1800-1985: Asthma Cigarettes

Elliot's Asthma Cigarettes*

So as you probably know by now by hanging out on this blog I had pretty bad asthma as a kid.  When I was 18 I walked into my doctor's office and he said, "Look, if you ever decide to smoke cigarettes, just let me know and I'll put you out of your misery myself."

The irony was a few days later I visited the Manistee County Historical Museum in Manistee, Michigan.  The museum is housed in the old A.H. Lyman Company building, which was a pharmacy.  In the back the old pharmacy shelves classic medicines.  On the box of one of these boxes was written: "Elliotts Asthma Cigarettes.."  What I saw was similar to what you see in the picture to the right.

Potter's Asthma Remedy*

If smoking was supposed to be so bad for asthma, I thought, why would doctors prescribe smoking cigarettes?  And what was in them anyway?  

What's in 'em?

Recently I set off on a quest to learn more about this interesting "medicine."  I learned the following about asthma cigarettes:

• They didn't contain tobacco, but crushed and dried herbs from the nightshade family of plants called solanaceae, which included datura strammonium, atropa belladonna, the hyoscyamus niger, Lobelia inflata and similar plants.  Indian Hemp and Cannabis are similar herbs also included in some brands.
• Such plants contained an alkaloid called Atropine that causes mild bronchodilation, and made breathing easier. 
• Smoking wasn't considered hazardous; it was actually seen as beneficial. 

Who first inhaled 'em?

It's difficult, if not impossible, to know when people first inhaled fumes of herbs to provide breathing relief or hallucinogenic effects.  In all likelihood it occurred by chance as the herbs were tossed onto hot coals and incidental inhalation resulted in hallucinogenic effects.  Later on an asthmatic inhaled these fumes, and he felt relief.  The herbs were probably believed to be a gift from the spirits or gods.

The first recordings of inhaling the herbs was around 4,000 B.C., which marked the dawn of the bronze age.  Ancient city states of Sumeria and the empire of Egypt were in their infancy, and the discovery of papyrus and cuneiform soon allowed societies the ability to communicate from one generation to the next by writing, perhaps with a reed stick.

Kinsman's Asthma Cigarettes*

The Ancient Egyptians had plentiful access to  atropa belladonna.  It was a pungent smelling herb that grew to be about three feet high with oval shaped, pointed leaves that grew about three to six inches long with reddish or purplish flowers.   (1)

Folks experimented with this herb and discovered its poisonous effect.  When too much was inhaled the person died.  This gave the plant the reputation as the "deadly nightshade."  Egyptians soon learned the best recipe involved picking the leaves, stems and roots, drying them under the hot sun, crushing what was left, and using the byproduct in a variety of ways.

Encyclopedia.com describes how Egyptian women squirted drops in their eyes "for the allure given by large, black pupils: hence the name belladonna — ‘fine lady'."  It made pretty eyes prettier and helped beautiful Egyptian women woo men. (1)

Ad for Schiffmann's Asthma Cure (1899)*

Physicians used it as a remedy for just about any respiratory ailment.  The dried and crushed herbs were tossed on bricks preheated on hot coals, and the smoke was inhaled to provide temporary breathing relief.  Over time a funnel was sometimes added to channel the smoke toward the patient's airway.

Inhaling the herb also provided a hallucinogenic effect, especially if enough was inhaled.  This may have been beneficial to the asthmatic as well, considering it helped take their minds of their trouble. Inhaling the smoke may have been beneficial to anyone suffering from a chronic illness, and was probably smoked regularly simply for recreational hallucinations.

However, there were risks, such as dry mouth, increased heart rate, dilated pupils, nausea and headache. If ingested or inhaled in high enough quantities, it may even cause death, hence the name deadly nightshade.

Kellogg's Asthma Cigarettes*

Who smoked the first pipes?

Again, it's impossible to know who carved out, let alone smoked the first pipes.  It's also impossible to know for whom the first pipe was carved for, nor what herbs were stuffed inside it.

It's possible the idea of using a sharp tool to hollow out a piece of wood for smoking herbs may have occurred to various inventors in various societies at different times.  The component smoked depended on what herbs were available.

For example, in India the incentive to carve out pipes was to smoke strammonium, belladonna, or Indian hemp for it's hallucinogenic effect. The fact the herb had other medicinal properties may have been learned later, or earlier.  Who knows?

Yet what we do know is the first medicinal use of pipes to smoke a medicine for asthma-like symptoms was recorded in ancient India around 100 A.D.  There were many herbs the Indians had access to, and one such was datura strammonium.  The herb produces an unpleasant smell and grows to be about five feet tall with a pale green stem with spreading branches and puplish leaves coarsely sedated along the edges.  Its flowers are white or purple.  (2)

By empirical means its entertaining effect was learned, as well as its poisonous qualities when too much was inhaled or ingested, which mainly included hallucinogenic effects.  At times it must have been observed the medicine made you mad, which may explain the name.

Datura comes from the ancient Hindu word for plant, dhatura.  Stramonium is a New Latin word meaning thornapple.  Strammonium originally came from the Greek word strychnos which means nighshade and mankos meaning "mad."  (3)

Other than thornapple, common names I've found during my research that refer to strammonium are jimsonweed, Jamestown weed, drowny thornapple, Devil's trumpet, angel's trumpet, mad apple, stink weed and tolguacha.  It was obvious by these names the side effects of inhaling too much was well known

Like belladonna, the leaves, stems and roots were dried and crushed into a fine powder the Indians stuffed into their pipes and smoked it.  The benefits obtained must have been of higher quality than simply inhaling fumes from igniting the herbs on bricks.  Although either technique may have been used, depending on what the patient had access to.

Obviously the herb may have been used for entertainment, although medicine men and physicians ultimately learned of the medicinal benefits.  By 100 A.D. Indian physicians recommended smoking  strammonium for diseases of the lungs and throat, or simply for its hallucinogenic effect.  Again, the hallucinogenic effect may be desired when no other remedy was applicable

The famous Greek physician Hippocrates wrote about stramonium and belladonna, so we know Greek physicians had access to such wisdom.  With the fall of Cordova Greek medicine made its way to Rome, so we know the Romans had access to it too.   With the fall of Rome all such knowledge was lost for over a thousand years.

So how did such wisdom come to us?

A long time passed before British physician and asthmatic James Anderson visited India and enjoyed the mild breathing relief he obtained after smoking a cigarette containing datura strammonium.  The year was 1802.  (4)

Anderson returned to England and reported his find to his friend Dr. Sims in Edinbergh.  Sims trialed it, noted the benefits, and published a report in the Edinbrugh Medical and Surgican Journal.  After this report asthma cigarettes were entered into British and American pharmacopoeia, and ultimately became popular for the treatment of asthma in these western nations.  (5, 12 page 55)

Of course it also should be noted here that there were no standards or regulations regarding dosing in those days, and no recommendations as to how much of a medicine should be consumed, or in this case inhaled.  Dr Sims reportedly died a year after his report from an apparent overdosing of Belladonna.  (5, page 55)

So American Indians smoked pipes too?

Yes, American Indians smoked dried herbs stuffed into pipes too.  Now, did they get this wisdom from travelers from far off lands, or did they come up with the idea on their own.  No one knows for sure, and either theory is a possibility.

Either way, American Indians had access to another member of the nightshade family called lobelia inflata.  Various folks experimented and observed it's effects when ingested and inhaled, and soon it was learned of the hallucinogenic effect.  At first it must have been tossed into fires, later on heated bricks or in pots, and ultimately the herbs were stuffed into pipes and smoked.

Now did they come up with this on their own, or did they get the idea from others.  Your guess is as good as the best historians.  Either way, they smoked it for relief of asthma symptoms and for other benefits too, and it's for this reason many refer to it as Indian Tobacco or Asthma Weed.

American physicians were introduced to lobelia and used it for asthma releif, yet they also used it to make some patients vomit.  The idea here was that along with vomit toxins would be removed from the body to balance the humors and cure the ailment.  For this reason it was often referred to as pukeweed and vomitwort.  (6)

What was the secret ingredient?

Well, there had to be something in the nightshade family of plants that produced the medicinal effect, and this component was the alkaloid Atropine.

Atropine was first derived from the belladonna plant in 1833.    By 1867 Atropine was isolated by von Bezold.  It was then determined to be a component alkaloid of the various nightshade plants found in India, including the datura strammonium, atropa belladonna, and the hyoscyamus niger (black henbane), and Lobelia inflata (7)

Early studies showed atropine was the potent component in the plant, the same component that dried secretions, increased heart rate, opened air passages, and produced a hallucinogenic effect.  It was the ingredient that that made the nightshade family of plants so sought after.

What started the Asthma Cigarette craze?

By the mid 19th century the market for inhaling ingredients and powders grew steadily.  Some pharmacists gathered the ingredients and sold them to individuals.  Some folks placed some powder on plates, igniting it and inhaling the fumes.  Some stuffed it into homemade pipes, inhaling it that way.  Others rolled it into cigarettes, inhaling it that way. 

Some pharmacists gathered the ingredients and further prepared them into powders to be further prepared by the patient.  Some pharmacists went a step further and rolled the powder into cigarettes that could be purchased in packs.  So there were a variety of options.

Potter's Patient Inhaler (funnel device)*

By 1879 an asthma cigarette craze struck America and Europe.  (8)  More and more companies entered the market in an attempt to benefit off the plight of asthmatics.  Belladonna, stramonium, lobelia, henbane, atropine, and even cannabis were packaged in cans and placed on shelves in pharmacies.

The products were marketed for just about any respiratory condition, including asthma, chronic bronchitis, whooping cough, cholera, croup, catarrh, and hay fever.  By the 1880s technology progressed so some companies pre-rolled cigarettes, packaged them, and sold their product at pharmacies.

Asthma cigarettes from a variety of companies could be found on pharmacy shelves like the A.H. Lyman Company.  According the Inhalatorium, the most famous brands were:

Potter's Asthma Cigarettes*

• Schiffmann’s Asthmador
• Blosser’s
• Potter’s 
• Marshall’s
• Kinsman’ 
• Dr Guild’s green Mountain
• Kellogg’s  
• Page’s
• Regesan’s

In my studies the brand I've come across most often was Potter's Asthma Cigarettes, which you can see in the picture to the right or by clicking over to inhalatorium.com.  This was among the most popular brands in Britain.

The main ingredient in Potter's cigarettes were stramonium, belladonna and atropine.  Mark Sanders over at Inhalatorium.com notes that Potter's also had a variety of asthma remedies that included cigarettes, incense, pills and powders to be inhaled by Potter's funnel device

Potter's Asthma Pills*

An asthmatic patient of mine who grew up in 1950s America said she remembered her dad smoking cigarettes from a green package.  We later figured the produce was Dr. Schiffmann's Asthmador Cigarettes.

When did the craze end?

The end of asthma cigarettes was slow. Even as better products were introduced to the market, asthmatics didn't want to give up something that worked for them. It's no different than today's asthmatics fussing over the end of popular medicines like Chromolyn, epinephrine and theophylline.

Asthma cigarettes continued to be popular even after the discovery of epinephrine in 1900 and as the solutions of epinephrine and atropine became options for home use with the invention of the mass-producible electric nebulizer in the 1930s, asthmatics still lit up the powders.

Sales of asthma cigarettes and powders stayed consistent because they provided breathing relief, were less expensive than those other options, and were available without a prescription.  Plus the nebulizers available were bulky and fragile, as well as expensive.

Yet while asthma cigarettes were the preferred choice due to convenience and cost, that all changed in 1957 with the invention of the inhaler, and the release of the Medihaler-Iso and the Medihaler Epi.  These inhalers provided instant relief, were relatively inexpensive, and easily carried in pockets and purses.

Easy to use & fast acting Medihaler (1957)

As sales of asthma inhalers sales went north, asthma cigarette sales went south.  Yet despite the decline in sales, the cigarettes were still a viable over the counter option until the early 1980s.

The end came due to growing concerns teenagers were purchasing asthma cigarettes not for asthma relief but for their hallucinogenic effects. (9)  So studies were conducted to confirm whether or not asthma cigarettes really worked, and whether they should be taken off the shelves.

By this time there were many other options for asthmatics, which included safer asthma rescue medicine such as Ventolin and Alupent, theophylline, and a refined and safer version of Atropine called Ipatropium Bromide (Atrovent).  These medicines could also be delivered in preset doses via inhalers and solutions to be nebulized.

H.L. Elliot and J.L. Reid described in a 1980 article published in the British Journal of Clinical Pharmacy a study that concluded asthma cigarettes made of "herbal preparations containing Atropine-like alkaloids" were just as effective as using ipatropium bromide (Atrovent).

Dr. R. Schiffman's Asthma powder*

The researchers concluded that "an overdose of of asthma cigarettes is manifestly capable of producing pharmacological effects (hallucinations, delerium, tachycardia)." They also concluded that the dose of medication getting to the lungs is "variable and unpredictable."

Likewise, they noted that "In view of increasing evidence of abuse, there appears to be good reason to restrict availability of these preparations. Although a herbal cigarette might possibly be recommended for the asthmatic who insists on continuing to smoke," a majority of asthmatics would get just as much benefit with fewer side effects by using thier Atrovent inhaler. (10)

By 1985 asthma cigarettes were removed from the shelves of all U.S. Stores.  Yet while being generally extinct in western nations, they are still available in some third world nations.

I will leave you today with a recipe for asthma cigarettes from the National Druggist, Volume 30, 1900:

---

Asthma Cigarettes------

(W.B.C. Cleveland Ohio)  The following formula is one that the writer has used for several years occasionally, and has found effective and not unpleasant, provided that the cigarettes are used not to frequently, or to excess:

• Strammonium leaves.....................8 parts
• Green tea leaves............................8 parts
• Lobella Leaves..............................6 parts
• Plantain leaves.............................2 parts

Mince the leaves to a condition suitable to rolling in cigarette form, and moisten the mixture with cold saturated solution of potassium nitrate in water, dry thoroughly, and pack in air tight cans or jars.  Lavel "Asthma Cigarette" mixure.  Directions:  When an attack of asthma is imminent take sufficient of the mixture to make one or two cigarettes of the ordinary size, roll in cigarette paper, and smoke slowly, inhaling the smoke as deeply as possible.  If relief is not afforded by the first, a second cigarette should be used.

---

So there you have it, the history of asthma cigarettes.  It was an options that provided hope and some relief for many asthmatics for a long time.  

eferences:

1.  "Belladonna," Encyclopedia.com,  http://www.encyclopedia.com/topic/belladonna.aspx
2. "Plants poisonous to livestock," Cornell University's Department of Animal Science,  http://www.ansci.cornell.edu/plants/jimsonweed/jimsonweed.html
3. "Plants poisonous to livestock," ibid
4. Sneader, Walter, "Drug discovery: a history, 2005, England, page 96\
5. Sneader, ibid
6.  University of Maryland Medical Center, "Lobelia,"  http://www.umm.edu/altmed/articles/lobelia-000264.ht
7.  Encyclopecia.com
8. "The Scarcity of Cubebs," The Chemist and Druggist," 1887, Feb. 26, page 268 of  Chemist and Druggist: A Weekly Trade Journal, 1887, Vol. XXX, January to June 1887
9. Jackson, op cit, page
10. H.L. Elliot and J.L. Reid, "The Clinical Pharmacology of a Herbal Asthma Cigarette"British Journal of Clinical Pharmacy (1980, 10, 480-490) 
11. *  Picture used with permission from Inhalatorium.com.  Check out the site for more picutures, ads and descriptions of asthma cigarettes and other asthma remedies.
12. Smyth, Hugh D.C, Anthony J. Hickey, "Controlled Pulmonary Drug Delivery," 2100, Springer New York Dordrecht Heidelberg London

Further reading:  

• Jackson, Mark, "'Divine Stramonium': The Rise and Fall of Smoking for Asthma,"  Med Hist., 2010 April; 54(2): 171–194.

1900-2012: History of steroid use for asthma x

So now in our quest through the anals of asthma history we come to corticosteroids.  If we consider the discovery of Epinepherine to be the most important discovery as far as asthmatics are concerned, the discovery of cortisone must be considered the second greatest discovery of all time.

The discovery of cortisone occured the same year epinepherine was discovered in 1900.  According to Barry E. Brenner in his history of asthma, "at that time Solis-Cohen prepared a crude extract of the adrenal gland and used it in the treatment of acute asthma." (1)

In the late 1930s it was isolated, and it was used successfully for the first time in 1944, according to Meriam-Webster dictionary.  It was initially used to reduce inflammation for patients with rheumatoid arthritis, yet it was ultimately discovered that it would help reduce inflammation in the air passages of asthmatics. (2)

According to Answers.com, "Schering-Plough," cortisone was synthesized in 1949 by Merck & Co, yet through a series of legal loops Schering obtained access to cortisone information.  This made it possible to make cortisone, and made it easily available to physicians.  (3)

What you have to realize, however, is at this time asthma was believed to result in inflammation only during an asthma attack.  Brenner explained that several studies were completed in the 1940s and 50s, and in 1955 prednisone was discovered as the first synthetic corticosteroid and marketed as an effective treatment for acute asthma symptoms. (4)  Medicine.net reports that it was approved by the FDA in 1955. 

Medrol Steroid Pack

Schering marketed prednisone as Metricorton in 1957.  Paracort and Deltasone are other generic options on the market. 

Another similar product is prednisolone which was also approved by the FDA in 1955.  It was marketed as either Sterane or Delta-cortef, although is available under as variety of products such as Pediapred and Orapred as well as generic names.

Dexamethasone also entered the market in the 1950s as Decadron.  Some believe this is a more potent steroid that lasts anywhere from 1-3 days in your system, making it ideal for kids who won't reliably take yucky tasting pills or solutions. 

Dexamethasone was actually the first corticosteroid to be marketed as a solution to be nebulized, and this was shown to benefit asthmatics in studies done in the 1960s.  (5) 

Methylprednisolone was later marketed as a varient and marketed as Medrol and Solu-medrol.  Medrol is the pill form and comes in what is referred to as a Medrol Steroid pack, or simply a steroid pack.  If you're an asthmatic chances are you've been prescribed a steroid pack at one point or another. 

The pack comes with five rows of 4 mg pills:  7 in the top row, 5 in the second row, 4 in the third row, 3 in the fourth row, 2 in the fifth row, and 1 in the sixth row.  You take the top row on day one, the second row on day two and so forth.  The idea is you take fewer pills each day to wean yourself off. 

I often get asked what's the difference is between prednisone, prednisolone, and methylprednisolone.  The answer is that they are simply the same or simlar products made by different companies.  Some say that methylprednisolone has fewer side effects, yet that's like saying Albuterol is better than Xopenex, or snow is better than rain.  In other words, which one a doctor prescribes is based on personal preference.

To treat acute episodes of asthma the medicine could be given as an injection, or the pill or liquid version could be taken at home.

Yet once you start taking steroids you had to slowly be weaned off.  Your body produces corticosteroids, and if you take the pill form your body will think you have enough and stop production.  For this reason, if you're given a high dose of corticosteroid medicine and then you stop cold turkey you leave your body with no corticosteroids and you'll die.  So you must wean, and that was one of the nice things about the steroid pack.  A doctor gave you a shot of Solu-medrol at the office and sends you home with a pack to wean you off.   

Sales of systemic corticosteroids boomed during the late 1950s and 60s.  It didn't take long for doctors to note a major problem with this medicine.  There were certain individuals who had persistent or chronic arthritis or asthma who required steroids on a daily basis.  Since there was little data on ideal dosing, some physicians prescribed high doses long-term for some patients.  It soon became evident there were some severe consequences to such long term, and high dose use of systemic corticosteroids.

Beclovent Inhaler

Noting the success of the Medihaler-epi and Medihaler-iso, pharmaceuticals hoped to take take advantage of the booming inhaler market.  In 1960 beclomethasone was introduced as the first inhaled corticosteroid by Allen & Hanbury, the makers of the Albuterol inhaler.  (7)  The product was marketed as Becotide in 1972, and the recommended dose was four puffs daily. 

GlaxoSmithKline's version of beclomethasone was Vanceril, and Schering-Plough's version was Beclovent, and both were approved by the FDA for sale in the U.S. in 1982. 

I was prescribed Vanceril from the late 1970s until 1985, yet from time to time other generic forms entered my home.  (You can see a 1979 ad for Beclovent and Ventolin here.) 

After the CFC propellants were set to be phased out in 1989, the hunt was on to find an environmentally friendly inhaler.  3M Pharmaceuticals developed an HFA version of beclomethasone called Qvar, and it was approved by the FDA in 2000.  By 2001 GSK stopped production of Vanceril, and soon thereafter Schering-Plough ceased production of Beclovent.

Studies actually show that (aside from the spike in cost), this changeover might have worked to the advantage of asthmatics as the new version has been proven to get deeper into the lungs providing better distribution of the medicine (I wrote about this in more detail in this post). 

However, according to Dr. H. Morrow Brown at Allergiesexplained.com, beclomethasone was almost written off as a useless medicine.  Many doctors preferred to treat asthma by desensitization with allergy shots, and this was done with me. 

I have the medical records to prove it. I remember getting allergy shots through the 1970s all the way until 1985.  As some point you'd have thought my doctors would have caught on they weren't working, considering my asthma continued to get worse and worse instead of better.

So desensitization was a top line therapy for athma and inhaled steroids were relatively ignored by physicians until a study was reported in The British Medical Journal in 1971 and 1972 showing beclomethasone was effective in controlling asthma. (8)

Becotide Inhaler

This turned out to be a great achievement because the inhaled medicine is absorbed in the lungs where it's needed and very little gets in the system, as opposed to oral or injected steroids which cause systemic effects. 

From the 1970s until the early 1990s systemic steroids were prescribed for severe episodes of asthma, and other than that acute episodes were managed by rescue medicine and inhaled corticosteroids like Becotide because side effect (although still expected), were believed to be far less than systemic steroids. 

Perhaps as a result of this, between 1957 and 1985 the market for asthma inhalers (which also included bronchodilators) skyrocketed so that in 1985 asthma inhaler sales were 25 percent of the asthma prescription market (theophylline was also at 25 percent of this market). 

The problem that remained until the early 1990 -- perhaps due to the 1950s scare -- was that doctors were still afraid that inhaled steroids used long term would produce the same side effects as systemic steroids.  For this reason they were leary of prescribing them as an every day medicine, and recommended them for use only during an acute attack to limit side effects. 

A second problem was that scientists had yet to discover that inflammation in the lungs wasn't just there during an acute attack, that it was chronic (always there).  For both these reasons, corticosteroids -- either systemic or inhaled, were only prescribed for moderate and severe asthma, and rarely mild asthma. 

Vanceril Inhaler

In the 1960s triamcinolone entered the market as Azmacort.  In 1975  Schering-Plough introduced its version of beclomethasone as Vanceril.  In the early 1980s Budesonide was introduced to the market as Pulmicort. 

Studies showed Pulmicort was the safest and most effecteve nebulized corticosteroid.  Decadron is sometimes given by aerosol in hospitals in the emergency rooms, but rarely, and usually not for asthma but inflammation of the throat.  Pulmicort has earned the respect of physicians, and it's basically the only nebulized corticosteroid available for home use. 

Perhaps my doctor had me trial all these at some point, yet the one I remember becoming friends with was the Vanceril inhaler.   It was a little pink inhaler designed the same as the Ventolin inhaler.  I have a note from my doctor following a 1981discharge from a local hospital after an asthma admission that says:  "Use your Vanceril for two weeks, then use only when you have trouble breathing."

By 1985 my asthma continued to be high risk, and I was using my asthma rescue medicine several times daily.  Sometimes I'd use my Ventolin inhaler in less than a week, and made several unscheduled doctor visits and emergency room for uncontrolled asthma.  I survived this, yet many asthmatics did not. 

My local doctor decided he couldn't help me, so I was shipped to National Jewish Hospital/ National Asthma Center (Now National Jewish Health).  Doctors there were up to date on the latest asthma wisdom and weren't afraid to prescribe inhaled steroids. 

The Azmacort inhaler with built-in spacer

Knowing my asthma was high risk, my doctor at NJH put me on Azmacort, and instructed me to take four puffs four times every day to control my asthma.  I was not to stop taking it no matter what, even if I felt good. 

The neat thing about this inhaler was it was the first inhaled steroid with a pleasant taste (at least I thought so).  The only problem was you needed four puffs four times a day to equal two daily puffs of our modern inhaled corticosteroids. 

This many puffs was a pain in the butt, but when I was compliant it worked like a charm.  So long as I took my inhaled steroid every day there would be just enough steroid in my system to prevent an asthma attack. 

By 1989 there were enough studies to confirm the approach NJH doctors used on me was the best way to treat asthma.

The results of the research showed that NJH was on the right track in treating asthmatic children with a daily dose of inhaled corticosteroids.  That experts now had to come up with a way to educate regional doctors of this approach so that other asthmatic children could benefit.

Thus, in 1989 the NHBLI's asthma guidelines were created. The guidelines highlighted the following:

• Asthma is often underdiagnosed
• All asthmatics have some degree of chronic inflammation
• A small amount of steroids in asthmatic lungs obtained from inhaled corticosteroids is often all that's needed to control this inflammation and prevent asthma symptoms.
• The amount of steroid inhaled from an inhaler is very small compared to systemic steroids, and therefore side effects are rare and minimal at worse.  Thus, the benefits far outweighed the risks for many asthmatics with uncontrolled asthma.
• Thus, the emphasis for asthma treatment was changed from focusing on controlling acute asthma symptoms to preventing asthma from occurring by treating the underlying inflammation and preventing bronchospasm.
• Inhaled steroids should be used daily to prevent asthma, and rescue inhalers should only be used when needed to treat acute asthma episodes. 
• Inhaled steroids are safe to use for mild asthma to prevent airway remodeling that may cause asthma to become moderate to severe. 

In 1992 A National Heart, Blood and Lung Institute-sponsored Childhood Asthma Management Program (CAMP) was created to study the impact of long-term inhaled steroid use in children.  The pediatric department at NJH conducted a landmark study of 1,041 children between the ages of 5 and 12 for 20 years.  The results confirmed the idea that daily inhaled corticosteroid use for asthma was effective and safe.

The inhaled steroid used in the study was Budesonide.  The results showed that Budesonide (inhaled corticosteroid use) for asthmatic children:

1. Reduced hospitalizations by 43%
2. Reduced Urgent Care visits by 45%
3. Reduced Prednisone use by 43%
4. Reduced use of Albuterol
5. Increased episode free days (10)

Loaded with this new wisdom, physicians started prescribing inhaled corticosteroids more often.  This helped many asthmatics better control their asthma, and use of rescue medicine declined.  Now asthma experts refer to uncontrolled asthma as using rescue medicine more than twice in a two week period.

Greg Minton, in his book "Breathing Space" explained that after the release of the asthma guidelines sales of inhaled steroids soared, and flunisolide, marketed as Aerobid, lead the charge.  Minton described that "in the first three months of 1991, prescriptions of Aerobid doubled those of the entire previous year. Aerobid was the fastest growing inhaled steroid on the market." (9)

In 1992 the National Heart Blood and Lung Institute sponsored Childhood Asthma Management program (CAMP) provided research

At one point my regional doctor decided Azmacort wasn't good enough for me and he prescribed Aerobid as a replacement.  I took two puffs of it -- just once -- and rejected it on the grounds the mist tasted like rotten mints.  Surely Aerobid required fewer puffs, but I decided I'd rather puff away at the better tasting Azmacort.

By the late 1980s Pulmicort became the first dry powder inhaler on the market when the Pulmicort Turbohaler was introduced.  I never used this inhaler on myself, although I have instructed it to patients from time to time.  Considering the horibble taste, I can't fathom that Aerobid sold so well. 

The market for inhaled corticosteroids proved to greatly benefit asthmatics not simply by controlling and preventing asthma, but by reducing unscheduled doctor visits, emergency room visits, hospital admissions, and the cost of treating the disease. 

Other pharmaceuticals rushed to enter this market, and this brought about the longer lasting and more potent inhaled corticosteroids we use today. Fluticasone was introduced as Flovent in the 1990s and Mometasone furoate in the 2000s. 

Interesting to note that each new inhaled steroid was a little more selective than the previous, and lasted a little longer. This is the main reason some of the older inhaled steroids have been phased out in favor of fluticasone, mometasone furoate, and other new ones on the market or in the oven. (11)

Advair entered the market in the late 1990s ad the first combination inhaler with a long acting beta adrenergic (rescue medicine) and an inhaled steroid.  It was a combination of fluticasone and salmeterol.  It quickly became the best selling asthma product because it controlled asthma and only required two puffs a day.

Symbicort and Dulera are similar products to enter the market.  Since the patent for Advair expired in 2010 generic versions are expected to hit the market soon, and hopefully lower the price.

So you can see we have come a long way since cortisone was discovered at the turn of the century, since prednisone was discovered in the 1950s, and beclomethasone hit the market in 1972.  While physicians were once hesitent to prescribe a daily dose of inhaled corticosteroids to control asthma, steroid inhalers have since become a top line therapy for preventing and controlling asthma. 

Click here for more asthma history.

References:

1. Brenner, Barry E, ed., "Emergency Medicine," 1998, from chapter one "Where have we been?  A history of acute asthma," page 18
2. Meriam-Webster dictionary, "Corticosteroid," http://www.merriam-webster.com/dictionary/corticosteroid
3. "Schering-Plough: Information," Answers.com, http://www.answers.com/topic/schering-plough-corp
4. Brenner, op cit, page 18
5. Schleimer, Robert P., et el, "Inhaled Steroids in Asthma," vol. 163, 2005, New York, page 5
6. "Schering-Plough: Information," op cit
7. Primary Care Respiratory Journal,"A brief history of inhaled asthma therapy over the last fifty years," Volume 15, Issue 6, December 2006, Pages 326-331
8. Dr. H. Morrow Brown at Allergiesexplained.com,  http://allergiesexplained.com/
9. "Mitmann, Gregg, "Breathing Space:  How allergies shape our lives and landscape, 2007,  page 247 (a great read if you want to learn more about the history of asthma/ allergies
10. Werner, Alison, "Taking a Long-Term Look at Childhood Asthma Treatment," RT: For Decision Makers in Respiratory Care," January, 2012, www.rtmagazine.com, page 18-21
11. Schleimer, op cit, page 45

1957: The invention of the rescue inhaler x

When Americans unite and put their minds and imaginations together in a quest to obtain a united goal, anything can be accomplished.  This was what occurred during WWII.  While war is bad, it can bring about many good things.  In this way, the metered dose inhaler -- the rescue inhaler you have in your pocket right now -- is a byproduct of war.

A 1957 ad for the Riker inhaler (a)

Allied troops fighting in the fields of Europe were often infested with bugs that caused Malaria.  This was impeding the war effort.

To remedy this problem the U.S. Government hired researchers to come up with a bug repellent that would help allied soldiers attack bugs.

Lyle Goodhue and William Sullivans must have first looked to the past to find a solution.  They would have learned that in 1790 pressurized aerosols were introduced in France to create carbonated beverages.

They would have learned that in 1837 the first spray can was made of heavy steal in Perpigna.  The can had a valve in it that allowed it to create the spray.  Several prototypes were tested in 1862, although nothing ever came of it. (1)

They would have learned that in 1927 a Norwegian man named Erik Rotheim patented the first spray can that was capable of holding pressurized contents and spraying them.  It's now considered the forerunner of modern spray cans.

Goodhue and Sullivans then took these old ideas and combined them with ideas of their own and came up with a design capable of carrying a pressurized propellant called flurocarbon.  The bug spray was added to the propellent and the spray can allowed for the bugs to be sprayed and killed.

So while the first spray cans were used to hold bug sprays during the war, the concept soon evolved to other products, such as paint and perfume.  It was the perfume market that Riker Laboratories (a subsidiary of what is now 3M Pharmaceuticals) was thinking of when it started tinkering with this product.  They wanted to create a spray perfume. (2)

Yet Riker researchers soon realized there was a demand by asthmatics for a convenient to use and portable spray can for asthma medicine.  This was how the first inhaler came to fruition.  In 1956 Riker inventors created the asthma inhaler market with a Medihaler-Epi that contained epinepherine and medihaler Iso that contained Isophrenaline.

The Riker inhaler was a major breakthrough.  This product was incorporated with the first ever actuator with a one-way valve that allowed for the medicine and propellant to be sprayed in a uniform dose (a metered dose), and soon became known as the metered dose inhaler (MDI).  The Medi-Iso delivered a metered dose of 0.15 mg and the Medi-Epi delivered a dose of 0.06 mg.  The inhalers were  easy to use, provided fast relief, and were easy to lug around. (2)

The design of this original inhaler was very similar to many of the inhalers we lug around today, such as the Ventolin inhaler.  It could easily fit into a boy's front pocket or a mom's purse, and using it was as as easy as squeezing the actuator.

Electric nebulizers in the 1950s were large, bulky and made of glass.  They were also expensive, so many asthmatics had less expensive nebulizers that required them to squeeze a bulb to aerosolize the medicine.  Many asthmatics continued to smoke asthma cigarettes, insents, or other palliative asthma remedies.

So getting asthma relief was inconvenient when the medihaler was introduuced, and the relief given wasn't very good. So this was the market advertisers for Riker Laboratories aimed for when they started their first advertising campaign.

1956 ad for the Medihaler (b)

An old advertisement for the Medihaler (see image) used the inconvenience of these other devices as a marketing ploy:

Medihaler with your favorite bronchodilator:

• No rubber bulbs to deteriorate
• No breakage of costly glass nebulizers
• No spilling of solution in pocket or purse

The Medihaler became an instant hit.  It, coupled with the discovery of theophylline, caused the market for asthma medicines to boom.

Gregg Mitman, in his book "Breathing Space: How allergies shape our lives and landscapes," explained that between 1972 and 1985 prescription drugs in the United States showed a modest 7 percent increase in the number of prescriptions filled.

During the same period, prescriptions for asthma drugs increased 200 percent."  The market for asthma inhalers was so bullish that other pharmaceutical companies raced to make their asthma remedies available as an inhaler.  (3)

Mitman further explained that the sale of asthma inhalers alone (both beta adrenergics and others), accounted for "25 percent of all prescriptions dispensed for the treatment of asthma in 1985."

So it didn't take long at all for pharmaceuticals, doctors and asthmatics to catch on to the convenience of the rescue inhaler.  Life for asthmatics changed forever, and for the better.


Click here for more asthma history.

References:

1.  About.com, "History of spray cans,"  http://inventors.about.com/od/astartinventions/a/aerosol.htm (provides a good history of the spray can)
2. Brenner, Barry E, ed., "Emergency Medicine," 1998, from chapter one "Where have we been?  A history of acute asthma," page 23
3.  Mitmann, Gregg, "Breathing Space:  How allergies shape our lives and landscape, 2007,  page 237 (a great read if you want to learn more about the history of asthma/ allergies)

Pictures:

1. (a)  Deco Dog, http://www.decodog.com/inven/medical2.html, you can purchase or check out old asthma inhaler ads here 
2. (b)  Deco Dog, ibid

1933-1957: Research leads to asthma rescue medicine

So hormonal therapy was first used therapeutically in the late 19th century, and by 1901 epinephrine was isolated.  This set off a series of experiments to synthesize and learn about the actions of epinephrine on the body.

It was soon learned that the hormone adrenaline was a neurotransmitter.  It was released by the adrenal gland in response to stress, and attached to receptors that lined smooth muscles and vessels throughout the body.  This results in vasoconstriction that resulted in increased rate and force of the heart, increased cardiac output and blood pressure.  It also caused smooth muscle dilation, including dilation of bronchioles to make breathing easier.

This theory was basically rejected by the medical and scientific community and considered a speculative theory.  Yet in the year 1933 the theory was proven and validated, and slowly but surely these theories were accepted, and interest peaked so much that the two of the researchers responsible for this theory were given the noble prize.

This knowledge was extremely important for asthmatics, because the more scientists, pharmacists and physicians knew about how these medicines worked, the better medicine they could create. Once the theory was accepted, scientific progress continued.

1936: Iseotharene was synthesized as the first successful modification of epinephrine. (1)

1940s: Iseotharine was marketed as Aleudrin in Germany

1946:  Swedish physiologist and pharmacologist Ulf von Euler (1905-1983) discovered that norepinephrine (noradrenaline) not adrenaline (epinephrine), was the sympathetic transmitte responsible for sympathetic messages to be sent from the nerve ending to the effector site (smooth muscle, heart or vessel).  This is yet another method by which the sympathetic nervous system works. The idea that neurotransmitters worked in this was was postulated in 1905, only to be proved by von Euler.  He won the Noble prize with fellow scientists working with chemical transmitters Julius Axelrod and Bernard Katz.  (2,4,5)

1948:  Working with the research of van euler, Raymond Ahlquis (1914-1983) discovered that there are various types of receptor cells used by the sympathetic nervous system.   Beta 2 adrenergic receptors (B2) were discovered to line smooth muscles that wrap around air passages in the lungs.  When these receptors were stimulated these smooth muscles relaxed, and this dilated the air passages to make breathing easeir  Since this discovery, rescue medicine is sometimes referred to as beta-2 agonists, beta adrenergic agonist, or simply beta agonists. (2)

Alquist also discovered the following: (2)

• Alpha Affect:  noradrenaline is stronger than adrenaline is stronger than isoprenaline
• Beta Affect:  isoprenaline is stornger than adrenaline is stronger than noradrenaline (3)(4)

The idea here is that the "flight or fight" response initiates the adrenal gland to release epinephrine, which attaches to B2 adrenergic receptors and causes the bronchioles to dilate.  Beta adrenergic medicine (such as epinephrine) can mimic this response.  So such medicine that mimic the sympathetic system in this way are called sympathomimetic agents.  . 

The terms Beta 1 Adrenergic (B1) and alpha-1 adrenergics (A1) are also described by Raymond Ahlquis.  A1 and B1 receptors line smooth muscles in the heart and that wrap around vessels, and when stimulated the heart rate increases in rate and force.  Epinephrine was found to be attracted to B1, B2 and A1 receptors.  So this explained why the instant breathing relief came with cardiac side effects.  The quest was now on to create a drug that had a strong B2 effect without the B1 and A1 effect.

Isopretoronol was learned by Raymond Ahlquist to have a stronger B2 effect than epinephrine, yet it also had a strong B1 effect that caused the heart to speed up "even when administered via inhalation."  So Isopretoronol still had to be used with discretion. (2)

1951: Iseotharine was approved by the FDA and marketed as Bronkosol.   It became yet another option via the nebulizer route, although, like epinepherine, it only lasted one and a half to two hours. It was the first B2 specific rescue medicine to hit the market.   It had a stronger beta effect and less of an alpha effect.  It was marketed as the first B2 specific inhaled aerosolized bronchodilator.  Bronkosol had less of a B2 effect than Isopretoronol, yet it was more desirable because of the decreased cardiac affect.  The medicine still only lasted one and a half to two hours.  (2)

1954:   It should be noted here that Alquists experiments were initially rejected by many of his peers.  It wasn't until 1954, when he was invited by Victor Drill to write a chapter in Pharmacoloy in Medicine, that his ideas were accepted.  So, thankfully, "Ahlquist took advantage of the opportunity to promote his theory, which ultimately enabled it to gain general acceptance. The concept not only prompted fresh thinking about adrenergic receptor pharmacology, it also vaulted scientific research into new directions that would guide future drug development." (4)

1957:  The first metered dose inhaler hits the market.  Riker Pharmaceuticals introduced the Medihaler-Epi and the Medihaler-Iso which had epinephrine and isoprotoronol respectively.  For the first time ever asthmatics had a handy little inhaler to carry with them wherever they went.  The medicine provided instant relief from an asthma attack without the hassle of hunting down a doctor, or dealing with fragile and complicated nebulizers, solutions and hand held squeeze bulbs.  I wrote about this in more detail here.

Further reading:

• 1893-1933: How does adrenaline work? (7/22/14)
• 1900-present: The evolution of rescue medicine
• How does respiratory medicine work (what we know now)?

Click here for more asthma history.

References:

1. Brenner, Barry E, ed., "Emergency Medicine," 1998, from chapter one "Where have we been?  A history of acute asthma," page 23
2. Rau, Joseph L., "Inhaled Adrenergic Bronchodilators: Historical Development and Clinical Application," at AARC.org (American Association of Respiratory Care, July, 2000, Vol. 45, number 7),
3. Pang, Humphrey P., Maureen M. Dale, James M. Ritter, Rod J. Flower, Graeme Henderson, "Rand and Dale's Pharmacology," 2012, Esevier Churchill Livingstone
4. Rubin, Ronald P., "A Brief History of Great Discoveries in Pharmacology: In Celebration of teh Centennial Anniversary of the Founding of the American Socieity of Pharmacology and Experimental Therapeutics," Pharmacological Reviews, December, 2007, vol. 59, no. 4, pages 289-359 (This article provides a good history of the discoveries of the sympathetic nervous system, the neuromuscular synapse, and how hormones such as adrenaline work)
5. "Ulf on euler Biography (1905-1983)," faqs.org, http://www.faqs.org/health/bios/15/Ulf-von-Euler.html, acessed 3/9/13

1858-1929: History of nebulizers x

While we asthmatics should consider epinephrine the greatest discovery in the history of medicine, the greatest invention may be that of the nebulizer and inhaler.

Ancient doctors as far back as 10,000 B.C had access to various herbal remedies for asthma-like symptoms, and as early as 5,000 B.C. they learned the best mode of delivery was inhalation.  Yet the only methods they knew of were steam and smoke.

The Ancient Egyptians inhaled smoke from dried and crushed belladona burned on bricks.  Ancient Indians burned cigarettes with dried and crushed strammonium.  Insents were ultimately used as well.

As we travel forward to the mid 19th century not much has changed.  Enter any random home and you'll quickly be able to tell if an asthmatic lives there by the bittersweet smell of smoke wafting through the doorway  

Surely there were a few devices called nebulizers and inhalers at this time, yet they were large, bulky, fragile, hard to operate and very expensive.  Operating them was often difficult and time consuming, and the medicine available wasn't much good anyway.

Sales-Giron and his portable nebuliser (1858)*

The first nebulizer was actually produced in 1858 by a French inventor named Dr. Sales-Girons.   His nebulizer was unique in that it had a pedal that acted like a bicycle pump, and when pulled up air was forced through an atomizer and a mist was created to be inhaled.  (1)

(A picture and good description of this first nebulizer can be seen here at Inhalatorium.)

One thing to note as we delve into the past here is that nebulizers of old came by varying names.  Some were called atomizers, some nebulizers, and some inhalers.

The idea is that an atomizer refers to any device that converts a liquid to a fine spray.  Likewise, nebulizers and inhalers create an aerosolized mist to be inhaled.

So sometimes atomizers were referred to as atomizers, sometimes nebulizers, and sometimes inhalers.  Which name was used was left to the discretion of the inventor or marketer of the device.  And while some were called inhalers, they were nothing like the inhalers we use today.

Dr. Siegel inhaler (1872)

In 1864 Dr. Siegel invented Siegle’s steam spray inhaler that used the force of steam through a small tube to draw up the medicine and turn it into a vapour that is inhaled through a glass mouthpiece.  The principle used here is similar to modern nebulizers, only now we use air instead of steam. (2)


Siegel's invention is often considered the beginning of nebulizer therapy.

There were various attempts at copying Siegel's nebulizer, yet neither Siegel's nor any of the others were effective enough to become popular among asthmatics.  Again, the medicine available back then provided only minimal relief, and this fact probably made efforts to use these devices fruitless, and perhaps too expensive to make them worthwhile investments.

So the evolution of such devices was left at a standstill until the discovery of epinephrine in 1900. Now, for the first time ever, there was a medicine available that could end an asthma attack.   The only problem now was the asthmatic in need had to seek out a doctor and have the medicine injected into a vein.


Silbe hand-held rubber bulb nebulizer (1940)*

Doctors also quickly learned that the systemic delivery in this way of epinephrine into your body caused significant side effects, such as full and bounding heart rate, increased blood pressure, and hyperactivity.  The medicine also took several minutes to take effect.  Entrepreneurs sensed an opening to a new market, and searched for a device to help asthmatics better deliver this medicine.

By 1910 epinephrine was available as a solution to be nebulized, yet nebulizers continued to be too expensive and too difficult to operate to be of much use.  However, for those willing asthmatics, there were a few nebulizers available such as the:

•  Silbe Atomizer:  A hand held nebulizer with a bulb syringe that had to be squeezed
•  Colossol Nebulizer:   A glass nebulizer with a rubber squeeze ball



Glass Collosol Nebulator with rubber bulb*

•  Volatilizer Inhaler:  Dr. Coulter's vaporizer and inhaler was called the champion Volatizer.  It was steam powered and made of copper, brass and nickel plate. (2)

In 1929 various bulb syringe nebulizers (like this one) were available.  The asthmatic would draw up some of the epinephrine from a small vial and mix it with some water in the nebulizer cup and then squeeze the bulb to create a fine mist that could be inhaled.

As you can guess, this took a lot of time, coordination, and even muscle strength to get an adequate amount of medicine aerosolized to do any good.  I had a bulb to connect to my nebulizer cup back in 1985 to use in case of a power outage, and I tried it once just for kicks.  It took forever just to get minimal results


1892 ad for Dr. Couilter's vaporizer & inhaler*

However, I suppose if that's all you had available, you'd squeeze that bulb as long as you had to.  Yet we asthmatics yearned for something better, simpler, cheaper and easier to use.  Aware of the possibility of a new market, many investors and inventors worked overtime searching for the ideal device.

By the 1930s asthmatics finally got what they yearned for when the first electric nebulizers hit the market.  These nebulizers were a reasonable size, generally inexpensive and easy to operate.  Asthmatics could now have access to epinephrine in the comfort of their own home right away when they needed it.

Aerosolized epinephrine worked faster, almost immediately giving the asthmatic relief from an asthma attack.  Since it was inhaled instead of injected into a vein, side effects were significantly diminished.  In this way, the invention of the electric, mass producible nebulizer was a godsend to asthmatics.

Adrenalin Inhaler used to nebulize epinephrine (1930s)*

Nebulizers have continued to evolve since then, yet the general concept has not changed.

Click here for more asthma history.

References:

1. Rau, Joseph L., "Inhaled Adrenergic Bronchodilators: Historical Development and Clinical Application," at AARC.org (American Association of Respiratory Care, July, 2000, Vol. 45, number 7),
2. Inhalatorium.com provides pictures and descriptions of antique nebulizers and inhalers
3. * Pictures used with permission from Inhalatorium.com.  Check out the site for more antique nebulizers and inhalers.

1200-1600: Asthma in ancient Korea

If you were an asthmatic living in Ancient Korea you would have had to wait until the 13th century before you had any options available to you other than folk medicine.  

Folk medicine was basic philosophies and treatments of various disease processes handed down from generation to generation to anyone interested in learning them.  Remedies usually consisted of simple things such as concocting herbal remedies, applying ointments, drinking teas, or soothing massages.  (1)

It was around the 12th and 13th centuries when medical philosophies of Traditional Chinese Medicine started to influence Korean physicians, which were recorded in various Chinese texts.  Yet the first medical texts in Korea simply consisted of compilations of folk medicine, which up to this time was passed on only by word of mouth

It was in 1236 that all the folk medicine of the day was compiled into one treaties called "Hyang-yak kugup  pang" or "Emergency Remedies of Folk Medicine."  It's the oldest medical texts written by a Korean. (2)

At about the same time several other such treaties were compiled, including "Samhwaja hyangyak pang," or "Folk Remedies of Samhwaja."This was mainly a diagnostic guide.  (3)

All the medical wisdom from these books were compiled in 1433 into "Hyangyak chipsong pang," or "Compilations of Native Korean Prescriptions."  (4) Two centuries later, in 1610,  Korean philosopher Ho Chun compiled all the medical wisdom up to his time in "Tongui pogam," or "Exemplar of Korean Medicine."  (5)

Mark Jackson, in his book "On Asthma:  The Biography," explains that Korean physicians believed asthma-like symptoms or coughing were caused by excessive eating, fear and shock.  While folk medicine was the original treatment for any ailment, various remedies from Chinese medical texts worked their way into Korean medicine. (6)

While Traditional Chinese Medicine influenced Korean medicine, Korean texts were likewise respected in China.  It wasn't until the 18th century that Eastern and Western civilizations shared medical wisdom.  

Click here for more asthma history.

References:

1. WebMD,  http://dictionary.webmd.com/terms/folk-medicine
2. Lee, Ki-baik, "A New History of Korea," 1984, Korea, page 171
3. Lee, ibid, page 171
4. Lee, ibid, page 171
5. Jackson, Mark, "Asthma: The Biography," 2006, New York, page 43
6. Jackson, ibid, page page 43

500 A.D. Asthma in Ancient Japan

Fuiwara no teika ( (1162-1241)

If you lived with asthma in ancient Korea and Japan your asthma may have been recognized, yet treatment would have been mainly supportive.  It wasn't until the 6th century A.D. that Chinese medical ideals -- mainly in the form of the Nei Ching -- spread to these nations.

Chinese medicine was referred to as canpo in Japan, and asthma-like symptoms were referred to as zensoku as early as 700 A.D.  (1)

The most famous asthmatic in Ancient Japan was Fujiwara no Teika who is considered one of the most famous poets in Japanese history.  Legend has it that his poems became well read due to his cordial relationship with the Emporor Go-Toba (1180-1239).

Japanese children learned early that there were 404 different kinds of illnesses, and they learned of the various herbal formulas used as remedies, most of them indigenous to the region.  One interesting remedy for asthma was by eating a potion containing earthworms dried under the sun, cooled and then boiled.

Most asthma remedies were similar to what was recommended by Traditional Chinese Medicine.  So prior to the 6th century Japanese asthmatics would have been recognized although there wasn't much anyone could do other than offer support.

Yet if you were afflicted with breathing difficulties in the 6th century you would have had available to you many of the same treatments available to Chinese asthmatics, including Ma Huang, a very efficient bronchodilator.

Click here for more asthma history.

References:

1. Jackson, Mark, "Asthma: A biography," 2006, New York, page...