1981: Sus-Phrine: The greatest asthma medicine ever

"When we vacationed to California in 1976.
Dr. Gunderson gave us this to take along." Mom wrote

I think that the world's greatest medicine was Sus-Phrine (brand of epinephrine). It was actually a long acting version of epinephrine. It gave you your breath back within five minutes. I was given this medicine many times in the emergency room. It was a lifesaver.

A few years ago, as I began my quest to learn more about this medicine, a doctor told me that he liked it because a person would come in with status asthmaticus (asthma non-responsive to treatment), and he would prescribe a Sus-Phrine shot followed by a shot of a systemic corticosteroid.

The steroid would take 1-2 hours to reduce airway inflammation. In the meantime, the Sus-Phrine started working within minutes, and would last up from 6-10 hours. So, he said, the Sus-Phrine would keep airways open long enough for the steroid to take effect. Patients would have to stay in the hospital at least an hour after the shot so they could be monitored for potential side effects. Then they'd be sent home feeling good.

I would surely be feeling good. I would be wired. Sus-Phrine was essentially adrenaline. It's a medicine that essentially mimics the sympathetic (flight or fight) nervous system (sympathomimetic). It narrowed blood vessels to speed up the flow of blood to increase blood pressure. It increased the rate and speed of your heart. It caused palpitations. It made you excited. It made you jittery. It kept you awake for hours. But you didn't care, because it felt so good to be able to breathe.

Since 1901, epinephrine was available to be used for asthma. It started working in 3-5 minutes, but only lasted a few hours. This meant that repeat shots were often needed. It had to be given into the muscles, and this was most frequently the gluteal muscle (the butt). It also had to be given with a very large needle, which made the butt a good spot for injection. And kids were not keen to seeing a large needle, let alone having to drop their drawer and getting poked in the butt.

An An ampule of Sus-Phrine (1)

Sus-Phrine was first introduced to the market in the 1950s. Apparently, according to Emergency Medicine PharmD, it was the first medicine that didn't have to be given by intramuscular injection with a large needle. It was available in a concentration of 1:1200 (aqueous solution), which (if you are a nurse and I am not) can be delivered with any gauge needle and introduced to the body subcutaneously (meaning into the fat), meaning you could just get the shot in the arm with a small needle.

I only mention this because I started getting this shot in the mid-1970s and early 1980s when I would have been 5-10 range. Even though they would always assure me they had seen many naked butts before, it was always better to pull down my sleeve than to pull down my drawers. I'm sure this is the same for any kid.

Sus-Phrine (8)

Sus-Phrine became standard for asthmatics who presented to the emergency room during the 1970s to about the mid-1980s. This would have been about the time albuterol entered the mainstream of asthma treatments. It must have been discovered about this time that albuterol was just as effective as epinephrine in opening airways and ending asthma attacks. Giving 2-3 albuterol breathing treatments would also prove to offer the patient fewer side effects as a bonus.

I must have been given Sus-Phrine many times early on in my life. I know this, because, in 1976, my parents decided to take us to California. It was a three day car ride. This would have occurred just after I finished Kindergarten in June. My mom had my doctor write a note to any random doctor who might have to take care of me in case my asthma acted up. The note, written on a prescription pad, said:

Sus-Phrine (8)

"This boy is a known asthmatic undergoing hypersensitization program. If he has severe asthmatic attack without a fever he will respond well to 0.2cc Susphrine sub-q. Stat & observe 20 minutes."

By the late 1980s, and particularly between 1981 and January 1985, I made regular trips to the emergency room. I remember sitting on the hospital bed. I remember my dad saying, "In five minutes you will feel better."

Of course, they always had to give me an Alupent nebulizer treatment first. After a while I knew this wasn't going to work, but they always did it. As I inhaled the mist, I watched as a nurse would prepare the shot. When the treatment neared completion, the shot was given to me on my left or right arm.

Then I watched the clock. It was an oval clock on the wall right in front of me. It was 8 p.m.  I watched the red second hand go round and round as my shoulders dug deep into the mattress I was sitting on. I'd concentrate on my breathing. At first my breath would only go in half way. My chest was tight. I must have been near panic, or I wouldn't have asked mom or dad to take me.

Five minutes would go slow. But, right on cue: at the five minute mark my breath would start coming back. Each subsequent breath would go in deeper and deeper. Then I'd take in a deep breath and it would be easy. Then I'd take several deep breaths just because I could.

I can tell you with complete honesty that there is nothing better than all of a sudden being able to breathe after several hours of struggling to do so. It is just a great feeling. In fact, it usually created a feeling of euphoria. And, quite frankly, in retrospect, I'm not sure if that euphoria was the result of all of a sudden being able to breathe, or a side effect of the medicine. I imagine it was a little of both.

Nearly all of my ER visits were at West Shore Hospital. I remember going to the emergency room at West Shore Hospital in 1991 for an asthma attack. This was the first time I did this since 1985. I requested Sus-Phrine. The nurse never heard of it. The doctor had a vague memory of it, and consulted the pharmacist. The pharmacist and doctor talked about it for a while, and the pharmacist decided he had a cabinet that might have the medicine I requested.

This was the last time I was given the shot. It was discontinued within the next few years. A study published in 1991 in the Journal of the National Medical Association conclude that "Subcutaneous, long-acting epinephrine (Sus-Phrine) provides no additional benefit to a beta-2 agonist (albuterol) by nebulization for children with acute asthma." (6)

To be honest, I have never been given an epinephrine shot since then either, which spotlights the changing times as far as we asthmatics are concerned.

Further reading and references:

1. Emergency Medicine Pharm D: Throwback Drug Thursday: Sus-Phrine, An Aqueous Formulation of Epinephrine
2. Naterman HL. Ephinephrine base suspended in water with thioglycolate. J Allergy 1953; 24:60.
3. Unger AH, Unger L. Prolonged epinephrine action. Ann Allergy 1952; 10:128-130
4. Ben-Zvi Z, Lam C, Hoffman J, et al. An evaluation of the initial treatment of acute asthma. Pediatrics 1982; 70:348-353.
5. Ben-Zvi Z, Lam C, Spohn WA, et al. An evaluation of repeated injections of epinephrine for the initial treatment of acute asthma. Am Rev Respir Dis 1983; 127:101-105.
6. Kornberg AE, Zuckerman S, Welliver JR, et al. Effect of injected long-acting epinephrine in addition to aerosolized albuterol in the treatment of acute asthma in children. Pediatr Emerg Care 1991; 7:1-3.
7. Jenkens, Charles M, "A Clinical Study of 'Sus-Phrine,' an Aqueous Epinephrine Suspensionfor Sustained Action," Journal of the National Medical Association, March, 1953, 45, pages 120-122
8. Bezzant, John L., "Epinephrine: Comparison of short vs long acting," http://library.med.utah.edu/kw/derm/pages/ni18_3.htm, accessed 3/10/17
9. "Sus-Phrine (brand of epinephrine), Physician's Desk Reference," 1991, page 1006
10. Feldman, B. Robert, "The Complete Book of Children's Alergies: A Guide for Parents," 1986, Times Books
11. Brenner, Barry E., editor, "Emergency Asthma," 1999, New York, Marcel Dekker, Inc., page 322

1769: John Millar writes about asthma

John Millar (1733-1805) was a Scottish Physicians.  He cared for patients of all ages, although he tended to favor caring for women and children. So when an epidemic of asthma ravaged through the border counties of England and Scotland after great quantity of rain fell in 1755, Dr. Millar was among the first physicians called. (1, pages 11-14)(4, page 96)

He arrived on a blustery day, and was called to the home of a Baker.  A short, stout man wearing a white apron that was covered with white powder met the doctor as his buggy was parked by the entry of the Bakery.  The doctor could smell the sweet aroma of bread, and his stomach grumbled.  He climbed down from the buggy, reached back in for his bag, and followed the baker into his shop, up a narrow and steep set of winding stairs, to a small, hot, room, where a girl was sitting on the edge of a bed, leaning with her face on the edge of a window that faced the street.  He could hear a loud wheeze each time she took in a breath.  He could see by the vigorous shaking of her body that she was working arduously to suck in every breath.

He did not request for the girl to move, and instead squeezed his way around the bed and sat next to her, setting his bag along side him on the back of the bed.  He put his arm around the girls shoulder and hugged her.  "I'm going to help you feel better," he whispered.

He felt her head, and observed it was hot and clammy.  He also observed that she had picked away all the paint on the ledge of the window.  He touched her stomach, and his hand rode in and out as it undulated with each breath.  He said, "Does your stomach hurt? Are you sore down here?"

The girl did not respond, except by her tears and distressing look on her reddish face.  Her mother, however did respond.  She said, "She complained of a sore stomach, and she felt nauseated and vomited.  And she has been very nervous the past few days, refusing to go to school and to do her chores." Her husband, the baker, put his arm around her shoulder and held her tight. "We were so mad at her.  Now we wish we hadn't been."

"You didn't know," the doctor said.  "I believe her stomach indigestion, the fact that he suffers from a nervous affection, perhaps as from a hysteric or hypochondirac disease, and I presume it is asthma."

The doctor reached into his bag and pulled out a bottle and a spoon. He opened it and gave it to the girl.  He would give it to many sick girls and boys that day.  The last stop was at the house of a lawyer, whose girl was in the early stages of the disease.  She seemed to get immediately better when given the remedy.

The lawyer's wife asked him if he wanted to stay in the guest room, and he admitted he was tired.  Before he slept, he opened his bag and pulled from it a journal.  He wrote about every patient, and what he gave.

The next morning he went from business to business, home to home, to see other children, and a few adults, who were afflicted with this asthma.  At night he found a place to sleep, usually by the mother of the last child he saw that day, although on the last night before he planned to return home he slept in the Mayor's guest house.

It had been two weeks since he began treating sick children, and he had traveled from town to town, and had been treated well everywhere he traveled. Many children were cured by his remedies, although, a few times, he held a child during the last moments of life.

After a large meal cooked by the mayor's wife, he returned to the guest house for the night and pulled his journal from his bag.  He sat at a desk and wrote as much as he could remember about the past two week's events.  He wrote:

"Peruvian bark given early, seldom failed to perform a cure... the asthma was more or less frequent according to the state of the weather, that it prevailed most in spring and autumn, and especially in moist seasons. (1, pages 9-11)

He wrote that pure (spasmodic) asthma is most prevalent are places that have increased moisture, and have a tendency to be cold and damp, with the asthma presenting mostly in the spring and autumn. The remedy for this type of asthma is Peruvian bark. Without treatment death may ensue, or "remissions become less and less distinct." (1, pages 11-14)

While Millar described this epidemic as asthma, it was actually croup or some other related disease.  About 50 years later, after he had invented the stethoscope for listening to lung sounds, French physician Rene Laennec determined that the same disease was actually suffocative catarrh.  (4, page 96)

In the meantime, after caring for hundreds of children with what he considered to be asthma, Dr. Millar took his notes and decided to write a book to educate other physicians about this disease.  In 1769 his book was published as "Observations on the asthma and on the hooping cough."

Because his asthma was different than that described by ancient physicians, and even by other physicians of his era, he believed the ancients must have been wrong in their definition of asthma.  He wrote:

THE accounts which have been given of the Asthma by medical writers, seem only applicable to very advanced stages of it, or to other disorders, accompanied with a symptomatical difficulty of breathing; but perhaps without some previous knowledge of the original disease in its simplest form, more complicated cases can neither be clearly explained nor properly treated. The Author of the following Observations, having often seen it in children, unattended with any other complaint, hath given a description of it, as it really appeared, though very different from that which is to be found in books. (1, page i, ii) 

He said Hippocrates was the...

...first who to posterity a genuine history of diseases, and a rational method of treating them, founded upon faithful and accurate observations; but the simple and natural mode of medicine was soon vitiated by the introduction of false and absurd systems of philosophy. While such absurd theories were taught in the schools of medicine, the practice deduced from them was no less ridiculous; and as one or other of these opinions prevailed, the attention of the physician was employed in searching after medicines possessed of occult powers..."

Dr. Millar believed that it wasn't until the writings of Dr. William Harvey in 1628, who demonstrated "the circulation of the blood," that a rational practice of physic (medicine) was re-established. He said it was only after Harvey's discovery that a true understanding of the human body and its diseases could be learned. (1, pages 1-3)

The "theory and practice of physic" was only then begun.  It was Harvey's observation that resulted in "a careful attention to the rise and progress of disease, and to the effects of the medicines applied to them, (and this) is the only proper way to complete their history, and to establish a certain method of cure."  (1, pages 1-3)

He said that...

...Physicians fully convinced of this, and that no single person is sufficient for so great an undertaking, have long since established societies for collecting and publishing medical observations, which have contributed greatly to the improvement of the art." (1, page 3)

This was similarly noted by historian Fielding Hudson Garrison, who explained that there was an explosion of medical knowledge during the course of the 18th century, particularly regarding human anatomy, internal diseases, clinical medicine, and internal medicine.  Various physicians studied the human body, learning about the various diseases and the remedies that treat them.  (2, page 300, 330) 

Thanks to the discovery by Harvey regarding circulation of the blood, medicine as we know it today was born.  It was this discovery, and the eventual acceptance of it, that inspired physicians to race to learn as much about the human body as possible, and the ailments that plague it, and the remedies that fix it.  The result of all this research, and the discoveries that followed, squashed many of the old theories that enveloped the medical profession.*

Asthma was among the diseases studied and expounded upon, with physicians slowly coming to the realization, as noted by both Millar and his contemporaries, that asthma was more than a general symptom. 

Millar said asthma was among the diseases that was slow to be accurately defined.  He wrote:

Sir John Floyer, who was himself afflicted with this disease, describes the chronic asthma, and gives a just detail of its symptoms: but as he was first seized with it when a child, he gives no account of its beginning, nor of the method of treating that early period of it, in which, perhaps, alone a perfect and complete cure is to be obtained? .

What he is trying to say here is that Floyer only recognized adult asthma as opposed to infant and childhood asthma.  Millar continued:

Most other authors who have wrote on this subject, treat, under that denomination, of the Peripneumony, peripheral vomica, Pulmonum, Flatus,. Hypochondriac and. Hysterick Diseases, and, indeed, of almost every other disorder, accompanied with difficult respiration, excepting the least complicated state of that which they undertake to describe.

Here he is trying to say that most authors described asthma as the symptoms of shortness of breath, which is probably secondary to some other malady, as opposed to asthma in its pure form.  He said:

This will not appear surprising when we consider that an asthma, or difficulty of- breathing, is a leading symptom, in all the diseases already mentioned, as well as in many others; and, as it is painful and alarming, the patient, tho' a symptom only, deems it a primary disease, wishes ardently to be freed from it, and represents it principally to the attention of the physician.

On the other hand, as the least complicated species of asthma generally attacks children, or very young subjects, it is frequently confounded with the epilepsy, worms, teething, and other disorders incident to the early period of life, in which the physician can avail himself but little of the information of his patient, and is often misled by that which he obtains from others. Hence the accounts of it which we meet with in medical books, tho they may correspond to certain stages of it, or to the appearances of other diseases, in which a difficulty of breathing is a leading symptom, yet they convey no explicit idea of the origin and progress of the asthma in its simple uncomplicated state. (1, pages 4-5)

Basically he's saying here that there's more to asthma than what has been written about it by previous writers.  Millar breaks asthma down into the following categories.

1. Acute:  "Terminates in a few days in death, a perfect recovery..." (1, page 92)
2. Chronic:  It's "often a consequence of (acute asthma), and frequently continues for many years, and often during life." (1, page 92)  

The subheadings that follow here are my own, although I think this would be how Millar defines asthma the disease, as opposed to asthma the symptom of some other disease: 

1. Pure Asthma: "difficulty of breathing alone, which proceeds from some defect in the bronchial vessels."  (1, page 92)
2. Secondary Asthma:  Asthma occasioned by " an inflammation, or any obstruction of the lung, a pleurisy, perepneumony, hydrops pectoris, ascites, or any other ailment whither it appears as a concomitant or consequence of these.  

Over a hundred years later, when writing a book on asthma, Dr. Francis Ramadge would use Dr. Millar as a perfect example of how much was written, or assumed, about asthma without doing much investigating into the matter.  

Ramadge quoted Dr. Millar as saying:

The only dissection I ever made in the disease was of a child... (3, page 97)

Perhaps Millar was noting awareness of his limitations when, in the introduction of his book, he acknowledged that what he observed, and later concluded, about asthma was merely the beginning; that there was much more work to be completed regarding the definition of our term asthma.  He said:

Conscious of the difficulty of such an attempt, he does not suppose that he hath completed the history of the disease, but hath endeavoured to collect such observations, as may facilitate the further investigation of it; to point out the particular signs that distinguish it from other disorders in which respiration is only accidentally affected; and he proposes a method of cure which hath often been successfully applied, (1, page ii)

And he was right.  A wise asthma doctor indeed was he, or so we suppose, for the era for which he lived.

*For a list of all the diseases learned about check out reference Fielding Hudson Garrison's book, page 300-302.  He also lists the authors of various "histories of medicine" that were written during the 18th century.  See reference #2 below, or click here. 

References:

1. Millar, John, "Observations on the asthma and on the hooping cough," 1769, London
2. Garrison, Fielding Hudson, "An introduction to the history of medicine," 1913, 1st edition, Philadelphia and London, W.B. Saunders and Company
3. Ramadge, Francis Hopkins, "Asthma, its species and complications, or researches into pathology or disordered respiration; with remarks on the remedial treatment applicable to each variety; being a practical and theoretical review of this malady, considered in its simple form, and in connection with disease of the heart, catarrh, indigestion, etc." 1835, London,  Longman, Rees, Orme, Brown, Green, and Longman
4. Andral, M, notes, Renae Laennec, author, "A Treaties on the Diseases of the Chest and on Mediate Auscultation, Regius Professor of Medicine in the College of France, Clinical Professor to the Faculty of Medicine of Paris, &c, &c, &c., Translated from the Third French Edition with Copious Notes, a Sketch of the Author's Life, and an Extensive Bibliography, of the Different Diseases by John Forbes, Member of the Royal College of Physicians, Physician to the Chichester Infirmary, and Physician in Ordinary to his Royal Highness the Duke of Cambridge, to which are added the Notes of Professor Andral, Contained in the Fourth and Latest Edition, Translated and Accompanied with Observations on Cerebral Auscultation, by John D. Fisher, Fellow of the Massachusetts Medical Society," 1838, New York, Samuel S. and William Wood

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1871-1900: Pneumatometers (especially Walldenburg's) better than spirometers?

By the 1870s various engineers were tinkering with the Hutchinson Spirometer with the intent of improving upon it  Yet in 1871 Dr. L. Waldenburg invented a device that some physicians believed was better than the spirometer for diagnosing various airway diseases.

The main problem with spirometry was that volumes varied based on height and age.  This problem appeared to be remedied with the invention of the pneumatometer which measured more the force of a patient's exhalation, and therefore gave a better picture of the patients lung muscle strength.

This was a portable device that could be used to provide pressure changes to be used therapeutically to treat various diseases, such as emphysema, croup, bronchitis, and asthma.  The first such device was introduced by Hawke in 1870 called the Hawke Apparatus.  This device was nice because "air in the receiver can be condensed (increase in pressure) or rarified (decrease in pressure), and used in either of these conditions for respiration." (1)

(1)

Hawke believed his apparatus would be especially useful in croup and emphysema.  He believed that since emphysema resulted in air being trapped into the lungs, that expiring against rarified air (which was basically suction or vacuum) this would help empty this air from the lungs. In croup he believed condensed (positive pressure, pressure support) should be inspired. He later recommended inspiration of compressed air for consumption.(1)

After Hawke wrote about his apparatus he received "favorable results," although this type of device wasn't truly accepted by the medical community until Waldenburg improved upon it with his own device, called the Waldenburg Apparatus. And the neat thing about Waldenburg's apparatus is it had a graduated scale so you could measure the degree of pressure changes. This was nice for two reasons:

1. You could measure the amount of pressure used to benefit the patient, which allowed similar settings to be used at future visits or uses, and allowed physicians a guide to setting up future patients.
2. You could use it as a spirometer to measure the force of a patients exhalation, and to measure vital capacity.

It was likewise different from the spirometer -- even better -- because "spirometry deals with the vital capacity of the chest, which depends chiefly upon the circumference and height of the thorax, whilst in pneumatometry the height of the thorax has no influence." (3)

Paul Tissier described the device as a "U-shaped tube, open to the atmosphere and suitably mounted, is filled with mercury in both branches to the same level, which is marked zero. One branch is connected with a rubber tube and mouthpiece (or mask or nosepiece) used by the person under observation, whose expiratory and inspiratory force is measured by the ascent or descent of the mercury in the other branch, as shown upon a millimetric scale (Fig. 1)." (2, page 25)

So, "When the patient expires through the tube, the column of mercury sinks in the proximal limb of the manometer and rises in the distal, while with inspiration these movements are of course reversed, and in either case the amount of displacement is to be read off on the scale." (3, page 146)

Likewise, "Since the level of the mercury when at rest corresponds in both limbs to the zero of the scale, the reading obtained must, of course, be doubled to represent the true difference in the level of the two columns." (4, page 146)

Keeping in mind expiratory pressure is normally greater than inspiratory presssure, Waldenburg (and later other physicians) determined the following normal values for forced inspiratory and expiratory pressures for males and females (3 and 4):

• Male inspiratory pressure:  70-100
• Male epiratory pressure:  90-130
• Female inspiratory pressure: 50-80
• Female expiratory pressure: 70-80

The diagnostic purposes are as follows (3):

1.  Expiratory pressure is increased in relation to inspiratory in:

• Phthisis (even at a very early stage), 
• Stenosis of the air passages
• Pulmonary congestion
• Pneumonia
• Pleurisy
• Any abdominal affections as impede respiration by pressing the diaphragm upwards.

2.  Expiratory pressure is diminished until it becomes equal to or below the inspiratory in:

•  pulmonary emphysema.

Other than for diagnostic purposes, this test can indicate: (2)

1. The power of the respiratory muscles
2. The mobility of the thorax and expansion of the lungs
3. Elasticity of the parenchyma of the lungs. 

So, by performing tests on both the Hawke and Waldenburg apparatus's, physicians discerned the following facts: (1)

1. Emphysema results in imperfect expiration, while inspiration is normal or increased (the natural result of increased use of inspiratory muscles)
2. Catarrh of small bronchi results in imperfect expiration, and normal inspiration
3. Phthisis (tuberculosis, consumption) results in a decreased inspiration, and later expiration is imperfect.  
4. Stenosis of respiratory ducts results in imperfect inspiration, but expiration is normal
5. Inflammation of lung tissue and pleura results in similar effect as phthisis

There were a variety of similar products on the market, although Waldenbur's continued to be the preferred pneumatometer for both as a pressure apparatus and spirometer, at least through the turn of the 20th century, according to most sources I used as references.  

References:

1. Rose, A., "Treatment of Disease of Respiration and Circulation by the Pneumatic Method," New York, The Medical Record: A Weekly Journal of Medicine and Surgery, Edited by George F. Shrady, M.D., Volume 10, Jan. 2, 1875 to Dec. 25, 1875, New York, William Good and Co., page 577
2. 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., pages 296-224.  If the profession of respiratory therapy existed in their era, we would be reading their books.  However, as it was, their books were written for the medical profession. All of the material from this post is from Tissier's book unless otherwise noted in the above paragraphs. Tissier page 72
3. Brunton, Lauder T, The Practitioner: A Journal of Therapeutics and Public Health, Vol. XVII, July to December, 1876, London, MacMillan, "Pneumotachometry," page 216
4. Brown, John James Graham, "Medical Diagnosis," 2nd edition, 1884, New York and London, Birmingham and Co., "Pneumotameter," pages 25-26
5. Effects on the heart are questionable, although most studies conclude the pneumatometer  benefits asthma, bronchitis, emphysema, phthisis

1840-1903: Open air treatment for consumption

Figure 1 -1899, National Jewish Hospital, TB patients treated with sunlight (4)

Around the turn of the 20th century tuberculosis was a common ailment, and a leading cause of death.  Yet it also lead to a general feeling of gloom among the populace, especially considering little was known about it and there was no cure.  Yet if you had it there was hope, thanks to places like sanatoriums and hospitals like National Jewish Hospital for Consumptives in Denver Colorado.

In the 1840s Hermann Brehmer (1826-1889) was diagnosed with the condition and he told his doctor he might benefit from the open air of the Himalayas.  He also decided there might be benefits from isolating tuberculosis patients from the rest of the community, so he created hydrotherapy institution in Gorbesdorf, which is a village in Silesia, Germany. 

Bre

At first he had trouble convincing the medical community he was on the right track, but ultimately he became so successful that various sanatoriums opened in mountainous areas all over Europe and the United States.  One famous one in the United States was built in Denver, Colorado in 1899 by the Jewish Community. 

Many of the Jewish Community who were struck with tuberculosis were flocking to the Denver area because of it's fresh, dry, mountainous air.  Yet many of these victims were without enough money to be able to afford food or housing.

This was brought to the attention of Frances Wishbart Jacobs who worked hard to raise money to build shelter for these destitute victims of consumption.  She was able to find support from members of the Jewish Community and then to generate enough money to build an institution.  (1)

National Jewish Hospital 1892

In 1892 Jacobs died, and a year later the building was finished.  Yet the country was also mired in a recessions that year prompted by the silver crisis, and this resulted in a lack of funds to open the facility.  The building laid empty until Rabbi William S. Friedman took up a project to complete and open the institution.  (2)

The doors to the National Jewish Hospital for Consumptives opened in 1899 with the motto: "None may enter who can pay -- none can pay who enter." (1)  While it was originally built by the Jewish Community, anyone was allowed to enter who needed help.  (2)

One of the original therapies for tuberculosis patients in Denver was to receive heliotherapy, which was sunlight therapy (See figure 1).  It was believed that sunlight would help them "combat the disease."  (3)  This type of therapy, along with open air therapy altogether, was supported by Thomas Beddoes (1803-49), who performed many tests on respiratory patients, and Herrmann Brehmer (1826-89), who, as noted, opened the first sanitorium.  (3, page 37)

Figure 4 -- Open air therapy for TB patient at his home (3, page 38)

Studies were also done that showed TB patients recover faster in the winter than summer months.  In fact, "Dr. Otto Walther says he not infrequently had an inch of snow on his blankets.  At some localities tents are the only shelter, but whether the patients are housed in cottages or in tents, the free access of air must be absolute and uninterrupted. Drafts are not feared. At night the windows, which should constitute at least one side of the room or ward, are kept open; in some places the sashes are removed altogether; the sides of the tents are rolled up, except in the severest storms. In very cold weather the head and hands may be protected with woolen cap and gloves, and at all times the patients are well provided with blankets. In summer the beds or reclining chairs are moved into the open or into covered porches during the day; for the winter most places are provided with glass porches or sun parlors; where the patients spend their days in bed or reclining in steamer chair." (3, page 38)

(5, page 44)

The benefits of open air therapy as reported were: (3, page 39)

• Reduction of the fever
• Improvement of the appetite,
• Induction of sleep

As noted, "Cough and night-sweats disappear in a short time, and, as a logical consequence, the medicinal treatment is reduced to a minimum. Antipyretic drugs are never used and expectorants are rarely required. Suralimentation (the belief that consumption could be cured by forcing them to eat) is practised in many places, especially in the German resorts, where it is pushed to an almost incredible degree; even bed patients with considerable pyrexia are placed on a full diet of meat and vegetables. Trudeau and Flick * content themselves with giving their patients three full meals a day, allowing them to drink milk between meals if they have a desire for it; when, however, there is anorexia, the patient is given raw eggs beaten up with milk every two or three hours." (3, page 39)

While open air treatment was utilized "judiciously" and based on "individual cases," the therapy could also be recommended for home use as well. (See figure 4) Patients may also benefit from treatment in tents, walks or rides in the open air.  (3, page 39)

Another type of therapy was pulmonary gymnastics, or exercise.  While this was debated as an effective therapy, it was often recommended at the various sanatoriums.

In 1895 a German by the name of Wilhelm Konrad von Roentgen discovered the x-ray that allowed doctors to see the disease in its early as well as it's late stages.  This marked the first time that the disease could be diagnosed in its early stages instead of having to wait to see the late signs.  It also allowed doctors to see the tubercles in those who had survived the disease.  It showed both active and inactive tuberculosis.

References:

1. Gurock, Jeffrey S., ed., "American Jewish History," 1998, New York, vol. 3, part 3, pages 1095-6
2. "The History of National Jewish," NationalJewish.org, http://www.nationaljewish.org/about/whynjh/history/
3. Tissier, Pneumotherapy
4. Photo compliments of National Jewish Health, Facebook, http://www.facebook.com/photo.php?fbid=10151140094301092&set=a.140185801091.110191.41885201091&type=1&theater, accessed on 10/20/12
5. Picture from the Journal of the Outdoor Life," National Tuberculosis Association, Volume XI, January, 1914, 10 cents an issue or $1.00 a year

1876: The first modern Dry Powdered Inhalers

Figure 1 -- Gilewski and Rauchfuss Insufflator for
dry powder application. A, compressing bulb ;
B, slot covering D, aperture into which the powder
 is inserted; C, shower of powder leaving the instrument. (1, page 340)

Physicians prescribed inhaling powders for certain ailments going all the way back to the 1st century A.D., and probably further back then that. By the late 19th century physicians had access to some devices that we might aptly refer to as the first dry powder inhalers (DPIs).

John Solis Cohen was an expert on inhalation devices in the 19th century, and he published a book detailing inhalation devices in 1876.

He said Galen described an ancient technique of blowing astringent powders into the larynx using a bent reed. This technique, as Galen wrote, was used by the first century physician Aesculpius. Choen said this primitive DPI was still "being considered something of a novelty, even at the present day."   (1, page 336)

The problem with using a bent reed, Cohen noted, is the powder would be inhaled back into the oral cavity upon exhalation.  To remedy this problem, Cohen said that "Czermak attached a rubber ball compressor to flexible tubing, which is compressed at the proper moment.  The patient may do this treatment by his self, although most often it's done by the physician, or some assistant. (1, page 340)

F1g. 2.—Powder Inhaler Or Insufflator With Interchangeable Tubes.
It was designed by  Lewin and Oertel 

Yet, according to Cohen, these two methods are called insufflation as opposed to inspiration or aspiration. Insufflation is Latin for "blowing into." The patient must hold his breath after application of the insufflation, and resist the urge to exhale to improve deposition of the medicine.

Gilewski and Rauchfuss composed a good insuflator (Fig. 1), "which consists of a properly shaped tube, with a gum ball for the purpose of propelling the powder forwards. The powder is inserted into a slot in the tube, over which a tubular cover slides after the introduction of the medicine, which can be propelled in any direction desired by arranging the apertures of exit at the distal extremity of the tube"  There were various similar products composed, although none, according to Cohen, was better than the original. (1, page 340)

Cohen described a variety of insufflators, and so did his cohort, Paul Tissier.  Tissier would be our other expert on inhalation devices in the 19th century.

Lewin and Oertel devised an insuflator that, according to Tissier, "consists of a sort of horn furnished with an opening; through this penetrates a glass tube, to the outer portion of which is attached a rubber bulb; gentle manipulation of the bulb produces in the horn a thick cloud of dust, which is propelled toward the narrow end of the instrument, where it is directly breathed by the patient. In the United States there is sold an instrument (Fig. 2) to be used either with a hand-bulb or a current of compressed air from a reservoir." (2, page 446)

Two more old DPIs from Tissier's book

Bryant created an "auto-insufflator, consisting of a bent tube, having at one point an opening, which may be closed by a stopper. Through this opening the powder is introduced; one end is placed in the nose, the other in the mouth, and gentle blowing is performed. A simple rubber tube answers the same purpose. For insufflation into the larynx and trachea one uses special curved instruments. (Figs. 114, 115.) For insufflation into the pharynx and upon the tonsils any tube may be employed, such as a reed, quill, glass or rubber tube, or a special instrument," according to Tissier. (Fig. 116).

Various physicians provided various different recommendations for the medicine to be applied to the larynx for various disorders, such as hoarseness, inability to speak, and inflammation of the palate and throat.  Remedies included:  lycopodium, cinchona, acetate of lead, nitrate of silver, and tannin,  Other physicians recommend igniting the powder and inhaling the smoke.  (1 page 340)(page 448)

References:

1. Cohen, John Solis, "Inhalation in the treatment of disease," 1876
2. Tissier, Paul Lois Alexandre, "Pneumatherapy: including Aerotherapy and inhalation," 

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1979: Tedral Side Effects?

I got to thinking about the horrible side effects of Tedral described by other people my age who used it as a kid to control their allergies/ asthma. Many of them described having hallucinations. At first, I figured these descriptions of side effects were probably just exaggerations. However, there were a few events that occurred in my childhood that make me wonder if I had these side effects too, just blamed them on something else.

Actually, these descriptions were by people older than me. I was just a little kid when I took the medicine, and thankfully it was no longer used by the time I was ten. However, I was unfortunate (or fortunate, depending on how you look at it) enough to get to experience the tail end of its run as a top line allergy/ asthma treatment.

Here is one of the comments (unedited from medschat.com)

I took tedral in the 60's and another drug which was a smaller pill with a brown coating. I suffered mostly unpleasant hallucinations when I was small and they were not always when I was sick. I no longer have the life threating athsma as I did when I was a child. Over time my inquiries about the hallucinations were never answered. So it is interesting to read about others experiences here. I always thought it was a combination of the drugs and the reduced oxygen and air in my body. I think tedral probably saved my life also. The halluncinations very occasionally revisit me as I am falling asleep and if i am becoming ill.

Here's another:

I also took tedral on the late 50's for asthma and experienced similar side effects including hallucinations, but without the medication I'm not sure I would've lived. Our family doctor still made house calls and I can remember her coming to our house at all hours of the night to save my life. She was something else. I think the Tedral was the reinforcement if the adrenalin wasn't able to restore normal breathing.

And another:

Wow!!!!! I have always wondered why I would see the spiders on the ceiling's and what happened to them. I too remember taking the thick yellow asthma medicine (how I googled and ended up here) I used to surround myself with Teddy Bears to protect me. I never knew it was the medicine. I used it as a child 4 years old 1960''s to 1970's when primitine mist came on the market. I now know where my restlessness, inability to sleep and over abundance of energy /hallucinations came from and that I wasn't a bad child just effects of the medicine that I hated to take. Preferred the eperine shot in the arm even as a child.

And...

I thought i was mentally unbalanced. Seeing enlargements of real life in front of me. Increased hearing sensitivity. Shrinking rooms in front of me own eyes. For years thinking it was me. An unbalanced. Self. It all stopped as i got older until one day I was having an asthmatic condition and took the medicine the doctor had me take 3 times a day! Tedral!. The truck in front of my eyes, as i worked on the engine, seemed to shrink like what happened 5 ears previously. when I was taken tedral regularly. I wasn't crazy after all--- It was the medicine! Anyone else experience shrinking heads, feelings of speed' before the term existed? Why was it taken off the market? Everyone have these problems? It would be nice to hear from others about their Tedral experience. This occurred 1952 ...

That's how often I took it, sometimes.

 I don't want to dwell on this, but I do remember hallucinating at nighttime. I remember dreading going to bed sometimes. This was because, just after I was relaxed on the bed, shortly after I closed my eyes, I would still be wide awake but not be able to move. I would become completely paralyzed. These episodes would last several long moments. I would become very panicky, as you might imagine.

I swear I was not dreaming when these occurred. As I noted above, I would dread even attempting to sleep because I was afraid I would have one of these paralytic episodes. I was afraid that the next one might be the one that never went away.

I remember waking up and not wanting to even try going back asleep. I would be wired. I would read a book. I would write. I would even look at my homework and consider doing even that. That's how desperate I was not to go back to sleep.

So, I would finally get tired and would eventually fall asleep. Then I'd have these horrible dreams that I still remember to this day. I remember having this recurring dream about how this monkey would come through my window (even though it was closed) and would try to convince me to go with it. He would be wily and goofy, as monkeys can be. He would tell me how good it was. I would be scared to death of this monkey. I would try to get away. I would look at my door. But, as so often occurred in such dreams, the monkey had the power to paralyze me. I was unable to move for the door.

I would wake up horrified. My heart would be racing. I would go and open the door. I would turn on the light -- but the light would not come on. Sometimes the light came on and popped off, as though the monkey had used his power to make the light bulb burn out. I wanted so bad in these moments to wake mom up. But, they happened so often, that I had better not.

Then, the next morning, the light would work fine.

So, were these events hallucinations due to Tedral?

There were also moments I would be home with the flu. I always thought it was a treat to get to lie in mom's bed, and that's what I got to do when I was sick. However, I remember being so sick on these days that I didn't really get to enjoy it. Not only would I be extremely nauseated, I would also have a headache so horribly bad that I felt my head was going to explode. I would feel so miserable that I would cry. I know mom felt bad for me, but there was nothing she could do. These episodes would last about one day. The next day I would be fine, and I was probably back at school.

Now, it's surely possible these episodes were caused by the flu. However, I have had the flu many times since then, but have never had it that bad. So, this makes me wonder: was it the Tedral? Was it an accidental Tedral overdose?"

I mean, none of these events may have been the medicine. However, considering similar stories I have now read about Tedral, one can't help but wonder.

Anyone out there have any Tedral experiences, please feel free to share your stories in the comments below.

1836: The beginning of pressure therapy and Tabarie's Sphere

G

Galileo (1564-1642) was perhaps the first to consider the idea that air had weight.  Yet it was his pupil, Evangelista Toricelli (1608-1647), who proved the existence of atmospheric pressure.  From there, it didn't take long for ideas to evolve for using changes in atmospheric pressure as therapy for various diseases, such as lung ailments  (3, page 52)

Tabarie's Sphere (3, page )

The major question Toricelli set out to answer was:  Why is it that water is prevented from being pumped up higher than 32 feet?  He performed a test, and proved the answer was due to the weight of the air, or atmospheric pressure.

Apparently influenced by folks who described the benefits of climate change or high altitudes, Nathaniel Henshaw (1628-1673) was the first to create a chamber for artificially raising or lowering atmospheric pressure so that it could be used to help people feel better.  Henshaw's called his chamber the "Domicilium," which was basically a "sealed room," that was attached to a "pair of large organ bellows."  This chamber is now considered the first hyperbaric chamber.  (5, page 1)

According to Tissier, the "chamber was built of masonry and supplied with doors and windows that could be closed hermetically.  It communicated with two bellows (the organ bellows) provided with valves, which worked in opposite directions, in such a way that it was possible, at will, to obtain compression or rarification of air." (3, page 55)  

Here we require a couple definitions:

1.  Compressed Air:  This was the original term used to describe increases in atmospheric pressure.  It's air with a larger volume of oxygen than ordinary air.  It is positive pressure. 

2.  Rarified Air:  This was the original term used to describe decreases in atmospheric pressure.  This is air that contains less oxygen that normal room air.  It is negative pressure. 

So, basically, Henshaw's organ bellows, when pressed, forced air into the chamber, and therefore increased the atmospheric pressure inside.  When the bellows were relaxed, pressure was decreased inside the chamber.  Future chambers, and portable apparatus's, would apply a similar technique to compress and rarify air.  

Other than Henshaw's work, there's little evidence pressure changes were considered for therapeutic use for diseases until the 1750s.  Yet by 1800 there was such strong speculation for the therapeutic use of pressure therapy that the Royal Society of Haarlem opened the idea up to a competition to determine "The influence of condensed air on animal and vegetable life."  Yet it was to no avail. (1, page 43)

However, the idea continued to circle the profession, and Sir John Sinclair suggested, based on his observations of the effects of pressure on animals, that changes in pressure may have therapeutic benefits for humans.  (1, page 43) 

Among the first to come to the challenge were Emile Tabarie and Junod.  In 1833 Tabarie discussed the topic with the Parisian Academy of Science, (2, page 19) and in 1835 Tabarie performed the first experiments.

Junod reported that when the "natural pressure of the atmosphere is augmented by one-half, the following effects will be observed:"

1. Disagreeable sensation of pressure in the ears, subsiding as equilibrium is re-established
2. Respiration is Facilitated.  The inspiration becomes deeper and less frequent
3. Circulatory changes occur
4. Functions of digestive apparatus are stimulated
5. Secretions of salivary glands and kidneys are very profuse

There were various theories to account to the perceived benefits of pressure changes on breathing. The pressure seems to open and keep the alveoli open to better receive the next breath.  The vessels of the body appear to be compressed, which stimulates the pulse to increase so it is "full and easily compressible. the caliber of the superficial veins is diminished, and the lumen may even become completely obliterated, so that the blood on its way back to the heart courses through the deeper veins."  (3, page 72)

If this is true, it was determined that the same effect must occur to the pulmonary vessels, and this results in "the quantity of venous blood contained in the lungs (to) diminish; and this probably explains why a much greater quantity of air can be drawn into the lungs at each inspiration that is possible under normal pressure. (3, page 72)

"Further, if an increase in the density of the air tends to diminish the caliber of the veins, it follows necessarily that a greater quantity of blood will enter the arterial system and more blood will also reach the principal nerve-centers; especially those in the brain, because the latter is protected from the direct pressure of the atmosphere by the resistant bony calvarium. The cerebral functions are accordingly enhanced, the imagination becomes more active, and in some persons there is a peculiar exaltation which stimulates drunkeness." (3, page 72)

By 1838 Tabarie had performed a variety of tests to study the effects on pressure changes on the various parts of the body, all except for the head. He studied the effects of both condensed and rarified air. By his experiments Tabarie determined that condensed air "retards the action of the heart and steadies the rhythm. This effect is very slight and may not be noticeable under normal conditions, but becomes quite evident in disease." (3, page 72)

Tabarie ultimately devised a chamber, or sphere, that was made of iron that allowed up to twelve people to enjoy the benefits of pressure changes.  "He advised sittings of two hours duration with an increased pressure of from one-half to two-thirds of an atmosphere.  Bertin, who used the spheres, reported the cure of fifteen cases of uncomplicated emphysema, and ninety-two cases of nervous and catarrhal asthma with associated emphysema.  Air chambers, cumbrous, expensive and not portable, were thus far used." (1, page 44)

Various pneumatic chambers were devised and used around this time, with a variety of shapes being used. However, they were all based on the design of Tabarie's Chamber. They contained two pipes, one for for supplying the air and connected to a hydraulic compressor operated by steam.  The other pipe was for ventilation.  

References:

1. Minnesota State Medical Society, "Transaction of the Minnesota State Medical Society," 1886, St. Paul, H. M. Smyth Printing Co.
2. Foster, Frank, editor, "Practical Therapeutics," Volume I, 1897, New York, Appleton and Co., page 19
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., pages 296-224.  If the profession of respiratory therapy existed in their era, we would be reading their books.  However, as it was, their books were written for the medical profession. All of the material from this post is from Tissier's book unless otherwise noted in the above paragraphs. Tissier page 72
4. Rose, A., "Treatment of Disease of Respiration and Circulation by the Pneumatic Method," New York, The Medical Record: A Weekly Journal of Medicine and Surgery, Edited by George F. Shrady, M.D., Volume 10, Jan. 2, 1875 to Dec. 25, 1875, New York, William Good and Co., page 577
5. Clarke, Dick, "History of Hyperbaric Therapy," Chapter 1 of the book, "Physiology and Medicine of Hyperbaric Oxygen Therapy," 2008, Philadelphia, Saunders, page 1-2
6. Picture is from an advertisement placed in the Medical Press of Western New York, volume II, No. 6, June, 1887, Roswell Park M.D., editor, New York, Bigelow Brothers, page 338