1851-1913: The history of asthma sputum

Ernst Victor von Leyden (1832-1910 discovered
crystals in asthmatic sputum, and suspected these
to be the cause of asthma. During his era, he was
the closest supporter of Dr. Robert Bree's
bronchitic theory of asthma. (9, pages 14-15)
He believed these crystals somehow irritated the
"vagus in the mucus membrane of the bronchials,
and hereby caused by reflex action a spasm
of the muscles of the small bronchial tubes."
(10, page 8)

Most people find sputum disgusting, and so will have nothing to do with it. But as far back as 400 B.C. the medical significance of it was observed by ancient Greek physicians, and probably even earlier than that.

If you mention it at the dinner table your mother might smack your hand. But for the sake of gaining a complete grasp on the history of asthma and respiratory disease, we must delve into the topic of sputum.  Sorry, but we must.

It must have been observed at an early date in history that people with breathing issues produce sputum, sometimes consisting of a putrid smell, often consisting of many varied colors such as red, yellow, brown and white.

Yet rather than being petrified by the grossness of the substance, Greek philosophers became fascinated by it. They even gave it its own classification as one of the four humors that, along with determining ones personality, also determined whether was healthy or sick.

Prior to the philosophical medicine of the ancient Greeks, other ancient societies, and the primitive clans and families that roamed the lands before them, believed sputum was the production of some evil spirit, demon or god. When a person expectorated the substance, they were in essence expectorating an evil substance that caused the symptoms they were suffering from.

From the ancient world to the scientific revolution there were few changes in the way physicians viewed diseases and treated their patients.  In 1799 Dr. Robert Bree speculated that sputum contained a poison that it was trying to get out of the body, and asthma was the result.  This theory wasn't much different than any idea Hippocrates might have postulated.

Since the sputum preceded the asthmatic fit, Bree essentially speculated that asthma was essentially bronchitis, and thus created the bronchitic theory of asthma.  Others, without much more evidence, speculated sputum was the effect of asthma rather than the cause.

Such speculation gradually tapered off, but never really came to an end, during the scientific revolution, and mainly due to the inventions of the microscope, which allowed physicians to see that the human body was made up of substances too small to be seen by the unassisted eye, and the stethoscope, which allowed physicians to hear changes that occurred inside the chest and to diagnose diseases with accuracy prior to autopsy.

The microscope allowed physicians to learn that air passages were surrounded by smooth muscle, and that it was capable of spasming when stimulated.  The stethoscope allowed them to hear when sputum accumulated in the chest, and learn that it was the effect and not the cause of asthma.

So, pretty much, prior to the 1850s asthma was basically considered to be a disease of excess sputum, mainly because this was all physicians could observe with the unaided eye and ear.

Yet by the 1850s it was looking pretty clear that asthma was also a disease associated with spasms of the air passages, particularly by the wheezes heard by air flowing through narrowed air passages, and rhonchi heard as air flowed through sputum lined air passages.  (1, pages 592-595)

In 1851, Dr. Beau, along with his assistant Cozart, observed that fits of asthma usually ended with a wad of sputum being coughed up. Beau used this observation as evidence to support his theory that asthma was a disease of chronic catarrh, and that asthma was caused by increased sputum in the air passages.  (3, page 31)

When this sputum dried out mucus plugs formed that were capable of blocking the air passages, thus resulting in dyspnea and other symptoms of asthma, including the "sonorous and sibilant rhonchi -- their 'rales vibrants' heard upon auscultation with a stethoscope."  (3, page 31)

The fit, therefore, was resolved when mucus plugs were broken up with a fit of coughing.  (3, page 31)

Then, in 1878, at a time when most physicians had accepted the nervous and spasmotic theories,  J.B. Berkart used Beau's research as evidence of the bronchitic theory of asthma.

Berkart said:

With the displacement of the mucous plug into the larger bronchus, or on its expulsion by means of a fit of coughing, the dyspnea ceases, and with it also the rales disappear.  This form of bronchitis is, in their (Beau and Crozant's) opinion, due partly to an idiosyncrasy of the patient, partly to exciting causes, which greatly vary in different individuals."

Tiny crystals were first observed in sputum in 1851 by Jean Martin Charcot, but it wasn't until 1872 that these crystals were linked to asthma by Ernst Victor von Leyden. So history has given credit for this discovery to both men by calling the crystals Charcot-Leyden crystals.

Leyden, whose asthma theories were similar to Dr Bree's bronchitic theory, believed Charcot-Leyden crystals caused asthma by irritating...

...the peripheral extremities of the vagus nerve, and produce reflex spasm of the bronchial muscle."  

The asthma attack, as Bree and Beau observed, ended when a wad of sputum was coughed up during a fit of coughing. (4, page 14-15

However, it was the discovery of these Charcot-Leyden crystals that would ultimately put an end to the bronchitic theory of asthma.  This was noted by Dr. John Charles Thorowgood in 1878.  He said that these crystals were found in sputum obtained from patients with "ordinary catarrh and croupus bronchitis."  (4, page 15)

Thorowgood said:

The asthmatic patient while in a fit presents abundance of symptoms distressing enough to endure or to witness; and yet, when things seem to be at their worse, and the patient well-nigh at his last gasp, a remission comes on, the spasm yields, air enters the lungs, and the attack subsides, coincidentally often with access of cough and mucous expectoration." (4, page 16)(9, page 1,2)

In 1879, bacteriologist Paul Erlich discovered the eosinophil, and it was soon discovered that elevated levels of eosinophils (eosinophilia) was commonly found in asthmatics. (5)

In 1882 Heinrich Curshmann observed other spirals in asthma sputum and believed they were associated with causing asthma. He believed since Leyden's crystals didn't cause asthma, perhaps his crystals did. (5)

Later Curshmann's crystals were determined to be fragments of mucus plugs associated with asthma, and Leyden crystals were determined to be fragments of eosinophils. Eosinophils were later learned to be a type of white blood cell that, along with mast cells, are involved in the allergic reaction.

In 1911 Hermann Sahli described eosinophils in asthmatic sputum. Yet Sahli noted another author from 1891 who described eosinophils in asthmatic blood, and he concluded that these must be pathological with asthma. Yet he also noted that neither the cause of the eosinophils nor their origin was known. (7)

Sahli could isolate the area where the sputum came from based on epithelial cells in it, yet he did not understand the mechanisms of its production as we do today. (7)

Dr. James Adams describes asthma sputum in 1913: (8)

"Asthmatic sputum varies. Often there is none till the end of the attack; then it is in the typical form of small, tough pellets expelled by laborious coughing. The attack may then cease, or it may go on till a more free and profuse expectoration occurs."

He also wrote:  (8)

"The sputum does not readily decompose, and is said to be wonderfully free from microbes; but this is not always so, as I have occasionally found it teeming with them."

The true purpose of sputum is to ball up microbes inside the lungs and haul them out, and in this way the lungs stay sterile.  Surely asthma can be caused by inhaling a microbe, such as a bacteria, but it's also caused by asthma triggers (dust mites, smoke, fumes, chemicals, pollution, animal dander) that are innocuous to most people, and non infecting agents.

So this might explain why Adams most often found asthmatic sputum without an infecting agent, and sometimes "teeming with them."

Backing up a moment to 1906, Australian pediatrician Clemons van Pirquet coined the term allergy when he observed that some of his patients were hypersensitive to substances that did not bother other people (what we now refer to as allergens, or asthma triggers).  This was the first time asthma was linked with allergies.

By 1910 Histamine was discovered and found to be a major component in the allergic response.  So some went on to speculate that finding a way to block histamine would cure both allergies and asthma.

By 1946 antihystamines hit the market, and within a decade they were among the most commonly prescribed medicines.

Yet as time went by, it was learned that there was more to asthma and allergies than just histamine.  It was learned that asthmatic and allergic immune systems respond irrationally to allergens and asthma triggers by increasing production of eosinophils and this spearheads inflammation of the bronchial muscles.

Another weapon of the immune system is mast cells that line the respiratory tract and eyes, and these were discovered in 1953.  .

In 1967 Immunoglobulin E antibodies (IgE) were discovered.  It was later learned IgE has a significant role in the asthmatic and the allergic response.  The first time asthmatics are exposed to asthma triggers (allergens), say dust mites, their immune systems develop dust mite IgE antibodies that attach to mast cells that line the epithelial layer of the skin or respiratory tract.

The second time that person is exposed to that allergen (dust mites in this case), a mast cell that has a dust mite IgE antibody attached to it explodes and releases its contents:  the mediators of inflammation.  A mediator of inflammation called histamine was discovered in 1910, and others called cytokines and leukotrienes were discovered in the 1970s.

These mediators, when released into the blood stream, cause inflammation of the respiratory tract, thus causing the allergic and asthmatic responses.

In the allergic person, they can also cause inflammation of the upper respiratory tract, which includes the back of the throat and nose.  The offending substance (dust in our case) is recognized by the immune system, trapped in the mucus layer, absorbed by the mucus, balled up by the mucus, and sent on it's way up the respiratory track to be coughed up.

So this would explain what Dr. Bree, Beau, and Berkart observed. While hacking up a wad of sputum may have been related to the fit of asthma, it was not the cause, and had nothing to do with the cure.

Later it was learned that asthmatic lungs tended to produce an abnormal number of goblet cells, this results in an abnormal increase in mucus production during an asthma attack.  While some of this sputum may be coughed up, some becomes trapped in obstructed air passages, dries out to form mucus plugs, and this further blocks the air passages, thus compounding the asthma response.

When the fit ends, when the air passages relax and dilate, which may be a result of time or medications, the asthmatic will probably expectorate this sputum, which will usually be, if no bacteria or virus is balled up within it, white and sterile.  It will also have IgE and eosinophils in it, hence your Charcot-Leyden and Curshmann crystals.

So it's easy to understand how this production of sputum at the end of an attack could easily be misinterpreted as the cause, rather than the effect, of asthma.

References:

1. Lotval, J., "Contractility of Lungs and air tubes: experiments performed in 1840 by Charles J.B. Williams, European Respiratory Journal, 1994, (7) pages 592-595
2. Bree, Robert, "A Practical Inquiry into Disordered Respiration Distinguishing the Species of Convulsive Asthma, their Causes and Indication for a Cure," 4th ed, 1810, London, page pages 117-118
3. Berkart, J.B., "On Asthma: Its Pathology and Treatment," 1878
4. Thorowgood, John C., "Asthma and Chronic Bronchitis: A New Edition of Notes on Asthma and Bronchial Asthma," 1894, London, Bailliere, Tyndall, & Cox
5. Lipkowitz, Myron, Tova Navarra, "Encyclopedia of Allergies," 2001
6. Brenner, Barry E, "Emergency Medicine, 1998, page 10
7. Sahli, Hermann, "A treatise on diagnostic methods of examination," 1911
8. Adams, James, Asthma and it's Radical Treatment, 1913
9. Thorowgood, John C., "Notes on Asthma," 1878, 3rd edition, London, J & A Churchill
10. Shmiegelow, Ernst, "Asthma, considered specially in relation to nasal disease," 1890, London, H.K. Lewis

1851-1913: The history of asthma sputum

Ernst Victor von Leyden (1832-1910 discovered
crystals in asthmatic sputum and suspected these
to be the cause of asthma. During his era, he was
the closest supporter of Dr. Robert Bree's
bronchitic theory of asthma. (9, pages 14-15)
He believed these crystals somehow irritated the
"vagus in the mucous membrane of the bronchials,
and hereby caused by reflex action a spasm
of the muscles of the small bronchial tubes."
(10, page 8)

Most people find sputum disgusting, and so will have nothing to do with it. But as far back as 400 B.C., the medical significance of it was observed by ancient Greek physicians, and probably even earlier than that.
If you mention it at the dinner table your mother might smack your hand. But for the sake of gaining a complete grasp on the history of asthma and respiratory disease, we must delve into the topic of sputum.  Sorry, but we must.

It must have been observed at an early date in history that people with breathing issues produce sputum, sometimes consisting of a putrid smell, often consisting of many varied colors such as red, yellow, brown and white.

Yet rather than being petrified by the grossness of the substance, Greek philosophers became fascinated by it. They even gave it its own classification as one of the four humors that, along with determining one's personality, also determined whether was healthy or sick.

Prior to the philosophical medicine of the ancient Greeks, other ancient societies, and the primitive clans and families that roamed the lands before them, believed sputum was the production of some evil spirit, demon or god. When a person expectorated the substance, they were, in essence, expectorating an evil substance that caused the symptoms they were suffering from.

From the ancient world to the scientific revolution there were few changes in the way physicians viewed diseases and treated their patients.  In 1799 Dr. Robert Bree speculated that sputum contained a poison that it was trying to get out of the body, and asthma was the result.  This theory wasn't much different than any idea Hippocrates might have postulated.

Since the sputum preceded the asthmatic fit, Bree essentially speculated that asthma was essentially bronchitis, and thus created the bronchitic theory of asthma.  Others, without much more evidence, speculated sputum was the effect of asthma rather than the cause.

Such speculation gradually tapered off, but never really came to an end, during the scientific revolution, and mainly due to the inventions of the microscope, which allowed physicians to see that the human body was made up of substances too small to be seen by the unassisted eye, and the stethoscope, which allowed physicians to hear changes that occurred inside the chest and to diagnose diseases with accuracy prior to autopsy.

The microscope allowed physicians to learn that air passages were surrounded by smooth muscle and that it was capable of spasming when stimulated.  The stethoscope allowed them to hear when sputum accumulated in the chest, and learn that it was the effect and not the cause of asthma.

So, pretty much, prior to the 1850s asthma was basically considered to be a disease of excess sputum, mainly because this was all physicians could observe with the unaided eye and ear.

Yet by the 1850s, it was looking pretty clear that asthma was also a disease associated with spasms of the air passages, particularly by the wheezes heard by air flowing through narrowed air passages, and rhonchi heard as air flowed through sputum lined air passages.  (1, pages 592-595)

In 1851, Dr. Beau, along with his assistant Cozart, observed that fits of asthma usually ended with a wad of sputum being coughed up. Beau used this observation as evidence to support his theory that asthma was a disease of chronic catarrh, and that asthma was caused by increased sputum in the air passages.  (3, page 31)

When this sputum dried out mucus plugs formed that were capable of blocking the air passages, thus resulting in dyspnea and other symptoms of asthma, including the "sonorous and sibilant rhonchi -- their 'rales vibrants' heard upon auscultation with a stethoscope."  (3, page 31)

The fit, therefore, was resolved when mucus plugs were broken up with a fit of coughing.  (3, page 31)

Then, in 1878, at a time when most physicians had accepted the nervous and spasmotic theories,  J.B. Berkart used Beau's research as evidence of the bronchitic theory of asthma.

Berkart said:

With the displacement of the mucous plug into the larger bronchus, or on its expulsion by means of a fit of coughing, the dyspnea ceases, and with it also the rales disappear.  This form of bronchitis is, in their (Beau and Crozant's) opinion, due partly to an idiosyncrasy of the patient, partly to exciting causes, which greatly vary in different individuals."

Tiny crystals were first observed in sputum in 1851 by Jean-Martin Charcot, but it wasn't until 1872 that these crystals were linked to asthma by Ernst Victor von Leyden. So history has given credit for this discovery to both men by calling the crystals Charcot-Leyden crystals.

Leyden, whose asthma theories were similar to Dr. Bree's bronchitic theory, believed Charcot-Leyden crystals caused asthma by irritating...

...the peripheral extremities of the vagus nerve, and produce reflex spasm of the bronchial muscle."  

The asthma attack, as Bree and Beau observed, ended when a wad of sputum was coughed up during a fit of coughing. (4, page 14-15

However, it was the discovery of these Charcot-Leyden crystals that would ultimately put an end to the bronchitis theory of asthma.  This was noted by Dr. John Charles Thorowgood in 1878.  He said that these crystals were found in sputum obtained from patients with "ordinary catarrh and croupus bronchitis."  (4, page 15)

Thorowgood said:

The asthmatic patient while in a fit presents abundance of symptoms distressing enough to endure or to witness; and yet, when things seem to be at their worse, and the patient well-nigh at his last gasp, a remission comes on, the spasm yields, air enters the lungs, and the attack subsides, coincidentally often with access of cough and mucous expectoration." (4, page 16)(9, page 1,2)

In 1879, bacteriologist Paul Erlich discovered the eosinophil, and it was soon discovered that elevated levels of eosinophils (eosinophilia) was commonly found in asthmatics. (5)

In 1882 Heinrich Crushmann observed other spirals in asthma sputum and believed they were associated with causing asthma. He believed since Leyden's crystals didn't cause asthma, perhaps his crystals did. (5)

Later Curshmann's crystals were determined to be fragments of mucus plugs associated with asthma, and Leyden crystals were determined to be fragments of eosinophils. Eosinophils were later learned to be a type of white blood cell that, along with mast cells, are involved in the allergic reaction.

In 1911 Hermann Sahli described eosinophils in asthmatic sputum. Yet Sahli noted another author from 1891 who described eosinophils in the asthmatic blood, and he concluded that these must be pathological with asthma. Yet he also noted that neither the cause of the eosinophils nor their origin was known. (7)

Sahli could isolate the area where the sputum came from based on epithelial cells in it, yet he did not understand the mechanisms of its production as we do today. (7)

Dr. James Adams describes asthma sputum in 1913: (8)

"Asthmatic sputum varies. Often there is none till the end of the attack; then it is in the typical form of small, tough pellets expelled by laborious coughing. The attack may then cease, or it may go on till a more free and profuse expectoration occurs."

He also wrote:  (8)

"The sputum does not readily decompose, and is said to be wonderfully free from microbes; but this is not always so, as I have occasionally found it teeming with them."

The true purpose of sputum is to ball up microbes inside the lungs and haul them out, and in this way, the lungs stay sterile.  Surely asthma can be caused by inhaling a microbe, such as a bacteria, but it's also caused by asthma triggers (dust mites, smoke, fumes, chemicals, pollution, animal dander) that are non-infecting agents.

So this might explain why Adams most often found asthmatic sputum without an infecting agent, and sometimes "teeming with them."

Backing up a moment to 1906, Australian pediatrician Clemons van Pirquet coined the term allergy when he observed that some of his patients were hypersensitive to substances that did not bother other people (what we now refer to as allergens, or asthma triggers).  This was the first time asthma was linked with allergies.

By 1910 Histamine was discovered and found to be a major component in the allergic response.  So some went on to speculate that finding a way to block histamine would cure both allergies and asthma.
In 1937, the first antihistamine was synthesized in a lab, and in 1946 antihistamines hit the market. Within a decade they were among the most commonly prescribed medicines.

Yet as time went by, it was learned that there was more to asthma and allergies than just histamine.  It was learned that asthmatic and allergic immune systems respond irrationally to allergens and asthma triggers by increasing production of eosinophils and this spearheads inflammation of the bronchial muscles.

Another weapon of the immune system is mast cells that line the respiratory tract and eyes, and these were discovered in 1953.  .

In 1967 Immunoglobulin E antibodies (IgE) were discovered.  It was later learned IgE has a significant role in the asthmatic and the allergic response.  The first time asthmatics are exposed to asthma triggers (allergens), say dust mites, their immune systems develop dust mite IgE antibodies that attach to mast cells that line the epithelial layer of the skin or respiratory tract.

The second time that person is exposed to that allergen (dust mites in this case), a mast cell that has a dust mite IgE antibody attached to it explodes and releases its contents:  the mediators of inflammation.  A mediator of inflammation called histamine was discovered in 1910, and others called cytokines and leukotrienes were discovered in the 1970s.

These mediators, when released into the blood stream, cause inflammation of the respiratory tract, thus causing the allergic and asthmatic responses.

In the allergic person, they can also cause inflammation of the upper respiratory tract, which includes the back of the throat and nose.  The offending substance (dust in our case) is recognized by the immune system, trapped in the mucus layer, absorbed by the mucus, balled up by the mucus, and sent on it's way up the respiratory track to be coughed up.

So this would explain what Dr. Bree, Beau, and Berkart observed. While hacking up a wad of sputum may have been related to the fit of asthma, it was not the cause, and had nothing to do with the cure.

Later it was learned that asthmatic lungs tended to produce an abnormal number of goblet cells, this results in an abnormal increase in mucus production during an asthma attack.  While some of this sputum may be coughed up, some becomes trapped in obstructed air passages, dries out to form mucus plugs, and this further blocks the air passages, thus compounding the asthma response.

When the fit ends, when the air passages relax and dilate, which may be a result of time or medications, the asthmatic will probably expectorate this sputum, which will usually be, if no bacteria or virus is balled up within it, white and sterile.  It will also have IgE and eosinophils in it, hence your Charcot-Leyden and Curshmann crystals.

So it's easy to understand how this production of sputum at the end of an attack could easily be misinterpreted as the cause, rather than the effect, of asthma.

References:

1. Lotval, J., "Contractility of Lungs and air tubes: experiments performed in 1840 by Charles J.B. Williams, European Respiratory Journal, 1994, (7) pages 592-595
2. Bree, Robert, "A Practical Inquiry into Disordered Respiration Distinguishing the Species of Convulsive Asthma, their Causes and Indication for a Cure," 4th ed, 1810, London, page pages 117-118
3. Berkart, J.B., "On Asthma: Its Pathology and Treatment," 1878
4. Thorowgood, John C., "Asthma and Chronic Bronchitis: A New Edition of Notes on Asthma and Bronchial Asthma," 1894, London, Bailliere, Tyndall, & Cox
5. Lipkowitz, Myron, Tova Navarra, "Encyclopedia of Allergies," 2001
6. Brenner, Barry E, "Emergency Medicine, 1998, page 10
7. Sahli, Hermann, "A treatise on diagnostic methods of examination," 1911
8. Adams, James, Asthma and it's Radical Treatment, 1913
9. Thorowgood, John C., "Notes on Asthma," 1878, 3rd edition, London, J & A Churchill
10. Shmiegelow, Ernst, "Asthma, considered specially in relation to nasal disease," 1890, London, H.K. Lewis

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1820-1930: Pneumonia, the new "captain of the men and death

Thomas Addison (1793-1860

For most of human existence tuberculosis was known as the deadliest disease.  It was such a deadly disease by the 17th century, that John Bunyan (1628-1688), the famous author of "Pilgrim's Progress" referred to it as "the captain of men and death."  It wouldn't be until the early 20th century that tuberculosis would take a back seat to pneumonia.

While pneumonia has been present since the beginning of mankind, and the medical profession has been aware of it since the 5th century, little new information was learned about it.  It really wasn't until the end of the 19th century that physicians started to get a grasp on this disease.

Dr. Thomas Addison, a physician to Guy's Hospital in London,  was the first to write about pneumonia not being a disease that affected just the "interstices" of the lungs but the "air vessicles" themselves. (8, page 193)

Carl von  Rokitansky, a German physician, was the first to describe lobar pneumonia. (10, page 1308)

He said:

The red inflammatory product becomes gray and compact and indurated.  The air cells contract over the granulations, coalesce with them round their circumference, and become obliterated, their tissue being changed into a fibro-cellular structure, in which, from the similarity of their organization, the granulations are most probably also merged. (10, page 1308)

Various physicians described a pneumococcus associated with patients with lobar pneumonia.  (8,page 197)

Carl von Rokitansky (1804-1878)

In 1880 Sternberg found it in the saliva, and in 1881 Louis Pasteur discovered the same. (8, page 197)

In 1882 Ernst victor von Leyden and Gunther drew fluid from hepatized lungs of living pneumonia patients and discovered pneumococci in this fluid. (8, page 197)

Yet in all of these cases, the significance of the discovery went unnoticed.  (8, page 197)

It wasn't until 1875 that Edwin Klebs associated pneumonia with the bacteria, describing an "oval coccus" that he obtained from cases of lobar pneumonia. (8, page 197)(?)

A few years later Karl Friedlander and Hans Christian Gram started working together in the morgue of a hospital in Berlin and added to Klebs work by identifying the specific types of bacteria associated with pneumonia.

In 1882 Friedlander isolated streptococcus Pneunomiae in the sputum of a patient inflicted with pneumonia, and in 1884 Gram isolated Klebsiella Pneumoniae in the sputum of a patient  inflicted with pneumonia.

The procedure that Gram described when writing of his discovery was later called the gram stain.  It's a technique where a small sample of the sputum is stained, and this causes the cell walls of the bacteria to turn a certain color so the bacteria can be clearly identified. 

This technique is still used in labs to this day.  Yet while Gram simply used the technique to identify bacteria in sputum samples, it's used today to distinguish between different types of bacteria.

In 1888 Nikolia Fedorovich Gamaleia was working in Pasteur's lab when he inoculated sheep and dog with pneumococcus and this caused lobar pneumonia in these animals.

This experiment proved that pneumococcus was the cause of lobar pneumonia.  Gamaleia is also credited in 1888 as discovering bacteriolysins that destroy bacteria.  (11)

He also worked with pasteur to improve the process of inoculation.

By 1891, interstitial changes may occur in acute lobar pneumonia and this may result in fibroid pneumonia (fibrosis of the lungs), and this will be chronic.  (10, page 1309)

In 1896 French student Ernest Duchesne discovered penicillin, yet the significance of his discovery went unknown, and the discovery was left hanging.

William Henry Osler, in the early editions of his book, "The Principles and Practice of Medicine," mentioned using oxygen for emphysema and asthma, and by 1898, or the third edition, he finally recommended oxygen for pneumonia.

However, while he mentions oxygen as an option, he rarely prescribed it for his patients.

He wrote:

It is doubtful whether the inhalation of oxygen in pneumonia is really beneficial. Personally, when called in consultation in a case, if I see the oxygen cylinder at the bedside I feel the prognosis to be extremely grave. It does sometimes seem to give transitory relief and to diminish the cyanosis. It is harmless, its exhibition is very simple, and the process need not be all that disturbing to the patient. The gas may be allowed to flow gently from the nozzle directly under the nostrils of the patient, or it may be administered every alternate 15 minutes through a mask. (12)

In 1901, in his popular medical textbook "The Principles and Practice of Medicine," Dr. Osler referred to pneumonia as the new captain of men and death. He wrote:

The most widespread and fatal of all infectious diseases, pneumonia, is now the "Captain of the Men and Death," to use the phrase applied by John Bunyon to consumption." 

 By 1918 pneumonia became the leading cause of death, overtaking tuberculosis. In describing the new leading cause of death, Osler burrowed from Bunyan, describing pneumonia as "captain of men and death. (4)

References:

References:

1. "Leading Cause of Death, 1900-1998," http://www.cdc.gov/nchs/data/dvs/lead1900_98.pdf
2. Sturges, Octavius, "The Natural History and Relations of Pneumonia," London, 1876
3. "History of Pneumonia," The British Medical Journal,  Jan. 19, 1952, pages 156-158
4. Schmitt, Steven K., "Oral Therapy for Pneumonia:  Who, When, and With What?" editorial, Journal of Clinical Outcomes Management,  March, 1999, vol 6, No 3, pages 48-50
5. Bellis, Mary, "The History of Penicillin," http://inventors.about.com/od/pstartinventions/a/Penicillin.htm
6. Marrie, Thomas J, "Community Acquired Pneumonia," 2001, New York, chapter one by Jock Murray, "The Captain of Men and Death: The History of Pneumonia."
7. Auld, A.G., "The Pathological Histology of Bronchial Affections," The Lancet, Aug. 6, 1892, page 312
8. Allbutt, Clifford, ed, A System of Medicine, 1909, Toronto, chapter on "Lobar Pneumonia,"  by P.H. Pye-Smith, pages 191-205
9. Addison, Thomas, "A Collection of the published works of Thomas Addison," 1868, 
10. Auld, A.G., "Fibroid Pneumonia," The Lancet,  June 13, 1891, page 1308-1310
11. "Nikolai Fedorovich Gamaleia, The Free Dictionary by Farlex, http://encyclopedia2.thefreedictionary.com/Nikolai+Fedorovich+Gamaleia
12. Osler, William, "The Principles and Practice of Medicine," 1898, 3rd ed., New York
13. *Photo compliments of sciencephotolibrary.com
14. "Plutarch," britannica.com, http://www.britannica.com/EBchecked/topic/465201/Plutarch, accessed 7/20/14
15. Laennec, Rene, "Mediate Auscultation," translated by John Forbes, Notes by professor Andral, 4th edition, 1838, New York, Samuel S. and William Wood, pages 84-87 for bronchitis treatment, and 175-177 for emphysema treatment
16. Andras, author of the notes in the book, "Mediate Auscultation, by Rene Laennec," ibid
17. Reynolds, Arthur, R., "Pneumonia: The New Captain of the Men and Death," February 28, 1903, Journal of the American Medical Association," XL(9):583-586, http://jamanetwork.com/journals/jama/article-abstract/854678, accessed 1/2/16

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1800-1920: Oxygen cylinders and chambers

Fig 1-- Left to Right: Oxygen tank, rubber bag (400 cc), thermometer
in glass tube, water-manometer and small cannula (1908)(1, page 288)

While the benefits of oxygen therapy were known, it took a long time for its use to be accepted by the medical community. The main reason was that there were no efficient and inexpensive means of making it and delivering it to patients. Plus experiments provided sketchy results at best.  

So for the most part, oxygen wasn't used therapeutically during the 19th century until a cholera outbreak in Europe in 1832. In 1857 S.B. Birch described a "renaissance of oxygen." His writings did create a "renaissance" of sorts. Yet, once again, results were sketchy.  (1, page 282)

Ernst Victor von Leyden (1832-1910)

During the 1860s Ernst Victor von Leyden performed experiments, and soon thereafter gave up the task. He postulated the following theories why oxygen failed to be accepted by the medical commuity:

1. It was thought to have curative powers, and it doesn't
2. It's difficult and expensive to make, and difficult to transport and deliver to patient
3. When prepared by physicians it often contains poisonous gases
4. The apparatus to deliver it is clumsy
5. Hypercritical attitude of physicians
6. Negative results by experiments

The most effective means of employing oxygen during the 19th century was mainly by putting the patient in an oxygen chamber or room, pumping in pure oxygen, and having the patient breathe normal. This concept was used in the variety of oxygen parlors that opened up. Patients with various ailments, and probably some people just wishing to stay healthy, came to breathe the medicated air.

Henry Fleuss (1851-1933)

Henry Fleuss was working to create a method so that scuba divers didn't have to rely on a person working a pump to provide air for him to breathe. He was aware that the first person to discover oxygen in 1773 kept bees alive in a jar by drawing out the carbon dioxide. Later studies showed animals could survive in a sealed chamber if oxygen was supplied.(2, page 83)

So Fleuss intended to use this knowledge to invent an apparatus that allowed divers to supply themselves with air. He, in turn, invented the compressed air or oxygen cylinder in 1879.  (2, page 83)

The device allowed for a "breathing bag mounted on the chest and scuba canister mounted on the back. His device was called a "rebreather" because air was repeatedly rebreathed. Oxygen was added from the tank, and carbon dioxide removed. He used his device to rescue coal miners who were trapped in a mine.   (2, page 83)

So the oxygen cylinder was now available for use in therapeutics as well, if the medical community was willing to use it.  Various manufacturers were now producing oxygen and storing it in steel cylinders.  

Fleuss Apparatus

Tissier describes the tank in Figure 3 as containing "40 gallons of oxygen under 1800 pounds of pressure are contained in a cylinder 3 inches in diameter, less than 13 inches in height, and weighing but 11 pounds. The gas will have a purity of 95 or 96 per cent., being diluted by the small quantity of air in the container. Mounted on the cylinder are a rubber bag of one gallon capacity, and a wash-bottle—so arranged that the gas passes first to the bag and then through the wash-bottle to the patient." (3, page 304)

Tissier explained that a manometer may be attached, although generally the pressure can be estimated by watching the bubbles through the wash bottle. He said that a "gentle, steady stream that does not cause appreciable splashing, and in which the individual bubbles can be distinguished, is best." I imagine regulators at this time weren't very accurate anyway, and someone would be required to make regular checks on the cylinder anyway to make sure there was still oxygen in it. (3, page 304)

Figure 3 -- Oxygen tank, rubber bag, wash bottle,
rubber tubing, mouthpiece (3, page 304)

Oxygen flows from the oxygen tank, some is stored in the rubber bag, which acts as a reservoir, through the wash bottle, through the rubber tubing, and to the patient by means of a nose piece, mouth piece, or face mask. Tissier recommended a hard rubber mouthpiece to prevent the patient from biting through it. For the nostril, glass or rubber could be used. (3, page 304)

He also said: "if nothing better, a funnel of paper cone may be held over the nose and mouth, but not touching the face -- so that expiration may take place beneath it." (3, page 304

The oxygen is set at the desired flow, which there was no way of measuring with accuracy, so it was basically by the gut feeling of the operator. Then the flow is "allowed to flow for a definite time, or, in urgent cases, almost continuously, unless distressing to the patient." (3, page 304)

The funnel is really not preferable because, as Tissier said, it will probably waste a considerable amount of oxygen. However, particularly with pneumonia, it "may save a life."  

Oxygen Chamber for the treatment of pneumonia (6, page 480)
To view more pictures of the chamber click here.

Oxygen can also be given with a desired amount of pressure, if pressure is desired to assist with the patient's breathing and/or to help diminish dyspnea. If this is the case, the oxygen system may be hooked up to one of the various gasometers. Oxygen may also be blended into the air of pneumatic chambers if so desired. (3, page 305) (I will describe gasometers and pneumatic chambers in later posts)

By the 1890s pure oxygen could be piped into rooms or chambers, although this method wasn't often used. Still, in 1922 Alvin Barach (remember this name) wrote that piping oxygen into a room, or a room within a room (also known as an oxygen chamber) provided for the best means of giving oxygen to patients simply because it was the least cumbersome. However, the oxygen provided wasn't always enough to be therapeutic, and the the chambers were inconvenient and expensive. Plus they weren't portible.

Sir Joseph Barcroft (1872-1947)

An efficient oxygen chamber that was somewhat portable was introduced to the world during WWII by Sir Joseph Barcroft. He created an air tight chamber that is "leak tight in order to provide an atmosphere rich in oxygen and which is artificially ventilated in order to provide a comfortable environment. The oxygen content of oxygen is between 40-60 percent (21 percent is available in room air), which is considered the therapeutic range. It is ventilated in order to remove excess carbon dioixde, moisture and heat." (7)

Oxygen could also be provided to the patient by means of crude oxygen tents. These tents were comprised of a canopy that covered the patient's bed, and oxygen was piped into the canopy from a cylinder at the patient's bedside. Yet these early oxygen tents were poorly engineered.

Dr. Andrew H. Smith of New York provided one of the greater contributions to therapeutic oxygen when he wrote "The Inhalation of Oxygen in Acute Affections of the lungs," in 1898. He recommended oxygen for lung diseases that caused dyspnea. In the 1860s he showed the effectiveness of using oxygen to treat animals, and in 1870 he proved the inhalation of pure oxygen was harmless (although we later learned oxygen is a drug with side effects). (5)

Smith explained how methods of creating oxygen and filling rooms with oxygen were actually available in the 1860s, and experiments on animals proved that filling rooms with enriched oxygen can prolong the lives of people who would otherwise have died. Smith also wrote about the use of compressed oxygen, (5) which was discovered in 1895 by Karl Paul Gottfied von Linde of Germany and William Hampson of England.

Generally speaking, if patients required oxygen they would have to seek out an institution or physician with access to it. Oxygen wasn't available in hospitals until the 1920s.  

References:

1. Brainbridge, William Seaman, "Oxygen in Medicine and Surgery -- a contribution with report of cases," New York State Journal of Medicine, 1908, Vol. 8, June, No. 6, pages 281-295
2. Stephens, Jack, "Living Mirrors: A Coral Reef Adventure," 2003
3. Tissier,Paul Lewis Alexandre, edited by Solomon Solis Cohen, "Pneumotherapy: Including Aerotherapy and inhalation methods," volume X, 1903, Philadelphia, P. Blakiston's Sons and Co.
4. Arthur, T.S., et al, editors,  "Oxygen, The Great Health Restorer," Arthurs Home Magazine, 1882, Philadelphia, page 770
5. Smith, Andrew H. "The Inhalation of Oxygen in Acute Affections of the lungs," Trans Am Climatol Assoc, 1898, volume 14, page149-153
6. "Studies from the Rockefeller Institute for Medical Research,",volume XLII, New York, 1922,  Rockefeller Institute for Medical Research
7. Barach, Alvin L., "A New Type of Oxygen Chamber," April 26, 1926,  http://www.jci.org/articles/view/100060/files/pdf, reviewed 10/28/12

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