1800-1900: Eleven asthma theories

The 19th century was an "age of enlightenment" where physicians and scientists started to question old theories of medicine and come up with new ones.  This was an important time in our history, because without it we might probably still be stuck with primitive medicine.

This era was particularly important to the evolution of asthma, as all the theories regarding it, old and new, were hotly debated.  Some physicians were dogmatic, holding on to one particular theory for dear life, while others were more open minded.  Either way, the fact that the disease was openly discussed in the arena of ideas allowed physicians to better understand this disease.

Think of it this way:

• Before 400 B.C. asthma was just another mysterious disease caused by evil spirits or gods.
• In 400 B.C. the Hippocratic writers defined asthma as dyspnea. 
• Around 1700 John Fuller defined asthma as a disease entity of its own, slightly more severe than dyspnea and less severe than orthopnea 
• During the 18th century asthma was basically believed to be a disease in some way associated with and caused by sputum.

During the course of the 19th century there were eleven theories regarding asthma that were hotly debated.  Some were ancient ideas, and some were new.  The most prevalent of these theories are listed here. 

1. Humoral theory of asthma:  This theory postulates that asthma was caused by an imbalance of the four humours: black bile, yellow bile, phlegm and blood. This was the prevailing theory from about 400 B.C. (and probably sooner) when Hippocrates defined it, and the 1st century when Galen reaffirmed it, to the 19th century when scientific theories disproved it. More specifically, Galen believed asthma was caused by an over abundance of phlegm.
2. Dyspnea theoery of asthma:  That asthma and dyspnea are the same thing was established by Hipporates.  Basicallly anything that causes you to be short of breath is asthma; asthma is a symptom, an entity, as opposed to a specific disease. This theory was on the way out the door by the turn of the 19th century, although was pretty much the prevailing thought until the 18th century when scientists and physicians realized there were various causes of dyspnea, and started treating asthma as a disease and not just a symptom.  
3. Symptomatic theory of asthma:  Many physicians believed asthma was nothing more than a symptom of some other malady, such as heart, lung or kidney disease.  Sometimes the cause remained mysterious.  
4. Bronchitic theory of asthma:   Wheezes and dyspnea depend on obstruction of the air tubes by the inflammatory products of bronchitis. This results in excessive mucus production. Dyspnea is less severe and more constant than a paroxysm of asthma. This was the prevailing theory during the 18th century, and it made its way into the 19th century through the writings of Dr. Robert Bree.  A variation of this theory held great sway at the end of the 19th century and was referred to as the Theory of vessel turgescence.  This is basically inflammation of the mucosal membranes that line the respiratory tract, and we might think of it today as bronchitis.  
5. Spasmotic/ convulsive theory of asthma:  Convulsions, Contractions or spasms of the muscles that line the bronchioles are a main component of asthma.  Celsus defined asthma as being caused by "the narrow passage by which the breath escapes, it comes out with a whistle."  The theory was introduced to the medial community by Thomas Willis in 1682, and William Cullen in the next century fine tuned it.  It was a hotly contested theory during the 19th century. 
6. Nervous theory of asthma:  The belief that asthma is nervous in origin, or caused by things that influence the mind -- such as strong emotions like laughter, crying, stress, excessive happiness, excessive sadness, a yearning for the mother, etc -- goes back to the ancient world. Physicians early on observed no organic lesions in asthmatic lungs, and therefore assumed it must be nervous in origin.  They observed asthma was intermittent, sometimes with long intermissions between paroxysms.  This theory the nerves caused spasms in the lungs was introduced to the medical community in the 16th century by Jan Baptiste van Helmont and Thomas Willis, and in the 18th century by William Cullen.  It was proven by the experiments of Francis Ramadge in 1835, Joseph Bergson and Amedee Lefevre win 1836, and Francis Romberg in 1841.  It was given true credibility by the writings of Henry Hyde Salter during the 1850s. 
7. Paralytic theory of asthma:  Asthma is caused by paralysis of the respiratory muscles and this results in dyspnea.  This idea was first established by Dr. Rene Laennec around around 1810 or 1820.  "Bronchial muscles," he said, "are paralyzed and dyspnea is expiratory, more more constant, and less spasmotic."  We might now refer to this as emphysema. (1, page 37)
8. Diaphragmatic spasm theory of asthma:  This theory postulates that tonic spasms of the diaphragm causes asthma.  This theory may have been devised by examining the way asthmatic people breath, and was probably proposed by Thomas Willis and Neumaun (?).  It was also later supported by (M. Alton) Wintrich in the mid 19th century, and later confirmed by Heinrich von Bamberger around 1870.
9. Cardiac theory of asthma:  This is the theory that asthma is caused by blood being sucked into the lungs causing congestion and dyspnea. During the 19th and early 20th centuries it was often referred to as a type of asthma.
10. Reflex theory of asthma:  This theory postulated that something other than the lungs causes it.  Eating too much or eating certain foods can effect a nerve and send a "reflex" signal to the lungs, which responds by causing the airways to contract.  For example, catarrh or inflammation of the nose can cause spasm of the muscles of the lungs by reflex action.  Most who support this theory believed some form of disturbance in the blood was the result.  Other causes of this might be a response from the urea, disturbance of metabolism, dyspepsia, etc. However, some who support this theory believed it was just an extehnsion of the nervous theory of asthma.
11. Hay fever theory of asthma:  Hay fever leads to asthma.  Some speculate inflammation (or catarrh) of the upper airway leads to inflammation of the lower airways of the lungs, leading to bronchitis or asthma. This is a theory that has recently gained momentum.
12. Other:  Yes, lots of other theories existed.  Some doctors just let their imaginations fly free. Dr. Breuer, for example, "believed there was an automatic control of breathing through the vagi and that the stretching of the alveolar walls stimulates expiration and hinders inspiration. An increasing of the total lung volume," he said, "would tend to stimulate expiration rather than inspiration." (1, page 37) Some theories may have been scientifically justified, and others, such as Breuer's, mere speculation. Other physicians noticed asthma improved after removal of polyps in the respiratory tract and sinuses.

Of all the theories regarding asthma during this era, Orville Brown said in 1917 in 1917:

The multitude of theories some ingenious and helpful and others far fetched and convincing evidence of a fruitless search, have failed to receive much attention."  (1, page 25)

For the most part, each physician had a favorite theory, found evidence to support it, and adjusted the definition slightly as evidence indicated.

So, what theory won the era? 

References:

1. Brown, Orville Harry, "Asthma, presenting an exposition of nonpassive expiration theory," 1917, St. Louis, C.V. Mosby Company.  The above mentioned theory of vessel turgescence comes from this reference also on page 25. 

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1802: Heberden first physician to recognize hay fever

For most of history people were clueless about colds and allergies.  The symptoms associated with them -- itchy and watery eyes, stuffy and runny nose, scratchy throat, coughing, sniffling and sneezing -- were probably brushed off as minor ailments.  Most people did not seek help, as doing so would be a sign of weakness. Instead, they went about their business the best they could.

While there were occasional vague and allusory descriptions of these common ailments, there were more serious diseases called plagues that earned the attention of most medical writers.

The term "plague" became a generic term used through most of history to describe diseases that were both lethal and destructive.  (1, page 17)

It was not until sometime during the 17th century that the term "fever" began to replace the term plague in describing diseases.  A good example of this came in the year 1666 when Thomas Sydenham published his book "The Method of Treating Fevers." He described diseases such as scarlet fever, perpetual fever, malaria fever, hospital fever, and typhoid fever. (1, page 17)

Still, it wasn't until the mid 18th century, and mainly during the 19th century, when the causative agents of specific symptoms were identified, that the term "fever" was used with increased frequency.  Examples would include rose fever and hay fever, with hay fever gaining the most recognition.  These terms crept into medical nomenclature as physicians linked sniffles and sneezes with rose and hay season. (1, page 17)

A generic terms that was more generally accepted by medical authorities was "catarrh."  This term comes from the Greek term katarrho, which means to flow. It generally referred to the flow of humors, or secretions, due to congestion of the vessels (swelling and inflammation) of certain parts of the body, such as the eyes, nose and throat.

Generally speaking, the symptoms that resulted were generally brushed off as the common cold.  For instance, William Heberden, in his 1802 book "Commentaries on the History and Cure of Disease," described catarrh this way:

If such a catarrh lasts only a few days, it is called a cold in the head; but in many it becomes a chronical disorder, and has lasted with no long intervals for several months, for four years, or every night for ten years; or has returned periodically twice a month for several years, or once in three weeks. (2, page 113)

The problem with the term catarrh, and the probably reason it was eventually phased out of the materia medica for the most part, was because nearly every disease causes some form of catarrh.  It was such a generic term that it lost its relevance. By Heberden's time the phase out had already begun, although the complete extrication of the term would take another 100 plus years.

Another term often used was Coryza, although it was not mentioned by Heberden.  It was a more specific term used to describe catarrh of the nose and throat, and was frequently used to describe the common cold. It was yet another generic term to describe a cold, although it was later used to describe a symptom of hay fever.  The word comes from the Greek term koruza which means "running of the nose."

As part of his chapter on catarrh, of which he also referred to as "defluxion," he described what may people think is the first description of hay fever by a medical writer.

I have known it (catarrh's) return in four or five persons annually in the months of April, May, June, or July, and last a month with great violence. In one a catarrh constantly visited him every summer; and in another this was the only part of the year in which it ceased to be troublesome. (2, page 113) (3, page 14) (4, page 14)

While he did not use the term hay fever, or hay asthma, or rose cold, or any of the other terms to describe the condition that had gained the fancy of the public, it's quite obvious this is was he was describing here.

References:

1. Ergonul, Onder, Chris A. Whitehouse, editors, "Crimeon-Congo Hemorrhagic Fever: A Global Perspective," 2007, Netherlands, Springer
2. Heberden, William, "Commentaries on the History and Cure of Disease," 4th edition, 1816, London, Printed for Payne and Foss - Pall Mall
3. Smith, William Abbotts, "On Hay-Fever, Hay-Asthma, or Summer Catarrh," 1867, London, Henry Renshaw
4. Mackenzie, Morell, "Hay fever and paroxysmal sneezing," 5th ed., 1889, London, J&A Churchill

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1600-1700: Some abhorent remedies for asthma

So you have asthma in 1618, and you approach your physician about your problem. You sit in a wooden chair opposite his voluminous desk, leaning on his desk to expand your chest, your chest heaving with each slow breath.

As you're explaining your dilemma, in a huffy fashion, he opens a book on his desk.  You observe the title: "Materia Medica."  You wait as he sifts through the pages, and says, "hmmmmm.  Let's see here."  His finger traces what he's reading.  He leans back in his chair.  

He says, "Now, according to this "Materia Medica" we have a few options here.  Do you have anyone who can hunt for you."

You say, "Well, I'd love to hunt for myself, yet the consequences of doing it put me here."  

"I see." He leans back in his chair, puckers his lips as if in deep thought.

"So what do I need to do?" You ask.

"Well, it says here," he picks up the book, turns it so you can see the page, and he points to the heading "Asthma."  You read the section he's pointing to:

• Worms
• Lozenges of dried vipers
• Foxes Lungs

You say, "Well, I think I can find someone to get me a fox, but I'm not sure about the viper.  I think getting one of those would be next to impossible." You look into the doctor's eyes.  "Don't tell me a viper bite will cure me, doctor."

Your comment induces a laugh from the doctor, and you join in briefly.  The laughter induces a cough, and you produce a large amount of sputum.  The doctor reaches into his desk and offers you a handkerchief.
-----------

For kicks and grins, here are some of the other remedies in 17th century pharmacopaeas:

• Powder's of precious stones
• Moss from the skull of the victum of violent death
• Human urine
• Blood
• Fat
• Bile
• Horns
• Crab's claws
• Crab's eyes
• Bones
• Bone marrow
• Sexual organs
• Eggs
• Excreta of animals of all sorts
• Spider-webs
• Fur
• Feathers
• Hair
• Scorpions

No wonder physicians struggled to gain respect.  To their credit, though these remedies offered hope to patients, and there were also many other remedies that had an actual benefit to the patient.  Considering the medical ignorance of the time, physicians who offered such remedies must have felt good about their efforts to help a sick person.

Such remedies were slowly phased out of the pharmacopoeia, mainly due to the works of men like William Heberden (1710-1801) who championed to put "diseases upon a scientific basis," and "who did a most important service to therapeutics by dispelling current superstitions and banishing them forever from the pharmacopoeia" in his 1745 book "Essays on Mithridatium Theriaca."*  (1, page 370)

Obviously most of these abhorrent remedies were slowly phased out of the pharmacopoeia, particularly as better remedies were introduced.  For example, stramonium was introduced to the London Pharmacopoeia in 1721 by Sir Hans Sloane.  A few decades later, the authors of the 5th London Pharmacopeia of 1746 condemned the old practice of astrology and folk medicine, dropping the following remedies: (1, page 408)

• Human fat
• Spider Webs
• Moss from human skulls
• Unicorn's horn
• Virgin's milk
• Bones from stag's heart (1, page 408)

Can you guess what was in your asthma medicine?

*Mithridatium = remedy that cures everything, particularly poisons; theriaca = a compound of 64 drugs believed to be a cure for all poisons)

References:  

1. Garrison, Fielding Hudson, "An introduction to the history of medicine," 1922, Philadelphia, W.B. Saunders Company, page 291

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1798: Robert Bree's 4 Species of Asthma

Robert Bree, our formost expert on asthma during the first half of the 19th century, described four species of asthma in his 1797 book, "A practical inquiry into disordered respiration: distinguishing the species of convulsive asthma, their causes and indications of cure."   

His "species" of asthma are based on his theory that asthma, and dyspnea, are caused by some irritating or peccant matter, and the asthma will continue until this peccant matter is removed.  The asthma attack, hence, is the effort of the body, or lungs, to expectorate this matter.  In this way, an asthma attack usually ends with the expectoration of sputum.

Now that we understand that, here are his species of convulsive asthma:

1.  The first species:  It's called Periodic or sometimes Convulsive Asthma (as described by John Cullen).  It's usually preceded by dyspepsia (irritated stomach).  It may show symptoms for years before it turns into a fit of asthma.  Dyspepsia is aggravated during the attack of asthma.  This usually effects the melancholic personality.  This is irritation of the serum within the lungs.  (1)

Symptoms include ("When an asthmatic feels these symptoms, he may be convinced that his enemy is at hand.":

• Flatulence
• Distended bowel
• Pain over forehead and eyes, which may become worse in the evenings
• Eructation of wind (burping)
• The evenings are attended with sleepiness
• Irritability that repels friends
• Tingling and heat in the ears, neck and breast (itching of the lungs)
• A motion to expel contents of the bowels
• Uneasiness of abdominal muscles
• After sleeping, he wakes with great difficulty of breathing
• Feels need to have an erect posture
• Inspiration performed with great effort of the muscles, but never performed deeply
• Diaphragm seems to descend with great difficulty against a force
• Speaking becomes distressing
• Irritibility of mind continues
• Wheezing sound on respiration
• There is a propensity to make water (pee, urinate), which is copious (lots) and pale
• After several hours cough birngs up phlegm
• Relief follows
• Tranquil state of feeling induces sleep with wheezes
• Remission on second day
• Expectoration of phlegm on 2nd or 3rd day ends the episode

2.  The second species:  Like the first it's caused by an irritating matter in the lungs.  It's accompanied by little or not expectoration of mucus.  For this reason it's commonly called Dry asthma. This is irritation from areal acrimony within the lungs.  (2)

Symptoms include:

• Little sputum, or none
• It comes on suddenly
• Succeeds sudden changes such as alterations in the wind, or a change of situation.
• The cause is of acrid or offensive quality, such as a strong smell, or subtle matter carried by the air. 
• The irritant is inhaled and attaches to the bronchial pipes or tracheal membrane. 
• The irritant usually atatcks by day more so than night
• No wheezes
• Action of intercostals and abdominal muscles are increased (as in other species of asthma)
• Dry cough
• Inflammation
• Hoarseness
• More prevalent in populous places or manufacturing places
• May come on suddenly when you come upon a town, and go away when you get back to the pure air of the country

3.  The third species: This is when the irritating matter that causes convulsive asthma is found in some organ other than the lungs. These causative organs are generally found below the thoracic cavity, such as the stomach or other viscera.    However, it cannot be proven the irritating matter was not present in the lungs at the same time. The irritating matter of another organ might be removed by an unobserved power of absorption, and the irritating matter of the lungs may be removed through expiration.

Many physicians doubt another organ causes asthma, and therefore inappropriately give blame to the lungs.  Many people think the lungs are the cause because of the respiratory distress.  For example, some physicians have found a link between spasm of the bladder or rectum and spasms of diaphragm and abdominal muscles, which are muscles "subservient to respiration."  In this way, Bree believed abdominal problems can cause respiratory problems.  (3)

4.  The fourth species:  This is convulsive asthma that is dependent on the habit of the person, and caused by sensation, after the irritation has been removed from the thoracic or abdominal viscera. I believe the idea here is that the asthma is caused due to the treatment of some other disease. Paroxysms return by minute causes in effect, such as mental association with the idea of being short of breath.  This usually is seen in those with frequent episodes of species 1-3.  For this type opium or other antispasmotics seem to work quite well. (4)

Further reading:

• To see other remedies for the above species see this link.
• To learn more about Dr. Robert Bree's definition of asthma click here
• To view the history of asthma click here

References:

1. Bree, Robert, "A practical inquiry into disordered respiration: distinguishing the species of convulsive asthma, their causes and indications of cure," 4th ed., 1810, London, page 43- 56
2. Bree, ibid, pages 182-193, 286-287
3. Bree, ibid, page 194-212, 287-290
4. Bree, ibid, pages 213-233, 290-292

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1800-2012: Evolution of back-door bronchodilator

One of the oldest and most popular asthma medicines historically are anticholinergic or muscarinic medicines. The exact mechanisms to how these medicines worked remained a mystery for most of history, so the terms anticholinergic and muscarinic are recent terms. What was known early in our history is that inhaling the medicine offered relief for asthma attacks.

Ancient Egyptian medical documents reported taking dried and crushed herbs, mainly belladonna, and placing them on heated bricks. Then the asthmatic, or the person suffering from asthma-like symptoms, inhaled the medicated smoke and was offered some relief. This was among the most common asthma remedies in Egypt.

At different times in our history, various other civilizations inhaled either belladonna, or other members of this family plants. The common name is the nightshade family, otherwise known as the Solanaceae family of plants. They include:

• Datura stramonium 
• Atropa belladonna 
• Hyoscyamus niger (henbane) 
• Lobelia inflata.

As the ancient physicians discovered, the best effect was obtained when the medicine was inhaled, and in this way, it was used as a topical applied directly to the lungs. Over time, different methods were used for inhaling the medicine, which included:

1.  Burning herbs: Leaves, roots and stems from the herbs Belladonna and stramonium were sun-dried and crushed by ancient Egyptians, placed on rocks heated on coals, and the asthmatic would roll up stalks of a reed, place one end up to the crushed herbs and inhale the smoke. Surely this sometimes made asthma worse, yet more often than not the herb offered some relief. This method was first recorded in 4000 BC, yet it was probably done long before this.

2.  Pipes:  The sun-dried products of the herbs were ground, and the powder stuffed into crude pipes, lit, and the medicinal smoke inhaled.  This technique was discovered for the modern world in 1803 for Europe and the U.S. and the asthma cigarette craze began.

3.  Cigarettes: The powder was rolled into small paper and smoked cigarettes and cigars.  This technique was commonly used in India and was discovered for the modern world in the early 19th century. An asthma cigarette craze began around 1879 and lasted until the middle of the 20th century.

4.  Pills:  During the 19th century the medicine was formed into pills that were taken by mouth.  A popular brand was Potter's Asthma Pills.  These were common from around 1880 to 1950s.

Ad for Ozone Paper
showing endorsement
by Dr. Thorowgood
(1891)

5.  Nitre/ Ozonepaper:  By the 1850s paper was impregnated with potassium nitrate, strammonium, or belladonna and ignited to produce fumes that were inhaled as a treatment for spasmodic asthma.  By 1973 this was a common mode of treatment and recommended by Dr. John Thorowgood in the British Medical Journal.  (1)  (2)  It may also be referred to as ozone paper.  One advertisement for the product even mentions Dr. Thorowgood's endorsement (see picture to right.

6.  Nebulizers/ Inhalers:  During the 19th century various nebulizers and inhalers were invented to help asthmatics inhale various solutions of the medicine.   Nebulizers, of course, were fine tuned in the 1930s, and modern inhalers were fine tuned during the 1950s.

As scientists and Pharmaceuticals worked with the plants, they learned, in 1833, that the active ingredient inside it was atropine.  From there they learned how to synthesize the medicine to create modern anticholinergics.

These include:

1.  Atropine:  It was derived from the belladonna plant in 1833, and by 1867 it was isolated and determined to be a component alkaloid of the various nightshade plants found in India, Egypt, South America and other rocky, warm climates.

It was first available for asthma cigarettes, but around the turn of the 20th century was available as a solution to be nebulized. It ultimately became a top line treatment for asthma during the 1950s.  The medicine was still prescribed for asthma during the 1980s, although by the 1990s was phased out due to a synthesized anticholinergic medicine with fewer side effects. I was prescribed this medicine in 1985 and took it up to four times per day until around 1990.

It was ultimately learned that the medicine worked by blocking the effects of the parasympathetic nervous system. This system releases a neurotransmitter called acetylcysteine which binds to muscarinic receptors that are randomly scattered along the bronchial smooth muscle. This causes bronchospasm, increased secretions, and asthma symptoms.

Prior to the 1990s, this parasympathetic pathway was thought to be the main cause of bronchospasm in asthma. Atropine and Atrovent worked by binding with muscarinic receptors, thereby preventing acetylcholine from attaching to them, thereby blocking acetylcholine. The medicine became known as anticholinergic or antimuscarinic medicine.

It was at this time, during the 1990s, that researchers learned that most cases of asthma involved some degree of underlying airway inflammation (10),  the severity of which determined how severe a person's asthma was. This inflammation worsened due to exposure to asthma triggers, resulting in bronchospasm, increased mucus production, and asthma symptoms.

It was learned that the best medicines for treating this bronchospasm and underlying airway inflammation were beta 2 adrenergic medicines and inhaled corticosteroids. At this time, anticholinergic medicine was relegated to second-line asthma medicine status, as opposed to front-line status. So, this was another reason most asthmatics are no longer prescribed anticholinergic medicine.

Atrovent Inhaler

2.  Ipratropium Bromide (Atrovent):  This is a synthesized anticholinergic, and it was first introduced in Germany in 1975, followed by the rest of Europe by the late 70s.  It was available both as a solution to be nebulized and as an inhaler, and it was prescribed four times per day.  An HFA inhaler was approved by the FDA in 2004.  I was prescribed this medicine in 1990 and took it up to four times a day until around 1995.  It was initially a top line asthma medicine, although better medicines have replaced it.  I believe the inhaler was phased out in favor of the new Ipatropium Respimat. (3) (4)

As a side note here, up until the mid-1990's, atropine, and later Atrovent, were top-line asthma medicines. Up until this time, the main pathway of bronchospasm was thought to be the parasympathetic nervous system. By this, researchers understood that atropine

3.  Oxitropium Bromide (Oxiven, Tersigen): This was another synthesized anticholinergic released along with ipratropium bromide.  It was marketed as both an inhaler and solution.  Because it was available in higher doses, the frequency was only three times per day.  This medicine was never approved by the FDA for sale in the U.S. (6)

10.  Combivent:  This is a combination of Albuterol and Ipratropium bromide in an inhaler form. It was approved by the FDA in 1996 for the convenience of COPD patients and some asthmatics who don't respond to other top line asthma medications. The medicine was set to be phased out by December 31, 2013, but due to a public outcry a new version of the medicine was introduced to the market as a replacement (see Combivent Respimat)

Combivent Inhaler

 11.  Duoneb:  This is a combination of albuterol and ipratropium bromide premixed in plastic amps with 0.3cc of normal saline. It was introduced in the early 1990s and approved by the FDA in 1996.  The medicine was nice because it made for a quicker breathing treatment, as compared to mixing separate amps of albuterol and ipratropium bromide, both with 3cc premixed.  It continues to be a top line treatment for COPD, although is an option for asthmatics.

Spiriva HandiHaler

12.  Tiotropium Bromide (Spiriva Handihaler): This dry powdered inhaler was introduced to the market in Europe in 2002 and the U.S. in 2003. It's the first long-acting back-door bronchodilator, meaning it only needs to be taken once a day.  Studies show it is more effective than ipratropium bromide in improving lung function. It is recommended as a top line treatment for COPD.   (7)

Combivent Respimat

13.  Combivent Respimat: This is the new version of Combivent approved by the FDA in 2012. The device has no propellant, is breath actuated, and delivers a dose that is supposed to provide greater lung distribution of the medicine than a metered dose inhaler. The medicine was in demand because a non CFC version of Combivent was needed.  (8)

Studies show this type of medicine may produce mild bronchodilation and mild breathing relief. Personally, I never noticed any difference with the medicine. However, modern evidence suggests the medicine, when used daily, may act as a preventative medicine, keeping lungs dilated long term.

Modern studies have found that anticholinergics that anticholinergics don't benefit asthmatics as once was suspected, and so, while they remain an option, they are no longer a top-line option.  Spiriva continues to be a top line option for COPD, as studies show it improves lung function. Atrovent and Combivent are slowly being phased out in favor of the newer medicines.

Duoneb continues to be an option for COPD patients, although even it has seen better days.  Some physicians are phasing this medicine out in favor of long acting medicines that only need to be taken once or twice a day, such as Spiriva, Brovana, and Pulmicort.

So what started out as a medicine that was sporadically recommended and inhaled as smoke around a primitive cooking fire, has evolved into a medicine that is taken in the form of simple inhalations that are conveniently and safely delivered as simple inhalations.

Anticholinergics (or muscarinics) are medicines that, once inhaled, sit on cholinergic (or muscarinic) receptor sites that sit along bronchial smooth muscles. It binds to and sits in these receptor sites, thereby preventing the neurotransmitter acetylcystine from binding to them.

of the neurotransmitter acetylcysteine to prevent it from causing bronchospasm. Because the medicine is blocking a natural response as opposed to actively causing bronchodilation, it is often referred to as a "back-door bronchodilator."

The first "back-door bronchodilators" used came from the nightshade family of plants called Solanaceae, and were often included in ancient recipes for asthma remedies.  Some common plants used were:



References:

1. "Nitre paper," Drugs.com, http://www.drugs.com/dict/niter-paper.html
2. Thorowgood, John, "On Bronchial Asthma," British Medical Journal, 1873, Nov. 22, page 600
3. Sittig, Marshal, "Pharmaceutical Manufacturing Encyclopedia," 1988, vol. 1, New Jersey, page 837
4. Barnes, Peter J., Jeffrey M. Drazen, Stephen I. Rennard, "Asthma and COPD: Basic Mechanisms and Clinical Management," 2008, page 616-17
5. Ipatropium Bromide, package insert, http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.serdocBase=renetnt&folderPath=/Prescribing+Information/PIs/Atrovent+HFA/10003001_US_1.pdfingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Atrovent+HFA/10003001_US_1.pdf
6. Barnes, op cit
7. Barnes, op cit
8. "FDA Approves Combivent Respimat (ipatropium bromide and albuterol sulfate) Inhalation Spray," FDA.gov, http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm274684.htm
9. *Picture with much appreciated permission from Inhalatorium.com
10. Wright, Rosalind J., Mario Rodriguez, Sheldon Cohen, “Review of psychosocial stress and asthma: an integrated biopsychosocial approach,” Thorax, 1998, December, http://thorax.bmj.com/content/53/12, accessed 7/18/17

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1798: Bree's Symptoms of Asthma

The following are the symptoms of asthma as described by Robert Bree in his book "A Practical Inquiry into Disordered Respiration Distinguishing the Species of Convulsive Asthma, their Causes and Indication for a Cure."  It was written in 1810.

Note:  You must understand that Bree's undestanding of asthma was very puerile compared to our modern definition.  Much of his descriptions and theories on asthma are based on observation and personal experience with the disease as opposed to scientific facts.  However, some facts were available at this time and he used this information to support his opinions.  This was not uncommon for his day and age.

Anxiety:  Owing to the difficulty attending the efforts of nature to removing an irritating offense.

Itching of the skin of breast and neck:  This sometimes precedes the violence of the fit and declines as agony of the fit decreases. This may be an effect of sympathy with the lungs and first passages. Irritating matter in the stomach is the probable cause of this symptoms.  Another cause may be the difficulty to which venous blood is returned to the heart

Perception of heat:  You feel like you have a fever, but you don't.

Great desire of cool air:  Probably occassioned by a desire for oxygen, as you feel the means of obtaining it is increased by fresh air.

Closeness:  Areteaus wrote:  "The patient loves walking in the open air, with his mouth open, and is dissatisfied with the largest house, which seems to small to breathe in."

Dyspepsia:  (Upset stomach)  Always precedes periodic asthma.  This causes flatulence of the stomach and bowels and pain over the head and eyes and sleepiness.

The attack of the paraxysm in the night:  By concentrating, and by sacrificing sleep by staining up late and sitting in a recliner instead of the bed, this can often be avoided.

Diabetes:  By this I think he's referring to the need to pee a lot during an asthma attack. He says this is common, although it provides little relief to the asthmatic.  He gives a few reasons, none of which make any sense.  Such as in the case of hysteric asthma, he says the kidneys may be relaxed due to sudden passions of the mind.  He says the kidneys receive nerves from the intercostals, and there is likewise a strong association between the lungs, kidneys, and stomach.  May also be linked to edema, swelling of the ankles and legs.

The straightness of the breast:  He supposes that this makes it easier for the exchange of air when the air sacs are filled with secretions, which is often the case in asthma.  The rest of his several paragraphs describing this are simply meaningless poppycock.

Intermitting pulse:  John Floyer attriutes this to constriction of the arteries, by circumvolving nerves, may more probably proceed from this condition of the heart.  It may also be cauesd by dyspepsia because of the strong relationship between the stomach and the heart.

Spitting of black mucus:  He believes the coloring agent in the sputum to be carbon in the blood, which in the healthy person was exhaled

The pulse is generally feeble:

Urine is pale and copious:

Sleepiness:

Belly seldom regular:  Constiation may alternate with diarrhea, and may be attributed to dyspepsia (upset stomach). There is remarkable action of the abdominal muscles and all the muscles  used to discharge faeces.  And he flatters himself that evacuation of such will provide breathing relief.

The habit of the asthmatic is generally cold:  The temperature will be lower than normal.

The mind is impatient:  Not only does Bree write this as a symptom, he adds, "...and he suffers much from opposition to his method of management in his own case."  After several episodes of asthma he learns methods of comforting and satisfying himself, but help from others is often received with anxiety.  He becomes irritable during the fits, "and, with difficulty refrains his disposition to petulence."

Generosity:  Bree notes the following interesting fact:  "It may be observed generally as a fact, that the mind of an asthmatics is more susceptible of generous and grateful feelings than that of any other invalid, subject to a chronical disease equally obstinate."  Emphasis added by me.

Respirations more numerous during asthma attack:  They never exceed 30 without a considerable increase in pulse.  Bree recognized this is in general opposition to Floyer

References:

• Bree, Robert, "A Practical Inquiry into Disordered Respiration Distinguishing the Species of Convulsive Asthma, their Causes and Indication for a Cure," 1810, London, pages 117-140, Section IX

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1798: Bree's asthma remedies

Dr. Robert Bree was recognized as a predominant expert on asthma during the first half of the 19th century, as I wrote here.  In 1910 he wrote a book titled, "A Practical Inquiry into Disordered Respiration Distinguishing the Species of Convulsive Asthma, their Causes and Indication for a Cure."  The following are the remedies he recommends for asthma:

1.  Cathartics:  These are medicines or herbs that cause evacuation of the bowels, or purging.  Purging is the use of vomiting or laxitives to clear the stomach, according to dictionary.com.  For example, one patinet noted taking "10 grains of powder of jalap, and three grains of colomel when the fit commenced, which completely removed the fit, on many occasions by evacuating a load of bile."  Yet Bree wasn't a big fan of cathertics, and suggested that if this relieved the asthma the cause was something other thanas asthma.  However, he admits that cathertics to work for some asthmatics.

2.  Emetics:  These are medicines that induce vomiting, according to Dictionary.com.  Tartarized Antimony and Antimonial Wine or small doses of Ipecacohan can incuce vomiting.  Amid other things, they promote exhalation from the lungs and are therefore "powerful expectorants."

3.  Diaphoretics:  These are medicines that promote sweating, according to dictionary.com  He recommended "gentle diaphoresis, but not sweating."

4.  Bleeding:  This is where you cut a vein and allow blood to flow in an attempt to balance the humors.  He believes this has "doubtful effects" on asthmatics.  However, he does recommend it for most species of asthma.

5.  Diuretics: These are medicines that make you pee.  "Natron taken every night, in doses of eight grains, has been found to be very beneficial" for certain types of asthma.

6.  Issues:  These are medicines to treat mental or emotional problems, according to dictionary.com.  "In very old asthmatics, issues are sometimes necessary.  In younger subjects, when the disease is not yet inveterate, they may occasionally be useful, by diverting acqueous humour from the lungs, and giving a better opportunity for the operation of tonic remedies...  When the disease is complicated by dropsy (an old term for edema, according to dictionary.com), I have seen great advantage to the breathing, from from their application in the thighs."

7.  Antispasmotics:  These are medicines that relax smooth muscles, such as the muscles that wrap around the air passages in the lungs or that line the respiratory tract.  One common medicine is opium and it is enhance by the use of ether.  Calcined zinc has proven beneficial for epilepsy, although is not useful for asthma.  "Velerian, cardamine, camphor, musk, castor, belladonna, tobacco infusion, extract of  henbane, fetid gums, cuprum ammoniacle in various doses, more or less joined with the other antispasmotics, or tonic medicines, and combined with opium in large and small portions" helps sometimes but most often prolongs the paraoxym.

8.  Expectorants:  These are medicines that induce sputum production.  Ammoniac is a very valueable expectorant, although it should be given with opium to prevent purging (unless you want purging).  Squills are sometimes useful.  Squills also work when given with vinegar, similar to what John Floyer prescribed.  This is often called vinegar of squills.  A side effect is nausea and purging.  Tincture of squills combined with extract of henbane and the nitric acid is a good combination of expectorant and sedative.  Oxymell is efficatious if combined with vinegar or squill.  Honey and sugar are good for cough, but not so much for asthma.  Decoction of seneca can be useful in older persons, but is too irritating for younger people.  If asthma takes on the character of peripneumonia, decoction of seneca should be given with amonia during the febrile state, and when the fever goes away squill and camphorated tincture of opium will promote expectoration, perspiration, and urine.  All expectorants may cause nausea and vomiting, and this may be good in that it may remove the irritaing matter.  However, they also help relieve phlegm from the chest.

9.  Inhaling vapours:  "Hippocrates introduced the inhalation of vapours from various herbs and gums.  He used herbs and nitre boiled with vinegar and oil, and directed the vapour of such boiling compositions to be drawn into the lungs through a proper pipe."  Fumes can also be used to dry secretions that are known to cause asthma.  Frankincense, myrth, and many other gums, and these are occasionally mixed with arsenic.
Modern physicians recommended inhaling vapour of aether "raised in the steam of warm water."  However, aether can make asthma worse.  Vapour of hemlock leaves can be useful for some forms of asthma, and especially for it's narcotic qualities.

10.  Smoking tobacco:  Bree actually recommends asthmatics stop smoking "with great advantage to their health."

11.  Oxygen:  May benefit asthma when the color of the skin turns blue.  May help cease labored respirations.  It works expecially well for convulsive asthma.

12.  Hydrogen:  This has been proven to be beneficial to asthmatics, particularly spasmotic asthma.

13.  Stomachics:  "These remedies are absolutely necessary in asthma to correct dyspepsia (upset stomach), in whatever species of the disease it may appear.  Bitter tinctures are not to be used in the paroxysm, but bitter infusions and testaceous powders are generally beneficial.  Acetous acid is also grateful to the stomach when any bilious acrimony is present.  In this case "

14.  Diet:  Any food that is an exciting cause of asthma should be avoided.  Barley water and all weak liquors that are likely to ferment or relax the stomach should be avoided.  Infusion of coffee is good for any type of asthma except the second. "Pure cool water has frequently removed the bad effect of an imprudent meal.  If the asthmatic perceive his stomach to be disordered or uneasy, he may next expect more certain symptoms of a paroxysm.  In these circumstances I have experienced, very frequently, the advantage of repeated draughts of water, so that two or three pints have been taken in the whole, from the commencement of the uneasiness; and this has given perfect relief when coffee had failed."  It is wise not to eat more than the stomach can handle."  (page 204)

Note:  According to Bree, the above remedies vary in accordance to the species of asthma diagnosed by the doctor.  However, in order to simplify Bree's work I have left out which species of asthma the above remedies are for.  In either case, all of the above remedies were recommended for one or another species of asthma.  I did find Bree's writings to be quite complicated to understand, and I apologize if my interpretations of Bree's work isn't exactly as he understood.

References:

• Bree, Robert, "A Practical Inquiry into Disordered Respiration Distinguishing the Species of Convulsive Asthma, their Causes and Indication for a Cure," 1810, London, 4th ed., items 1-13 are obtained from pages 237-278, item 14 from page 292-294

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