1860: Salter disproves ancient asthma theories

Dr. Henry Hyde Salter was among the first physicians to believe that diseases ought to be defined based on personal experiences with the diseases, observing patients, and studying autopsies, as opposed to speculation.  Later physicians said it was this technique that made him the most famous asthma doctor of his era.  

In the opening chapter of his 1960 book "Asthma: Its Pathology and Treatment" he put to rest any theories about asthma that didn't support modern evidence. While he shunned the humoral ideas of ancient writers, he also shunned the bronchitic theories of the famous Dr. Robert Bree  who's believed asthma was caused by some peccant matter entering the lungs

Salter said that Bree was so convincing, and had obtained such a large following, that he had to dedicate almost an entire chapter to disproving his theories.

However, in the end, Dr. Salter said Dr. Bree's theory was disproved simply by the invention of the stethoscope.  He said if Bree had access to a stethoscope he would have easily heard the wheezes caused by narrowed air passages due to neurosis, and would have heard that the wheezes persist even after mucus is expectorated, as opposed to before.

One of the reasons Dr. Bree's ideas were so well accepted was because they were more in line with the Hippocratic doctrine, which was still well accepted by many prominent physicians when Bree first wrote his 1798 book "A Practical Inquiry into Disordered Respiration."

Since Hippocrates, many asthma experts believed asthma was caused by an imbalance of the four humors. Salter doesn't deny...

..."that in some cases the exciting cause of the attack is humoral; but what I would deny is, that the humoral derangement has any higher place than that of an exciting cause; and what I would insist upon is, that the heart and core of the disease is nervous; that the essential peculiarity of the asthmatic is a vice in his nervous system, a peculiar morbid irritability of it, whereby a certain portion of it is thrown into a state of excitement from the application of stimuli which another person would produce no effect at all, or a very different effect." (1, page 25)

Salter disproved the idea that congestion, or phlegm, or mucus, was the cause of asthma, because the attack usually ends with the expectoration of phlegm. He wrote:

"We admit the fact to be true, but doubt very much the correctness of the inference; at least it is certain that, in ordinary bronchitis, enormously greater accumulations of mucus take place with comparatively few signs of general obstruction. We think this position must be admitted by any unbiased observer; and it is, in our opinion, fatal to this theory. (1, page 25)

Given the tools available to Salter, wasn't hard for him to disprove old asthma theories in favor of science. He went on to prove that asthma was nervous and spasmotic, and was so convincing that his ideas were referenced by nearly every author on asthma for the next 50 plus years.

References:

1. Salter, Henry Hyde, "Asthma: It's Pathology and Treatment," 1864, Philadelphia, Blanchard and Lea

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1860: Salter proved nervous theory of asthma

Dr. Salter believed asthma was a nervous disease. He believed the evidence asthma was nervous was so abounding that it could not be denied.

While the idea asthma was nervous was postulated back in the ancient era, and even postulated by physicians such as Jan Baptiste van Helmont and Thomas Willis in the 17th century, and William Cullen in the 18th century, it really didn't engulf the medical community until it was re-introduced by Salter's mentor, Dr. Robert Bentley Todd. 

While Dr. Salter didn't accept all Dr. Todd's ideas about asthma, he did accept his notion that asthma was nervous.  By writing his famous articles on asthma that were ultimately published in the 1960 book "On Asthma: Its Pathology and Treatment," Salter brought the idea to the mainstream of physicians, many of whom accepted it as fact, even treating it as a nervous disorder.  Even 20th cen

Even the famous 20th century asthma expert Frances M. Rackemann was a supporter of Salter's nervous theory of asthma.  Even while disproved during the 1950s once the immune system was learned of, his ideas continued to be accepted, even into the 1970s and 1980s.

He even went as far as to offer to the  medical community evidence that asthma was nervous.

• Fatigue and mental emotion bring about an attack
• Remedies that appeal to the nervous system allay an attack, such as stramonium, antimony and chloriform. 
• The periodicity of asthma. It goes away and comes back without warning by recurrence of hay fever, indigestion after dinner, expectoration after a good nights sleep, etc. 
• Symptoms of asthma, such as clear urine (nervous urine), nervous headache, drowsiness, and an attack after laughter or animation. These are similar to hysteria and epilepsy.
• No organic change in the lungs during or following an attack. Post mortem exam of asthmatics shows no organic changes, or damage, to the lungs. They are essentially normal.
• Asthma is muscular in that it is caused by muscular fibre that spasm and squeeze the air passages of the lungs. Muscular disorders like this are always nervous as the nerves are connected with the mind (4 page 13-16)

Salter didn't deny asthma was a spasmodic disease of the lungs, yet he believed this was the result of a nervous condition of the patient.   He said:

The inflammation or congestion of the mucous surface appears to be the stimulus that, through the nerves of the air tubes, excites the muscular wall to contract. (6, page 92)

It was also for this reason he recommended remedies that would soothe the mind of the patient, such as alcohol, cigarettes, morphine, formaldehyde, strammonium, antimony, antispasmotics, and direct nervous depressants. (6, page 33)

His favorite remedy was chloroform because "just a few whiffs, and the asthma is gone; a dyspnea that a few seconds before seemed to threaten life is replaced by a breathing calm and tranquil." (4, page 33)

Thus, he wrote, remembering that the action of these remedies on the nervous system, "it is impossible to help seeing in this the most conclusive proof that the symptoms are due to a nervous cause."  (4, page 33 & 34)

He described one symptoms of asthma as itching of the skin under the chin.  I personally have experienced this when my asthma has been bad, and I think to this day there is yet no scientific explanation for it.  Yet Dr. Salter was convinced the cause was an "irritation at the roots of these nerves.  (5)

So he believed nervous asthma resulted in spasmotic asthma.  Actually, he believed nervous asthma was spasmotic asthma, and in this way he was a supporter of both the nervous and spasmotic theories of asthma.

He defined nervous, or spasmotic, asthma as "paroxysmal dyspnea of a peculiar character, generally periodic, with intervals of healthy respiration between the atatcks."

He said asthma was more common than believed, yet pure asthma, or "asthma without the slightest organic complications," was rare. (4)

However, if the nervous disposition lead to asthma attacks that were frequent, this may result in "permanent injury on the lungs, and even the heart."

He said:

"Asthma is not the less asthma because it has produced certain organic changes which complicate it; and many cases are primarily and essentially asthma that ultimately become, and are called, emphysema and heart disease." (4, page 17)

He was also a realist, and did not claim to offer a cure for the disease.  He believed that since the disease was nervous in origin, there really was not truly effective treatment.  He said:

"...the treatment is regarded as palliative. It must be admitted that the remedies for asthma are of very irregular and uncertain operation: that probably there is no single remedy that is not inoperative in a large number of cases; that that which is useful in one is valueless in another; while there are many cases that resist all remedies. If this intractability of asthma were doubtfull, the large number of remedies that have been suggested would be a sufficient proof of it."

 Further reading:

• 1823-1871:  Dr. Salter offers proof asthma is nervous
• 1850s: Dr. Salter's Asthma Features (2/14/14)
• 1850s: Dr. Salter's Varieties of Asthma (2/20/14)
• 1850s  Dr. Salter's asthma triggers (2/27/14)
• 1850s: Dr. Salter's asthma signs and symptoms (3/6/14)
• 1850s: Dr. Salter's Consequences of asthma (3/13/14)
• 1850s: Dr. Salter's Asthma Remedies (3/27/14)
• 1850s: Dr. Salter's prognosis for asthmatics (4/10/14)

Click here for more asthma history.

References:

1. "The Late Henry Hyde Salter," Medical Times and Gazette, Sept. 13, 1871. 
2. McCulough, David, "Mornings on Horseback," 1981, New York
3. Sakula, Alex, "Henry Hyde Salter (1823-71) a biographical sketch," Thorax, 1985; 40; pages 887-888.
4. Salter, Henry Hyde, "On Asthma:  Its Pathology and Treatment," 1861, London, Philadelphia
5. Kidd, G.H. Dr., "On the pathology of Asthma," Dublin Quarterly Journal of Med. Science," 1861, May,
6. Salter, Henry Hyde, "Asthma: It's Pathology and Treatment," 1864, Philadelphia, Blanchard and Lea

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1860: Salter: Why do young people outgrow asthma?

For many centuries it was believed that most cases of asthma were present in children, and that as one ages the asthma has a high tendency of disappearing.  The first person, to my knowledge anyway, to come up with a theory as to why this was believed, was Dr. Henry Hyde Salter. 

Dr. Salter believed that asthma was a nervous disorder, and that some exciting cause excited the nervous system and this ultimately caused spasms of the bronchial muscles that constricts the air passages.  When this occurs blood in the pulmonary vessels is unable to move through the blocked portions of the lungs, and becomes congested. 

When asthma is pure (free from any organic changes), it is intermittent, meaning that the attacks come upon the patient and then go away for a long period of time prior to occurring again.  The period of time between the attacks is random or periodic and cannot be predicted. 

Salter believed asthma was more likely to be of the pure form the younger people were when they acquired it.  So asthmatics under the age of 15 had a greatest chance of outgrowing it, those between 20 and 40 a fair chance, and over 40 a rare chance. 

"Now, why is this?" Salter asked.  "Why, caeterus paribus, (everything else being equal) should age have such a determining influence on the tendency of asthma?

He answered his own question:

1.  The young are more capable of repair:  "Partly for the reasons that I have mentioned—that in the young the powers of repair are great, in those advanced in life feeble; that in the young the pulmonary congestion that always accompanies asthma completely vanishes in the intervals of the attacks, the capillaries recover their tone, and the nutritional balance of the lungs is regained; whereas in the old the engorged capillaries are slower in recovering themselves, and the pulmonary congestion hangs about the patient some time after the asthmatic spasm has disappeared, manifesting itself by a profuse mucous exudation, and a certain thickness of breathing and incapacity for exertion. If the attacks are frequent this pulmonary congestion never entirely vanishes, and thus is produced a kind of spurious chronic bronchitis, with a tendency to aggravation by each attack, which is one of the worst and commonest complications of the asthma of the old."

2.  The young are less likely to develop chronic bronchitis:  "Another complication of asthma—dilated right heart —is much more apt to occur in the old than in the young, and for the very reason that the dyspnoea in the old is so apt, by the generation of this spurious bronchitis of which I have been speaking, to pass from the occasional and intermittent form characteristic of pure asthma, and become continuous and permanent . As far as I have seen, the right side of the heart never becomes dilated by asthma, however severe the dyspnoea may be during the attacks, if the intervals between them are considerable, and the recovery in those intervals complete. It is a continued and not an occasional and transient arrest of the pulmonary circulation that dilates the right side of the heart. It is from this fact that we see dilatation of the right side of the heart, venous stasis, and general dropsy so much more common as a result of chronic bronchitis than of asthma."

3.  The young have more room for hope:  "But this greater disposition in asthma to produce organic change in the old than in the young is not the only circumstance which imparts to age its determining influence on the tendency of the disease. In asthma, as in all other constitutional disorders, we have in the young much more room for hope from those changes in the type and build of the constitution which in them are so marked and striking; whereas in the old the constitution is set and fixed, and we have but little to hope on this score. Indeed, the existence of a constitutional peculiarity in a child is of itself almost a presumption that he will one day lose it; while in an old person it furnishes a presumption equally strong that it is fixed and indelible.

4.  Young lungs have more time to recover between fits:  "Again, in an old person the probability is that the asthma has existed longer than in a young one, and, as I shall show presently, the chances of recovery from asthma (as is the case in almost all diseases) are in inverse proportion to the length of time that the disease has existed."

5.  The young are more likely to have pure nervous asthma:  "But there is a special reason, depending on the nervous nature of asthma, that makes us sanguine of recovery in the case of the young, and which explains at the same time the greater frequency of pure nervous examples of the disease in the young than in the old. What, for want of a better name, we must call "nervous irritability" is much more marked in the young than in the old. It appears continuously to diminish from birth forward. Sources of irritation that in the young are adequate to the production of the most violent nervous phenomena, in mature life are powerless to produce such effects. The cutting of a tooth, for example, will send an infant into epileptic convulsions: one never hears of a fit from the second dentition. A young child will grind its teeth, or even be violently convulsed, from the presence of ascarides in its rectum; but one never sees such results from worms in the adult. And thus the diminution of nervous irritability, as childhood passes into youth and manhood, may make an attack of asthma less and less prone to occur on the supervention of its exciting causes, and less intensely spasmodic when it does occur. I believe, indeed, that this diminution of nervous irritability is the true explanation of that gradual recovery of young asthmatics which is so common, so almost universal."

6.  Youth asthma is not causes by organic changes:  Lastly, age influences unfavorably the tendency of asthma, not only because it is more apt in advanced life to engender organic disease, but because it is also more apt to have organic disease as its cause. The causation of asthma in youth and age is indeed very different. In age there is commonly some appreciable organic basis for it; in youth much more rarely.

So there you have it: six reasons why the youth are more likely to outgrow their asthma. 

References:

• Salter, Henry Hyde, "On Asthma: It's Pathology and Treatment," 1882, New York, William Wood and Company, pages 135-142  (original publication of chapters in magazines during the 1850s. The articles were compiled and published as a book, the first edition of which was in 1860 in London)

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1860: Dr. Salter, the famous asthma doctor

Figure 1 -- Dr. Henry Hyde Salter.

As a kid he suffered mightily from asthma, and when he grew up he made his disease the focus of his life.  He wrote a book that became the most famous asthma book of his era. His name was Dr. Henry Hyde Salter, the famous asthma doctor.

He was born on November 2, 1823. Within only a few weeks of his birth he suffered a bout of whooping cough that ultimately lead him to a lifetime of suffering from asthma. (1)

His dad was a prominent surgeon.  His grandpa, uncle and several members of his family were also physicians.  So it wasn't surprising that, after graduating from the University of London, he entered King's college to study medicine. (1)

He earned his medical degree in 1851 and soon opened a medical practice.  It probably didn't take him long to realize he had a special sort of empathy towards his asthmatic patients, particularly asthmatic children.

In 1851 he became assistant physician at King's College Charing Cross Hospital, and in 1852 he became assistant physician to Robert Bentley Todd (1816-92) in New York.  He sat in on Todd's lectures and took copious notes "almost verbatim," which were published in the Medical Gazette and ultimately this "added much to Dr. Todd's reputation. (1)

Likewise, in 1851, he became assistant-editor of the "Encyclopedia of Anatomy and Physiology."  He wrote articles on the tongue and pancreas, and he read and edited the entire collection.  (1)

In 1854 he returned to King's College where he lectured in physiology, physiological anatomy and medicine for the next 12 years.  His efforts as a writer, lecturer and physician earned him a spot as the youngest member of the Royal College of Chest Physicians in 1856 at the age of 33.  He gave a lecture to this group on dyspnea in 1866. (1)

From a photograph of an asthmatic, whose disease

dated from whooping-cough at three months old.

(One might wonder if this is a photo of a young

Dr. Salter.) (6, page 115)

Yet it was asthma that was his "special interest" in many of his research and study projects. (2) He gave many lectures, most about diseases of the thorax -- and asthma.  (5)

Dr. Salter's special interest in asthma gave him a unique inside take on what it was like to have asthma. This, coupled with his exemplary skill at writing, made him the ideal person to write on the subject.

In his book he provided some of the best and most vivid descriptions of asthma up to that time, as shown here:

"But not only is asthma not an uncommon disease, but it is one of the direst suffering; the horrors of the asthmatic paraxysm far exceed any acute bodily pain; the sense of impending suffocation, the agonizing struggle for the breath of life, are so terrible, that they cannot even be whitnessed without sharing in the sufferers distress." (6, page 17)

His description of the suffering was likewise vivid.  He wrote:

 "With a face expressive of the intensist anxiety, unable to move, speak, the head thrown back between elevated shoulders, the muscles of respiration rigid and tightened like cords, and tugging and straining for every breath that is drawn, the surface pallid or livid, cold and sweating -- such are the signs by which this dreadful suffering manifests itself." (6, page 18) 

As well as was his overall description of the asthma paroxysm.  He wrote:

But the dyspnoea of asthma tells a plainer tale than this; it tells us not only what it is not, but what it is. It gives the most positive evidence of narrowing of the air-passages. The asthmatic's breathing is what our forefathers called "strait," what we call " tight;" he feels as if a weight were on his sternum, as if his chest were compressed, as if a cord bound him, as if it would be the greatest relief to him if some one would cut his breast open and allow it to expand; he rushes to the window to get air, he cannot tolerate people or curtains about him, his clothes are loosened, and all the muscles of respiration tug and strain their utmost to fill his chest. But he can neither get air in nor out, he can neither inspire nor expire—his respiration is almost at a dead lock; he cannot blow his nose, ean hardly cough or sneeze, cannot smoke a pipe, and if his fire is failing, cannot blow it up; he has hardly air enough to produce the laryngeal vibrations of speech. (6, pages 37-38)

He even went as far to describe what life was like for an asthmatic between attacks.  He wrote:

"And even in the intervals of health, the asthmatics sufferings do not cease; he seems well, he goes about like his fellows and among them, but he knows he is altogether different; he bears about his disease within him wherever he goes; he knows he is struck... he is conscious that he is not sound... he only knows that a certain percentage of his future life must be dedicated to suffering; he cannot make engagements except with a proviso; and from many of the occupations of life he is cut off; the recreations, the enjoyments, the indulgences of others he dare not take; his usefulness is crippled, his life is marred; and if he knows anything of the nature of is complaint, he knows that his suffering may terminatein a closing scene worse only than the present." (4, page 17, 18)

Any person who ever suffered from an attack of asthma, or ever witnessed one, could easily relate to what Salter described.  It was such exemplary asthma prose that proved to his readers that he knew what he was writing about.  It was such that made him to be the famous asthma doctor.

After years spent suffering, and years spent studying his patients, and performing interviews and autopsies, he put his best asthma knowledge together during the 1950s in a series of articles that were published in medical journals throughout the decade.  Each article was ultimately turned into a chapter in his 1864 book "On Asthma:  It's Pathology and Treatment."

During the last four years of his life his asthma took a turn for the worse.  During the night he'd spend time leaning against the bed post with his shouders hunched while smoking datura leaves. During the day he ate lightly, and continued to work as a physician and to give lectures.

In 1871 he became thinner and weaker and was diagnosed with typphoid fever.  Yet ultimately it was discovered he developed a lung abcess and passed away on August 30, 1871, at the young age of 48.

Dr. Salter's book is referenced in nearly every article, every chapter, and every book on asthma for the rest of the decade.  Even the great Dr. William Henry Osler referenced Dr. Salter when he wrote his textbook for medical students.

Further reading:

• 1864:  Dr. Salter offers proof asthma is nervous
• 1864: Dr. Salter proves nervous theory of asthma (1/5/16)
• 1864: Dr. Salter disproves ancient asthma theories (12/30/14)
• 1864: Dr. Salter's Asthma Features (2/14/14)
• 1864: Dr. Salter's Varieties of Asthma (2/20/14)
• 1864  Dr. Salter's asthma triggers (2/27/14)
• 1864: Dr. Salter's asthma signs and symptoms (3/6/14)
• 1864: Dr. Salter's Consequences of asthma (3/13/14)
• 1864: Dr. Salter's Asthma Remedies (3/27/14)
• 1864: Dr. Salter's prognosis for asthmatics (4/10/14)

Click here for more asthma history.

References:

1. "The Late Henry Hyde Salter," Medical Times and Gazette, Sept. 13, 1871. 
2. McCulough, David, "Mornings on Horseback," 1981, New York
3. Sakula, Alex, "Henry Hyde Salter (1823-71) a biographical sketch," Thorax, 1985; 40; pages 887-888.
4. Salter, Henry Hyde, "On Asthma:  Its Pathology and Treatment," 1861, London, Philadelphia
5. Kidd, G.H. Dr., "On the pathology of Asthma," Dublin Quarterly Journal of Med. Science," 1861, May,
6. Salter, Henry Hyde, "Asthma: It's Pathology and Treatment," 1864, Philadelphia, Blanchard and Lea

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1860: Villemin's asthma theories ignored

Jean Antoine Villemin (1827-1892)

Most people of the civilized world were aware of a killer by the name of consumption, although no one knew where it came from nor what to do about it.  If you caught it you probably going to die. Fear of this killer created a feeling of doom and gloom that spread across Europe and the United States.

After obtaining his medical degree from Stassburg in 1853, Jean Antoine Villemin was sent to Val de Grace, the military school at Paris, for further study.  While a professor at Val de Grace he made the observation that men living in close quarters in barracks were most likely to catch the disease. So he set out to perform an experiment.  (1)(2, page 664)

Villemin obtained some tissue from a man who died of tuberculosis, and he inoculated it into rabbits.  He knew the rabbits were probably going to die, although he knew that he could save the lives of millions of people around the world if his experiment succeeded.  

Every day he checked on his rabbits, and by the third month his diligence paid dividends, as he observed tuberculosis lesions.  He published the results of his study, and they were ignored by the medical community.  By respecting his experiments physicians could have limited the spread of one of the most dreadful diseases ever to inflict mankind, yet their ignorance prevented them from doing so.

Villemin's work would ultimately be proven true by other scientists.  Yet until that time, Villemin worked overtime trying to convince the medical community that he was correct.  He would ultimately become a hero, although that time wouldn't arrive for several more years.  

By his investigations into the lungs, he was able to learn about other diseases as well, including asthma.  In 1860, he tried to disprove the nervous theory of asthma with his own scientific experiments, which were described by Dr. J. B. Berkart in 1878: 

Villemin professed to have demonstrated the pathological changes that deprived the pulmonary tissue of its elasticity, and predisposed the bronchial mucous membrane to hypersemia. He stated that emphysema originated in a proliferation of the inter-capillary nuclei, whose advancing growth tended to compress the alveolar vessels. As the nutrition of the air-vesicles became impaired, they were unable to efficiently perform expiration. At the same time, the respiratory surface was reduced, and the blood accumulated in the bronchi to such extent as to convert their mucous membrane into a kind of erectile tissue. This condition gave rise to no symptoms, either subjective or objective. Its existence became manifest only by the readiness with which trifling incidents produced their effect. Hyperaemia (inflammation?) rapidly ensued, and led to the dyspnoeal attacks that other writers consider as nervous asthma. The chronic inflammation of the alveoli, described by Villemin, is, however, not recognised by other observersIronically, 130 years later, asthma was found to be a disease of chronic inflammation. Should we go back now and give Villemin cretic in retrospect? (3, pages 33-34)

Like his tuberculosis theory, his asthma theory was ignored by the medical community. This was because the nervous theory was so popular at this time that there was no room for any other theory.  Villemin was yet another victim of how hard it is to change the minds of people who are already set in their ways. 

However, in the decades that followed Villemin's publication of his work on tuberculosis, the works of Louis Pasteur and Robert Koch would force the medical community to look at Villimin's work and accept it as fact.

Further reading:

• 1855:  Traube doubts nervous theory of asthma

References:

1. "Jean Antoine Villemin," britannica.com, http://www.britannica.com/EBchecked/topic/629218/Jean-Antoine-Villemin, accessed 3/3/14
2. Garrison, Fielding Hudson, "An introduction to the history of medicine," 3rd edition, 1821, Philadelphia and London, W.B. Saunders Company
3. Berkart, J.B., "On Asthma: It's pathology and treatment," 1878, London, J. & A. Churchill
4. "Obituary: Jean Antoine Villemin," The British Medical Journal, Nov. 13, 1892, 1860:  Villemin's asthma theories ignored, accessed 3/3/14

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1859: Benvenisti writes opinion about asthma

Moise Bervenisti published his asthma book in 1859 called Commentario Sull'asma.    J. B. Berkart summarized his view on asthma:

Benvenisti, again, complained of the disregard to pathological anatomy in cases of asthma. There were numerous pathological processes, such, for instance, an embolism of the pulmonary artery, sufficient to produce the most intense dyspnoea, yet not discoverable by physical diagnosis. To conclude, therefore, from the presence of sonorous and sibilant rhonchi as to the presence of a bronchial spasm appeared to him to be unwarrantable. (1, page 30) 

Orville Brown said:

Benvenisti took the position that there must be definite pathologic processes at the bottom of asthma even though often undiscoverable. (2, page 34)

At the present time that's about all I can find on M. Benvenisti.

References:

1. Berkart, J.B., "On Asthma: It's pathology and treatment," 1878, London, J. & A. Churchill
2. Brown, Orville Harry, "Asthma, presenting an exposition of nonpassive expiration theory," 1917, St. Louis, C.V. Mosby Company

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1859: Mathieu's Nephogene

Mathieu's Nephogine (Nebulizer) (1)

Modern nebulizers work by means of the Bernoulli Principle, where air is forced through a narrow tube, a negative side stream pressure is created, and medicine is sucked into the flow through a small opening in the tube, thus producing a fine spray or mist.  This concept was first used in a nebulizer in 1859 by M. Mathieu of Paris.  

A nebulizer is any device that creates a mist.  The first nebulizer was introduced in 1858 by M. Sales-Giron, and it required an operator to work a pump similar to a bicycle pump to generate a flow that caused the solution to spray onto a hard surface to produce a mist.  

Similar to Danielle Bernoulli's realization that the same mist produced by forcing water onto hard a surface could be produced by his Bernoulli Principle, Mathieu discovered the Bernoulli Principle would be ideal for creating an effective nebulizer.  He got the idea from the concept of treating ailments of the mouth and throat with a spray produced by squirting water out of a syringe.  (2, page 188)

On May 9, 1859, at the Paris Academy of Medicine,  he introduced his product, which he called the Nephogene (nebulizer), to the Medical Academy at Paris.  It was not a pulverizer or atomizer because it didn't pulverize nor atomize, it simply broke the solution into "a cloud or nebula"; it thus nebulized. (2, page 188)

The nebuliezr is described here:  (1, page 462-463)

"In it the subdivision of the medicated fluids is brought about, not by checking the jet against a solid body, but by forcing the fluid to escape at high pressure, along with a blast of compressed air, through a tube with a small opening. Fig. 2 shows Mathieu's original instrument. In it the air is compressed in the brass ball, A, by means of the pump above it, whilst the fluid to be atomised is put  into the glass ball, B. As soon as the instrument is set in motion the two stopcocks are opened, when; the medicated fluid escapes drop by drop into the tube c, and there meets the blast of compressed air, which forcibly projects it outwardVin the form of a very fine but cold spray." 

Another version designed by Mathieu can be seen in figure 18, and thus described here:

"This apparatus (Fig. 18) is composed of a glass reservoir c, in which the liquid to be employed is poured through the little funnel G. On compressing the air in the pump B, by motion of the lever A, the fluid is forced through a small groove in one of the plates forming the joint D, and by turning the screw H, the smooth plate is more or less compressed against the groove, thus regulating the delicacy of the stream. A stream as fine as the finest hair can be thus secured if the instrument be properly constructed. This capillary stream against the upper portion of the cylindrical metallic drum E, whence it is diffused in a very fine spray. A waste-pipe f, conveys the excess of fluid back into the reservoir. The force with which this little apparatus works is evident on removing the drum, when the stream will be projected up for several feet, then falling like a fountain. It is said that at a few inches distance the stream can be projected into the skin, thus forming a mode of endermic medication." (2, 193-194)

Before 1862 all the nebulizers produced were either based on the Sales-Giron or Mathieu design.  It was in 1862 the mechanisms of Mathieu's idea was greatly improved upon by a German named Dr. Bergson when he introduced the Bergson Apparatus and Inhaler in 1867.

Reference:  

1. Beatson, George, "Practical Papers on the Materials of the Antiseptic Method of Treatment," Vol. III, "On Spray Producers," Coats, Joseph, editor, "History of the Origin and Progress of Spray Producers  ", Glasgow Medical Journal, edited for the West of Scotland Medical Association, July to December 1880, Vol. XIV, Alex and Macdougall, pages 461-484
2. Cohen, Jacob Solis, "Inhalation in the treatment of disease: it's therapeutics and practice," 1876, Philadelphia, Lindsay and Blakiston

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1855: Duchenne proves diaphragmatic theory of asthma

Fig. 1: Guilluame Benjamin Amand Duchenne
(1806-1875) was the first physician to treat
nervous and muscular diseases with electric shock
 therapy. He was, therefore, the founder of
electrotherapy. (1, page 690)

In 1840 and 1855 respectively, William Budd and Alton Wintrich disproved the convulsive and nervous theories of asthma.  Guillaume Benjamin Amand Duchenne was a French neurologist who, unaware of the works of Budd and Wintrich, proved Budd right in 1855 --or so he thought.

Amand was born on September 17, 1806, to a family of seafarers at Boulogne, so it only mades sense his father wanted him to become a sailor Amand,  on the other hand, had a passion for science that he believed sailing would not satiate.   (1, page 690)(2)

So instead of sailing, he attended school at Paris, and among the physicians he trained under was Rene Laennec, the man who invented the stethoscope. Armand graduated in 1831 with a medical degree, practiced in Boulogne for a few years, and then in 1842 he moved to Paris where he dedicated his life to neurology (the study of nerves) and electrophysiology (the study of electrical properties of cells and tissues). (1, page 690)(2)

Medical historian Fielding Hudson Garrison described Duchenne as follows: 

Fig. 2: Michael Faraday (1791-1867) came from
poor parents and received little formal education.
In 1831 he invented the technology needed to
that would allow him to turn it to good use.  He
invented electromagnetic induction, and created
the basic ideas behind the electric generator and
transformer.  He coined words like electrode,
cathode, and ion. Named after him is faradisation,
or a method of applying electric currents to cells
of the body for medical reasons. This, along
with galvanization, were early means of
applying electricity to various parts of the body
for study. (4)(5)

His method of prosecuting his studies was peculiar. A strange, sauntering, mariner-like figure, he haunted all the larger Parisian hospitals from day to day delving into case-histories, holding offhand arguments with the internes and physiciansin-chief, who frequently laughed at him for his pains, and following interesting cases from hospital to hospital, even at his own expense. All this was done in an unconventional and eccentric way, which at first laid him open to suspicion and exposed him to snubs, but the sincerity of the man, his transparent honesty, and his unselfish devotion to science for itself, soon broke down opposition, and, in the end, when his reputation was made, he was greeted everywhere with the warmest welcome. Being timid and inarticulate in relation to public speaking, he was aided by his friend, the fair-minded and generous Trousseau, who, out of fondness for Duchenne, often voiced his ideas with effect in medical societies. (1, pages 690-691)

Through his intricate study of the nervous and muscular systems of the body, he became the first to describe many nervous and muscular diseases that plagued mankind (such as a disease that later became known as Duchenne's Muscular Dystrophy), and he became the first to use electric shocks as a treatment of these diseases.  (1, pages 691-692)(2)

As an expert on nerves and muscles it only made sense that he would study asthma, which, at that time, was considered a nervous disorder.  J.B. Berkard, in his 1878 book, "Asthma: It's Pathology and Treatment," said:

Fig: 3: Duchenne was the first to use electric shock therapy
to treat patients with nervous and muscular disorders,
such as paralysis and hypochondria. He used
faradisation or galvanization to shock or stimulate
specific muscular or nervous cells. While often effective,
it was also very painful for the patient (4)(5)
(Photo from 8, cover page. Caption underneath
reads: "Duchenne, faradising the frontal muscle."

Duchenne demonstrated that faradisation (see figure 2) of the phrenic nerve caused tetanus of the diaphragm. In the animals experimented upon, that operation was followed by distension of the lower half of the thorax, projection of the epigastrium, and extreme dyspnoea, the frequency of respiration being at the same time considerably diminished. Death, however, invariably followed when the electrical irritation of the nerve was continued for more than a few minutes. Unacquainted with the opinions of Budd and Wintrich, Duchenne was at first inclined to attach no importance to his discovery, because he thought a tetanus of the diaphragm was not as yet known to occur in man. Vallette, however, subsequently met with and reported a case of acute articular rheumatism, in which a fatal attack of dyspnoea had lasted for several days uninterruptedly, and from the symptoms of which he distinctly recognised a tetanus of the diaphragm. Duchenne thereupon concluded that a tonic spasm of this muscle was the main cause of the asthmatic paroxysm. (2, page 35)

By these experiments, he therefore unknowingly verified the evidence of Budd and Wintrich in disproving the nervous and convulsive theories of asthma, and proving the diaphragmatic theory of asthma.

Near the end of his life he developed arteriosclerosis of the brain, and he passed away on September 15, 1875. He was 69 years old. (1, page 669)(6)

Note: So the diaphragmatic theory of asthma has been supported by Budd, Wintrich, and Duchenne.  The next, and final, supporter will be Bamberger.

Note: You can view Duchen's book here. 

References:

1. Garrison, Fielding Hudson, "An introduction to the history of medicine," 3rd edition, 1821, Philadelphia and London, W.B. Saunders Company
2. Berkart, J.B., "On Asthma: It's pathology and treatment," 1878, London, J. & A. Churchill
3. Brown, Orville Harry, "Asthma, presenting an exposition of nonpassive expiration theory," 1917, St. Louis, C.V. Mosby Company, page 34
4. "Michael Faraday," http://www.bbc.co.uk/history/historic_figures/faraday_michael.shtml, accessed 3/5/14
5. "1830s Electromagnetism and Faradisation," http://www.theiet.org/resources/library/archives/exhibition/medical/electromagnetism%20.cfm, accessed 3/5/14
6. "Guillaume Benjamin Amand Duchenne," britannica.com, http://www.britannica.com/EBchecked/topic/172882/Guillaume-Benjamin-Amand-Duchenne, accessed 3/5/14
7. Duchenne, Guillaume Benjamin Amand Duchenne, "Selections from the clinical works of Dr. Duchenne," translated, edited, and condensed by G.V. Poore, 1883, London, New Sydenham Society 
8. Poore, G.V., "A short sketch of the life and work of Duchenne," in the book "Selections from te clinical works of Dr. Cuchenne," edited by G.V. Poore, 1883, London, New Sydenham Society, pages IX-XX

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1854: Dr. Wintrich almost disproves spasmotic theory of astma

After Charles J. B. Williams and Francois Longet performed experiments that seemed to prove the spasmotic theory of asthma, the theory "met with little opposition" until, in 1854, M. Alton Wintrich performed experiments of his own aiming to prove it wrong, said W.H. Geddings, in an 1885 article.  (1, page 194) 

Geddings wrote: 

The theory that asthma is due to spasm of the bronchial muscles met with but little opposition until 1854, when Wintrich, after a series of experiments, arrived at conclusions directly opposed to those of Williams and Longet in regard to the contractility of the muscular fibres of the bronchi, and refused to accept the spasm theory on the ground that it afforded no rational explanation of the phenomena of asthma. He believed that the various symptoms of that disease were due to tonic spasm (tetanus) either of the diaphragm alone or of the diaphragm and the other muscles of respiration. These experiments of Wintrich were so carefully conducted, and his standing as a specialist in respiratory diseases so high, that his theory found many supporters, and might perhaps have been generally accepted had it not been for the distinguished French physiologist, Paul Bert, who in 1870, with improved methods of scientific research, succeeded in demonstrating that Williams and Longet were after all correct in their statements as to the contractility of the bronchial muscles. (1, page 194)

While Wintrich tried hard to reproduce spasm of the bronchial tubes by irritation of the vagus, he never succeeded.  He therefore concluded that his studies disproved the spasmotic theory of asthma, and therefore the nervous theory of asthma. (3, page 34)(4, page 4)

Wintrich, however, does not deny completely that bronchial muscles are a part of the asthma response, simply not the the extent that other physicians claim. When broncospasm occurred, it was secondary to tonic spasm of the diaphragm, that bronchospasm was due to "disturbance of innervation," said Dr. J.B. Berkart in his 1878 book.

In other words, when bronchospasm occurred, it occurred as a result of irritation of one part of the body (such as the diaphragm) effecting the nerves that lead to another organ (such as the lungs or glottis). So, he concluded, the underlying cause of asthma was not bronchospasm, but diaphragmatic spasm.  (3, page 34)(4, page 4-5)

Ernest Shmiegelow, in his 1890 book, summed up the theory of Wintrich best:

Wintrich...thinks that asthma can be explained by a tonic spasm of the diaphragm alone or combined with the respiratory muscles... Only a tonic contraction of the diaphragm can explain the deep immovable position it occupies in many cases of nervous asthma. (4, page 5)

The ideas of Wintrich were later confirmed in 1870 by the experiments of Heinrich von Bamberger (1822-1888).  

Berkart explained: 

In a case of fatal dyspnoea he had occasion to observe the tetanus of the diaphragm, and to convince himself by post mortem examination of the absence also of structural lesions. Although the symptoms of that case by no means resembled those usually assigned to asthma, he, nevertheless, regarded them as characteristic of the disease. " (3, page 36) 

Guillaume-Benjamin-Amand Duchenne was a French neurologist who seemed to support the diaphragmatic theory by his own experiments.  Of this, Berkart said:

Duchenne demonstrated that faradisation of the phrenic nerve caused tetanus of the diaphragm. In the animals experimented upon, that operation was followed by distension of the lower half of the thorax, projection of the epigastrium, and extreme dyspnoea, the frequency of respiration being at the same time considerably diminished. Death, however, invariably followed when the electrical irritation of the nerve was continued for more than a few minutes. Unacquainted with the opinions of Budd and Wintrich, Duchenne was at first inclined to attach no importance to his discovery, because he thought a tetanus of the diaphragm was not as yet known to occur in man.. Duchenne thereby concluded that a tonic spasm of this muscle was the main cause of the asthmatic paroxysm. (3, page 35)

Wintrich wasn't the first asthma expert to consider the idea that the diaphragm might be responsible for asthma, as Dr. Thomas Willis considered this idea back in the 17th century. (4, page 4)

Another physician to consider the idea (which we refer to as the diaphragmatic theory of asthma) was William Budd.  He performed experiments in the 1840s that he believed disproved the spasmotic theory, and instead proved the diaphragmatic theory.

So the diaphragmatic theory of asthma stayed alive for a few more years, although it would ultimately be disproved once and for all by the experiments of M. Alton Biermer in 1870.

Note:  Other physicians who supported the diaphragmatic theory of asthma were Dr. Neuman (4, page 4) and Dr. Vallette.  (3, page 35)

References:

1. Geddings, W.H., author of the chapter on "Bronchial Asthma," in the book  "A System of Practical Medicine," edited by William Pepper and Louis Star,Volume 3, 1885, Philadelphia, Lea Brothers and Co.
2. Brown, Orville Harry, "Asthma, presenting an exposition of nonpassive expiration theory," 1917, St. Louis, C.V. Mosby Company
3. Berkart, J.B., "On Asthma: It's pathology and treatment," 1878, London, J. & A. Churchill
4. Shmiegelow, Ernst, "Asthma, considered specially in relation to nasal disease," 1890, London, H.K. Lewis
5. Thorowgood, John Charles, "Notes on Asthma," 1878, 3rd edition, London, J and A Churchill

You can view the 1865 book of M. Alton Wintrich, "Ueber asthma nervosum" by clicking here.

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1980s: The first corticosteroid inhalers

By the 1980s, it was evident that corticosteroids helped asthmatics gain control of their disease, although it was also evident that prolonged use of high doses resulted in severe and unwanted side effects. Despite this setback, efforts were ongoing to refine the chemical composition of steroids and to develop a method of delivery suitable and safe for asthmatics. This lead to the introduction of inhaled corticosteroids to the market in 1972.  (7)

This was the year that Allen & Hanbury introduced beclomethasone to the market as Becotide, with the recommended dose of 4 puffs daily of 100 μg per puff, a total of 400 μg per day.  (7)

Ten years later, in 1982, the FDA approved two beclomethasone inhalers in the United States: GlaxoSmithKline's Vanceril and Schering-Plough's Beclovent. Other oversease brand names were Becloforte, and Beconaise.  (You can see a 1979 ad for Beclovent and Ventolin from the Canadian Medical Association Journal here. )

Initial studies confirmed the benefits of daily use of this medicine, although it was usually only initiated by hospital physicians due to ongoing fears that even low dose steroids from inhalers could produce unwanted side effects.  (7)

I can use myself as evidence here. I actually have my discharge instructions from a hospital admission in 1984. A note to my mother says, "Have this boy take 2 puffs of Vanceril 4 times daily until he starts to feel better, then only use it when he feels symptoms."

Taking an inhaler four times daily was not easy for an eleven-year old. I would take it to school with me, and then I'd forget to use it. Or, worse, I would hesitate to use it because I didn't want to use it in front of my peers at school. Either way, for one reason or another, taking it compliantly was not easy.

Of course, when I left the hospital I was probably either recently removed from steroids or still on a Medrol pack. And as soon as I was weaned off of them, I was susceptible to the effects of whatever triggered my symptoms in the first place, which was probably dust mites. Sure I tried to avoid them, but the ubiquitous nature of dust mites makes them very difficult to avoid.

So, at some point, I'd be weaned off systemic steroids, would quit using my inhaled steroid, my symptoms would come back, and I'd end up using my Alupent inhaler with increased frequency. Actually, my asthma was so severe that even if I was taking my Vanceril compliantly I might still have symptoms.

During moderate to severe episodes, which was usually the case with me, I'd go through an Alupent inhaler pretty fast. Sometimes it would last a month, and those were the good times. More likely, it lasted a few weeks, or one week, or a matter of days. I know there were times I'd puff through an inhaler in one day.

And, when you're a boy with anxiety, and a boy who is shy like I was, and a boy who is self conscious and who doesn't like to ask for help, you don't seek help when you need it. So I'd suffer from asthma all day, sometimes praying it would go away and knowing it wouldn't. Usually, by the time I sought help I was beyond quick repair, and required a six day admission in a hospital.

For those of you who are wondering why my parents didn't recognize I was having trouble breathing, they probably did. You have to realize that this was back in the early 1980s, when there wasn't a whole lot of parental education about asthma. And even if my parents did know I was having trouble, I developed quite the skill of staying calm and not giving off the appearance that I was having trouble. So, my parents are off the hook.

And it's not that I didn't know better, because I did. I was very much aware that I needed help. It's just that I knew my parents were busy, and I didn't want to bother them. This was especially true when I had only recently visited the emergency room with one of my parents, and had felt guilty that I was overusing my rescue inhaler.

A side story here, and one for another post, is that I also felt guilty asking my mom to buy me another Alupent inhaler. This was especially true when she JUST bougth me one and it was empty already. So, by the time I got the nerve to tell mom I needed help, I was also nervous that they'd be able to tell I was abusing my Alupent.

However, in retrospect, they never said a word about this; they were just happy that I came in to get help, and they did a very good job of making me aware that they were happy I came in to seek help. The good folks at West Shore Hospital got to know "Little Johnny" really well, and the boy really like them, got to know some of them personally.

But I digress. As far as I knew, I was the only asthmatic who had it this bad in the entire world. Little did I know that I was not alone, and studies showed this. So, perhaps this was why my doctors never bothered me about my high frequency of Alupent use.

In 1982, Flunisolide was introduced to the market by Forest Laboratories as Aerobid. Aerobid was supposedly stronger than Azmacort, requiring fewer puffs daily. Many physicians were prescribing it for their patients, and mine was no exception. I, however, could not stand the taste, and was quick to complain about this to my doctor so I could get back to the better tasting Vanceril. Like beclomethasone, the standard dose was four puffs daily.

In 1973, budesonide (Pulmicort) was patentted, although it was not used clinically to treat asthma until 1981. A landmark study in 1982 by Wiley and company showed that two puffs daily (once in the morning and once before bed) of budesonide was as effective as four puffs daily of beclomethasone.

 by https://www.ncbi.nlm.nih.gov/pubmed/7037035

In 1984, Triamcinolome (package insert here) was introduced to the market by Abbott Laboratories as Azmacort. It's formula was slightly stronger than beclamethasone. It was a bulky white inhaler that had its own built in spacer. This was nice in that it required use of spacer with the medicine, improving coordination and increasing airway deposition to assure that the ideal dose was inhaled. Like beclomethasone, the standard dose was four puffs daily.

I was introduced to this inhaler in 1984. It was nice in that physicians for years had recommended I use my spacer when taking my inhalers, although spacers were large, bulky, and inconvenient to carry around with you. This made them less than ideal, as it was easier to pick up an inhaler and use it without a spacer. The Azmacort built in spacer was nice, although made it impossible to put into your pocket, pretty much assuring that any dose required during school hours would be missed.

At some point my dose of Azmacort was upped to 4 puffs 4 times a day, and, as you might imagine, this was very difficult to be compliant with, even for the most gallant of asthmatics.

I like to think of asthma similar to doing homework and getting good grades. Every semester I would work hard and try to get all A's. However, as time went by, it became harder and harder to study at night. For instance, there was other things to do, funner things to do, like playing football with my brothers. They would bug me until I gave in and played. Being compliant with my Azmacort was the same. I would get a new one and promise myself to take all my puffs, to be a gallant asthmatic. But soon enough I'd get busy, and forget, and puffs would get missed.

Through all of this I thought my doctor would say something. Through all of the extra puffs of albuterol and missed puffs of my corticosteroid inhaler, I thought my doctors would find out and lecture me. But they never did. Now, as an adult, I understand that they were probably aware of all this, and probably didn't say anything because they knew that they would have a difficult time with it, let alone a boy trying to get through life with severe asthma.

My doctor would review all my medicines with me at each appointment, and he would remind me of when I was supposed to take them. Actually, that didn't happen very often. Still,under it all, I'm sure he was aware that such a task was daunting. I know he empathized with me, otherwise he wouldn't have met mom and me at his office after hours. He did this more than once.

Noting the difficulty of taking four puffs daily, studies, studies, such as one conducted by Williams and company in 1986,  purported to show that 2 daily puffs of 200 μg was as effective as four puffs of 100 μg per dose, with a daily dose of 400 μg either way. 

Such studies were neat, in that during the 1990s most asthmatics were changed to a regular routine of 2 puffs daily for maintenance medicines, and this worked to greatly improve compliance with such inhalers. I know this to be true from personal experience. 

References:

1. Primary Care Respiratory Journal,"A brief history of inhaled asthma therapy over the last fifty years," Volume 15, Issue 6, December 2006, Pages 326-331
2. Williams, Hywel, et al., "Twice daily versus four times daily with beclomethasone dipropionate in the control of mild childhood asthma," Thorax, 1986, 41, pages 602-605