A brief history of COPD

The 42-year-old Alaskan woman sat by the crackling fire 1,600 years before the birth of Christ.  She was severely winded after just a short walk with the children.  Her chest heaved up and down, occasionally interrupted by a dry, hacking, painful cough.

“I can no longer do  this,” she decided, working hard to stop the tears.  The children stood around her silent and concerned.  These episodes were happening more frequently now, so often that she could barely stand it.  ”I’m fine,” she said.  It was a lie.

Looking into our prism we can see the woman obviously suffered from Cronic Obstructive Pulmonary Disease (COPD), although back then the disease she suffered from was poorly understood. In Alaska there may have been no treatment at all other than rest.

We know she probably acquired the disease gradually over time as she continued to inhale smoke from the same fires she used to cook food for the children and their parents.  We know she probably died slowly from lack of oxygen.

Nearly 1,600 years later a Greek physician names Hippocrates included every disease that causes shortness of breath, what he called dyspnea, under the umbrella term of asthma.  The term comes from the Greek word Aezean which literrally means gasping or panting.

It would be another 2,000 years, about 1,650 A.D, before the term emphysema was used in autopsies to describe lungs that were larger than normal because they held extra air.  The term comes from the Greek physe which means “to blow into.”  Emphysema would become a word to describe lungs inflated with extra air.

In 1679 a Swiss physician named Theophile Bonet (1620-1689) performed over 3,000 autopsies on patients he followed, and was among the first to describe emphysema as a medical condition of “voluminous lungs” in his book Sepulchretum. (2) (3) (4)

Giovanni Morgagni (1682-1771) wrote how he respected the works of Bonet, and he himself described several cases of “turgid” lungs in his classic work “On the seats and causes of disease.”

Dr. Samuel Johnson

In 1784 Dr. Samuel Johnson was a well known physician, and he also became well known for his breathing trouble. He was thought to have suffered from asthma from birth, and later he was determined to have died of fibrosis of the lungs.  Although from autopsy results future historians have concluded that what he died of was emphysema and cor pulmonale and not asthma.  (6)

Dr. James Arthur Wilson was only 19 when he performed the autopsy on Dr. Johnson, and he described the following:

“On opening into the cavity of the chest, the chest did not collapse as they usually do when the air is admitted, but remained distended, as they had lost the power of contraction; the air cells on the surface of the lungs were also very much enlarged… the heart was exceedingly large and strong.”

In 1721 Ruysh provided the first detailed description of emphysema coupled with pictures.  In 1799 and 1807 Matthew Ballie also provided a description of emphysema with detailed pictures.  He described the condition as “enlarged air spaces” in the lungs, and lungs that did not collapse.  He is beleived to have had the lungs of Dr. Samuel Johnson to help him with his descriptions. 


Matthew Ballie (1761-1823) was a prominent British physician who inherited his father’s anatomy school in 1783.  Throughout his career he studied the bodies of diseases patients, including some specimens handed down to him, such as the lungs of Dr. Samuel Johnson.  


He published a book in 1793, “The Morbid Anatomy of Some of the Most Important Parts of the Human Body.”  It’s believed to be the first book on pathology.  He described the lungs of emphysema patients, which included the following description of Dr. Johnson’s lungs:


“The lungs are sometimes, though I beleive rarely, formed into pretty large cells to resemble the lungs of an amphibious animal.  Of this I have seen three instances.  It is not improbable that this accumulation (of air) may break down two or three contiguous cells into one, thereby, form a cell of very large size.”  (5, page 2)

In 1814 British Physician Charles Badham became the first to use the term “bronchitis” to denote “inflammatory changes in the mucous membrane.”  Bronchitis would soon “supercede” the term chronic catahrr when referring to this condition.  Catahrr was a blanket term used to describe swelling of mucus membranes that resulted in excessive secretions. Throughout the 19th century catahr continued to be used to describe inflammation of the nasal passages (or hay fever).  (9)

Laennec accurately described emphysema (13)

In 1821 Dr. Rene Laennec — known as the father of chest medicine in part due to his invention of the stethescope — accurately described both emphysema and bronchitis as related conditions.  He defined bronchitis as “chronic mucous catahrr,” and “filled with mucous fluid.”  He defined emphysema as “lungs (that) do not collapse.  But they fill up the cavity completely on each side of the heart.”  (3)

Laennec also became the first to describe emphysema due to aging.  He also was the first to define emphysema as tissue damage in the peripheral air passages, and further defined emphysema as a breakdown of tissue in the parynchema of the lungs as opposed to air trapped in the alveoli due to an obstruction such as occurs in asthma and bronchitis.

In 1837 Dr. William Stokes became the first to use the term “chronic bronchitis” in his book ”The Diagnosis and Treatment of Diseases of the Chest.”  He defines bronchitis as “inflammation of the mucous membrane,” and that this condition may give rise to “dilations of the air cells and tubes, and to pulmonary emphysema.”  (8, page 45)

He also noted that bronchitis is evident in nearly all diseases of the lungs.  In noting this, he is drawing a similarity with bronchitis, pneumonia and asthma.  Bronchitis and emphysema were initially considered diseases under the umbrella of asthma, and now these diseases are slowly branching off as diseases of their own as more wisdom is learned about these diseases.

Like Laennec, Stokes was likewise among the first to explain the relationship between chronic bronchitis and emphysema, and believed bronchitis lead to emphysema.  He also was the first to describe different types of sputum, such as mocoid and mucopurulent.  (1, page 86).  He also mentioned increased secretions and chronic cough as part of the condition.

John Hutchinson’s spirometer

In 1846 John Hutchinson invented the spirometer, which ultimately was used to perform many tests on the lungs.  While he believed his device was limited in its purpose, it would become the perfect device for diagnosing and treating many diseases of the lungs.

His device was limited in that it could only measure vital capacity, which is the total amount of air that can possibly be exhaled.

In 1861 Dr. Henry Hyde Salter described in his book, “On Asthma: It’s Pathology and Treatment,” that he had never performed an autopsy on an asthmatic when he didn’t see evidence of emhysema.  Other doctors would make similar statements.  Salter also described the barrel chest common with asthmatic children.

However, Salter and other physicians of his day didn’t have the ability to differentiate from true asthma as we know it today and true emphysema and chronic bronchitis.  Yet to their credit, emphysema was a rare disease until after WWI when cigarette smoking became common place.

By 1870 emphysema and chronic bronchitis were clearly noted as related diseases, and descriptions were present regarding the breakdown of lung tissue that resulted in progression of the disease that resulted in hyperinflation of the lungs. 

In 1885 a physician by the name of Mendelssohn “stated that he had met many persons dying from tuberculosis whose symptoms never showed themselves until they worked with coal dust and smoke.” (10)  He was therefore among the first to observe the relationship between environmental inhalents and lung disease.

By 1898 the air sacs in the lungs were no longer called simply “cells,” they were referred to as alveoli in books and magazines such as The Clinical Review.  Emphysema was now clearly defined as “dilation of the alveoli of the lungs and atrophy of the alveolar walls.”   Doctors such as Joseph M. Patton started differentiating overdistention of alveoli due to obstructive diseases such as asthma with excessive air in the lungs due to tissue “atrophy.” (12)

By 1930 a plethera of descriptions of the conditions started to show up.  One physician described enlarged goblet cells in bronchitic lungs that resulted in increased secretions.   Another performed tests that showed airflow limitations in patients with emphysema, and explained that this was due to lost of lung elasticity.

By the 1930s emphysema was clearly understood to be a disease of loss of elasticity of the lungs that results in enlargement of the thoracic cage, which resulted in the appearance of a barrel chest. Because the chest was already expanded the regular muscles of inspiration would be of little use and this would require use of accessory muslces during regular breathing.  (11) 

In 1933 Ronald V. Christie, a professor of medicine at the University of London who specialized in emphysema, performed a study that showed the relationship between loss of lung elasticity and airflow limitations.  (1, page 87) 

With breakdown of tissue of the alveolar walls excess air enters this space and the result is overdistention.  This can also result in bulla, which are large areas of tissue breakdown and air trapping, meaning this entire portion of the lung will not be involved in the process of ventilation.

 In 1944 he suggested that because the lungs were always expanded due to loss of elastic recoil, expiration would have to be passive.  He wrote:

“With loss of elasticity there must be loss of elastic recoil, so that if the lung is to be deflated it has to be squeezed.  The respiratory musculature was not built for this task, and the intercostals have to be assisted by the accessory muscles on expiration: the muscles of the abdominal wall can often be felt to contract on expiration, which is prolonged as it is in other conditions, such as asthma and tracheal obstruction, in which the lungs have to be compressed by an active muscular effort.  With so extensive an impairment of both inspiration and expiration it is not surprising that the vital capacity and chest expansion are reduced.”  (11)

He describes lungsounds as faint except for in the bases where they may appear to be absent.  Diagnosis could be made by observation of the physical signs, such as a barrel chest, vital capacity measurements with spirometry, and obvious dyspnea on exertion not attributable to other conditions.  He also suggested diagnosis should be made based on signs of chronic cough or asthma.

By the 1950s physicians had learned so much about the lungs that they pretty much wiped the slate clean and redescribed both emphysema and chronic bronchitis for the medical community.

Experts determined there were various disease processes that could result in excessive air in the chest or overdistention of the alveoli such as acute asthma or chronic bronchitis.  This “overdistention” was no longer considered emphysema.  True emphysema would was now considered air in the interstitial spaces due to breakdown of parychemal lung tissue such as the pores of Kahn and the walls of the alveoli. 

Air trapping in asthmatics was determined to be completely reversible, and air trapping in chronic bronchitis patients may be partially reversible.  As with emphysema, both may result in a barrel chest, although emphysema results in a chronic barrel chest.

During the 1960s and 1970s pulmonary function testing was used with increased frequency to study lung diseases, and it was during this era that the term FEV1 was first used to measure expiratory flow.  By the 1980s pulmonary function testing would become commonplace in diagnosing COPD, with the measurement of FEV1 as the most important measurement in diagnosing diseases of airflow obstruction like COPD and asthma..

While physicians like Dr. Wilson keenly observed the large heart in those suffering from lung diseases, physicians now understand diseased lungs make the lungs stiff, and this causes the right heart to work extra hard to pump blood through it.  The extra work causes the heart to become enlarged, like the muscles of someone who pumps iron.

In 1972 the mummy of a 1,600 year old woman was discovered in Alaska. The woman was found to have evidence of emphysema, and this may be the oldest reported case of COPD.  (1, page 85).

1. 
   Qutayba Hamid, Joanne Shannon, James Martin, “Physiologic Basis of Respiratory Disease,” 2005, Montreal, page 85-99
   


2. 
   Bhatia, K. Sujata, “Biomaterials for Clinical Application,” 2010, London, page 100
   


3. 
   Petty, Thomas L, “The History of COPD,”Int. J. Chron. Obstruct. Pulmon. Dis., 2006, March; 1(1): 3-14
   


4. 
   
   
   

   Crellin, J. M.D., “Selected Items from the history of pathology,” Am J Pathol. 1980 January; 98(1): 212.
   

   
   

   
   

   
   
   
   


5. 
   Thurlbeck, Wright, “Thurlbeck’s Chronic Airflow Obstruction,” 1999, Canada, pages 1-6
   


6. 
   Reich, Jerome M, “Convulsion of the lung: an historical analysis of the cause of Dr. Johnson’s fatal emphysema,” Journal of the Royal Society of Medicine, Vol. 87, December, 1984, page
   


7. Laennec, Rene, “Treaties of the diseases of the chest,” 1821


8. 
   Stokes, William, “The Diagnosis and Treatment of Diseases of the Chest,” 1837, Dublin
   


9. 
   Gee, Samuel, “Bronchitis, Pulmonary Emphysema and Asthma, ” The Lancet, March 18, 1899, page 51
   


10. 
    Klotz, Oskar, Wm. Charles White, ed., ”Papers on the Influence of Smoke on Health,”  Bulletin #9, 1914, page 36
    


11. Christie, Ronald V, “Emphysema of the Lungs: Part II, British Medical Journal, Jan. 29, 1944, page 143-146


12. Cleveland, Geo. Henry, “The Clinical Review: AJournal of Practical Medicine and Surgery,” Vol. VIII, April-Sept. 1898, Chicago.

Photos:  

1. http://library.medicine.yale.edu/about/adopt/laennec

1851-1913: The history of asthma sputum

Okay, so few of us want to talk about it.  If you mention it at the dinner table your mother, or grandmother, may send you to your room.  Yet people taking care of the sick people over the years, especially sick people with breathing trouble — i.e. asthmatics, had no choice but to pay attention to it.  Some even devised speculations and theories explaining its appearance.

Originally all shortness of breath, and all causes of excessive sputum production, were defined as asthma.  And since sputum was so often associated with such dyspnea, ancient physicians may have surmised the sputum was caused by evil spirits, and expectoration of sputum was associated with the expectoration of evil spirits.  Such speculation most likely satiated ancient sufferers and their families.

Actually, such speculations may have satiated sufferers of asthma and their families even through the middle of the 19th century, as most people continued to be ignorant about such things.  And when your physician told you one thing, you tended to believe it.  Ditto can be said of wive’s tales: when your mother tells you something, you tend to believe it.

As time went by physicians and scientists came up with other more carefully thought out theories about asthma sputum, some speculating it was the cause, others the effect.  Although, in the end, most of these theories weren’t any better than ancient speculation.

In a report on the experiments of  Charles J.B. Williams (the man who proved the spasmotic theory of asthma), J. Lotvall notes that “the main theory about asthma in the 18th century was that it was a disease of excess mucus, and in the 19th century it was recognized that airflow obstruction may also be due to airway smooth muscle contraction.”  So we see that was very common to speculate asthma was caused in some way by the sputum.  (1)

A good example here is the theory postulated by  Dr. Robert Bree in 1798.  He guessed that sputum was the main component of asthma.  He believed some irritating or peccant matter entered the lungs, and it was this matter that triggered the asthmatic response.  The attack didn’t end until the irritating matter was expectorated in a wad of sputum.  (2)

Bree gained a lot of respect by the medical community for his theory, although during the 1850s Dr. Henry Hyde Salter would reject this theory and bring the spasmotic and nervous theories to the forefront of the medical community.  Regardless, many physicians continued believe sputum had a significant role in asthma.

In 1851 Dr. Beau and his assistant Cozart insisted asthma was caused by increased sputum in the lungs that was capable of blocking the air passages with mucus plugs.  In 1878, J.B. Berkart wrote about a Dr. Beau who worked with his pupil Beau to come up with his observation that asthma attacks end with a spit of sputum.  They believed asthma was caused by increased sputum and resolved when sputum breaks up with a coughing fit. (3, page 31)

Berkart explained that Beau basically believed asthma was a disease of chronic catarrh, or inflammation of the air passages.  He believed this sputum was capable of obstructing the air passages, and this is what caused the symptoms of asthma, “as well as the sonorous and sibilant rhonchi — their ‘rales vibrants.”  (3, page 31)

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

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

Leyden, whose asthma theories were similar to Bree’s theory, believed Charcot-Leyden crystals caused asthma by irritating “the peripheral extremities of the vagus nerve, and produce reflex spasm of the bronchial muscle.”   The asthma attack, therefore, ended when these were coughed up.  (4, page 14-15

In 1878 Dr. John Charles Thorowgood explains that subsequent experiments disproved Leyden’s theory, and this was further disproved when Charcot-Leyden crystals were also found in the sputum produced from patients with “ordinary catarrh and croupus bronchitis.” (4, page 15)

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

I added italics for emphasis.

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

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

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

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

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

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

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

He also wrote:  (8)

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

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

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

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

Yet as time went by, it was learned that there was more to asthma and allergies than just histamine.  It was learned that asthmatic and allergic immune systems respond irrationally to allergens and asthma triggers by increasing production of eosinophils and  this spearheads inflammation of the bronchial muscles. Another weapon of the immune are mast cells that line the respiratory tract and eyes, and these were discovered in 1953.  .

In 1967 Immunoglobulin E antibodies (IgE) were discovered.  It was later learned IgE have a significant role in the asthmatic and the allergic response.  The first time an asthmatic, for example, is exposed to an asthma trigger (allergen), say dust mites, his immune system develops dust mite IgE antibodies that attach to mast cells that line the epithelial layer of the skin or respiratory tract.

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

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

What can compound this problem is that asthmatic lungs tend to produce an abnormal number of goblet cells, so mucus production during an asthma attack can become exorbitant. Some of this may make it’s way to the upper respiratory tract, although much of it can become trapped inside already spasming air passages.

When the fit ends, when the air passages relax and dilate, the patient will probably expectorate this sputum, which is usually (if no bacteria or virus is present) be white and sterile.  It will also have IgE and eosinophils in it, hence your Charcot-Leyden and Curshmann crystals.

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

References:

1. Lotval, J.,  ”Contractility of Lungs and air tubes: experiments performed in 1840 by Charles J.B. Williams, European Respiratory Journal, 1994, (7) pages 592-595


2. Bree, Robert, “A Practical Inquiry into Disordered Respiration Distinguishing the Species of Convulsive Asthma, their Causes and Indication for a Cure,” 4th ed, 1810, London, page pages 117-118


3. Berkart, J.B., “On Asthma: Its Pathology and Treatment,” 1878


4. Thorowgood, John C., “Asthma and Chronic Bronchitis: A New Edition of Notes on Asthma and Bronchial Asthma,” 1894, London, Bailliere, Tyndall, & Cox


5. Lipkowitz, Myron, Tova Navarra, “Encyclopedia of Allergies,” 2001


6. Brenner, Barry E, “Emergency Medicine, 1998, page 10


7. Sahli, Hermann, “A treatise on diagnostic methods of examination,” 1911


8. Adams, James, Asthma and it’s Radical Treatment, 1913


9. Thorowgood, John C., “Notes on Asthma,” 1878, 3rd edition, London, J & A Churchill

Asthma History

For an ongoing asthma history click here

The following links may be obsolete.  However, the above link will continue to be ongoing.

This is a living history of asthma. By living I mean I will be updating this history often based on what I learn through reading or through emails and comments from my readers. This history will not become stale, so feel free to come back often for more fun with history.

History of Asthma Coming Soon

Asthma History
Asthma History Timeline
History of Asthma definitions
History of Asthma Treatment
Asthma History Books
History of Asthma Clinics

In the meantime, Check out these great link

• 
  Asthma timeline by asthma.org.uk


• Asthma history timeline from the Museum of Royal Pharmaceutical Society


• 100 years of asthma treatment and onward by Respiratory and Critical Care Medicine


• The inhalatorium: A collection of inhalers and asthma therapies


• 
  Asthma: The Biography by Mark Jackson


• 
  Asthma history from Google
  
  

History of Asthma Definitions

As we travel back in time we will learn the definition of asthma has grown through the years.

• 30,000 B.C.:  Diseases are noted by their symptoms as opposed to their causes.  The symptoms of shortness of breath, wheezing, anxiety, nausea, headache, itchy and watery eyes, runny nose, etc are caused by the unseen spirits and gods.  


• 10,000 B.C.: Theories started to evolve in most societies that diseases (symptoms) were caused by some kind of imbalance inside the body.  These types of theories would hold strong through most of history.  


• 5,000 B.C.:  Asthma-like symptoms were described in ancient Egypt, although no respiratory diseases were described. 


• 
  2,697 B.C. Chinese physician Ch’i Po provides the first description of asthma (maybe):  ”Those who do not rest and whose breathing is noisy have disorders in the region of Yang Ming (the ‘sunlight’).  The Yang of the foot in descending causes the present disturbance and is ascending it causes the breathing to be noisy.”  You can read more by clicking here. 
  


• 800 BC?  The first reference to asthma was made by Homer in his epic poem The Illiad.    ”asthma” was derived from the Greek word aazein, which means to exhale with an open mouth or to pant.  Actually, asthma is derived from the Greek word Panos which means panting.  Homer used the term to reference any dyspnea, including shortness of breath after exertion from fighting in a battle. So here asthma was basically an umbrella term that represented all causes of dyspnea (asthma, hay fever, bronchitis, emphysema, kidney failure, heart failure, pneumonia, tuberculosis, etc.)


• 400 B.C.:  Hippocrates introduced the term asthma into the medical community, using it to describe any medical condition that caused dyspnea.  Pneumonia and tuberculosis are the first two respiratory diseases taken out from under the asthma umbrella.  The cause of asthma was the same as any other disease, it was caused by an imbalance of one of the four humors: Blood, Phlegm, Black Bile, Yellow Bile.


• 
  1 A.D.: Celcus was the first to distinguish dyspnea from asthma.  He defined dyspnea as Moderate, unsuffocative breathing without a wheeze (it’s chronic); he defined asthma as Vehement breathing that is sonorous and wheezing (it’s acute)
  


• 
  100 A.D.: In India, asthma-like symptoms were referred to as Tamaka Swasa, with swasa meaning breathlessness.  It’s a condition that closely resembles our modern description of asthma such as wheezing, shortness of breath, increased phlegm and coughing (kawa).  When severe it may result in sweating, trouble lying down and trouble speaking.
  


• 
  100 A.D. Aeretaeus of Cappadocia defines asthma this way: ”If a difficulty of breathing is produced either from running, excessive exercise, or any other cause, it is denominated asthma, or any other cause, it is denominated asthma: that disease likwise known by the name orthopnea, is called asthma, because the patients during the paroxysms are affected with difficulty of breathing, it obtains the appelation orthopnea from the patients not being able to breathe easily, unless in an erect posture of body, in a reclining state, there is danger of suffocation taking place.” The cause was “coldness of breath with moisture: the matter consists of thick gutinous humors lurking internally.” Treatment was based on your age and sex. 
  


• 150 A.D.: Galen mostly agreed with Hippocrates that asthma was a humoral disease, and he was the first to define asthma as a disease of wheezing.  He noted that ”if the breathing is rough and noisy it indicates that a large amount of thick and sticky humors in the bronchial tubes of the lungs has accumulated and become annoying because it is difficult to expectorate.” 


• 
  650 A.D.: Paulus Aegineta defines the asthmatic as “those who break thick without fever, like those who have run fast…The affection arises from thick and viscid humours becoming infarcted in the bronchial cells of the lungs… Dyspnea is a common symptom which accompanies these and many other complaints… 


• 960 A.D.: Haly Abbas, like Galen, refers to asthma as a collection of gross phlegm about the cells in the lungs. His remedies are of an attentuant and incisive nature, and he particularises the vinegar of squills.  He cautious asthmatics to be aware of indigestion, and, therefore, forbids exercise after food, but recommends it before a meal.  After exercise he enjoins hard friction, no doubt with the intention of favouring the cutaneous perspiration
  


• 1000:  asthma was a chronic disease in which patients often suffered ‘acute paroxysms with similarity of epilepsy and spasm.’  The flow of thick humours from the head to the lungs produced a situation in which ‘the patient finds no escape from rapid panting, like the labored panting of one who is being choked or rushed’. 
  


• 
  1180:   Maimonides might have been the first to describe nervous asthma when he wrote how a patient who is “mentally agitated” causes his physical well-being to suffer and eventually he becomes physically ill. He was also to think asthma might be caused by pollutants in the air.  He believed asthma usually began with a cold and advanced to shortness of breath. 
  


• 
  1400:  Korean physicians believed asthma-like symptoms or coughing were caused by excessive eating, fear and shock.
  


• 
  1600: Jean Baptiste Van Helmont was the first to describe asthma as anything other than simply a symptom.  He was the first to propose the idea that asthma was a disease of bronchospasm when he wrote:  ”The lungs are contracted or drawn together.” He was the first to describe asthma as a nervous disorder. 
  


• 1650:  Thomas Willis is actually given credit for the nervous theory of asthma because he wrote more extensively about it. He described asthma as “obstruction of bronchi by thick humors, swelling^ of their walls and obstruction from without.” He describes three types of asthma: 




• 
  Pneumatic Asthma:  Dyspnea is a result of air passages in the lungs being obstructed or not open enough


• 
  Convulsive Asthma:  The primary fault of dyspnea comes from the lungs themselves, “in the moving fibres or muscular coats of the air vessels or in the diaphragm and muscles of the chest or in the nerves of the lungs and chest or of the origin of those nerves in the brain.”


• 
  Mixed Asthma:  Both pneumatic and convulsive.




• 1675:  John Floyer described a hereditary component of asthma, and numerous exacerbating factors such as air pollution, infection, cold air, exercise, sleep, psychological stress, and tobacco smoke, and astutely observed the benefits of clean air and environmental change.  He was the first to separate asthma from other causes of shortness of breath.  You can read more here. 


• 1700 Bernardino Ramazzini was the first to describe occupational asthma.  


• 
  1750 William Cullen was the first to start removing lung diseases out from under the umbrella of asthma, defining asthma as dyspnea caused by spasp.  He defines asthma as: “Difficult respiration recurring at intervals, with sense of stricture in the breast, respiration performed with a wheezing noise; difficult cough at the beginning of the fit, sometimes none, free towards the end; and often with copious discharge of mucus.”
  


• 
  1800:  Robert Bree believed asthma was a humoral disease and not a spasmotic disease.  He believed that some sort of paroxysm was present in the air tubes that caused asthma.  As the asthma fit progressed, the asthmatic would ultimately cough up some sputum, and with the sputum would be expectorated the causative agent. 
  


• 1850:  Henry Hyde Salter believed asthma was a condition of airway spasms or convulsions caused by a nervous disorder.  He strongly inculcated the idea that asthma was nervous.  He was the first to state that asthma was not a humoral disease, but an actual disease of the lungs and mind.  


• 
  1859: American physician J.A. Swett acknowledged that bronchospasm was important, but regarded ‘bronchial inflammation’ as the ‘principal exciting cause of the paraxysm’. (1, page 109, 110)


• 1859: Berkart rejected the idea that ‘mysterious derangements of the nervous system’ caused asthma, yet he saw little evidence that anti-spasmotics of that time benefited the disease. Based on this wisdom he believed asthma was a product of transient obstruction of the bronchi. (1, pp. 110)


• 1873: Charles Harrison Blackley argued that symptoms of hay asthma (hay fever) were due to inflammation of the ‘submucous cellular tissue’ of the bronchi rather than ‘spasm of the circular muscles of the bronchial tubes’. (1, pp. 110)


• 1870s: Mucus plugs were discovered in the lungs of asthmatics(1, pp. 110)


• 1890s: Eosinophils in both the sputum and the blood of asthmatics were found, which confirmed that inflammatory exudates layed a pivotal role in bronchial asthma (1, pp. 110).


• 1892: In The Principles and Practice of Medicine, William Osler believed the theory of bronchospasm was not proven, and he suggested attacks of asthma were due to ‘swelling of the bronchial mucus membrane’ (later referred to as inflammation), otherwise referred to as inflammation of the smaller bronchi. He also believed asthma was caused by a reflex spasm of the diaphragm and other respiratory muscles. He acknowledged asthma as neurotic. He believed the relationship between hay fever and asthma deserved attention, because he believed if the changes in the mucosal membranes that occured with hay fever were to occur in the lungs, this would further explain a paroxysm of asthma (1, pp. 111, 112).


• 1894?: Edouard Brissaud condisered the symptoms of asthma to be the product of both bronchospasm and hypersecretion, which constituted a form of ‘bronchial urticaria’ (1, 111).


• 1895: Arthur Foxwell suggested attacks of asthma were characterized by a combination of bronchial oedema, bronchial constriction, and contraction of blood vessels in teh lungs (1, pp. 111).


• 1959: The Condition of subjects with widespread narrowing of the bronchial airways changes its severity over short periods of time either spontaneously or under treatment. (American Thoracic Society: Am Rev Respir Dis 85: 762-785, 1962)


• – Asthma experts at this time were working hard to differentiate asthma from COPD. Although it was basically defined, in 1959, as a form of intermittent airway obstruction that could be reversed with bronchodilators. Chronic bronchitis was defined as productive cough, and emphysema was defined as dilation of the air-spaces distal to the terminal bronchi.**


• 1962: Asthma is a disease characterized by an increased responsiveness of the trachea and bronchi to various stimuli and manifested by a widespread narrowing of the airways that changes in severity either spontaneously or as a result of therapy (Ciba Foundation Guest Symposium: Thorax 14: 286-299, 1959)


• 1975: A chronic condition is characterized by recurrent bronchospasm resulting from a tendency to develop reversible narrowing of the airway lumens in response to stimuli of a level or intensity not inducing such narrowing in most individuals (World Health Organization: Bull World Health Organ 52; 251-260, 1975)


• 1985: Reversible Obstructive Airway Disease: The acronym R-O-A-D was what I was taught in 1984 during my time at National Jewish Hospital/ National Asthma Center.


• 1987: A clinical syndrome is characterized by increased responsiveness of the tracheobronchial tree to a variety of stimuli. Major symptoms are paroxysms of dyspnea, wheezing, and cough, which may vary from mild and almost undetectable to severe and unremitting (status asthmaticus). The primary physiological manifestation of this hyperesponsiveness is variable airways obstruction. This can take the form of fluctuations in the severity of obstruction, after the use of bronchodilators or corticosteroids, or increased obstruction caused by drugs or other stimuli. There is evidence of mucosal edema of the bronchi, infiltration of the bronchial mucosa or submucosa with inflammatory cells, especially eosinophils; shedding of epithelium; obstruction of peripheral airways with mucus. (American Thoracic Society: Am Rev Respir Dis 136: 1285-1298, 1987)


• 1991: A lung disease has the following characteristics (1) airway obstruction that is reversible (but not completely so in some patients) either spontaneously or with treatment; (2) airway inflammation; and (3) increased airway responsiveness to a variety of stimuli. (National Heart Lung and Blood Institute, National Institutes of Health: Guidelines for the diagnosis and management of asthma, NIH pub no 91-3642, Bethesda, MD, 1991.)


• 1992-1997: A chronic inflammatory disorder of the airways in which many cells play a role, particular mast cells, eosinophils, and T lymphocytes. In susceptible individuals this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough in early morning. These symptoms are usually associated with widespread but variable airflow limitation that is at least partly reversible either spontaneously or with treatment. The inflammation also causes an associated increase in airway responsiveness to a variety of stimuli. (National Heart Lung and Blood Institute, National Institutes of Health: International Consensus report on diagnosis and management of asthma, NIH pub no 92-3091, Bethesda, MD, 1992


• 2010: A lung disease that is associated with chronic inflammation of the air passages (bronchioles) of the lungs. The bronchioles are therefore sensitive to various stimuli (asthma triggers) that should be harmless. The degree of inflammation determines severity. When exposed to asthma triggers the inflammation worsens, thus causing acute spasming of the muscles of the air bronchioles (bronchospasm) which causes the bronchioles to become narrow, thus trapping air inside the lungs. This is called an asthma flare, and results in coughing, wheezing, chest tightness and shortness of breath. The episode is reversible sometimes on its own, and sometimes with therapy. Between episodes breathing is normal for most patients.

History of Asthma: 1981 (Asthma medicines)

To start our history of asthma, let’s travel back to 1981. This information is from a package I received when I was a patient in 1985 at National Jewish Health (NJH). Back then the hospital was called National Jewish Hospital and Research Center/ National Asthma Center (NJH/NAC), and the package was titled, “Learning about asthma.”

In the last section of the packet is a list of all the medicines used to treat asthma at that time. Most of these medicines I was on, and if you had asthma in the 1980s, chances are you were on one or more of these too.

So, without further adieu, here is the list of the top line asthma medicines for 1981. Or rather, here is the medicine and the facts about them as per 1981 wisdom. I’m going to reproduce it here as it was actually written in lecture format:

---

I. Facts about medicine for the child with asthma

A. No curative medicine
B. Control asthma when taken as prescribed
C. Medicine must be evaluated for effectiveness
D. Take only the medicine prescribed for you

II. educations

A. Theophylline

1. Most effective and used medicine
2. Action on the bronchial muscles and known as a “bronchodilator“

3. Prescribed under many brand names:

• Aminophylline


• Somophyllin


• Choledyl


• Elixophyllin


• Theolair


• Slophyllin


• Theodur


• Theospan and many others

4. Side effects

• Gastro-intestinal system


• Central nervous system

5. Evaluated by blood level determinations

B. Beta2 Adrenergics and related medicines

1. Medicines similar to epinephrine and are bronchodilators

• Metaproterenol (Alupent and Metraprel)


• Terbutaline (Bricanyl and Brethine)


• Isoetharine (Bronkosol)


• Isopreterenol (Isuprel)


• Epinephrine (Adrenalin)

2. Side effects

• Gastro-intestinal system


• Central Nervous system

C. Cromolyn (Intal)

1. Acts by lessening response of lungs to triggers
2. Needs to be taken regularly
3. No effect after wheezing starts
4. Inhaled as a dry powder and may stimulate coughing

D. Steroids

1. Related to cortisone, a hormone naturally secreted by the adrenal glands
2. Inhibit inflammatory reaction
3. Most effective medicine for a flare-up of asthma symptoms
4. Side effects

• Change in body shape: (1) Increase appetite, (2) Weight gain, (3) Round-faced look


• Change in growth: (1) Growth interfered with during long term use, (2) Severe asthma my interfere with growth


• Adrenal suppression: (1) Adrenal glands become “lazy”, (2) Gradual reduction of steroids to stimulate production of glands again

5. Common medicines

a. Prednisone (Deltasone, Paracort, Meticorten)
b. Prednisolone (Sterane, Delta-Cortef)
c. Methylprednisolone (Medrol)
d. Beclomethasone (Vanceril, Beclovent)

• Inhaled into lungs


• Avoid side effects of steroids taken by mouth


• Disadvantages: (a) Difficult for small children to use, (b) Not effective for acute attacks of asthma, (3) May irritate the throat, (4) May allow thrush to develop in mouth

E. Other medications

1. Decongestants and Antihistamines
a. Given for relief of congestion and/ or allergic rhinitis
b. Many brand names

1. Antihistamines: (a) Chlortrimeton, (b) Teldrin, (c) Atarax, (d) Benadryl


2. Decongestants: (a) Sudafed


3. Combination (Antihistamines and Decongestants): (a) Drixoral, (b) Actifed, (c) Dimetapp

c. Side effects

1. Drowsiness


2. Hyperactivity

2. Anti-Cholinergics

a. Atropine

1. Inhaled

III. Administration of medicine

A. Take as prescribed by physician
B. Learn all about the medicine
C. Devise a system of taking medicine to help with compliance

1. Self-care model

---

So you can see there have been a lot of changes as far as medicine is concerned when it comes to treating asthma since the 1980s. I was actually surprised to see Theophylline as the #1 asthma medicine, but I shouldn’t have been. It was a top line medicine from the 1950s until about 2000.

This era was right at the peak of trying to prevent asthma attacks as opposed to just treating acute asthma symptoms. Yet it was known back then that airway swelling (inflammation) was involved in the acute asthma attack, it was not known asthma was a disease of chronic (always there) inflammation.

Theophylline is now rarely used, and Intal is off the market. Epinepherine is rarely used, replaced by Ventolin (continuous if necessary) in emergency rooms. All the other beta adrenergics listed above are no longer available due to side effects.

I was surprised to see that Ventolin, Azmacort and Atrovent weren’t on the above list, as they were all on the market.  One reason may be (I’m guessing here) was that they were all under patent and more expensive than other options on this list.  Of course this list was made in 1981 and I was a patient in 1985, and was prescribed a ventolin inhaler and azmacort.

Some pretty good opitons were available back then.  We asthmatics were pretty fortunate compared to… well, we were just fortunate.

Respiratory Therapy History

Respiratory therapies were described since the beginning of written language.  The Ancient Egyptians describe inhaling fumes of herbs on heated bricks, and in ancient Indian authors described inhaling herbs burned in crude pipes.  By the early 19th century burning such herbs in cigars and pipes became a common remedy for asthma, and by the late 19th century asthma cigarettes were introduced.  While pressure ventilators are considered modern machines, prototypes were invented in the early 19th century.  Tracheotomies were used to create airways as early as 4,000 B.C., and when a crisis of diphtheria hit in 1839, intubation was attempted. While that attempt failed, it inspired later physicians to try again and again, until finally, in 1880, the intubation technique was mastered. Crude nebulizers and inhalers were available in the 19th century, but were never mass produced until the 1930s when electricity was available.  Most of the first nebulizers were expensive and fragile, yet as we travel to the late 20th century they decrease in price, are made of disposable plastic, and become readily available for anyone with a lung disease.  Oxygen was first introduced in the 18th century, some crude devices were available to administer oxygen therapeutically during the 19th century,  and by 1920 an oxygen revolution of sorts occurs.  By the 1940s there were a variety of respiratory therapy equipment, and managing it became overwhelming for doctors and nurses, so the profession of inhalation therapy was born.  At first strong, male orderlies and nurses aides were trained to lug huge tanks and iron lungs around, setting them up for various patients, and taking care of them.  This profession matured into the respiratory care profession.  

Now let’s journey back, way back, to the beginning…

Respiratory Therapy History:
(Dates denote when the post will be published.)

• 
  Asthma history (our beginning starts here)  Yes!  It all starts with asthma… 
  


• 
  History of inhalers and nebulizers  They were not, however, originally prescribed for breathing…
  


• 5,000  B.C.: An Egyptians hero thinks about air (11/6/14)


• 4000-2000 B.C.: The birth of tracheotomy(5/19/15)  The original artificial airway
  


• 800-400 B.C.: Ancient Greeks define tracheotomy (5/28/15)


• 124-200 A.D.: Roman physicians describe tracheotomies (6/4/15)


• 400 B.C. to 1900:  A history of ‘vital air’ (1/3/13)  The first theories: What keeps us alive?
  


• 400-1743:  The first use of the term influenza (8/29/13)


• 800 B.C.:  The first mouth to mouth respirations (5/19/15)  The first artificial respirations?
  


• 1-1619:  Jews, Arabs and Latins practice tracheotomies (and mouth to mouth breathing)


• 1213-1644:  The discovery of gases (1/11/13)


• 1500-1750:  TB spreads across the world
  


• 1530:  The bellows of Paracelsus (5/21/15)


• 1546-1783:  Physicians experiment with tracheotomies (6/18/15)


• 1600-1900:  Native American Fumigations (2/3/15)


• 1654:  Bennet describes the inhaler (8/20/13)


• 
  1700-1900: Physicians invent intubation and mechanical ventilation
  


• 1743:  The first mechanical ventilator
  


• 1750-1850:  TB wreaks havoc (8/27/13)


• 1750-1870:  Air is defined (1/18/13)


• 1765-1874: Tracheotomies recommended for croup (7/7/15)


• 1774-1922: Humane Society spreads word of Prone, Sylvester Methods artificial breathing (6/30/15)


• 1776:  The double chambered bellows of Dr. John Hunter (6/2/15)


• 1790:  The first feeding tube (5/26/15)


• 1800-1920:  Oxygen cylinders and chambers (1/25/13)


• 1800-1900:  Oxygen used to treat asthma (2/7/13)


• 1800-1900:  The birth of the TB sanatorium
  


• 1800-1900:  The beginning of pressure therapy (8/5/14)


• 1800-1900:  The beginning of pressure therapy (Part II) (8/12/14)


• 1800-1900:  Evolution of Artificial Respiration (8/16/14)


• 1800-1987:  The rise and fall of polio (10/15/13)


• 1823:  Native American Sweat Houses, an early panacea (2/10/15)


• 1832-1900:  Origins of Negative Pressure Ventilation (9/2/14)


• 1840:  The first incentive spirometers
  


• 1840-1903:  Open air treatment for consumption (Opening of NJHealth)(9/3/14)


• 1866: Catologue of stethoscopes (7/17/14)


• 1871: Waldenburg’s Pneumatometer (8/5/14) (???)


• 1871-1900:  Pneumatometers as Spirometers (9/9/14)


• 1872:  George Catlin describes Native American Respiratory Therapists (1/15/15)


• 1873:  The Trendelenburg position is born (10/17/13)


• 1896:  The ideal pulmonary inspiratory (4/16/15)


• 1899:  Bronchitis triggers
  


• 1903:  The earliest pressure machines (8/5/14)


• 1903:  The earliest pressure machines (part II) (8/12/14)


• 1903:  The earliest pressure machines (part III) (8/26/14)


• 1900-1950:  Evolution of artificial respiration
  


• 1900-1950:  The slow death of a disease called consumption (9/5/13)


• 1907: The first mechanical ventilator:  The Pulmotor (6/25/15)


• 1908:  The Bratt’s Resuscitator (6/2/15)


• 1910-1903:  Early PEP and Insentive Spirometers (8/19/14)


• 1910-1920:  The oxygen revolution (2/14/13)


• 1912-2001:  Dr. Martin Wright (11/12/13)


• 1918:  A killer worse than a war (10/3/13)


• 1920:  The Lungmotor (a resuscitation device) (7/7/15)


• 1920-1940:  The birth of the RT profession (2/21/13)


• 1920-1980:  The evolution of oxygen delivery devices (2/15/13)


• 1920s:  Early resuscitators were over-hyped (7/9/15)


• 1929: The Drinker Respirator (7/21/15)


• 1931:  The Emerson Respirator (7/23/15)


• 1930s-1990s: Vodka aerosolization for pulmonary edema (3/31/15)


• 1940-1980:  Evolution of artificial respiration (4/4/13)


• 1940-1970:  The decline and return of TB (9/26/13)(


• 1940-1960:  The RT Profession Matures (2/22/13)


• 1955:  Bird Mark 7 Universal Respirator  (6/23/15)


• 1960-Present:  From RITT to RRT (3/7/13)


• 1950:  Life for polio victims inside an iron lung (7/23/15)


• 1950s:  The first peak flow meter (11/19/13)


• 1953: The introduction of the Ambu-bag?
  


• 1955-1985:  The IPPB revolution


• 1980-2012:  Evolution of artificial respiration (8/14/12)


• 1941:  Dr. Christie defines emphysema and how to treat it


• 1970-Present: History of Incentive Spirometry


• History of Pulse Oximetry (11/5/13)


• History of Spirometry


• Hypoxic Drive Theory:  A History of the Myth


• History of COPD


• History of Pneumonia


• History of Cystic Fibrosis


• History of BiPAP


• History of Croup


• History of Heart Failure (see asthma history)


• Mysthenia Gravis (Garrison, page 263, 1921 edition; Thomas Willis first to describe it)

Hungry for more?

1. 
   drgrespiratory.com (Dennis Glover wrote the History of Respiratory Therapy and provides some awesome pictures from the history of respiratory therapy)
   


2. 
   inhalatorium (Mark Sanders has a unique collection of antique inhalers, nebulizers and  has shared his collection with us on his website.  Check it out!
   


3. See any of the links on any of the above posts

Please note:  This history is a work in progress.  As new material becomes available posts will be updated.  As time becomes available, posts will be edited for grammar, accuracy, etc.  If you see an obvious error, feel free to chime in.  If you have access to further knowledge on any topic, feel free to share.  If you want to use this material for your own research projects, please feel free to do so.  While you are free to quote me, I also recommend you refer to the references listed with each post.  Thanks.  Rick Frea.