Company, page 340-3

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1833: Atropine Discovered as active ingredient in asthma cigarettes

Figure 6 -- A variety of asthma cigarettes were available.

There had to be something in the nightshade family of plants that produced the medicinal effect, and this component was the alkaloid Atropine.

Atropine was first derived from the belladonna plant in 1833.   By 1867 Atropine was isolated by von Bezold.  It was then determined to be a component alkaloid of the various nightshade plants found in India, including the datura strammonium, atropa belladonna, and the hyoscyamus niger (black henbane), and Lobelia inflata (According to encyclopecia.com)

Early studies showed atropine was the potent component in the plant, the same component that dried secretions, increased heart rate, opened air passages, and produced a hallucinogenic effect.  It was the ingredient that that made the nightshade family of plants so sought after.

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1957: The invention of the rescue inhaler

A 1957 ad for the Riker inhaler (a)

When people unite and put their minds and imaginations together in a quest to obtain a united goal, anything can be accomplished.  A perfect example was the Manhatton project, where some of the world's best minds got together and invented the atomic bomb the helped win the war. Another invention that came about through the war effort was the technology the ultimately lead to the invention of the first inhaler little more than a decade after the war was over.

So, the concept of the modern inhaler was born during WWII, but it had nothing to do finding a cure for asthma. It had to do with allied troops fighting in the fields of Europe that were infested with bugs that caused Malaria. These bugs were impeding the war effort.

A quest was begun to remedy this pesky problem. This lead to the U.S. Government hiring researchers to come up with a bug repellent that would help allied soldiers get rid of these 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.

1956 ad for the Medihaler (b)

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 propellant 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 epinephrine 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.

Asthmatics at this time had few options that were convenient and inexpensive. Epinephrine was available, but it had to be administered by a doctor. Glass nebulizers were available to deliver the medicine at home, although they were fragile, bulky, and expensive. There were electric air compressors, although the least expensive nebulizers were operated by a rubber squeeze bulb, so getting the medicine was a arduous and time consuming project.

Making matters worse is that none of these nebulizers were easily portable, meaning they had to be used at the doctor's office or at home or in the office. For this reason, many asthmatics resorted to asthma cigarettes, incense, or other palliative asthma remedies. So, efforts to get asthma relief was, to say the least, rather inconvenient.

This created an ideal market for Rikker. People who tried it found that it was lightweight and easy to carry around. It also provided instant relief from asthma symptoms. So this was the focus of Rikker's first marketing campaign for their new product.

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 the subsequent discovery of a medicine called theophylline, caused the market for asthma medicines to boom.

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

1819: Laennec uses stethoscope to redefine asthma

After he invented his stethoscope in 1816, Rene Laennec set out to use his newly developed tool to compare breath sounds with what he later found on autopsy. What he learned was that many diseases were incorrectly diagnosed as asthma. He therefore used his stethoscope to redefine the term asthma.

He listed a variety of diseases he suspected as having similar symptoms as asthma, and that other physicians often diagnosed as asthma, or a variety of it.  Some of these include: (1, page 435, 438-439)

• Heart disease (diagnosed as cardiac asthma)
• Diseases of the large vessels of the heart (diagnosed as cardiac asthma)
• Dry catarrh (congestion of blood in the vessels of the lungs, inflammation)
• Pituitous catarrh (inflammation with mucus, humid asthma)
• Mucous catarrh (inflammation with increased mucus, humid asthma)
• Chronic catarrh, either dry, pituitous or mucous (diagnosed as humid asthma)
• Emphysema of the lungs 
• Edema of the lungs (sometimes diagnosed as asthma)
• Effusions of the pleural cavity (sometimes diagnosed as asthma)
• Breathlessness caused by epilepsy (seizures)
• Breathlessness caused by apoplexy (stroke)
• Breathlessness caused by hysteria (psychological, nervous disorder)
• Breathlessness caused by syncope (passing out) 
• Hypertrophy or dilation of the heart  (1, page 435, 438-439) 
• Congestion of blood in the lungs (1, page 442)

None of these, he said, should be diagnosed as asthma, and most of these should be diagnosed correctly by a trained pathologist.  (1, page 435)

He therefore refined the definition of asthma as such:

Nervous Asthma: Dypsnea with no signs of vascular congestion nor organic lesions of the lungs.  It is therefore caused by the nervous pathways, and is rarely fatal.  (1, page 435-436, 443)

There are two forms of nervous asthma:

1.  Asthma with puerile respiration: "The patient constantly feels the want of still more extensive respiration than he enjoys."  In other words, the patient can't catch his breath. The patient can't catch his breath due to "dilation of the pulmonary cells to their full capacity, and over the whole extent of the chest."  This occurs so that the patients "have not capacity enough to satisfy the wants of the system." (1, page 436-437)

The sound of the breathing is quite puerile. It is caused by a nervous response that causes an obstruction in the air passages by a "temporary obstruction of the bronchi by by a little mucus (that) impedes the transmission of the air to even a small portion of the lungs, the patient experiences an extreme oppression." (1, page 437)

This type of asthma is not very common, and usually short lived, because the patient usually easily expectorates the "little mucus" causing the problem.   (1, page 437)

It's common in patients with chronic mucus catarrh, although it can also be present in patients with nervous affections such as hysteria, or in those with poor tolerence to exercise, such as in obese folks.  (1, page 438)

2. Spasmotic Asthma:  Circular fibers, first discovered by Reisseissen, wrap around the air passages wrap around the bronchi (air passages) of the lungs. Spasmotic contraction of these of these fibres may obstruct the air passages "to such a degree as to prevent the transmission of air to a greater portion of the lung." (1, page 440)

He notes to having verified observation of these fibres, and says that it's impossible to deny that they might spasm, considering all muscles are prone to spasm.  (1, page 440)

Things that might trigger asthma are things that might "disturb the nervous influence:"

• Odors (such as stored apples, tuberose, and heliotrope)
• Changes of atmospheric electricity
• Enclosed apartment
• A vast plain
• Want of light and free circulation of air
• Emotions

The following are the treatment for asthma:

• To treat catarrh: (1, page 449)
• Emetics
• Soap
• Alkaline salts
• Kermes
• Squills
• Ipecacauanha (1, page 449)
• To treat nervousness: All of the following should be trialed "one after another" until the medicine that works best is found. The best general rule for their administration is, to begin with a small dose, to increase this gradually, and to employ the plants in substance, well preserved and recently powdered.  If we employ extracts, they must have been recently prepared and preserved with great care."  The medicines are:
• Narcotics (decreases respiration, dyspnea, and spasms in lungs) (1, pages 449-450)
• Opium
• Belladonna
• Stramonium
• Phelladrium
• Aquaticum
• Aconitum
• Napellus
• Colchicum
• Tobacco (smoked or taken internally)
• Cicuta
• Dulcamara
• Hyoscyamus (1, page 450
• Vegetable substances "that act powerfully on the nervous system."
• Laurocerasus
• Nux vomica
• Boletus
• Suaveolens
• Meadow Saffron
• Substances equally irritating to stomach and nervous system. They work to ease respiration, but not as well as narcotics. (1, page 450)
• Tincture of cantharides
• The arsenical solution 
• Arsenic in vapor
• The sulphate of zink
• The muriate of barytes
• Distilled water of cherry laurel (Laennec trialed)
• Diluted prussic acit (Laennec trialed
• Nitric aether
• Sulphric aether (1, page 450)
• Acetic aether (1, page 450-451)
• Resins of fetid gums: No other class of medicine has a better effect on nervous dyspnea.  They "frequently relieve dyspnea, and moreover favor expectoration when there exists any catahrral complication. Even the mere smell of these substances in general, frequently produces a temporary alleviation; sometimes, however, it is injurious " (1, page 451)
• Musk (give speedy relief)
• Castor (give speedy relief)
• Gum ammoniac
• Assafaetida
• Camphor (singly or dissolved in the oil of petroleum)
• Myrrh (1, page 451)
• Cinchona: Good for asthma paroxysms of a "strongly marked periodical character... (It) diminishes their severity, and sometimes stops them altogether."
• Iron:  Dr. Bree say it "may dissipate an asthmatic paroxysm when present, but to prevent its return."  Dr. Laennec says that "subcarbonate of iron, given in graduated doses, from a scruple to a dram, was beneficial in retarding the accessions and in lessening their violence, in persons of a pallid and lymphatic constitution, and in habits relaxed by a long course of indolent enjoyment."  Works for asthma associated with dry catarrh and asthma that is purely nervous. (1, page 451)
• Coffee: Also noted by Bree to stop and prevent an attack.  Several other physicians have also noted the usefulness of coffee.
• Eat little (1, page 450
• Sleep much (1, page 450
• Breathing oxygen (1, page 450)
• Electricity:  Recently done in the form of galvanism, has sometimes lessened dyspnea, although sometimes made it worse (1, page 451)
• Emetics:  They work as "evacuants (helps you move bowels, purge), derivitives, and expectorants (helps you spit up phlegm), but also by directly influencing the nervous system; as their employment is often followed by an intermediate alleviation of the paroxysm." 
• Blood letting (venesection): Must never omit it as an option "wherever the lividity of the countenance, the strength of the patient's constitution, or the over-action of the heart, indicate pulmonary congestion (inflammation); but we must be careful not to abuse this practice, which in general produces only a temporary advantage. Venesection is rarely useful after the first days; and its too frequent repetition, by weakening the patient, induces a risk if not of life, at least of greatly prolonging the duration of the attack." (1, page 451)

Overall, by using his stethoscope, Laennec separated asthma from other diseases that cause dyspnea.  In the process, he redefined pure asthma as mainly a nervous disorder associated with spasms of the air passages.   

References

1. Laennec, Rene Theophile Hyacinthe, "A treaties on the diseases of the chest, and on mediate auscultation," tranlated by John Forbes, 1838, New York, Philadelphia, Samuel S. and William Wood, Thomas Cowperthwaite and Company

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1768: Bosier de Sauvages classifies asthma

Francois Boissier de Sauvages (1706-1767)

One of the key figures in the early days of nosology was the French physician and nosologist Francois Boissier de Sauvages (1706-1767). He worked with the disease classification system created by Thomas Sydenham, and divided diseases into ten categories based on symptoms in his 1763 book, "Nosologie Methodique (diagnostic methods)."  (1)(2)

De Sauvages, like Sydenham, was from the vitalist school of medicine in Montpellier. It is Sauvages who is often given credit for making vitalism popular among the medical community in the 17th century.

Vitalism was an ancient system of medicine that was started by the ancient Greeks (if not earlier) and perhaps first described through the writings of Hippocrates and Aristotle.  It was a belief that a vital spirit, or a soul, was responsible for maintaining the balance of health and sickness.

They believed that the vital spirit within the body was determined by the opposing humours within the body: black bile, yellow bile, phlegm, and blood.  As noted earlier in this history, even the Chinese had a system regarding the balance of substances in the body, such as Qi.  So systems of vitalism, of sorts, existed from an earliest moments of civilization.

Vitalism was revitalized, so to speak, by George Ernest Stahl (1660-1734).  He believed a significant difference between living organisms and inorganic bodies was that living organisms possess a vital spirit.  This view was worded well by the authors of Encyclopedia Britannica:

From his observation that organic bodies decompose rapidly after life ceases, while inorganic bodies remain chemically stable, he concluded that the strong corruptibility of organic matter must result from its material nature (that is, chemical composition) and that there was an immaterial reason that kept a living body from its natural decomposition. Stahl identified this reason with the principle of life, which he sometimes called “natura” (nature) and sometimes “anima” (soul). This natural reason of anima was the source of the remarkable self-healing power of the organism, and when misled, such as by emotions, it produced illnesses. This double character of the vital principle made it the foundation of physiology and pathology, and it dictated that physicians should work to facilitate or restore its healing power based on attentive observation. (6)

Stahl, like most vitalists, understood that the body was a complex system, but he rejected the idea that it was purely mechanical, (6) or consisted of a system of "pulleys and levers" that worked together to maintain health. He did not believe that health could be explained by physical or mechanical means. (5)

Stahl believed it was this soul, or anima, or vital spirit, that made the difference between living organisms like human beings and inanimate objects. The vital spirit was the vital principle of life, health, and healing. (6)

Following the beliefs of Stahl and his vital principle were Sydenham and then Sauvages.

Dr. John Charles Thorowgood, in 1879, said during a lecture on asthma to the Medical Society at London, that by the mid 17th century physicians started to take notice of the periodicity of asthma, or the fact that asthmatics tend to go long periods between episodes. (3, page 5)

Thorowgood said that Sauvages, In his 1768 book Genera Morborum, defined  asthma as "Difficultas spirandi periodice recurrens, chronica (difficult breathing that recurs periodically and is chronic)."  (3, page 5)

In 1879, Francis Ramadge said Sauvages used the term suspirium (sigh) instead of the term asthma.    However, Ramadge said that Sauvages made the same error as the ancients "by giving to asthma a sense almost as extensive as that which belongs to dyspnoea. (4, page 5)

References:

1. "Francois Boissier de Sauvages," encyclopedia.com, http://www.britannica.com/EBchecked/topic/525610/Francois-Boissier-de-Sauvages, accessed 10/12/13
2. "Francois Boissier de Sauvages," neuroportraits.eu, http://neuroportraits.eu/portrait/fran%C3%A7ois-boissier-de-sauvages, accessed 10/12/13
3. Thorowgood, John Charles, "The Lettsomian Lectures delivered at the medical society at London, 1879, on on bronchial asthma: its causes, pathology and treatment," 1879, London, Bailliere, Tindall, & Cox
4. Ramadge, Francis Hopkins, "Asthma, its species and complications," 1835, London, Longman, Rees, Orme, Brown, Green, and Longman
5. "Vitalism," Dictionary.com, http://www.merriam-webster.com/dictionary/vitalism, accessed 10/12/13
6. "George Ernst Stahl," encyclopedia britannica.com, http://www.britannica.com/EBchecked/topic/562520/Georg-Ernst-Stahl, accessed 10/12/13

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1768: Asthma classified as a disease

Girolamo Fracastoro of Verona (1484-1553)

Prior to the 19th century the symptom was the disease, and the treatment was some form of supernatural remedy. And even when an herb was the remedy, the reason it worked was rationalized by superstition. Of course the other common remedy was a simple prayer, or maybe a magic incantation.

If you were short of breath you were probably diagnosed with asthma, unless the physician had reason to suspect you had pneumonia, pleurisy or tuberculosis.

T.E. Weckowicz and H. Liebel-Weckowicz, in their book "History of Great Ideas in Abnormal Psychology," explain that prior to 18th century (and even during the 18th century for the most part) illness was categorized by the Constitutional models that were devised by Hippocrates and Galen, which emphasized symptoms. Your symptom, which in your case was asthma (gasping breaths) was your diagnosis.(1, page 168)

However, it was during the course of the18th century that a shift was made away from the Constitutional model and toward the disease model of medicine.  Weckowicz and Weckowicz propose three theories as to why this may have occurred.  (1, page 68)

1.  They suggest that various epidemics of diseases "suggested the possibility of contageon."  They mention Girolamo Fracastoro of Verona (1484-1553) who "wrote a famous poem about syphilis.  He postulated that diseases were caused by minute germs which passed from one person to another. He recognized that smallpox, measles, bubonic plague, and phthisis were all contagious diseases." (1, page 68)

Athanasius Kirchner (1602-1680)

They also mention Fracastro, the Jesuit Father, Athanasius Kirchner (1602-1680) who "claimed to have found microscopic worms in the blood of patients suffering from infectious diseases."  While the "link between bacteria and infectious disease was not definitely established until the middle of the nineteenth century," the idea was beginning to grow in the minds of the medical profession, or at least the scientific community. (1, page 68)

2.  They suggest that "clinitians tended to isolate the symptoms of disease from the total patient and to treat them as entities in themselves." (1, page 68)

3.  They suggested "There was a growing interest in morbid anatomy. The bodies of dead people were dissected, the diseased organs were examined, and the pathology of the organs was linked with the symptoms of the patients."

An example here may be the diagnosis of the disease pneumonia by the observation of fluid or puss in the parts of the lungs that they ultimately attributed to the symptoms the person had prior to death, such as dyspnea and coughing up colored secretions. (1, page 68)

Felix Plater (1536-1614) believed asthma could
get an asthmatic absolved from crimes.

Weckowicz and Weckowicz list the significant figures in the birth of nosology, or the classification of diseases, and I will list some of the ones most significant to our asthma and allergy history here.  (1, page 68-9)

1.   Felix Plater:  (1536-1614)  He considered asthma as a mental disorder.  He observed the asthma attack when nothing else seemed to be wrong.  He classified nervous disorders, dividing them into "idiots, morons, cretons, mutes, and melancholics." (1, page 69)

2.  Thomas Willis: He was the person often given credit as the first to classify asthma as a nervous disorder. He's also known as one of the first two men to classify psychological diseases. He classified mental patients as "melancholics, maniacs, idiots, and Apoplectics." (1, page 69)

Theophile Bonet (1620-1689)

3.  Dr. Thomas Syndenham:  He was among the first to favor the disease model as opposed to the constitutional model of Hippocrates and Galen.  He stressed, in his book Medical observations Concerning History and Cure of Acute Diseases (Sydenham, 1848), that "each disease should be treated by the specific remedy for it." (1, page 68)

He also stressed the importance of nosology, and he suggested such classification should be made similar to the methods used to classify plants and animals. He also classified diseases according to their symptoms. (1, page 68-9)

4.  Theophile Bonet of Geneva:  "He compiled all the existing knowledge of pathological anatomy in his work Sepulchretum." (1, page 68)

Carl Linneaus (1707-1778)

5.  Dr. Carl von Linne (Linneaus):  (1707-1778) He continued work on the classification system started by Sydenham, and he classified plants according to genera, families, and orders.  He also "treated diseases as plant species." (1, page 71)   He published his works on nosology in his 1763 book "Genera Morborum."

6. Francois Boissier de Sauvages de Lacroix: (1706-1767) He classified disease in his book "Nosologie Methodique (Systematic Nosology."  In this book "he distinguished twenty-four hundred diseases which he divided into ten classes, each further divided into several orders and genera. (1, page 71)

Lineaus was a medical student when Sauvages first book was published in 1731, and the two met and started corresponding.  This led to a lifelong friendship whereby the two "influenced one another" in forming classification systems.  In 1763 they both published their own treaties on nosology, Linnaeus published Genera Morborum and Sauvages published Methodical Nosology. (3, page 98)

Sauvages also was mentioned by Dr. John Charles Thorowgood in his 1878 book "Asthma and Chronic Bronchitis." Thorowgood said the following:  (2, page 10)

As knowledge and observation progressed, the intermittent character of the breath difficulty of asthma was duly observed and insisted on; and we find Boissier de Sauvages, in his 'Genera Morborum' (1768), defining asthma as 'difficultas spirandi periodice recurrens, chronica.'(2, page 10)

In this way, Boissier de Sauvages may have actually been the first person to classify asthma as a disease as opposed to just a symptom. 

You can read more about Sauvages in this post.

7.  William Cullen:  (1710-1790)  I'm actually adding him to this list on my own because he was also among the first nosologists.  He was a physician from Edinburgh, and he was among the first to base his theories of asthma on studies he performed.

He believed most diseases, asthma included, were caused by some disorder of the nervous system.  He found it difficult to classify asthma as a disease mainly because most other physicians of his day believed all or most cases of dyspnea were asthma.

He was among the first physicians to study signs and symptoms of diseases while a person was alive, and compare this with findings on autopsy.

According to Thorowgood, Cullen defined asthma in his 1772 book "Synopsis Nosologiae Methodicae" as follows: (2, page 13)

'spirandi difficultas, cum angustise in pectore sensu, per intervalla subiens.' (2, page 13)

He believed spasmotic asthma was caused by constriction of the muscles that wrap around the smaller bronchiole tubes.  This theory, which was also supported by John Floyer, received a lot of attention among the medical community through the 19th century, said Thorowgood.  (2, page 13)

There were many ardent supporters of this theory during the course of the 19th century, and I will list them and discuss their contributions to asthma in a later post.

Thorowgood also said that Cullen further classified asthma into the following three groups: (2, page 13)

1. Idiopathic Asthma:  There are 8 varieties of this
2. Symptomatic Asthma: There are 2 varieties of this
1. Gouty Asthma (asthma arthriticum)
2. Syphilitic Asthma (Asthma Venereum)
3. Other:  This "consists of a long list of asthmas, dyspnoeas, and orthopnoeas symptomatic of cardiac and pulmonary difficulties and obstructions  (2, page 13)

Conclusion:  So these are some of the earliest nosologists responsible for the early categorization. The systems created by Sydenham, Linneaus and Sauvages made nosology popular, and during the 1760s through the 1780s there were an abundance of treaties dedicated to nosology, with Cullins work being among them. (3, page 98)

So, throughout the 18th century, physicians were on a quest to match the symptoms that occurred in life with what they saw on autopsy. The more they did this the more diseases they discovered, and this resulted in an effort to classify these diseases in order to organize them.

The next rush among the medical community would be to further understand the various diseases. Yet physicians would agree with ancient physicans that asthma left no scars, and therefore was not so easy to define. The debate as to what causes asthma would be fought long and hard by many physicians during the 19th century.

References:

1. Weckowicz, T.E. and H. Liebel-Weckowicz, "History of Great Ideas in Abnormal Psychology,"1990, New York, Elsevier Science Publishing Company, Inc. 
2. Thorowgood, John C., "Asthma and Chronic Bronchitis: A New Edition of Notes on Asthma and Bronchial Asthma," 1894, London, Bailliere, Tyndall, & Cox
3. Flangsmyr, Tore, J.L. Heilbron, Tobin E. Rider, editors, "The Quantifying Spirit in the Eighteenth Century," Berkley, Los Angeles, Oxford, University of California Press
4. Butlin, H. Trentham, President of the Laryngological Society of London, "Proceedings of the Laryngological Society of London elected at the annual meeting January 13th, 1897," 1897, London, Printed by Adlard and Son

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1767: Dr. Phillip Stern writes book for asthmatics

Photo of Stern's inhaler,
Used here by permission.
(inhalatorium.com)

So it's the year 1767 and you have asthma.  For the price of just one schilling you can purchase a copy of Dr. Phillip Stern's book called, "Medical advice to the consumptive and asthmatic people of England."  It's one of the first medical books ever written specifically for you, the patient.

Now there's a catch here of course.  He apparently admits to writing the book directly to the patient because he apparently had a falling out with his fellow physicians.  Perhaps it was because his ideas are rejected by the medical profession.  Or perhaps it was because he rejects the methods of the medical community and postulates his own.

Many historians presume his ideas were rejected by the medical community specifically because he wrote his book to the public, and not to physicians (which was the norm back then).  And, to be honest, Dr. Stern does use some harsh wording when referring to his physician contemporaries.

Regardless, he provides a brief anatomical review of the heart, vessels, diaphragm and respiratory system.  He describes how the lungs are "divided into two principle lobes which are inclosed in two distinct bags, formed by a membrane called the pleura; so that the right and the left lobe of the lungs have not the least communication."

Now this separation of the two lungs is important, because when a portion of one lung becomes diseased or dies, perhaps due to pneumonia or consumption, the patient can continue to live.  He writes:

"But here it may naturally be asked, how it happens, when a part of an organ, so indispensably necessary to life, is destroyed, that the patient does not immediately die.  I answer that Nature, in this instance, has been particularly kind to us; for the two lobes of the lungs, have no communication, are not immediately affected by each other's diseases; besides, every minute branch of the same lobe is so contrived, as to perform its office independent of the rest; therefore every single vessel continues to receive and return its portion of air, till it be actually destroyed." (1, page 11)

So the lungs are resilient to disease, and parts of them can continue to work regardless of the diseased parts.  This is good when it comes to diseases like pneumonia or consumption which can close off portions of the lungs to the reception of air.

The majority of Sterns book describes the disease consumption, his theories as to the pathology of the disease and his perceived remedies.  It isn't until we get to page 33 that we learn about asthma, "that disorder, the chief symptom of which is difficulty of breathing.  It is either continued or by fits."  (1, page 33)

Regarding the cause he writes: "Now, though the cause of the disease is frequently in the lungs, yet it is sometimes owing to a morbid affection of some of the other organs of respiration, as the diaphragm, the intercostal muscles, or the windpipe, or some of the neighboring viscera."

Pretty much that's all he offers us about our disease.  He then jumps right into his only remedy, his own balsamic medicines, the same medicines he recommends for consumptives.  He explains the first remedy to asthmatics is bleeding, yet after that he recommends balsamics to be provided by the inhaler he invented.

Here we must pay attention to his explanation:

"Well; but then we administer a quantity of saccharine, oily and mucilaginous medicine, in the form of an emulsion, intending, no doubt, thereby to sheathe and obtund the acrimony, which causes the irritation in the lungs.  The intention is certainly laudable; but it happens unfortunately that these balsamics go down, not into the lungs, but into the stomach, where they immediately go through such a change, as to carry but little of their balsamic qualities even into the intestines, where they are still farther mixed and adulterated, particularly by the addition of a certain quantity of bile, immediately on quitting the stomach."  (1, page 14)

He further explains that medicine can be taken by the mouth, pass through the stomach, gather access to the vessels of the body, and effect the heart, and even act as poisons in this way.  However, he notes the following:

"Now it must be remembered that the seat of the disorder which, by their healing medicines, we are endeavouring to cure is not in the blood vessels, but in the air vessels of the lungs; and that these air vessels have no communication with the arteries, except by means of tubes or pores so extremely small, as not to admit the red globules of the blood; consequently the constituent particles of our medicine must be smaller than these, otherwise no part of it can possibly be thus applied to the part injured." (1, page 15-16)

He therefore concludes that "the only possible way of applying medicine directly to the lungs, is through the windpipe."  (1, page 16)

Later he explains to the asthmatic:

"If... these balsamics, taken into the stomach, can do nothing toward the cure of consumption, how much less likely are they to relieve an asthmatic patient?  For if they could ever be applied immediately to the part affected, they possess no one virtue that might authorize such expectation." (1, page 34)

Here he makes an observation that was probably first made by ancient people, as even the ancient Egyptians, and Ancient Indians, observed that medicine to improve affections of the airway often works better when inhaled.  And that is exactly what Stern is prescribing here: the inhalation of his balsamic powders with an inhaler that he invented.

He writes that "when the cause of the asthma is spasmotic contraction of the lungs, or windpipe, which is very frequently the case, especially when the disease returns by fits, I then expect considerable advantage from the antispasmotic powders of this vapour; and when in a continuous difficulty of breathing, the cause of the disorder is an infarction of the lungs from viscid mucus, my hopes are then build on the attenuating power of the vapour exhibited in the manner I recommend. Let those who are capable of reasoning, judge whether my expectations are well founded." (1, page 34)

The medicine may be inhaled through the use of any teapot, although for consumption (or asthma) "a more copious application is necessary.  For this purpose I have contrived a simple machine, by means of which a much greater quantity of the balsamic effluvium is received into the lungs... It holds about a pint.  Half a pint of boiling water must be poured in, and the medicine immediately dropped into the water.  The head being then fixed upon it, the patient applies his mouth to the pipe, and thus draws in the steam with his breath, removing the pipe from his lips at every expiration.  The vessel is made of pewter.  Those who are acquainted with the nature of evaporation will not be at a loss to account for the conic form of the vessel."

Note he did not use the word 'inhaler.'  (3, page 54)  In reality his invention may be the first inhaler. However, perhaps because his ideas were rejected by the medical community, his inhaler never caught on.  He also didn't use the word inhaler. So perhaps for this reason it wasn't his, but Dr. Mudge's inhaler invented a decade later, that is often given credit as the first inhaler.  Yet for the first time, we will give Dr. Stern full credit here:  Dr. Phillip Stern invented the first marketable inhaler.

He also recommends inhaling the balsamic vapours using his contraption of which he does not refer to as an inhaler, as such a word will be used by one of his contemporaries.  (2) 

The medicine:  Dr. Sterns Balsamic Vapour or Dr. Sterns Balsamic Ether

Ingredients:  Dr. Sterns will not reveal his ingredients, although we might assume he enters into it some or all of the following, which are mentioned in his book:

•  Antiseptic powder
•  Ether
•  Balsams (of Gilead, Copaiba, Peru, Tolu, and Canada)
•  Dry Balsams (Benjoine, Storax, Labdanum, Myrrh, Mastich)
•  Terpentines
•  Antispasmotics
•  Opium

Research:  Dr. Sterns did a test using the vessel and his balsamic ether on himself, and it worked.

Indications:  Common colds, hoarseness, tuberculosis, asthma, etc.

Cost:  Six Schillings and sixpence per bottle

Where:  Various shops

Directions:  "I usually drop 30-40 drops into half a pint of boiling water immediately after it is taken from the fire, ordering the patient to hold his mouth over the vessel, so as to draw in with his breath as much as possible of the vapour, continuing the operation as long as the steam will rise.  I then order him to drink the water as soon as it is cold enough for that purpose: for, though I depend  entirely on the vapour for the cure of the lungs, yet, as of all the juices in the body may in some degree affected by the matter absorbed from the lungs, this balsamic water, received into the stomach, will be of some advantage." (1, page 24)

Or...

"30 or 40 drops to be dropped into a quart of boiling water, and the vessel to be placed near the bed of the patient, and to be repeated three or four times a day; or the water to be kept boiling over a lamp, in any part of the room, until it is entirely evaporated, if the disorder be of a very putrid nature, and especially in the small pox."  This technique may also be beneficial in sore throats "whether inflammatory or putrid."

Frequency:  The Stern's "Inhaler" may be used by adding half a pint of water, boiling it (2), "and by holding my head over a common pint vessel, keeping my mouth generally shut, that the steam might pass through my nose, and repeating the operation several times a day, for two or three days." (1, page 24)

When to use:  Use during an attack of asthma, although it is best to "prevent a disorder than to cure it, and as colds do no injury to the lungs, except in their remote effects, I thought it rational to suppose, if immediately after taking cold, I could dilute or obtund the acrimony of the humour that irritates and inflames the lungs, I should probably prevent the bad consequences of obstructed perspiration, at least as far as it concerned the lungs." (1, page 34)

References:

1. Stern, Phillip, "Medical advice to the consumptive and asthmatic people of England," 1870, London  (1st edition was 1767)
2. Sanders, Mark, "Dr. Stern's Inhaler," Inhalatorium.com,  http://inhalatorium.com/page133.html.  Mr. Sanders also provided us with permission to use the picture on this page.  Please check out the Inhalatorium to see for yourself the history of aerosolized therapy.  You may also check out a slideshow presentation by Mr. Sanders,    "The Innovators of Inhalation," http://www.ddl-conference.org.uk/files/DDL20presentations/19.Sanders.pdf
3. Smyth, Hugh D.C, Anthony J. Hickey, "Controlled Pulmonary Drug Delivery," 2100, Springer New York Dordrecht Heidelberg London
4. RT Cave Facebook Page

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1785: Withering recommends fox-glove for asthma

William Withering (1741-1799)

William Withering was a contemporary of William Cullen.  While Cullen was the first to describe asthma as spasmotic constriction of the muscular fibers of the bronchi, Withering was the first to recommend for asthma a remedy called foxglove.

Withering was a physician from Shrophire, England. He graduated from Edinburgh in 1766 and then had a "large and lucrative practice at Birmingham.  

While he had other accomplishments, he is best known for his discovery of a treatment called foxglove for asthma caused by dropsy of the heart.  

So, what is dropsy of the heart? Or, better yet, what is dropsy? 

Dropsy is essentially an old term referring to edema, or swelling and redness.  It comes from the Greek term hudrop-piasis hudrops, which refers to a dropsical person.  The term hudro means hydro, which means water.  (3)

Since there was no standardization in those days, sometimes other terms were used to mean the same thing. For instance, the terms "congestion" and "hydrops" and "anascara" were also used when referring to the build-up of fluid in a certain part of the body.

When physicians like Withering observed the build-up of fluid in a certain part of the body, or a certain organ, he would simply use dropsy, hydrops or congestion, followed by the part of the body or organ affected.  To understand how these terms were used consider the following chart. 

Old term	Description	New term
Cerebral Dropsy	Fluid on the brain	Hydrocephalis
Dropsy of ankles, legs, feet	Fluid in ankles, legs feet	Pedal edema
Dropsy of the lungs Congestion of lungs	Fluid in lungs	Pulmonary edema
Dropsy of the throat	Swollen throat	Croup or Epiglotitis
Hydrops Abdominus	Fluid in the abdominal cavity	Ascites
Hydrops Pectoris	Fluid in cavity surrounding the lungs	Pleural Effusion

Of course it must be understood for our purposes that dropsy of the lungs was usually associated with asthma, which was a generic term meaning dyspnea, or shortness of breath.  

So, what is foxglove?

Foxglove was a common remedy used in Withering's day and age for just about any ailment in the book. However, it was not prescribed because it had any beneficial effect, but because it worked to extricate fluid from the body, and thereby balance the humors.  

Foxglove the flower

You see, the dogmatic ideas of Hippocrates were still taught in medical schools, although they were adjusted slightly to suit the times.  

Noting the abuse of this medicine (sort of like albuterol in the 21st century), Withering set out to learn more about this remedy, where it came from, and what it was actually good for.  

Through his research, he learned that foxglove was first discovered by Fuchsius in 1542. He gave it the name foxglove because the blossom of the plant looked like the finger of a glove. (5, page xiv)

Shortly thereafter, he said in describing its discovery, the experimenting began, with various parts of the plant being ingested or added into the recipes of various foods and drinks and ingested that way. The toxic effects of the plant were soon noted, such that taken in large amounts caused vomiting. (5, page xiv)

Another effect soon observed was that foxglove also acted as a diuretic, meaning that it made you pee. Upon further experiment, it was learned that it worked great as a remedy for various diseases. Of course since anatomical wisdom was anemic in those days, the reason it worked, and for what remedies it truly benefited, remained inextricable. (1)(5, page 2)

Eventually the remedy was discovered to be useful for asthma, although, once again, the reason for this remained a mystery.  Therefore it was suspected that it its diuretic and nauseating properties probably helped to balance the humors, thus curing asthma.  

Knowledge that foxglove helped in cases of asthma passed to a lady who kept this a secret for many years. When she was an elderly lady living in Shrophire, Withering heard wind of her remedy for asthma, and interviewed her to learn more about it. She said foxglove was good for dropsy, and that it caused nausea (1)(5, page 2)

So now Withering started his own experiments with the remedy. He verified that in high doses it did cause nausea, although he soon learned that even patients given small amounts of the remedy had increased urination. (5, page 4)

He then realized that it was the diuretic effect of the plant, and not the nauseating effect, that was beneficial for asthma. It was by this means he learned that it was useful for dropsy. In fact, he noted that "if the medicine purges, it is almost certain to fail in its desired effect." (5, page 4)

It was in this way that he discovered the desired effect of the medicine was removal of excessive fluid in the body, which helped with pretty much any ailment that resulted in dropsy, hydropsy or congestion. (5, page 2-6)

In other words, he learned foxglove was a "powerful diuretic." It was useful as a remedy for dropsy of the lungs and hydrops of the legs, ankles and feet.  It was also useful for hydrops abdominis and hydrops pectoris.  (5, page 2-6)

It was not, however, effective for cerebral dropsy caused by head trauma. (1)

In 1785, about ten years after he began his research on foxglove, he published his findings in the book "Account of the Foxglove." He described foxglove and all the remedies he discovered it benefited.  (5, page v) 

However, as any judicious physician describing a new treatment should do, he warned that physicians should restrain themselves in its use, although not condemn and reject it as "dangerous and unmanageable." (5, page v) 

The book, he said, was essentially...

...a protest against the abuses of digitalis, which were already creeping in. (1)

Regarding foxglove and asthma, Withering wrote the following in his book:

ASTHMA

(9) THE true spasmodic asthma, a rare disease is not relieved by Digitalis. 

(10) In the greater part of what are called asthmatical cases, the real disease is anasarca of the lungs, and is generally to be cured by diuretics. This is almost always combined with some swelling of the legs

(11) There is another kind of asthma, in which change of posture does not much affect the patient. I believe it to be caused by an infarction-of the lungs. It is incurable by diuretics; but it is often accompanied with a degree of anasarca, and so far it admits of relief. 

ASTHMA and ANASARCA

(12) IF the asthma be of the kind mentioned at (9 & 11) diuretics can only remove the accompanying anasarca. But if the affection of the breath depends also, upon cellular effusion, as it mostly does, the patient may be taught to expect a recovery.

ASTHMA and ASCITES

(13) A RARE combination, but not incurable if the the abdominal viscera are sound. The asthma is here most probably of the anasarcous kind (10) and this being seldom confined to the lungs only, the disease generally appears,in the following form.

ASTHMA, ASCITES, and ANASARCA.

(14) THE curability of this combination will depend upon the circumstances mentioned in the "'preceding section, taking also into the account the strength or weakness of the patient. (5, page 196-7)

He also recommended asthma for phthisis pulmonalis, although he said this was not a new discovery as other physicians had found it useful and had recommended it. (5, page 9)

Note that Withering, as with other physicians of his era, regarded asthma in it's pure form, which would be asthma accompanied by no other ailments, as being a rare condition.  He offered no new wisdom about pure asthma.

He said most patients who present with asthma (dyspnea) present with more than just "pure asthma," and in these cases, the most common complication is anascara of the lungs, and it is this that he proved benefited from foxglove for its diuretic effect.

He must have also observed that many of these patients also present with dropsy of the ankles.

Thanks to his research, the medicine foxglove (digitalis) was entered into the Edinburgh Pharmacopoeia in 1783, but did not appear in the London Pharmacopoeia until 1809.(1)

Note: During the course of the next 50 years, it would be discovered that asthma caused by dropsy of the lungs or hydrops pulmonais, were actually caused by heart or kidney failure. These would ultimately become disease entities of their own, and therefore would be separated from the umbrella term asthma. In 1827 Richard Bright became the first person to distinguish between dropsy of the lungs caused by heart failure and kidney failure.  .

References: 

1. Garrison, "An introduction to the history of medicine," 1921, 3rd edition, Philadelphia and London, W.B. Saunders Company , page 367-368, 408)
2. Cullen, William, "First Lines of the Practice of the Phsych," 1784, Edinburgh, Vol. 3, 4th ed., 387-88, 397
3. "Dropsy," The Free Dictionary by Farlex, http://www.thefreedictionary.com/dropsy, accessed 6/23/13
4. "Digitalis," Drugs.com, http://www.drugs.com/npp/digitalis.html, accessed 6/23/13
5. Withering, William, "An account of the foxglove and some of its medical uses with practical remarks on dropsy and other diseases," 1785, London, Paternoster Row

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