1940-2012: The dry powdered inhaler (DPI) rewriting

For almost 8,000 years asthmatics inhaled medicine by smoking it.  This changed in the 1930s with the invention of the electric nebulizer and again in the 1950s with the invention of the metered dose inhaler (MDI).  A third option that has been slowly gaining momentum is the Dry Powder Inhaler (DPI). 

A DPI allows you to inhale the powdered version of a medicine, which comes in the form of a capsule or blister that is cracked open inside the inhaler.  There is no propellant, and instead the medicine is breath actuated.  This means the medicine enters your airway as you inhale.  

There are advantages to DPIs:

1. Since they are breath actuated no propellant is needed
2. Coordination is generally easy
3. They are easier to use than MDIs
4. Dose is easily measured

Of course there are also disadvantages:    

1. The patient must be able to generate enough flow
2. Each company markets its own device, which means there may be many to learn
3. You will have to place the capsule into the device prior to inhaling the medicine
4. The devicess tend to be expensive to manufacture and expensive to purchase

To learn about the history of DPIs we actually have to travel back to before the first MDIs hit the market in the 1950s.  In fact, according to Mark Sanders in his 2007 article, "Inhalation Therapy: an historic review," the first patent for a DPI was made in 1964 by Newton.  The medicine he used was potassium chlorate, a medicine Sanders notes was ultimately determined to be a lung irritant.

However, while Newton's device wasn't a commercial success, "He observed that the powder needed to be finely pulverized and that it had to be kept dry -- principles that still apply to dry powder inhalers today."  (1)

According to A.R. Clark in his 1995 article, "Medical Aerosol Inhalers: Past, Present, and Future, Aerosol Science and Technology , the first DPI was patented in 1939.  I would imagine he's referring to DPIs that resemble what we use today, as opposed to the Newton's device.  

Clark explained that the 1939 inhaler  was not used as an asthma inhaler, though, but to inhale "aluminum dust  for the chelation of inhaled silica.  It was intended for use by miners who suffered from silicosis induced by inhaling dust."  Yet the product never gained popularity and was never marketed.  (2)

By the 1940s pharmaceutical companies learned that systemic injection of asthma medicines like epinephrine and atropine caused significant side effects.  They were in an all out race to develop a device that allowed asthmatics to inhale medicine and, thus, generate an immediate effect with fewer side effects. 

In 1949 the Aerohaler was introduced as the first marketable DPI, and also the first rescue inhaler.    The medicine was Isoprenaline sulphate.  Yet it never gained popularity and was later overshadowed when the first MDIs hit the market in 1957 in the form of the Medihaler Epi and the Medihaler Iso.

For all practical purposes, it was ultimately realized DPIs don't work well with rescue medicine because when the medicine is needed many asthmatics have trouble generating enough flow to suck up the medicine.  While Ventolin is available overseas as a DPI, none are currently approved by the FDA for sale in the U.S.

When the CFC propellant (see lexicon) used in MDIs was determined to harm the environment in the 1990s, DPIs were determined to be a solid delivery device for asthma controller medications, and this is the main reason they have become a common site in asthmatic homes.

Aerolator with glass vial containing 3 small epi/ penicillin vials

So, without further adieu, here are your DPIs:

Aerohaler:  Released by Abbot laboratories in 1949 as the first marketed dry powdered inhaler (DPI).  The medicine was Norisodrine, isoprenaline sulphate.  It was the first rescue inhaler. It didn't really get much of a chance to gain the love of asthmatics mainly due to the invention of the metered dose inhaler (MDI) in 1957. Just imagine, if the MDI wasn't invented, asthmatics everywhere would probably have an aerohaler.

A.R. Clark, in a 1995 article for Aerosol Science and Technology, described this inhaler this way:

"The device consisted of 'sifter' cartridges containing the powdered dose out of the cartridge and a mouthpiece through which the aerosol was inhaled.  There was very little control over the delivered dose, other than patient symptoms titration, and there was no dispersion mechanism inside the device to aid aerosol generation." (2, page 382)

Each glass vile contained three smaller vials (sifter cartridges) that were set on the inhaler device.  The patient then inhaled the powder through the nose.  There were some disadvantages to this device, the most significant was the release of the MDI in 1957.

The Aerohaler was also used in the late 1940s and 50s as a means to deliver penicillin.  A modern version of the Aerohaler was remarketed and available in some countries, yet it has little in common with the original.

1971: Spinhaler:

The Intal Spinhaler was introduced by Fison in 1971. It was a neat little contraption. Once a physician prescribed the medicine, the patient received a box of Intal Spincaps and an Intal Spinhaler. The spoinhaler was taken apart and the spincap placed on a holder. The spinhaler was put back together. The blue part (see figure) was clicked forward to crush the capsule and release the powder. The patient then put his mouth over the white mouthpiece to inhale the medicine. If the patient was lucky he did not cough.

Warnings on the packaging warned that the produce may incite a cough and bronchospasm. This occurred as the powder impacted the back of the throat, triggering the cough reflex. This may result in bronchospasm and asthma attack. Warnings also noted that the product must be used daily as an asthma controller medicine, and not as a rescue medicine.

Another problem with the medicine is that the patient had to handle each dose. Proper technique also had to be used in order to assure an adequate dose and to prevent the medicine from triggering a cough. A CFC inhaler was available for Intal, and it was approved by the FDA in 1992.  This provided a more convenient and safer delivery device. It also probably improved compliance.

Chromolyn was very popular during the 1980s and 1990s. The spinhaler was ultimately phased out due to the inhaler. The inhaler was phased out due to the Montreal Protocol. A non-CFC chromolyon was never made. One theory for this was declining sales due to better asthma controller medicines that were on the market by the 2000s. It was set to be phased out by December 31, 2010.

It was also available as a solution to be inhaled by nebulizer. It initially came in a glass vial that had to be snapped open, and was probably mainly used in hospitals. Eventually a plastic vial was available. I do not know if the solution was available for home use, although I would imagine so.

By the time I became a respiratory therapist in 1995 I had not used the medicine in over 10 years. I quit on my own because I didn't feel it did any good. In the hospital setting it was mainly just prescribed for children. A reason for this might have been reluctance to prescribing inhaled steroids for kids.



Intal Spinhaler and Intal Gelcap

Spinhaler:  Fisons introduced this device in 1971 as the mechanism to deliver disodium cromoglycate (sodium cromolyn or simply cromolyn).  It was approved by the FDA in .  The product was marketed as the Intal Spinhaler to be used with the Intal Spincaps, and remedied many of the problems of the Aerohaler.  It was the first commercially successful DPI.  The caps were made of a hard gelatin and guaranteed the same dose with each inhaletion (a metered dose).  They had to be removed from the foil package and placed in the spinhaler by the patient.  The patient then cocks the outer shell of the inhaler and needles inside the device pierce the capsule.  The patient then places his mouth on the mouthpiece and inhales.  The flow generated causes a fan inside the device to rotate, and as this occurs the powder is inhaled.  The Intal Spinhaler was very popular as an asthma controller medicine during the 1980s and 90.  It was ultimately phased out because the powder caused some patients to cough and this caused some asthma attacks.  It was replaced by the Intal inhaler in the late 1990s.  I wrote more about the Spinhaler here.

Ventolin Rotahaler and Rotacaps

3.  Rotahaler:  In the early 1960s Allen and hanbury introduced the Ventolin Rotacap to go along with the Ventolin Rotahaler.  The product was marketed throughout the 1980s and 1990s but was ultimately discontinued because some asthmatics who needed the rescue medicine had trouble generating enough flow to suck in the medicine.  Another problem was that each individual unit dose Rotacap had to be handled by the patient and carefully inserted into the device.  The Ventolin Rotahaler was a failed experiment, and since it was discontinued only asthma controller medicines have been available as DPIs.  The Rotahaler was later refined so it contained a month supply of capsules and re-marketed as the Becotide Rotohaler and the Spiriva Handihaler in 2009.

4.  Turbuhaler:  Astra Zeneca introduced this product as one of the first multi dose DPIs in the early 1990s. The Pulmicort Turbuhaler was approved by the FDA in 1997, and the Symbicort Turbohaler in 2000, according to FDA.gov.  Various other products have been marketed in other countries such as the Bricanyl Turbuhaler (terbutaline) and Formoterol Oxis Turbuhaler.  The Pulmicort DPI has since been discontinued.

Diskhaler

5.  Diskhaler:  GlaxoSmithKline intruduced the disk in the early 1990s and asked for FDA approval in 1992. The original discus contained 4-8 blisters per cartridge, which made it so the patient didn't have to worry about handling each dose.  The device has since been refined so each discus contains 60 capsules, or two capsules for each day, or one month supply.  The recommended dose is one puff twice daily.  Each disc is equivalent to two puffs of the MDI version of the medicine.  A blister of capsules are stored in a roll, or disc inside the device.  All the patient has to do to prepare a dose is to open the device and pull down a lever.  This moves a new capsule into the delivery chamber and decreases the counter by one so the patient knows how many doses are left. The Serevent Discus was FDA approved in 1997 and the Advair Discus in 2000 according to fda.gov.  The Flovent Discus was approved in 2000 but was never marketed. The Serevent Discus may also be referred to as Seritide, Viani, ForAir, and Foxair in some countries.  Advair is a combination of Serevent and Flovent.  The Advair Discus is currently the most popular asthma controller medicine on the market.  The discus is referred to as the autohaler or diskus in some countries.  Other products available but not approved by the FDA are the Becodisk which contains beclomethasone, and the Ventolin Autohaler

6.  Inhalator:  The device is marketed by Novaris.  I've found various articles that mention studies comparing salmeterol (Serevent) inhaler with the formoterol inhalator (Barotec) from as far back as 1985, although I'm not certain it was actually approved for use in any country at this time.  The inhaler was improved upon by 2001 and renamed the Centihaler.  It was this product that was finally approved by the FDA in 2001 as the Foradil Centihaler.  In 2006 the FDA approved the Foradil Aerolizer which will be under patent until 2019.  (3)  The recommended dose is two puffs of the inhaler twice daily or one puff on the DPI.  As a note here, the FDA seems to have the strictest policy for drug approval.  As a rule of thumb, if the FDA approves a medicine chances are it's been run through the gambit and is proven relatively safe, or at least the benefits far outweigh the disadvantages.  I believe this product was slow to be approved by the FDA due to it being linked to asthma related deaths.  However, many believe it wasn't the medicine so much as poor education that resulted in the deaths, yet it was never proven either way.  A similar problem plagues salmeterol.  The problems was addressed in 2003 with a black box warning on the packaging. 

7.  Cyclohaler:   This is another DPI introduced to the market in the early 1990s.  The medicine is stored in hard gelcaps that are inserted into the cyclohaler with each use.  The mouthpiece is long to optimize drug distribution even if the patient isn't able to generate enough flow. Several puffs were often necessary to get an optimal dose.  The initial product was marketed as the Aerolizer Cyclohaler, and the products available were albuterol and ipatropium bromide.  Since the product wasn't marketed in the U.S. the medicine was referred by it's non-U.S. name, such as the Salbutamol Cyclohaler and Salbutamol Cyclocaps.  The product has since been refined and marketed with other medicines such as  salbutamol (Sultanol), beclomethasone (Becotide), Formoterol (Foradil) and  budesonide (Miflonide).  The latest version is marketed as the cyclohaler 400.

8.  Other:  By 2008 there would be over 20 different DPIs on the market (4), and by 2012 that number would rise to 35.  While many are available for use in Europe, only a select few have been approved by the FDA.  DPIs currently on the market (as of 2012) are (you can view pictures of the various devices here):

• Acu-Breathe (Respirics)
• Aerolizer (Novartis)
• AIR (Civitas/Alkermes)
• Airmax (Teva)
• Aspirair (Vectura)
• Axahaler (S.M.B.)
• Breezhaler (Novartis)
• Clickhaler (Vectura)
• Conix Dry (3M)
• Cricket (Mannkind)
• Cyclohaler (Teva)
• Diskhaler (GlaxoSmithKline)
• Diskus (GlaxoSmithKline)
• Dreamboat (Mannkind)
• Easyhaler (Orion)
• EZ Aer (Aerovance)
• Flexhaler (AstraZeneca) -- Pulmicort
• Genuair (Almirall)
• Gemini (GSK)
• Handihaler (Boehringer Ingelheim)
• MicroDose (MicroDose Therapeutx)
• Next DPI (Chiesi)
• Novolizer (Meda)
• Oximax (Mantecorp)
• Podhaler (Novartis)
• Pulmojet (sanofi-aventis)
• Pulvinal (Chiesi)
• Skyehaler (SKyepharma)
• Solis (Sandoz/Novartis)
• Taifun (Akela)
• Taper Dry (3M)
• Trivair (Trimel Bipharma)
• Twincaps/Flowcaps (Hovione)
• Twisthaler (Schering /Merck)
• Turbuhaler (AstraZeneca) (5)
• Dura Spiros (3M) -- battery powered (introduced in 1990s)

Click here for more asthma history.

References:

1. Sanders, Mark, "Inhalation therapy:  an historic review," Primary Care Respiratory Journal, 2007, 16 (2), pages 71-81
2. Clark, A.R., "Medical Aerosol Inhalers: Past, Present, and Future, Aerosol Science and Technology, 1995, 22:4, 374-91
3. Foradil Aerolizer Briefing Document, Available to the public without redaction, pulmonary drug advisory committee on the safety of long acting beta agonist bronchodilators, fda.gov, http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4148B1_02_01-Novartis-Foradil.pdf, page 9
4. Patterson, Roy, "Patterson's Allergic Diseases," 7th ed., page 610
5. "Dry Powder Inhalation: Technology, Devices, Markets and Opportunities," prnewswire.com, Jan. 19, 2012, New York, http://www.prnewswire.com/news-releases/dry-powder-inhalation-technology-devices-markets-and-opportunities-137656553.html 

x1968-2010: Mast Cell Stabilizers for asthma

Intal Spinhaler used by asthmatics in the 1970s, 80s and 90s

In the early 1980s my doctor introduced me to the Intal Spinhaler that crushed a capsule with a medicine called disodium cromoglycate or chromolyn.  It was a white powder that was proven to improve lung function by decreasing inflammation. 

It was also proven to improve exercise related asthma. 
Each month you'll pick up a small white and yellow box from your pharmacist that contained a bunch of small capsules called Spincaps wrapped in tinfoil.  You unwrapped one and set it aside. 

Now you grab the inhaler and hold it so the mouthpiece is facing down.  You unscrew the cap and place  it onto a cup on the propeller, screw the body back on the mouthpiece, and slide the outer sleeve (the blue part in the picture) down as far as it will go and then back up again.  This pierces the capsule and makes the spinhaler ready for use. (1)

You exhale as much air as you can, place your mouth over the mouthpiece, and inhale.  As you inhale the powder will enter your airway, with a good portion going to your air passages.  You can feel the powder as it enters, and taste it.  This is how you know you did it right. 

This was the first dry powder inhaler that hit the market.  It was a great medicine, and when used with an inhaled corticosteroid it worked great to prevent asthma.

When I was a kid I had what my doctors referred to as high risk asthma. I was allergic to pretty much everything outdoors, and had exercise induced asthma (EIA).  Unless I was in an allergy proof bubble my asthma was usually acting up.  By the time I entered the 9th grade in September of 1984 I pretty much stopped going to gym class per my doctor's instructions.

By January of 1985 I had made so many trips to the ER I was admitted to NJH/NAC in Denver.  Once they managed to get my asthma under control they did some pulmonary function testing (PFT) on me to see what medicine might help me with my EIA. 

In one test I took no medicine and ran on the treadmill.  My lung function dropped significantly.  A week later I did another PFT, this time taking two puffs of Alupent before I ran on the treadmill.  My lung function once again dropped significantly, indicating Alupent had no effect. 

A week later I used my Intal Spinhaler before exercise, and while my lung function declined it wasn't as steep of a decline, indicating that disodium cromoglycate prevented EIA. (You can see my PFT tests here).

Intal Inhaler

I was using this inhaler four times a day (which was a pain in the butt anyway), so there was no need for me to use it prior to every time I exercised.  Yet the medicine was proven to reduce inflammation in your air passages so your asthma triggers don't irritate you as much, and don't constrict your air passages as much.

In a way, it worked the same way inhaled steroids worked, yet apparently not as well.  Prior to being at NJH/NAC my doctors had me using my Intal every day all the time, and only using my inhaled steroids as needed.  Yet by the time I left NJH/NAC in July of 1985 I was using both medicines four times every day, along with a ton of other medicines as you can see here.  Yes, this was a lot of medicine.

Yet the Intal Spinhaler was a good medicine for asthmatics since it was introduced to the market in 1968.  The medicine disodium cromoglycate was isolated by Roger Altounyan who had bad asthma himself and decided to test a variety of substances that were already proven to benefit asthma. He was working at Bengers Research Laboratories.  (2)

Cromolyn Nebulizer Solution

Khella was used by local natives living in Eastern Mediterranean countries for quite a few years to treat asthma with some success.  They made various "concoctions" from the seeds of the plant Amni Vasnaga, from which the substance Khellin was extracted in 1879.  (3)

Various studies in the 1940s and 50s showed the medicine relaxed smooth muscles throughout the body, including the muscles surrounding air passages in the lungs.  Yet the bronchodilating effect was less than epinephrine.  The various studies showed the medicine accumulated in your system if used regularly, and was proven effective for both asthma and other lung diseases. (4)

In 1953 The American Journal of Physical Medicine published the results of a study that showed inhaling aerosols of  7mg of Khellin improved lung function.  Perhaps it was studies like this that inspired Altounyan to study this extract.  (5)

Amps of Cromolyn solution

By experiments in the lab Altounyan produced a safer version of khellin called disodium chromoglycate.  While his goal was to improve his own asthma, what he ended up with was a new product.  It was marketed by Fisons and sold as the Intal Spincaps and Intal Spinhaler.  It became yet another option for many asthmatics worldwide suffering from asthma and allergies. 

Along with being the first dry powder inhaler, it was also the first mast cell stabilizer.  It prevented inflammation by preventing mast cells from releasing the mediators of inflammation (like histamine) which ultimately cause the inflammatory response. 

A problem with the spinhaler was that it couldn't be used during an asthma attack, and the dry powder entered your airway at such a force it was known to cause a fit of coughing and, thus, cause some asthma attacks.  I never experienced this problem however.  It was a nice option for me until modern inhaled steroids made it unnecessary.

Tilade inhaler

Nedicromil Sodium was approved by the FDA in 1992 as an alternative to Intal, and was marketed as the Tilate inhaler. (6) It was equally effective in treating inflammation and reducing allergy and asthma symptoms.  I never used Tilade, and I have little clinical experience educating it to patients either.

By 1995 Chromolyn was available as a solution to be nebulized, and this was ultimately a good option for pediatricians to prescribe for kids with asthma.  I have no recollection of ever giving this via aerosol to an adult, and rarely gave it to kids either for that matter.  I believe we no longer carry it in our stock. 

The Intal Spinhaler was ultimately phased out in the U.S. and Europe in favor of an inhaler, and the inhaler was ultimately phased out on December 31, 2010.  I imagine by information I've read on the Internet it's still a viable and cheap option for some asthmatics in 3rd world nations.  Yet here in the U.S. it's an antique. 

Tilate was phased out on June 14, 2010.  Altounyan's product was a great option for many asthmatics for many years, and for that we owe him thanks.  Perhaps some form of this product will make a comeback someday and replace the need for inhaled corticosteroids. 

References: 

1. "Intal Spincaps Powder for Inhalation, Sodium cromoglycate, Consumer Medicine Information, " package insert for the Intal Spinhaler and Intal Spincaps, 2005
2. Jackson, Mark, "Asthma: A biography," 2009, New York, page 187
3.  Kennedy, M.C.S, J.P.P. Stock, "The Bronchodilator Action of Khellin," Thorax, 1952, 7, 43, pages 43-65
4. Kennedy, ibid, page 43
5. Braun, K, E. Eilender, "Khellin Aerosol in Bronchial Asthma," American Journal of Physical Medicine, Dec., 1953, Vol. 32, Issue 6,
6. "Tilade approved by FDA; Fisons Announces Co-Promotion Agreement with Rhone-Poulenc Rorer," Press Release, TheFreeLibrary.com, http://www.thefreelibrary.com/TILADE+APPROVED+BY+FDA%3B+FISONS+ANNOUNCES+CO-PROMOTION+AGREEMENT+WITH...-a013101159

1781-1826: Laennec: The inventor of the stethoscope

Figure 1 --Rene Laennec (1781-1826).  Along with
crediting an old kid's game with giving him the idea of
creating his first stethoscope, he was also skilled with
the flute.  His memory and his musical skill  helped him
come up with the ingenious plan of rolling up paper into
a hollow tube.  He then used this to listen to lung sounds.
He later modestly chimed that he was amazed the device
wasn't invented years ago.  Hippocrates was known for
performing auscultation by placing his ear upon his
patient's chest.  A simple stethoscope would have
greatly benefited the ancient physician. (4, page xxiii)

Before the 19th century the only way for a physician to auscultate (hear) heart and lung sounds was to place his ear upon his patent's chest.  This would change thanks to a brilliant invention by Doctor Rene Laennec.

This method of auscultation was first described by the Hippocratic writers as far back as 400 B.C.  Laennec quotes Hippocrates from De Morbis as writing:

You shall know by this that the chest contains water and not pus, if in applying the ear during a certain time on the side, you perceive a noise like that of boiling vinegar. (4, pages 28-29) 

This method, called mediate auscultation, was never further investigated by the successors of Hippocrates, and therefore never became standard practice. Plus some patients were gross, filthy, and disgusting, mainly because the concept of bathing daily was not a standard practice among the populace.  Or, as Laennec said it, the technique can be disgusting. (4, pages 29)

Plus, for a gentleman doing this to a lady , the experience might be a bit uncomfortable for both the patient and the doctor.  Obesity also posed a problem because fat tissue muffles sound.

When he was 38-years-old on a hot and humid day in 1816, Rene Theophile Hyacinthe Laennec was posed with all of these problems, yet the need to auscultate his patient's heart and lung sounds was essential.  He came up with an ingenious plan that helped him assess his patient, yet which also helped him improve the assessment skills for all physicians.

Who was Rene Laenec? 

Laennec was born on February 17, 1781, to to an a"advocate of the provincial courts, and held some appointments under government, in his native country (France)... Fortunately his son was heir of the more solid parts of his genius; without his wit, but without his volatility.  (1, page xix)

At an early age he was put under the care of his uncle, a clergy man in charge of the parish of Eliam, in the vicinity of Quimper.  However, after the French Revolution broke out his care was transferred to another uncle, Dr. Laennec of Nanates. (1, page xix)

 Dr. Laennec was a man of highest respectability both as to talent and conduct, and directed the studies of his nephew with the interest and affection of a parent. The young scholar did credit to his friends and teachers; having obtained considerable distinction from his fellows at the chief school of the department of the Lower Loire, wither he had been sent by his uncle. Having completed his preparatory studies at this seminary, his thoughts naturally turned towards physic as a profession. He willingly engaged himself as the pupil of his uncle, and entered upon the study of his future profession with the zeal inherent in his character, and with success indicative of his subsequent eminence. Besides the instructions derived from his uncle, who was at that time senior physician of the hospital, and afterwards Professor of Medicine and Materia Medica at Nantes, he attended the courses of anatomy given by the surgeons of the same establishment, and is said, even at this early age, to have shown a decided predilection for morbid anatomy and clinical observation.(1, page xix)

Shown here:  Matthew Baille (1761-1823)
While under the tutelage of Corvisant,
Laennec became good friends with
Matthew Baillie.  Ironically, both were
famous for their studies of diseases of
the lungs, and both were diagnosed with
consumption,and eventually died of this disease.  

In 1800 he attended the medical school of La Charite, which was where he came to tutelage of a well respected and well known physician by the name of Jean Nicolas Corvisant (1755-1821).  He also became good friends at this school with Matthew Baillie, who himself would go on to gain great fame as a physician.  (1, page x)

He had actually gained recognition earlier in his career, for while in school he wrote a history of medicine, and, in the year 1802 at the age of 21, published articles that were well received by his fellow physicians.  (1, page x)

He opened a clinic in and began seeing patients.  In 1816 he was appointed chief physician to the Necker Hospital.  It was here where he was presented with the opportunity whereby he came up with an ingenious plan that changed medical diagnosis forever.  (1, page xxiii)

What was Laennec's ingenious plan? 

So on a hot and humid day in 1816, a 36-year-old physician by the name of Rene Laennec came up with an ingenious plan.

According to Kendall F. Haven in his book "One hundred greatest inventions of all time," Laennec was a "well established doctor and diagnostician of chest and abdominal disorders when he was asked by a fellow physician to assess an obese young woman with breathing difficulties." (2, page 96)

Not that it matters, but for the record the patient's name was Marie-Melanie Basset, and she was only 40.

Haven said:

Laenec's normal technique was to have the woman partially disrobe so he could place his ear against a hanker chief over her chest.  He'd listen to lung sounds over five spots:  the underside of each arm, each side of upper back, and upper breast bone. 

Gabriel Andral (1797-1876)
He was a French pathologist at the
University of Paris.  He is best known
for his work on blood chemistry.
Andral wrote the comments in
the margins of the 1838 edition
of Laennec's book.

Yet he heard nothing, so he tried percussion, a method useful for diagnosing diseases of the chest that he learned from his teacher, Dr. Corvisant.  It was a method of tapping on the chest, and the resonance heard would indicate the different diseases of the chest. For instance, air trapped in lungs from asthma causes a hollow sound, and fluid in the lungs from pneumonia amplifies sound.

While Leannec suspected the lady had heart failure, he was unable to diagnose her by heart and lung sounds. So, he came up with an ingenious plan.

Thinking off the cuff, Haven said he "grabbed 24 sheets of paper, rolled them tightly into a bundle, and secured them in shape with paste glue," wrote Haven. "He applied one end of this paste roll against the young woman's chest, and the other to his ear." (2, page 97)

Leanecc was "delighted" to learn he could hear the woman's heart and lung sounds better this way than with the unaided ear against her chest.  He was so excited at how simple a device could make this job so much easier that he set out to do a series of experiments to find metals and tubes that would aid his ear in hearing heart and lung sounds.  (2, page 96)

He actually wanted to name the device le cylindre claiming it was frivolous to name such a device.  However, his colleagues thought it should have a name, and they came up with some of their own. Yet once he decided he didn't like any of these names, he decided to call it a stethoscope.  Stethe coming from the Greek term for chest, and scope coming from the Latin term for aim.  (2, page 97)

In the ensuing years the model was adjusted by others, and eventually a stethoscope with two ear pieces (binaural) was invented.  In 1852 George Camman fine tuned the stethoscope so it was similar to the models we use today.

In his book "A treaties on the diseases of the chest, and on mediate auscultation," Laennec recollected a little kid's game, and it was this that gave him an idea.

He wrote:

In 1816, I was consulted by a young woman laboring under general symptoms of diseased heart, and in whose case percussion and the application of the hand were of little avail on account of the great degree of fatness. The other method just mentioned (auscultating with an ear to the chest) being rendered inadmissible by the age and sex of the patient, I happened to recollect a simple and well-known fact in acoustics, and fancied it might be turned to some use on the present occasion. The fact I allude to is the great distinctness with which we hear the scratch of a pin at one end of a piece of wood, on applying our ear to the other. Immediately, on this suggestion, I rolled a quire of paper into a kind of cylinder and applied one end of it to the region of the heart and the other to my ear, and was not a little surprised and pleased, to find that I could thereby perceive the action of the heart in a manner much more clear and distinct than I had ever been able to do by the immediate application of the ear. (4, page 6)

Figure 2 -- Laennec's Monaural Stethoscope (1820).  It was an inch
and a half in diameter and a foot long, perforated longitudinally
by a bore three lines wide, and hollowed out into a funnel shape
at one end to the depth of an inch and a half. A plug of wood
was fitted into this hollowed extremity with a perforation through
it of the same diameter as that of the rest of the tube. The plug
was used in auscultating heart sounds, and discarded in
 stethoscopes made at a later date. It was made in two sections
for convenience of carrying. (6, page 626)  Perhaps it
 provided some solace to Laennec that he was diagnosed with
consumption using a stethoscope similar to this. Photo Copyright
Science Museum/ Science and SocietyPicture Library

So he thereby discovered that his invention was better for hearing sounds inside the human body than the ear alone.  He found it very useful, and would incorporate his new tool as a means of assessing all of his patients.  He likewise used it in his efforts to study many diseases, such as tuberculosis, pneumonia and asthma.

What was the first stethoscope like? 

Laennec described his first stethoscope in his book Mediate Auscultation:

The first instrument which I used was a cylinder of paper, formed of three quires, compactly rolled together, and kept in shape by paste. The longitudinal aperture which is always left in the centre of paper thus rolled, led accidentally in my hands to an important discovery. (4, page 7)

He  also set off on a quest to study and perform experiments using the device, and he fine tuned it until he came up with a better product.  He trialed a variety of materials, lengths, and sizes of aperture, until he came up with the product he thought was idea.

He said:

In consequence of these various experiments I now employ a cylinder of wood, an inch and a half in diameter, and a foot long, perforated longitudinally by a bore three lines wide, and hollowed out into a funnel-shape, to the depth of an inch and a half at one of its extremities. It is divided into two portions, partly for the convenience of carriage, and partly to permit its being used of half the usual length. The instrument in this form—that is, with the funnel-shaped extremity,—is used in exploring the respiration and rhonchus: when applied to the exploration of the heart and the voice, it is converted into a simple tube, with thick sides, by inserting into its excavated extremity a stopper or plug traversed by a small aperture, and accurately adjusted to. the excavation. (See figure 2)  (10, page 7)

He also used his new device to study diseases of the chest. He said:

From this moment I imagined that the circumstance might furnish means for enabling us to ascertain the character, not only of the action of the heart, but of every species of sound produced by the motion of all the thoracic viscera, and, consequently, for the exploration of the respiration, the voice, the rhonchus (the sound of air flowing through diseased air passages), and perhaps even the fluctuation of fluid extravasated (leaked) in the pleura (sack around the lungs) or the pericardium (sack around the heart). (4, page 6)

Figure 3 -- Laennec listens to man with tuberculosis*

He took upon this opportunity to study diseases of the chest at the Necker Hospital where he also received patients at his clinic.  He therefore bravely came into close contact with some of the sickest and contagious people in France at the time, which can be seen in figure 3.  It was this type of dedication to his work whereby he contacted the disease that ended up ending his life.

How was the stethoscope accepted by Laennec's peers? 

Despite how useful he found this new tool in diagnosing and researching diseases of the chest, it was initially rejected by his peers in the medical community.

"What a ridiculous idea," his colleagues would say.  "We doctors are called upon for our brilliant medical minds.  To say we should carry some frivolous tool around with us is absolutely ridiculous and below us." 

This is a plate of the parts of the Laennec's stethoscope
as it appeared in the first edition of his book in 1819.
(4, pages 783) 

Another doctor wrote, "He that hath ears to hear, let him use his ears and not a stethoscope."

This was yet another example of a dogmatic and proud medical profession refusing to accept anything new or different. For thousands of years physicians rejected any scientific idea that opposed Galen's superstitions, and now they flat out rejected a tool that would allow them to do their jobs better.

Perhaps under the encouragement of Corvisart, Laennec published a book reporting what both he and Corvisart had learned about the diseases of the chest by using their new discoveries of chest percussion, vocal fremitus, and the stethoscope.  The book was published in 1819 and titled "De VAuscultation Mediate, ou Traitt du Diagnostic des Maladies despoumons ct du Cceur, fonde principalement sur ce nouveau moyen." 

The book was well received, and, in 1821, it was translated into English by John Forbes.  Slowly over the next few years his hard work payed off.  So even though he only lived six years after his discovery that was not so well received initially, he was able to see its acceptance before he passed away in 1826.

Perhaps there was no better evidence as to his tool's usefulness than by his own perseverance in studying the various diseases of the chest, a quest which may have ultimately cost him his life.  

Figure 4 -- Painting of Laennec using his stethoscope on a boy.
This picture was taken from a painting by Robert Thom,
copyrighted in 1960.  

Conclusion:

Laennec married in 1824 and had two children. However, he was only able to enjoy his young family for a short time.

He continued to work arduously at his clinic, both seeing physicians and performing research.  He also worked hard in perfecting the book he became famous for, releasing the second edition in 1826.

In the process accomplishing this, along with his other duties as a physician and researcher, he became so exhausted that he was forced to give up his work and return to the home he was born in. Although some say he was simply tired from being ridiculed by his colleagues.

Either way, he was ultimately diagnosed with phthsis pulmonalis, which the Latin form of consumption, or tuberculosis.  He was diagnosed using the very same tool that he invented.  Perhaps this was consolation, proof that the passion of his life's work was finally accepted.

So, despite his ingenious idea originally being rejected by the medical community, Laennec would end up with the last laugh.  By the time he passed away on August 13, 1836, his stethoscope, or some variation of it, was a standard tool to assess and diagnose patients.

References:

1. Forbes, John, The life of the author, translator of "A treaties on the diseases of the chest, and on mediate auscultation," a book written by Rene Theophile Hyacinthe Laennec, 1838, New York, Philadelphia, Samuel S., pages xix-xxiii
2. Haven, Kendall F, "One hundred greatest inventions of all time," 2006, U.S., Greenwood Publishing Group, Inc., pages 96-98
3. "Now I hear:  The history of the stethoscope,"  http://antiquemed.com/, 1998-2011, accessed 12/28/13
4. Laennec, Rene Theophile Hyacinthe, "A treaties on the diseases of the chest, and on mediate auscultation," translated by John Forbes, 1838, New York, Philadelphia, Samuel S. and William Wood, Thomas Cowperthwaite and Company
5.  Barchers,Suzanne, "I've Discovered Sound," Brainworks, 2009, Leopard, page 9
6. Camman, Donald M, "Historical Sketch: Stethoscopes," A Reference Handbook for Medical Sciences, edited by Albert Henry Buck, by various writers, volume VI, 1888, New York, William Wood and Company, 626-628

1800-2012: Evolution of back-door bronchodilator

Anticholinergics are medicines that, once inhaled, sit on receptor sites of the neurostransmitter acetylcysteine to prevent it from causing bronchospasm. Because the medicine is blocking a natural response as opposed to actively causing bronchdilation, 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:

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

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

1.  Burning herbs: Leaves, roots and stems from the herbs belladonna and strammonium 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 as 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 spasmotic 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 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 and COPD during the 1980s, although by the 1990s was phased out due to a synthesized anticholinergic medicine with less side effects. I was prescribed this medicine in 1985 and took it up to four times per day until around 1990.

Atrovent Inhaler

2.  Ipatropium 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)

3.  Oxitropium Bromide (Oxiven, Tersigen): This was anther synthesized anticholinergic released along with ipatropium 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)

Combivent Inhaler

10.  Combivent:  This is a combination of Albuterol and Ipatropium 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)

 11.  Duoneb:  This is a combination of albuterol and ipatropium 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 ipatropium bromide, both with 3cc premixed.  It continues to be a top line treatment for COPD, although is an option for asthmatics.

Spiriva HandiHaler

12.  Tiatropium 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 ipatropium 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 bronchodiliation and mild breathing relief. Personally, I never noticed any difference with the medicine. However, modern evidence suggests the medicine, when used daily, may acts 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.


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

1960-2012: Evolution of asthma controller meds

Previously I described the history of steroids for the use of asthma, and how inhaled steroids became the preferred method of preventing asthma.  In this post I shall list the asthma controller medicines that have been used since the 1960s.

The following are asthma controller medicines past and present:

1.  Beclomethasone:   First marketed by Allen & Hanbury in 1960 and marketed as Becotide in 1972 overseas with a recommended frequency of two puffs four times 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.  Other oversease brand names are Becloforte, and Beconaise.  The initial inhalers were made with the chlorofluorocarbons (CFC) propellant and these have all been since phased out in favor of the HFA verions called Qvar (see below)

2.  Fenoterol:  It was a non-selective long acting beta agonist that asthma patients were allowed to use at home.  It was marketed as Barotek.  It was introduced to the market in New Zealand in 1976.  Shortly thereafter the asthma death rate soared in New Zealand to a rate significantly higher than other nations.  Fenoterol overuse was blamed for the deaths, however, this was never proven.  Some believe that poor education about asthma medicines encouraged some asthmatics to continue using the medicine instead of seeking help.  The New Zealant asthma death rate declined slightly after warnings were incorporated into the package in 1981, yet the death rate in New Zealand continued to be higher than other nations.  The death rate fell 50 percent in 1990.  Despite the warnings, sales of the product remained consistent and actually increased slightly in 1989-90.  (1)  Despite consistent sales, the product was taken off the market in the 1995 due to the scare. The product was also available in Japan and Canada.

Intal Spinhaler

3.  Chromolyn:  The Intal Spinhaler hit the market in the 1960s.  It was and was prescribed as an alternative to inhaled corticosteroids to treat inflammation in asthmatic airways.  It was popular in the 1980s and 90s.  You can read more about the Intal Spinhaler here.  The main problem with the spinhaler was the powder inhaled often precipitates coughing and asthma, plus the patient has to handle each dose.  The FDA approved an MDI (with the CFC propellent) in 1992 which ultimately replaced the spinhaler.  Due to decline in prescriptions of the medicine and the Montreal Protocol's ban on CFC inhalers, the medicine was phased out by December 31, 2010.

Azmacort inhaler

4  Triamcinolome:  It was introduced to the market by in the early 1980s as Azmacort and approved by the FDA in 1984.  It's formula was slightly stronger than beclomethasone and became another inhaled steroid option.  It was the first inhaler to come with its own built in spacer, which assured proper use of the inhaler, and increased compliance.  However, it was bulky and difficult to carry.  Sales started to decline in the late 1990s due to long acting inhaled steroids that required fewer puffs, such as fluticasone  After the declaration by the Montreal Protocol the  medicine was phased out by December 31, 2010.  However, in 2008 the FDA approved an HFA version which continues to be an option to this day. 

Tilade inhaler

5  Nedocromil Sodium:  It was approved by the FDA and introduced to the market in 1993 as an alternative to Tilade  It was an inhaler with the CFC propellant  Since sales of this product declined by the late 1990s due to better asthma controller medicines on the market. After the Montreal Protocol set a timetable to ban the use of the CFC propellant in asthma inhalers, the product was phased out by June 14, 2010.

6.  Flunisolide:  It was approved by the FDA in 1982 introduced to the U.S market as Aerobid.  This turned out to be perfect timing for entry into this market, because in 1989 the National Heart, Lung and Blood Instute's (NHLBI) Asthma Guidelines were created.  The guidelines recommended inhaled steroids as a top line asthma treatment, and sales of inhaled steroids skyrocketed, with Aerobid leading the way. Aerobid was the best selling inhaled steroid during the 1990s mainly because it had a stronger formula than triamcinolome and beclomethasone requiring fewer puffs to achieve the desired dose.


Aerobid inhaler

7.  Fluticasone: The Flovent CFC MDI was approved by the FDA and entered the market in 1996.  By 2000 the Flovent Diskus was approved as the DPI version of the medicine.  Soon thereafter the CFC MDI was taken off the market.  The Flovent HFA MDI was approved by the FDA in 2004.  The doses were:  44 mcg, 110 mcg, and 220 mcg.  The medicine is a stronger inhaled steroids than its predicessors and only needed to be taken twice daily.  One puff of the Diskus is equal to 2 puffs of the MDI.

8.  Salmeterol:  It was approved by the FDA in 1994, and became the latest long acting beta adrenergic (LABA) to enter the market.  The medicine attached to beta 2 adrenergic receptor sites in the lungs and continued to release the medicine for up to 12 hours.  All that was needed was two puffs twice a day. The Advair Diskus, a dry powdered inhaler, was approved by the FDA in 1997.  The diskus was green to distinguish it from the brown Flovent Diskus and eventually the Advair purple Diskus).  By 2008 some suspected the medicine was the cause of asthma related deaths and a black box warning was placed on the product.  The NHLBI Asthma Guidelines ultimately recommended the medicine not be used by itself in the treatment of asthma.  If asthma is bad enough that this medicine is needed, the guidelines recommended taking it with an inhaled steroid to control inflammation.  The product is still available as a treatment for other lung diseases such as COPD.

Advair Discus

9.  Advair:  This is a combination drug with both Fluticasone and Salmeterol that was introduced to the market in the 1990s, approved by the FDA in 2000 for ages 12 and up.  The recommended dose is 100/50 (Fluticasone/Salmeterol), 250/50, and 500/50.  It's recommended to start at the lower dose and increase as needed.  The 100/50 dose was approved for children ages 4 and up in 2003.  Some patients, especially younger ones and the very old, may have trouble generating enough flow to actuate the medicine.  For these patients an Advair HFA inhaler was approved by the FDA in 2006 that can be used with a spacer to improve coordination.  Source for above dates is FDA.gov.

The medicine was marketed as an asthma controller medicine to prevent bronchospasm and inflammation in asthmatic lungs to prevent asthma.  Because it combined the two medicines and the frequency is one puff twice daily, it greatly improves compliance with asthma medicine (I can personally attest to this).  Sales skyrocketed during the 2000s and it continues to be the top selling asthma controller medicine. Some fear salmeterol is related to asthma deaths and a black box warning was placed on the packaging in 2008.  I wrote about this in more detail here.The patent for Advair expired in the U.S. in 2010 and will expire by 2012 in most European countries.  It's expected that soon generic products will enter the market which would increase competition and lower the cost of the inhalers (currently priced at over $100).

Foradil Inhaler

10.  Formoterol:  Introduced to the market as an alternative to salmeterol.  The Foradil Aerolizer was approved by the FDA in 2001 and the product was marketed in the U.S.  Oxeze, Atock, Atimos and Performist were common names used overseas.  The Foradil Aerolizer was a dry powdered version of the medicine.  The Foradil Centihaler was approved by the FDA in 2006. The NHLBI Asthma Guidelines ultimately recommended the medicine not be used by itself in the treatment of asthma.  If asthma is bad enough that this medicine is needed, the guidelines recommended taking it with an inhaled steroid to control inflammation.   According to the FDA.com, as of 2007 there were no FDA approved formoterol products on the market in the U.S.  However, it's currently marketed by AstraZeneca in other countries as the Oxis Turbohaler.  The medicine is available, however, in the combination inhaler sold by AstraZeneca known as the Symbicort inhaler (see below).

11  Budesonide:  The inhaled steroid solution of Pulmicort was introduced to the market in the early 1980s as the only inhaled steroid available as a solution for home use.  Studies showed it was the safest and best corticosteroid solution.  It was mainly prescribed for kids, however it's recommended for any asthmatics who requires inhaled steroids and has trouble coordinationg an inhaler. From what I can tell it has the same potency as Flovent.  A Pulmicort Turbohaler hit the market in the late 1980s as the first corticosteroid as a dry powder inhaler.  In 1997 the Pulmicort Turbohaler  was approved by the FDA as the first DPI inhaled corticosteroid.  The inhaler never caught on and was later discontinued.  In 2000 Pulmicort Respules became the first corticosteroid nebulizer solution to be approved by the FDA.  However, due better inhaled steroids and the Monteral Protocol, the Pulmicort Turbohaler was phased out by June 30, 2011.  The Pulmicort Respules continue to be marketed as an inhaled corticosteroid option for children and adults with poor coordination skills with their corticosteroid MDIs.

Symbicort inhaler

12.  Symbicort:   Marketed by AstraZeneca and approved by the FDA in 2006. 
It basically works the same as Advair except the LABA (formoterol) is faster acting and appears to have a stronger cardiac effect.  The steroid in this inhaler is mometasone furoate (see below).  It's availabe as either a metered dose inhaler or dry powder inhaler via the Turbohaler.  Note:  Some countries have adopted the Symbicort Smart program whereby you can use your Symbicort as a rescue inhaler.  I wrote about this here. 

13.  Beclomethasone:  I'm mentioning this again because the older CFC versions of this inhaler were taken off the market and replaced by an HFA inhaler which has been rebranded as QVAR.  It was approved by the FDA in 2000.  The medicine is the same, yet some studies show the smaller particle size allows the medicine to penetrate deeper into the lungs as compared with other inhaled corticosteroids presently on the market.

Symbicort Twisthaler

14.  Mometasone furoate:  It's the latest long acting inhaled corticosteroid to enter the market.  It was approved by the FDA in 2008.  It's a once a day medicine, or twice a day if need be, that was introduced to the market as Azmanex.  It's a dry powder inhaler taken via the Azmanex Twisthaler.  I have never tried this medicne, although I had to teach myself how to use the inhaler so I could teach how to use it to patients. 

15.  Dulera:  It was approved by the FDA in June of 2010.  It hit the market as an alternative to Advair and Symbicort.  It containes Mometasone and Furosimide.  Other than that it works similar to Advair and Symbicort.  Whether one of these works better than the other is a matter of personal choice and physician preference.  I trialed this medicine once and it make my heart beat like a jackhammer and I went back on Advair. 

Singulair pills

16.  Montelukast sodium:  This product was introduced to the market in 1998 as Singulair.  It was the first leukotriene receptor antagonist.  What it does it it blocks the affects of leukotrienes and prevents them from causing inflammation and bronchospasm.  Leukotrienes are released from mast cells during the allergic response along with histamine.  While histamine causes inflammation of the respiratory tract, leukotrienes do this, but they mostly cause bronchospasm.  So Singulair was marketed as a product to help allergic asthmatics.  With insurance these pills cost about $1.00 each, or $30 for a month supply (as of this writing in January 2012). I took this medicine the past three years, but with my doctor's permission I just quit becasue I haven't noticed any results.  My doctor said he's recommending all his asthma patients quit taking it. 

17:  Zafirlucast:  This was another leukotriene receptor agonist admitted to the market as Accolate to compete with Singulair.   It was approved by the FDA in 1999.

18.  Zileuton:  This was another leukotriene receptor agonist marketed as Ziflo.  It was introduced to the market in 2007 and was discontinued in 2008 (you can read the discontinuation letter here).  It failed to take off becaue the other options only had to be taken once daily, while this one had to be taken four times daily. 

19.  Omalizumab:  This is the first medicine on the market to block the effects of IgE, an antibody that is responsible for the allergic response.  The medicine is marketed as Xolair and consists of a series of injections.  It costs $10,000 to $30,000 for an annual prescription, and for this reason it's only recommended for severe, persistent asthma (hardluck asthma) non responsive to other asthma remedies.  It was approved by the FDA in 2003.

Further reading:

• More asthma history click here
• Evolution of inhaled corticosteroids click here

References:

1. Beasley, Richard, Sankei Nishima, Neil Pearce, Julian Crane, "Fenoterol and Asthma Mortality," The Lancet, August 8, 1998, volume 352, Issue 9126, page 486

Asthma History Lexicon

The following are the basic medical terms used throughout this history.  Many of these terms are no longer used.  The terms are not in any particular order.

Basic terms by Hippocrates:

1. Dyspnea:  Shortness of breath
2. Asthma: More severe shortness of breath (gasping, panting)
3. Orthopnea: Shortness of breath that requires  the person to sit up to breathe. 

Basic Medical/ Historical Definitions:

• Magico-religious:  Treatment for diseases that involves either incantation (magic) or prayer religious). 
• Emperico-rational:  Treatment based on experience and observation.  
• Rational (civilized):  A word that means physical, dietic, and pharmacological treatments that are not mystical in themselves.  They are generally treatments used by physicians, although they can work their way into the magico-religious.  For example, common ailments such as colds, asthma, stomach aches may be treated with herbs, but the unexplained diseases may be treated with magic.  We must be careful when using the term rational, as we must put it into the perspective of the beliefs of the people we are referring to.  While magic may not appear to be rational to us, it is to the ancient Egyptians, for example.  Usually, rational is used from our perspective, and in which case magic is considered not rational (irrational), and in this sense the term rational is equivalent to the term civilized.
• Civilized:  Empirical medicine. It's what we would see as rational in the modern world.  For example, treating asthma with an incantation is not civilized, and treating asthma with inhalation of herbs on stones is rational because it would actually work.  
• Natural:  These are diseases that are normally occurring , such as your common colds, aches and pains, pneumonia, pleurisy, etc.  They are generally treated with herbs, massage, broths, salves, etc.
• Herbs:  Herbs were available to ancient people.  They may have known of their effects, yet not the why or how.  Such herbs were used to treat naturally occurring ailments such as aches and pains and colds.  Common herbs were opium, coca, cinchona, ephedrine, caffeine, carcara, sagrada, chaulmoogra, digitalis, ipacacuanha, podophyllum,, pyrethrum, squill, belladonna, and strammonium.  The modern medical profession may recognize these as many have been synthesized into many of the modern medicines we use today.  
• Amulet:  An object that possesses magic properties to ward off evil spirits.  Generally it can be anything from a bone from prey, a chip of human bone (as from trepidation), an animal, an object such as an ax, knives, etc.  They meet and destroy evil spirits.  They catch and neutralize black magic directed toward the owner of the amulet.  These are often the chief means of preventative medicine in many ancient societies.
• Black Magic:  Spells with the intention to do harm. 
• White Magic:  Spells with the intention to do good. 
• Fetish:  An object that  is the seat of magic power.  It may be the abode of a spirit or may have been charged by the medicine man with the mystic power, mana, or manitou, or whatever it may have been called.  It may be an object of worship.  The owner of a fetish expects it to act according to his intentions.
• Omen:  A message believed to tell the future.  It was very common for ancient societies to see temples and priests, and even to dissect organs of humans and animals, for signs as to what will happen in the future.  It was important to medicine in that it could give the people hope and faith that good things are to come, such as victory in battle.  Of course it could also predict gloom, and in this case the person would be wary and careful.  
• Totem:  An object reminding a group of their ancestry.  It could either be an object or an animal.  
• Charm:  Stating of a magic spell
• Talisman:  An object that possesses magic properties and brings good luck
• Mascot:  An animated talisman, a person or animal that brings good luck
• Incantation:  A magic spell used as medicine.  It's generally said to rid the body of black magic or evil spirits.
• Prayer:  Petition to a deity, such as God or a specific god in the pagan world, for something good.  We don't think of it this way, but prayer is a form of medicine.
• Pagan:  Polytheistic medicine; many gods; a follow of polytheistic medicine; 
• Polytheistic:  Many gods
• Monotheistic:  One god
• Literati:  The educated.  In the ancient world few are educated, so it was special to be a member of the literati. 
• Scribe:  A person who understands language and can read and write.  It was a very prominent position in the ancient world, and usually such individuals held high status.  
• Physician:  A person who uses rational or emperico-rational treatment to treat the sick.  The first physicians by this definition were seen during the Ancient Egyptian era of about 3,000 B.C. They relied less on religion and magic and more on reality.
• Priest:  These are people who treat diseases with incantations and prayers.
• Sorcerer: See witch and magician; They diagnose what demon is in you, or what god is mad at you. Cures are based on the diagnosis, and generally are incantations, fetishes, amulets, etc.  They perform rituals, dances, touches, massages or whatever their society has decided is necessary to drive the demon out or satiate the angry god.
• Fetish:  An object thought to have magical powers to protect and aid its owner.  
• Magic:  Sorcery; the use of made up charms and spells to cure diseases; see white magic and black magic.  
• Spell:  Incantation
• Superstition:  Trust in magic; belief that what you do or say will effect your health; examples include: if you walk in front of a black cat you will have bad luck; if you toss salt over your shoulder you will have good luck.  It's also belief that incantations will actually work.  
• Shaman:  A better term for medicine man.  Inspirational type of medicine man who is voluntarily possessed, through whom the spirit speaks, who exorcises and prophesies.
• Seer:  The non-inspirational type of medicine man who is not possessed but has a guardian spirit that speaks to him not through him, who does not exorcise and is not a prophet.
• Medicine man:  A person who embraces the totality of transcendental forces.  He is concerned not only with the people's health but with their general welfare, ranging from crops to victory in war.  It is his function to avert evil that may threaten the individual or tribe in any form to propitiate the spirits for the benefit of his people, and also to destroy the enemy.  He is, therefore, priest, sorcerer, and physician in one.  He is often the chief of the tribe, the king who rules over the people.  He often knows the stories and songs that tell of the origin of the world and the deeds of the tribe and it's heroes in a far remote age.  This secondary role is very important in a script less society.  For specific medicine men see Shaman and Seer. 
• Humor (Humour):  Bodily fluids.  Throughout most of the ancient world it was believed there were four humors: blood, phlegm, black bile and yellow bile.
• Blood:  Sanguine; if you have too much or too little you had a sanguine personality, or a specific ailment.  Curing it is to render the opposite humor.  If a person is believed to be sick due to too much blood, bleeding is the obvious remedy.
• Phlegm:  A humor considered to be copld and moist. 
• Black bile:  Not a normally occurring humor unless the person has been obsessed or cursed with some form of black magic.  An excess results in a melancholy personality.
• Yellow bile:  Humor secreted by liver and causes the skin to be yellow.  
• Primitive man:  man who lived pre-civilization, out in the wilderness, and daily in search of food and shelter.  In the modern world it means men who live outside civilization, such as the aboriginies of Australia.  They may participate in non rational or uncivilized medicine.
• Serfs:  People who were bound to the soil or to the shop
• Diathesis:  Hereditary predisposition to get a disease, such as asthma or allergies
• Naturalistic:   Health and healing involving the use of preparations of the various plants and natural products.  
• Supernaturalistic:   Health and healing involving incantations, prayers and exorcisms.  
• Synthetic:  A chemical composition of a medicine that is similar in effect and cause as the original medicine.  It is the medicine made in a factory as opposed to grown on a farm or extracted from animals.  For example, atropine is a natural component of the thorn-apple plant, although atrovent is a synthetic form of atropine made in a factory (atrovent is synthetic).  Epinephrine is drawn from the thyroid of animals, whereas Iseotharene was synthesized as the first successful modification of epinephrine.  Epinephrine is natural, Iseotharene is synthetic. 
• Physic/ physick:  Medicine; the art of medicine
• Pharmacology: The making of medicines; this was a component of the Egyptian "black art," or chemistry.  It was originally to be an evil art, mainly because most of the solutions made were poisonous.  When solutions were mixed in adequate doses and given at adequate frequencies, these potions worked as remedies.  However, the potions must have been trialed on unwitting slaves or prisoners to learn what the results would be.  For a person who was severely ill, it may have been worth the risk of trying such a preparation.  
• Chemistry:  Some think it comes from the Egyptian term khemia, which means "black land." Egypt was called the black land as opposed to the dessert being called the red land.  It was called chemistry because the Egyptians were thought to be the first to mix various liquids together.  This is also believed to be how pharmacology got its start.
• Black Art:  Chemistry; comes from the Egyptian art of chemistry; pharmacology
• Alchemy:  Art of mixing chemicals in search of the combination of chemicals that make gold or the ultimate cure.  This was the method of making many of the proprietary remedies. 
• Proprietary Preparations:  Medicines made by combining a variety of chemicals and herbs and sold on the market under the guise that it is the ultimate cure for a specific ailment, or as a panacea or preventative for all ailments; folk medicine. The medicine usually involved solutions (mostly alcohol) that were bottled and sold to a naive or ignorant populace
• Patent Medicine:  Proprietary preparations that were patented, bottled and sold under colorful names and labels.  This was a popular fad of the 17th, 18th and 19th centuries.  Most proprietary preparations of the 19th century were called patent medicines even though most were not patented.  Even the products not patented came under that claim that they were, indeed, patented.  
• Folk Medicine:  Medicine practiced by people not associated with the medical profession; medicine practiced based on myth, theories, and lies. 
• Proprietary Medicine:  See proprietary preparations or patent medicine
• Nostrum Remedium:  Medicines that were sold but not tested (Latin).  In the middle ages such preparations were referred to as proprietary preparations; In the 19th century they were called patent mediicne. 
• Morbidity:  Causes disease or distress
• Mortality:  Causes death

Anatomy/ or Anatomy Related Terms: 

• Circular muscles of the bronchial tubes:  A 19th century description of the muscles that wrap around the bronchial tubes or passages; bronchial muscles; see bronchiole muscles
• Bronchioles:  The are the air passages in your lungs. The air you inhale moves through these tubes. They are often referred to as the bronchiolar passages or simply air passages.
• Bronchiole muscles:  These are muscles that wrap around the bronchioles. They are often referred to as bronchiolar muscles.  In the older days, they may have been referred to as: "circular fibres of the branchiae."
• Bronchoconstriction:  This is when bronchiolar muscles spasm and squeeze the air passages causing them to become narrow.  This makes it so air has trouble moving past the constriction.  This is the main component of an asthma attack.
• Bronchodilation:  This is when the air passages open up, or when broncoconstriction is reversed.  This is what's necessary to reverse an asthma attack. 
• Beta 2 Adrenergic Receptors (B2):  These are receptors that line bronchiolar muscles. Stimulation of these causes bronchodilation. They are often referred to as B2 receptors.  The ideal bronchodilator is specific to these receptors.
• Beta 1 Adrenergic Receptors (B1):  Line heart muscle and, when stimulated, cause vasodilation, increase blood pressure, and speed up rate and strength of heart rate.  The ideal bronchodilator will not be selective to these receptors to limit side effects.
• Alpha 1 Adrenergic Receptors (A1):  Line heart muscle and, when stimulated, cause vasodilation, increase blood pressure, and speed up rate and strength of heart rate.   The ideal bronchodilator will not be selective to these receptors to limit side effects.  
• Beta 2 adrenergics:  This is medicine that sits on B2 receptors and cause bronchodilation.  These are sometimes referred to as beta agonists, B2 agonists, front door bronchodilators, asthma rescue medicine, or rescue medicine.  I prefer the term rescue medicine.  Examples include epinephrine, metaproterenol , albuterol, and levalbuterol.
• Acytylcholine:  This is a neurotransmitter that sits on receptor sites on bronchiole muscles and cause bronchoconstriction.  

Diagnosis/ Symptoms (symptoms often were the diagnosis): 

• Paroxysm:  Convulsion; A sudden attack of a disease; asthma symptoms; acute symptom
• Exacerbation:  Acute worsening of a disease process, i.e., asthma exacerbation; exacerbation of asthma
• Hypertrophy:  Enlarged, bigger.  An example is when you workout your muscles become hypertrophied; an overworked heart becomes hypertrophied
• Spasms:  Involuntary contraction or convulsions of muscle or group of muscles; i.e., bronchospasm
• Convulsions:  Spasms; 
• Exciting cause:  Trigger; it causes a paroxysm
• Asthma:  It was first defined as a disease entity by Hippocrates around 400 B.C., although he pretty much defined it as dyapnea, or short, gasping breaths.  Asthma wasn't separated from the umbrella of dyspnea and defined as a disease of its own until around 1700 by John Cullen.  Through the 17th century it was believed to be caused mainly by sputum, and in 1840 Dr. Charles J.B. Williams proved the spasmotic theory of asthma.  Through most of history asthma was also believed to be a nervous disorder, and this wasn't disproved until around 1950.  For a more thorough definition of asthma, read through this asthma history.  
• Dyspnea:  Shoreness of breath; short, gasping breaths; air hunger. We now use it to describe air hunger, although it's used by its generic for as simply shortness of breath. The term comes from Greek terms dysp for "ill" or "hard" and pnoe from the term pnein which means "breathing" or "to breathe." (from Dictionary.com)
• Orthopnea:  Shortness of breath so severe that it requires a person to sit up in order to breath.  John Fuller defined it as more severe than asthma.  We now use it to describe the requirement to breath due to heart failure and foaming pulmonary edema (fluid in the lungs). 
• Pulmonary edema:  It's actually blood that backs into the lungs when the heart fails as a pump.  It generally presents as pink and frothy.  I like to refer to it as foaming pulmonary edema.   
• Catarrh:  This is an old term that means swelling or inflammation of the respiratory tract that causes increased secretions.  It's usually used to refer to swelling and drainage in the nose. It's an old way to describe a cold, although "catarrh" can also exist due to other ailments, such catarrh of the lungs is bronchitis.  It may also refer to a symptoms of influenza or asthma.  . 
• Ordinary Catarrh:  An old term used to describe the common cold.  It was probably also used early on to describe hay fever until hay fever was defined by John Bostock in 1819.
• Dry Catarrh:  Described by Rene Laennec as catarrh that is not associated with increased sputum production.  It was more associated with asthma as compared with chronic bronchitis.  Laennec defines it as dyspnea associated with narrowing of the bronchi by swelling of the mucus membrane. 
• Coryza:  Common cold. Acute inflammation of the upper respiratory tract.  It's an old term that is not used anymore now that we have more specific disease processes such as colds, allergies, bronchitis, and asthma.
• Pleurisy:  Pain in chest with each breath.
• Perepneumony (peripneumonia): Pneumonia
• Pericarditis:  Inflammation or swelling of the heart
• Hydrops pectoris:  Pleural effusion; fluid in the pericardial sac surrouding the lungs
• Ascites:  Fluid in the abdominal cavity
• Nephrosis:  edema
• Hydrothorax:  Dropsy of the chest; fluid in the lungs
• Edema:  Nephrosis; Increased fluid in tissue or organ; inflammation
• Edema of lungs:  Pulmonary edema or foaming pulmonary edema caused by heart or kidney failure
• Pulmonary Edema:  Fluid in lungs; see foaming pulmonary edema
• Foaming Pulmonary Edema:  Fluid in lungs that foams; pink frothy secretions that seep from the nose and mouth during severe, end stage heart or kidney failure; symptom with it include severe orthopnea and dyspnea
• Dropsy:  An old term for edema. It's an accumulation of fluid in a body cavity; a greater than normal quantity of water in a body cavity.  It generally presents with tightening of the skin due to fluid under the skin, and usually presents in the lower extremities, such as the ankles.  There are various forms of dropsy, which general are diagnosed by using the word dropsy coupled with the body part involved.  For example, fluid in the lungs was referred to it as dropsy of the lungs.  Water on the brain was referred to as cerebral dropsy. Other examples include dropsy of the eye, dropsy of the tongue, and dropsy of a joint.  Dropsy is the English version of the Greek term for water. 
• Hydro:  Another Greek term for water.  It may be used in place of dropsy.  For instance, if a patient has dropsy of the brain, it may be referred to as hydrocephalus.  If a person has dropsy of the eye it may be referred to as hydrothalmia.  Dropsy in the paricardial sac around the heart was hydrocardia.  
• Hydrops:  Another term for water.  For example, hydrops ascites is water in the belly. 
• Hydropsy: Full name for dropsy 
• Cor Pulmonale:  When your heart is overworked due to forcing blood through stiff lungs, the right heart eventually becomes hypertrophied.  As the disease progresses, this often results in left heart hypertrophy by default.  This is generally not a concern with pure asthma, although it is with other chronic lung diseases such as cystic fibrosis, chronic bronchitis, emphysema, farmer's lung, etc. However, it may be linked to asthma in older texts where one or more of these diseases was thought to be asthma due to the symptoms that present.  
• Heart Failure:  Also referred to as Congested Heaart Failure.  This is when your left heart becomes weak and becomes an inefficient pump.  The result in blood gets backed up into the lungs and this results in pulmonary edema.
• Winter Catarrh:  Common cold
• Summer catarrh:  Hay fever 
• Catarrhus aestivus:  Hay fever
• Hay asthma:  Dyspnea caused by hay fever, or during the hay fever season
• Summer Catarrh:  Hay fever 
• Autumnal Catarrh:  Hay fever
• Hay Fever:  An old term for allergies; sneezing, stuffy nose, nasal drainage, wheezes, itchy eyes and nose, and the like that were linked with the hay fever season; rhinitis
• Rose Fever:  An old term for allergies; sneezing, stuffy nose, nasal drainage, wheezes, itchy eyes and nose, and the like that were linked with the rose blooming season
• Fever:  Modern definition is a temperature of the human body that exceeds 98.7 degrees Farenheit; hyperthermia.  The old definition is any malady of the human body.  
• Laryngo-bronchio-catarrh:  A term used by Dr. Philip Phoebus in the 19th century to describe inflammation of the respiratory passages due to contact with pollen.  
• Aniphylactic shock:  A sudden and severe allergic reaction that results in drop in blood pressure and inability to breathe; pharynx and larynx and bronchioles swell so much it's impossible to get air in or out of lungs.  
• Inflammation:  Swelling and redness; edema
• Turguscence:  Swelling and redness, inflammation; edema
• Lung Fever:  Pneumonia
• Lung Sickness:  Tuberculosis
• Gripp (Grippe):  Tuberculosis
• La Grippe:  Tuberculosis
• Pthisis:  Tuberculosis of the lungs; chronic wasting away
• Pott's Disease:  Tuberculosis of the spine
• Consumption:  Tuberculosis
• King's Evil:  Tuberculosis of neck and lymph nodes
• White Plague:  Tuberculosis
• Plague:  Any disease with a high morbidity and mortality rate
• Marasmus:  Chronic wasting away (malnutrition); often used in referring to tuberculosis
• Long Sickness:  Tuberculosis
• Galloping Consumption:  Pulmonary tuberculosis
• Potter's Asthma:  Tuberculosis
• Polio Potter's Asthma:  Poliomyelitis
• Poliomyelitis (polio):  Disease that causes infantile paralysis
• Neuralgia:  General discomfort (i.e., neuralgia of the head is a headache)
• Costiveness:  Constipation
• Croup:  Inflammed (swollen) larynx; laryngitis, diptheria, strep throat
• Cyanosis:  Darkened skin, bluish discoloration of skin, due to lack of oxygen in blood to that part of body
• Debility:  Lack of movement; not able to get out of bed
• Diptheria:  Contageous disease of throat
• Dysury:  Difficult urination
• Dropsy of lungs:  Edema of lungs; water in lungs; hydrothorax
• Epitaxis:  Nose bleed
• Quinsy:  Tonsillitis
• Rose Cold:  Hay Fever; seasonal coriza, seasonal catarrh
• Hay Fever:  Seasonal allergy, summer catarrh; winter catarrh, spring catarrh, etc.; Rhinitis
• Suffocative Catarrh:  Croup
• Epidemic Catarrh:  Influenza, coryza (common cold or flu)
• Chronic Bronchitis:  Inflammation of the bronchi
• Melancholia:  Depression; severe depression
• Dysentery:  Disease of intestine causing fever, pain and diarrhea
• Flux:  Dysentry
• Flu of humor:  Circulation
• Dysphasia:  Difficulty of speech
• Frogg:  Croup (voice/ breathing sounds frog-like)
• Kink:  Fit of coughing; fit of choking
• Lumbago:  Back pain
• Mania:  Insanity
• Horrors:  Delerium tremons
• Infantile Paralysis:  Polio
• Membranous Croup:  Diptheria
• Pertussis:  Whooping coug
• Turgescence:  swollen, inflamed; buildup of fluid inside a tissue
• Congestion:  Accumulation of fluid in one area, as in the lungs. 
• Melancholy:  Gloomy, depressed, pessimistic; caused by an accumulation of black bile (see Spleen)
• Spleen:  The ancient Greeks believed the spleen produced the humor black bile.  With an increased supply of black bile in the system, the person had a tendency to be melancholy (depressed) in nature.  Due to this belief, a depressed, gloomy person person was generally diagnosed with Spleen or Melancholy.  
• Splenetic:  Melancholy, spleen, depressed; caused by an accumulation of black bile in spleen
• Choleric:  The ancient Greeks believed a person with an increased supply of yellow bile had a tendency to become overly organized and controlling.  
• Phlegmatic:  The ancient Greeks believed a person with an increased supply of phlegm had a tendency to become overly relaxed, easy going, friendly, peaceful (and also stubborn and pessimistic) 
• Sanguine:  The ancient Greeks believed a person with an increased supply of blood had a tendency to be overly jovial and social.  
• Cachexia (cachectic): Loss of appetite and weight due to chronic disease; chronic wasting away
• Palsy:  An old term for paralysis or uncontrolled movement (shaking) of a body part.  It may be specific to a body part, such as the face (cerebral palsy), face, hands, legs, feet.  It may be specific to the heart, lungs, or body in general, which is generally associated with high mortality.
• Torpor:  A state of sluggishness, lassitude, languor, lethargy, apathy, indifference.  
• Lethargy:  A state of being sleepy; barely awake; awakens, although quickly falls back to sleep 
• Apoplexy:  Old term meaning to become crippled or paralyzed (palsied) due to a stroke
• Pituitous:  Full of phlegm

Allergy/ Asthma: 

• Chronic:  It's always there
• Acute:  It's going on right nowAtopic:  A predisposition to an over reactive immune system that results in hay fever, asthma, allergies and eczema. It's from the Greek word atopia which means out of the way or uncommon (an abnormal response)
• Allergy:  A hypersensitivity to an an antegen that causes the immune system to over react and this results in symptoms of inflammation of the respiratory tract and eyes, that results in congested nose, sneezing, runny nose, itchy eyes, eczema, hives, and etc. The immune system over reacts to an allergen
• Allergen:  Something that causes an allergic reaction, such as dust mites, cockroach urine, trees, grass, pollen, etc. 
• Asthma:  The definition has changed over time.  The latest definition is chronic underlying airway inflammation that makes the bronchial muscles hypersensitive to asthma triggers. When exposed to an asthma trigger the inflammation becomes worse and bronchospasm occurs.  
• Chronic asthma:  Inflammation of the airways that is always there.  All asthma is essentially chronic.
• Acute asthma:  Asthma that is acting up right now; asthma exacerbation; bronchospasm
• Asthma exacerbation:  Asthma that is acting up right ow; bronchospasm
• Hypersensitive:  Over sensitive
• Hypersensitivity:  A predisposition to over react to a trigger, such as an asthma trigger or allergen allergen; i.e. asthmatic lungs are hypersensitive to asthma triggers, eczema patients have skin that is hypersensitive to certain allergens

Remedies: 

• Prophylaxis:  a protein entered into the body to offer it protection; to prevent the spread of disease
• Anaphylaxis:  Hypersensitivity to causative agent such as an allergen; a protein entered into the body that does not protect it; a severe allergic reaction can result in anaphylaxis or anaphylactic attack that can become severe and life threatening (i.e. inflammation of the air passages that can inhibit your ability to breathe. 
• Trepaning (trepination):  Process of opening up the skull for medicinal or spiritual purposes
• Bleeding:  Allowing some blood to escape by cutting a vein; usually done to balance the humors to cure diseases, such as pneumonia and sometimes asthma; also called phlebodomy or venesection
• Venesection:  Bleeding, phlebodomy; the drawing of blood from a vein
• Phlebotomy:  Bleding, venesection; the drawing of blood from a vein
• Fumigation:  Inhalation of fumes of smoke or steam for medicinal purposes.  It could involve smoke from a fire or steam from bath houses or other. 
• Cleansing:  Various primitive and ancient cultures believed that a good cleansing of the body would either cure diseases or prevent them; it was also a means to expectorate poisons from the body.  The means of doing this would be by causing sweating, vomiting, bowel movement, urination, removal of sputum, etc. (diaphoresis, emetic, purge, diuretic, expectoration, etc.) 
• Expectorate:  Cough up sputum; to spit
• Emetic:  Substance that makes patient vomit (ipacec); expel poisons by mouth; treatment for dysentry
• Diuretic:  Makes patient pee (lasix)
• Enema:  Substance that makes a person have a bowel movement; cleanse out the bowels.
• Purgative:  A remedy that cleanses the system by causing evacuation of the bowels; stimulates the bowels; laxative; cathartic
• Purging:  To remove impurities from the body; to cleanse the body, by evacuation of the bowels.  Methods used were enemas and laxatives. 
• Cathartic:  Substance that accelerates defacation (makes you poop); Stimulates the bowel; acts as a purgative or laxative; expels poisons by rectum
• Laxative:  Substance that softens defacation to make passage of bowel easier
• Diaphoresis:  Sweating; medicine that induces sweat; remedy such as steam baths, steam rooms, showers, or any other means of inducing a sweat
• Diuretic:  Causes urination
• Diuresis:  Process of urination
• Astringent:  Constricts body tissues to stop flow of blood or secretions
• Narcotic:  Anything that dulls the mind or blunts the senses, and causes euphoria, such as opium, morphine, belladonna, strammonium, marijuana, alcohol, etc.
• Opium:  Juice of poppy that has a narcotic effect; causes relaxation; soporific; analgesic; dulls the mind
• Analgesic:  Reduces pain
• Soporific:  Induces sleep
• Sedative:  Induces relaxation
• Hallucinogenic:  Relaxes the mind; causes mind to wander so you forget you're short of breath; dulls the mind
• Solanaceae (Nightshades):  A variety of plants that contain alkaloids that have poisonous or healing effects on the human body, such as Datura Strammonium and Atropa Belladonna.
• Strammonium (Datura Stramonium, Thornapple, Jimsonweed, jamestown weed, etc.):  It's a member of the  Solanaceae family of medicinal plants.  Used as a herbal remedy to make breathing easier and as a hallucinogenic; any part of the plant could be dried and crushed.  It was then burned and inhaled (inhaled, sniffed, snorted, smoked, etc.) It also thins secretions, so it can make breathing easier that way. 
• Belladonna (Atropa Belladonna, Deadly Nightshade):  It's a member of the Solanaceae family of medicinal plants.  Used as a herbal remedy to make breathing easier and as a hallucinogenic; any part of the plant could be dried and crushed.  It was then burned and inhaled (inhaled, sniffed, snorted, smoked, etc.)  It also thins secretions, so it can make breathing easier that way. 
• Cannabis (Marijuana):  The plant is dried and inhaled to produce a hallucinogenic effect, and also it makes breathing easier. 
• Indian Hemp (Apocynum cannabinum, Hemp dogbane): Similar to Cannabis, and grows mostly in America.  Inhaling various forms of the plant can ease the mind to take the edge off dyspnea.  Appocynum means "poisonous to dogs."  It must have been observed that dogs ingesting it died (probably of heart failure). 
• Atropine:  It's the active component of the members of the Solanaceae family (such as Belladonna, Stramonium, Indian Hemp, Canibis, etc. It causes the bronchial muscles to relax, and in this way opens up the air passages to make breathing easier.  It also dries secretions, which may help both breathing.  It can also benefit some stomach ailments, as it dries secretions there too. 
• Ipacac (ipacacuanha): It's used to induce vomiting 
• Clysters:  Enema inserted into rectum

Inhalers/ nebulizers: 

• Atomization:  Nebulized; made into tiny particles that can be inhaled
• Purvurization:  Pulverizing the particles so they can be inhaled.  An example is when water from a waterfall smashes into the rock turning the water into a mist.  The first mist nebulizers worked in this manner.  
• Pulverizer:  A device that uses pulverization to create a mist to be inhaled 
• Atomizer:  A device that creates a mist to be inhaled, although the particles vary in size from large to small.  Some of the first nebulizers were atomizers, although by the 1920s atomizers were reserved for sprays, such as perfume sprays.
• Nebulizer:  A device that creates a fine mist (usually by using the Bernoulli Principle) to produce a mist small enough to penetrate the air passages of the lungs. 
• Inhaler:  A device that allows for the inhalation of medicine, such as herbs.  Primitive use involved smoke and steam.  Modern use involves a small, pocket sized device that allows for the inhalation of aerosolized medication that is small enough to penetrate the air passages of the lungs.  
• Anticholinergic medicine:  This is medicine that sits on receptor sites and prevent acetylcholine from causing bronchoconstriction.  In this way, this type of medicine is a bronchodilator, or a back door bronchodilator.  I prefer to refer to them as back door bronchodilators.  Examples include Atropine, Ipatropium Bromide, and Tiatropium Bromide

Lung sounds: 

• Stethoscope:  A device used to listen to lung sounds.
• Auscultation:  Using a stethoscope to hear lung sounds.
• Rhonchi:  This is an old term that originally referred to any continuous high or low pitch sounds heard in the lungs.  Today this lung sound is still used, and mainly refers to coarse or low pitch wheezes (sonorous wheezes).  However, some use it to describe secretions in the air passages (see rhales). In many old text, rhonchi is used instead of wheeze, and rhonchi is broken down into two types: sibilant and sonorous (see below).
• Rhales (Rales):  This is an old term used to describe wet lung sounds.  The wet sound may be produced from excessive secretions (as with chronic bronchitis) or frothy blood (as with heart failure).  When Rene Laennec came up with this term, heart failure and chronic bronchitis were often looped under the umbrella term of asthma, and therefore you may see it used in relation to asthma.  Today the term is generally no longer used, and coarse crackles is used instead.  Rhales are generally heard on inspiration and expiration, and generally compose at least 3/4 of the lung fields. 
• Rales Vibrants:  Same as Rales (see above).  It basically refers to the rapid, vibrating, sound of fluid moving around in the lungs as the patient inhales and exhales.  
• Sibilant Rhonchi:  This is a constant high pitch sound of air moving through narrowed air passages in the lungs, and we now refer to it as a sibilant wheeze, or simply a wheeze.
• Sonorous Rhonchi:  This is the constant low pitch sound of secretions moving through the air passages.  It's generally a coarse sound and is now simply referred to as rhonchi (see above). 
• Sibilant Wheeze:  This is a constant high pitch sound of air moving through narrowed air passages.  It is generally associated with bronchospasm.  This sound is almost always inaudible and can only be heard on auscultation.  
• Sonorous Wheeze:  This is a constant low pitch sound of air moving through secretion filled air passages, as in chronic bronchitis or pneumonia.  It is not associated with bronchospasm.  This sound can be audible or inaudible, and can sometimes be heard with or without auscultation. 
• Wheeze: This is the same as sibilant wheeze.  However, many simply refer to any respiratory high pitch or low pitch sound as a wheeze.  
• Crackle:  This is a modern used in an attempt to be more specific than rhales.  It's a fine "crack" of the lungs popping open, or it can be the sound of fluid (either mucus or blood) moving around in the lungfields on inspiration and expiration.  This term is nonspecific, and is ideally broken down into fine crackles and coarse crackles.
• Fine Crackles:  This generally refers to the sound of the air sace (alveoli) popping open on inspiration.  This sound is generally isolated to certain lung fields.  For example, chronic bronchitis patients are unable to take in a deep breath, and therefore these may be heard in the bases upon a deep inspiration. When heard in only one or two lobes (such as left lower lobe and left upper lobe) it can be an early sign of pneumonia.
• Coarse Crackles:  This generally refers to the sound of fluid in the lungs.  This sound is generally gravity driven, whereas when a person with fluid in his lungs lies on his left side, coarse crackles will be heard on the left lung fields.  When the person is sitting or standing, they will be heard in the bases. This lungsound, therefore, is not specific to one or two lobes.  
• Stridor:  This generally refers to the sound of air moving through large airways (such as the throat) that are inflamed or filled with secretions.  This sound is generally harsh and it can be audible.  

Medical theories: 

• Spasmotic theory of asthma:  The belief that contraction or spasms of the muscles that line the bronchioles is a main component of asthma
• Nervous theory of asthma:  The belief that asthma is nervous in origin, or caused by things that influence the mind, such as strong emotions (laughter, crying), stress, excessive happiness, excessive sadness, a yearning for the mother, etc. 
• Pneumatic asthma:  A term used by Thomas Willis (1621-1675) to refer to all descriptions of asthma before his time.  It is when the lungs are "obstructed or not open enough."  Samuel Gee  (1839-1911) wrote that the ancients regarded all asthma as "pneumatic and dependent on bronchial obstruction."
• Psychosomatic theory of asthma:  Another name for the Nervous theory of asthma.  It's a term that  was sometimes used by the medical community during the 20th century.  
• Bronchitic theory of asthma:  Wheezing and dyspnea depend on obstruction of the air tubes by the inflammatory products of bronchitis. 
• Convulsive theory of asthma:  That asthma is caused by convulsions or spasms of the bronchioles, also see spasmotic theory of asthma and brochospasm theory of asthma
• Spasmotic theory of asthma:  That asthma is caused by convulsions or spasms of the bronchioles, also see convulsive theory of asthma and bronchospasm theory of asthma
  Bronchospasm theory of asthma:  That asthma is caused by convulsions or spasms of the brochioles, also see convulsive theory of asthma and spasmotic theory of asthma

Other: 

• Chlorofluorocarbon (CFC):  A liquified gas propellant used in used in asthma inhalers until the Montreal Protocol was signed in the late 1990s and a goal was set to ban the propellant to protect the ozone. 
• Hydroflouroalkane (HFA):  A new propellant used in inhalers that is safe for the environment.  Most inhalers on the market now use this propellant or are propellant free.
• Montreal Protocol:  A pact by various countries to ban CFC propellants and replace them by something else.
• Papyri (papyrus):  Paper-like material made from the papyri tree.  It was the material used for writing in ancient Egypt and was usually rolled into scrolls.  
• Georg Eber Papyri:  A papyri found between the legs of an Egyptian mummy believed to be the oldest medical document in recorded history.  It was purchased in 1873 by George Eber, and is believed to be dated back to 1550 B.C.  It's s 110 page scroll and 20 meters long. It is believed to contain copies of older texts.  It contains descriptions of internal diseases and treatments, which generally involve magic.  It is written in hieroglyphics.  
• Edwin Smith Papyri:  It's the oldest known surgical text dating back to 1500 BC.  It does not involve as much magic as the Eber Papyri because most of the ailments described are actual and seen, such as broken bones and cuts.  It's considered to be the first document of rational medicine.  It's a 17 page scroll and 4.6 meters in length.  It's believed to be copies of older medical texts.