Sunday, February 12, 2012

Asthma and Allergy History Timeline

30,000 B.C: Anyone who got short of breath generally toughed it out, although some experimented with various herbs and plants in an attempt to find relief. This is considered the dawn of medicine.

Pre-5,000 B.C. Most asthmatics had to tough it out, although if you were lucky you knew someone who was aware of an herbal remedy to drink or inhale. The most common remedy was to say a chant, or the soothing hand of a priest/doctor or family member. Keep in mind too that the term asthma was not used back then. Generally, the symptom was the disease: dysnpne, chest pain, cough, excess sputum, etc. All respiratory ailments, regardless of cause and seriousness, were treated the same. Pure asthma as we know it today was relatively rare. Those with illness were a burden to society, although many societies did the best they could to help you out.

3,000 -1,000 B.C Nei Ching was written by Huang Ti that described asthma-like symptoms and the use of the plant Ma Huang plant as a remedy. (In 1900 ephedrine was extracted from this plant.) Other treatment was steam and inhaled cinnamon

2640 B.C. King Menses is believed to have suffered a life threatening allergic reaction (anaphylaxic shock) when he was stung by bees. El-Razi observed redness and swelling of the nasal passages in some of his patients, and what he described in his writings were what we would now consider allergic rhinitis or hay fever.

2700 B.C.: The Hermetic books were written by the Egyptian god Thoth, or at least they were communicated to an Egyptian priests (perhaps Imhotep) who inscribed them in pillars of stone. The texts were necessary in order to provide credence and justification to priests/physicians who were seen as contributors to the black arts (evil arts) by their magic potions, remedies, chemistry, and pharmacology. The last six of these books contained all medical wisdom and rules that physicians were not allowed to deviate from. The disadvantage of these books is they discouraged physicians from being creative in treating patients, and therefore must have stalled the advancement of medicine.

2,600 B.C.: Imhotep, the vizier (consultant) to the King Djoser heals many ailments with his brilliant medical knowledge. He was so famous that he was later worshiped as a deity. He is remembered by history as the first physician (although he isn't really). As a scribe he recorded medical wisdom for other physicians and students, although none is known to have survived the test of time. Some, however, surmise he may have been the original writer of the Edwin Smith Papyrus, one of the oldest medical texts known to exist. It was found in the 19th century, possibly with the Georg Eber Papyrus (mentioned above), between the legs of a mummy in a tomb in the necropolis of Thebes.

1500 B.C. The Eber Papyrus was written by Ancient Egyptians and described asthma-like symptoms that were treated by burning herbs of belladonna on bricks and inhaling the fumes. Other treatment was eating elephant and crocodile dung, enemas, and herbs such as squill and henbane. A more common remedy would be to wear a magical amulet and say an incantation each morning. Another common remedy was to simply tough it out.

1500 B.C. Despite their proficiency at embalming, Egyptians were not permitted to study the human body for causes of disease or any other reason because this was considered offensive to the gods, and for this reason knowledge of anatomy was minimal at best. Ancient Egyptian physicians believed the heart continued to grow about two drachums in weight every year until a person was 50, and then it loses about two drachums a year until the person dies. So death was the result of continual loss of the heart. "They also believed about four demons ruled over the body. Hunger and thirst were not regarded as bodily wants but as quasi-poisonous substanes, which forced themselves into the body and required to be neutralized by eating and drinking, in order that the they might not destroy it. A similar superstition also prevailed regarding the dead, and thus these too required food.* The Egyptians were aware that the heart was the seat of all vessels in the body, and that the heart beat could be felt at various spots on the body. They were efficient in the art of surgery (as invented probably by Thoth), and were skilled in castration and circumcision. They were also very knowledgeable in diseases of women, the eyes, kidneys, etc. Each physician specialized in a specific condition of the body, such as disorders of the eyes, the kidneys, and anus. Other specialties included disorders of women, pregnancy and child bearing, etc. Temples were built where gods of health and healing were worshiped, and the sick would sleep there in hopes the god would appear and provide a vision of healing. These visions were interpreted by a priest. Those too sick to visit temples could send for a specialist to visit them at home. The Egyptians had a variety of drugs in their pharmacopoeia, including one containing dried and crushed roots and stems of the herb belladonna that was tossed on heated bricks and inhaled, and was probably the first inhaler. They were also privy to the poppy seed, or opium. They were aware of the need of good hygiene to stay healthy, and many used enemas and purgatives regularly to cleans the body. They also made ointments, oils, pills made of dough, and potions using various herbal recipes, although these were considered magical gifts offered by the gods. They also used steam for inhalations, and such fumigations were often utilized during disease outbreaks to ward off the evil causing the disease.

1500 B.C.? Moses grew up and was educated in Egypt, meaning he was probably adept in medical knowledge. As reported in the Bible, he, through God, recommended various methods of cleanliness and cleansing in order to prevent disease, which included avoidance of people with contagious diseases such as leprosy, and cleaning after touching animal carcases, etc. He did not mention asthma per se, although these efforts were meant to prevent all diseases. He must have known it was better to prevent disease, as once one was obtained it was nearly impossible to cure.

800 B.C. The term asthma was first used by Homer in his epic poem The Iliad. The term was used to describe anything that caused dyspnea (shortness of breath), including short of breath caused while running in a marathon. At this time in Ancient Greece asthma was considered a sacred disease that earned a visit from the gods, at least according to some historians.

400 B.C. Hippocrates becomes first to use asthma as a medical term in Corpus Hippocraticum, and was the first to treat it as a real disease state and not just a spiritual disease. He believed diseases were an imbalance of the 4 humors: blood, phlegm, yellow bile and black bile. His remedies included eating healthy, exercise, staying clean, and sleeping well. He also recommended avoiding quack medicine. If needed he recommended bleeding to balance the humors, massage, herbs and purging. Keep in mind, however, that he defined asthma as dyspnea. So asthma might be pure asthma, heart failure, kidney failure, bronchitis, or any other such disorder. He did however have a separate definition for tuberculosis.

315-240 BC. Erasistratus became the first to describe the valves of the heart. He described anatomy of the body.

100 A.D. Physicians in India had access to datura stramonium. They sun-dried the herb, crushed it, and smoked it in crude pipes to relieve asthma-like symptoms. They did not use the word asthma, however.

99-55 B.C. Lucretius was an ancient Roman physician who became the first to accurately describe allergies for the medical community. He is famous for the quote, "What is good for some may be fierce poisons for others." He was probably referring to allergies or, more specifically, what we now call allergens.

4-65 A.D. Seneca provided a great description of asthma, and wrote that asthmatics should be fortunate and not say things like "why me." No potions. No magic. No herbs. Seneca might have been one of the first asthma experts to recommend, mainly due to his own experiences, the importance of relaxing to control asthma.

41-55 A.D. Roman Emperor Claudius's son Brittanicus suffered from a reported "allergy" to horses. Because of his weakened condition his step brother Nero succeeded him to the throne, and Nero had his brother poisoned only a few months after his reign began.

25-50 AD Aurelius Cornelius Celsus was the first to describe asthma as the cause of dyspnea. He was the first to describe difficulty breathing and wheezing due to narrowed airways during an attack. When asthma comes out without a wheeze, it's dyspnea. When it comes out with a wheeze, it's asthma. He therefore was the first to define asthma as a disease of its own, even though his definition was mainly a more severe form of dyspnea.

32-79 AD Pliney the Elder's book "Science in the Ancient World" is written, and ultimately becomes one of the most widely read books in the world for the next 2,000 years. He described asthma and remedies such as blood of wild horses and eating snails.

100 A.D. Arateaus of Cappadocia wrote the first clear medical description of many diseases such as pleurisy, diphtheria, tetanus, pneumonia, diabetes epilepsy and asthma. He believed health was maintained by the balance pneuma, or "vital air." He used checking the pulse to see if the four humors were balanced. He may also have been the first to describe an asthmatic's yearning for cooler outside air.

150 A.D Galen became became the first to speculate on the cause of asthma. He was the first physician to make the connection between bronchial constriction and asthma. He also believed that vicious mucus flowed into the air passages and obstructed them. He wrote volumes on medicine, and his works were still read and believed for over 1500 years after his death. He was also the first to describe blood.

700 A.D.Chinese medicine in the form of the Nei Ching made it to Japan and was referred to as canpo, and asthma-like symptoms were referred to as zensoku

850 A.D. Physicians observed many of their patients developed sneezing, nasal stuffiness and runny noses when the roses were blooming. Upon further examination they observed redness and swelling in the nasal passages that resulted in the runny nose, and they referred to this condition as rose fever.

1198 Maimonides wrote a "Treaties on Asthma" recommended against trying any magical cures for any ailments, and any such remedies should treat the cause as opposed to just the symptoms. He described the disease as possibly seasonal, and he provided an accurate description of pollution in city air as a possible cause. He was the first to recommend chicken noodle soup as a remedy for breathing trouble and travel to dry regions.

1236 all the folk medicine of the day was compiled into one treaties called "Hyang-yak kugup pang" or "Emergency Remedies of Folk Medicine." It's the oldest medical texts written by a Korean. At about the same time several other such treaties were compiled, including "Samhwaja hyangyak pang," or "Folk Remedies of Samhwaja."This was mainly a diagnostic guide.

1280-1348 Xi is often regarded as the first Chinese physician to provide a modern description of asthma. He combined chuan and Xiao to come up with chuan xiao, which many historians believe is similar to the Western world's description of asthma. From this time on Chinese physicians believed Chuan xiao was caused by an imbalance of yin and yang.

1350 and 1400 A.D The medical term catarrh was first used to describe the miserable condition that result in a runny nose

1433 All previous Korean medical wisdom is compiled into "Hyangyak chipsong pang," or "Compilations of Native Korean Prescriptions."

1452-1485 King Richard III knew he had an allergy to strawberries and he used this knowledge to kill his enemy Lord William Hastings. The King purposely ate some strawberries and blamed his allergic reaction on a curse from Lord Hastings. Lord Hasting's was beheaded as punishment, and his head was served on a platter.

1514 Andreas Vesalius proved Galen was not a god, and that Galen dissected apes not humans. He believed the best teacher was human body, and he wrote the first accurate book of human anatomy.

1543 Vesalius publishes his book, "De humani corporis fabrica" and this is recognized by many as the birth of the scientific method, at least as far as our understanding of anatomy is concerned. The main method of science then was empirical (experience and observation). This was an essential moment in history as medicine slowly began changing from mere speculation to rational.

1550 Felix platerus (1536-1614 was among the first to advocate the treatment of mental patients. Back then asthma was considered a mental disorder. He believed that "an obstruction in the small pulmonary arteries is the cause of asthma. But he mentions also that the bigger nerves from the dorsal medulla, when disturbed by defluxions, occassion dyspnoea, e.g., in asthmatics. He observed the attack when nothing abnormal in the lungs could be found.

1602 William Henry proved the body circulates blood.

1609 Jean Baptiste van Helmont became the first to disagree with the theory of the 4 humors and instead described asthma as a disease of narrowing of the pipes of the lungs. He was also the first to describe the nervous theory of asthma. By his experiments he discovered carbon monoxide, but he didn't call it that.

1610, Korean philosopher Ho Chun compiled all the medical wisdom up to his time in "Tongui pogam," or "Exemplar of Korean Medicine."

1621 Paulo Zacchia published Quaestiones Medicolegales which provided the legal information about insanity. Asthma was considered to be a psychological disorder, and therefore it was believed asthmatics should be absolved of criminal inquiry because fear can trigger an asthma attack.

1656 A French doctor named Pierre Borel suspected one of his patients developed a rash when this patient ate eggs. So one day he attempted to test his theory by placing some egg particles on the patient's skin. When blisters developed on the patient's skin the physician knew he had made the correct diagnosis.

1661 Marcello Malpighi proved Henry right when he discovered vessels in the lungs that connected the arteries and the veins, and he called them capillaries.

1670 Paul Ammann published Medicina Critica which was a compilation of legal cases. Like Zacchio he recommended absolving asthmatics of crimes because fear might trigger an asthma attack.

1678 Thomas Willis became first to describe asthma as something other than disease of spirits, and he therefore narrowed the definition of asthma. He described it as obstruction of bronchi by thick humors, swelling of their walls and obstruction. He was first to describe asthma as more than dyspnea and wheezing, and therefore started the evolution of asthma to what it is today. He was the first to categorize all the diseases of asthma: pneumatic, convulsive and mixed. He's often the first to link food, emotion, heredity, and asthma.

1700 John Floyer rejected van Helmont and Willis as quacks and reconfirmed ideas of Galen and Hippocrates. He was more famous and readily accepted than the aforementioned. He wrote "Sir John Floyer's A Treatise on Asthma" and invented the pulse watch because he believed each disease was linked to a certain pulse

1700 Bernardino Ramazzini became the first to describe occupational asthma in bakers, tinsmiths, gilders, glass workers, runners professors (due to fumes), and horseback riders (dust). Recommended doctors ask about where a person works when they complain of shortness of breath.

1768 Savage described 17 different types of asthma because there were so many diseases categorized under asthma.

1790 pressurized aerosols were introduced in France to create carbonated beverages, the evolution of this product would influence the evolution of asthma rescue medicine in the 1940s and 50s.

1794 William Cullen was first to use science to describe asthma as spasmotic and nervous. He also describes inflammation of the lungs during an attack. He also described asthma as hereditary, effecting both sexes. He descried it coming on suddenly and noted it was short lived. He also wrote that asthma goes into remission, it effects different people differently, each person has unique triggers, and it's there for the whole life. He also described an array of asthma triggers including warm bathing, cold air, dust, odors and warm weather.

1797 Robert Bree wrote in favor of old humoral theories and tried to disprove the spasmotic theory of asthma. He believed spasms in lung were lungs natural mechanism to rid excess phlegm. His book remained popular the first half of the 19th century. He was among the first to recommend coffee in the treatment of asthma.

1800 George Lipscomb tried to prove Robert Bree wrong and Cullen right. He believed asthma was nervous and spasmotic.

1802 when Dr. James Anderson of the Royal Society of Physicians General at the Madras Hospital in India benefited from the treatment of asthma cigarettes containing stramonium, and reported this to his friend Dr. Sims in Edinburgh. (Asthma in the 19th century)

1803 the technique of inhaling dried and crushed stramonium in pipes was introduced to the West by an asthmatic doctor from Britain who visited India and found relief from an asthma cigarette. Asthma cigarettes and pipes became a popular treatment for asthma during the 19th century and through the 1950s.

1808 Franz Reisseisen performed experiments that proved muscular fibres wrap around the air tubes of the lungs

1812 Sims published a report in Edinbrugh Medical and Surgical Journal about the benefits of smoking cigarettes containing the leaves of Datura Strammonium. After this report asthma cigarettes became popular for the treatment of asthma.

1816 Rene Leannec invented the stethoscope and came up with the terms rhonchi and rhales. He believed asthma was caused by bronchospasm and catarrh (inflammation), although he believed this was all caused by some nervous stimuli.

1819 Dr. John Bostock further defined hay fever as a disease that caused inflammation of the upper respiratory tract that lead to the annoying symptoms. Ultimately, however, we would learn that the condition we now refer to as hay fever has nothing to do with hay or hay fever. Yet the term "hay fever" became a common term of describing a condition we now refer to as seasonal allergies.

1820s: Wealthy hay fever sufferers started participating in what became known as hay fever holidays.

1822 Richter reduced the categories under asthma to 11

1833 Atropine was first derived from the belladonna plant

1835 Ramadge wrote an essay supporting the nervous theory of asthma and made it popular. He described food as an asthma trigger and asthma being mostly a nocturnal disease. He discouraged use of opiates because they impede respirations that are already impeded. He recommended stramonium.

1836 Bergson and Lefevre wrote essays supporting the nervous theory of asthma and likewise popularized the movement. Lefevre described asthma could only be caused by bronchospasm, although this bronchospasm is caused by the mind.

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

1840 Charles J.B. Williams proved by his experiments that irritants caused bronchospasm. Budd rejected bronchospasm theory of asthma. He even doubted circular fibres that wrap around the lungs were muscular.

1841 Romberg confirmed Reissiessen's and Williams discovery by confirming galvanization of the lungs caused bronchospasm.

1842 Francois Achille Longet proved irritation of vagus nerve caused bronchospasm, confirming bronchospasm and nervous theory of asthma.

1843 George Hirsh said he (Hirsh) didn't understand how asthma could affect so many boys if it were a nervous disorder.

1846 Spirometry was invented by John Hutchinson.

1848 Rudolph A. von Killiker confirmed the works of Williams and Reisseissen when he isolated smooth muscles of the lungs

1851 Romberg described asthma as two different affections of the vagus nerve, and he called them bronchospasm and paralysis. Bergson denied paralytic asthma existed and he did experiments to prove asthma was only spasmotic

1851 Beau Cozart rejected asthma was a disease of bronchospasm and rejected the nervous theory. He insisted asthma was a disease caused by increased sputum in the lungs that was capable of blocking the air passages with mucus plugs.

1853 Jean Martin Charcot observed crystals in sputum. A hollowed out syringe referred to as the hypodermic needle was invented by Dr. Alexander Wood to make it easier to give blood transfusions to patients. It's one of the top ten inventions of all times.

1855 Dr. Ludwig Traube denied nervous asthma but believed asthma was rare and the dyspnea that resulted was caused by "fluxionary hyperaemia of the bronchial mucous membrane." He believed in swelling (inflammation) of the mucus membranes caused asthma.

1858 the first nebulzer was invented in France by Dr. Sales-Girons. It was pneumatic, fragile, and to cumbersome to become marketable.

1859 Bervenisti believed that a doctor could not possibly diagnose bronchospasm by listening to lung sounds alone. He believed sonorous and sibilant rhonchi are also present with a pulmonary embolism, which also causes dyspnea.

1860 Jean Antoine Villemin tried to disprove the nervous theory with his own scientific experiments. He believed hyperaemia (increased blood flow to the mucous membrane or inflammation) rapidly ensued, and led to the dyspnoeal attacks that other writers consider as nervous asthma. The chronic inflammation of the alveoli, described by Villemin, is, however, not recognized by other observers

1860 Henry Hyde Salter published his book "On Asthma." His book would ultimately become the main source for asthma teaching in the later half of the 19th century, making Salter the pre-eminent asthma expert of his day. He provided an accurate description of asthma, and defined it as a spasmotic disorder caused by a nervous affiliation.

1860 Bamberger believed asthma was caused by spasm of diaphragm

1861 Armand Trousseau described an attack after spending time in a hayloft. The attack followed an attack of hay fever. He observed cats and rabbits trigger asthma in some. He recommended stramonium, ether, chloroform, potassium nitrate fumes as remedies for asthma.

1864 Dr. Siegel invented Siegle’s steam spray inhaler that used the force of steam through a small tube to draw up the medicine and turn it into a vapour that is inhaled through a glass mouthpiece. Siegel's invention is often considered the beginning of nebulizer therapy.

1864 Alfred Wilhelm Volckman did experiments that once again verified the bronchospasm theory, yet he could find no evidence of the nervous link to asthma

1864 Henry Hyde Salter published his book "On Asthma: It's pathology and treatment," and supported the nervous and bronchspasm theory of asthma, he also provided a great description of asthma, it's causes and treatment. This book was the most popular on asthma in the 19th century. He also wrote about asthma as a hereditary disorder and a disease of inflammation.

1867 Atropine was isolated by von Bezold. It was then determined to be a component alkaloid of the various nightshade plants found in India often used in asthma cigarettes, It was then determined to be a component alkaloid of the various nightshade plants found in India, including the datura strammonium, atropa belladonna, and the hyoscyamus niger (black henbane), and Lobelia inflata

1869 Dr. Charles Blakely performed the first allergy test on himself in an attempt to study his own hay fever. He also proved allergies were caused by grass pollen and not hay (and also not roses, which are not bee pollinated and not wind pollinated).

1870 Biermer believed it was a disease of the bronchial tubes. Paul Bert, with improved methods of scientific research, succeeded in demonstrating that Willis and Longet were after all correct in their statements as to the contractility of the bronchial muscles.

1870 John Charles Thorowgood wrote about ozone paper that contained potash (potassium hydroxide) or potassium iodide and was smoked. He recommended smoking stramonium, chloroform, ether, nitre paper, sprays of lobelia and smoking belladonna.

1871 Ernst Victor von Leyden observed crystals in sputum and he linked them to asthma, although they weren't always in asthma sputum. Jean Martin Charcot observed these in 1853 but Leyden often gets credit because of his link to asthma. Sometimes they're referred to as Leyden-Charcot crystals (they were later identified as IgE particles.

1873 Leber wrote that he believed asthma was both disease of bronchial tubes and a disease spasming diaphragm. He believed asthma was caused by dilation of the blood vessels in the lungs. Nitre paper was recommended for treatment of asthma by Dr. John Thorowgood in the British Medical Journal.

1876 Dr. George Miller Beard wrote about the nervous theory of hay fever, something already suspected in the medical community (another baseless theory)

1878 J.B. Berkart explained that "ALL early historical traces of the affection at present called asthma are lost. For in the former systems of medicine, all cases presenting the same conspicuous symptoms were, regardless of their anatomical differences, considered as of a kindred nature, and grouped into classes according to imaginary types."

1879 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 the mid 20th century a synthetic version called disodium cromoglycate (cromolyn) was discovered and later was marketed as the Intal Spinhaler. Asthma cigarettes became a craze among asthmatics in America and Europe. Asthma pills and nitre paper also became popular for inhaling antispasmotics like strammonium, belladonna, atropine, Indian hemp, and cannabis.

1882 Heinrich Curshmann found spirals in sputum and suspected they caused bronchospasm because they were more often found in asthma sputum than Leyden crystals.Paul Ehrlich discovered the eosinophil

1884 M. Alton Wintrich proved bronchospasm and nervous theory of asthma as false. He believed tetanus of the muscles of respiration with spasm of the glottis or other muscles of respiration were the main causes of asthma. He believed asthma was caused by spasm of diaphragm.

1885 William Pepper and Louis Star explained that prior to the 19th century all dyspnea and all that wheezes was designated as asthma.

1886: The ampoule was invented by Frenh pharmaist Stanislas Limousin to help physicians conserve injectable solutions. This made it easier to preserve and transport medicinal solutions, which previously were prone to deteriorate due to the production of molds.

1889 Gollasch discovered eosinophilia in sputum

1890 Eosinophilia was found in the blood of asthmatics by Fink and Gabritschewsky

1892 William Osler defined asthma as a disease of inflammation and bronchospasm. He liked chloriform for temporary relief. He also prescribed morphine, belladonna, henbane, lobeline, and stramonium cigarettes. He also recommended Nitre paper. He may also have been one of the first to recommend for doctors to try oxygen. A preventative therapy was potassium iodide. Unlike some doctors, he recommended living in the city rather than the country.

1900 Epinepherine was discovered by a Japanese man names Jokichi Takamine. Cortisone was also discovered and Solis-Cohen prepared a crude extract of the adrenal gland and used it in the treatment of acute asthma." Willem Einthoven (the inventor of the EKG) evaluated the bronchospasm theory of asthma and spasming diaphragm theory of asthma and proved the bronchospasm theory. Due to these discoveries and others, the year 1900 is often marked as the birth of "effective" rational medicine. Prior to 1900 you may have been better off not seeking medical help.

1901 Epinepherine was trademarked under the name adrenaline. Also in this year Paul Portier and Charles Richet discovered that repeated exposure to extracted toxins from allergens would make a person sensitive to that allergen. Subsequent exposure to that toxin will cause an allergic reaction, and even death. He referred to this severe allergic reaction as anaphyxicis.

1902 Charles Richet discovered and defined the term anaphylaxis

1903 Epinepherine was first used on an asthma patient. It was given by injection. Isoproterenol is synthesized as the first modification of epinephrine, and marketed in the U.S. as Isuprel. It was also referred to as isopropyl adrenaline and marketed as Isoprenaline overseas.

1904: Dr. William Dunbar released to the market Pollantin, a serum he believed would cure hay fever. It was a salve or powder placed on mucous layers of eyes and nasal passages. It was called passive immunization.

1906 Clemons van Pirquet came up with the term allergy. It's from the Greek word allos (maning other). From then on asthma and allergies were considered relatives. Austrian pediatrician Clemons Von Pirquet coined the term allergy when he observed that some of his patients were hypersensitive to substances that did not bother other people. These substances were ultimately referred to as allergens. He was also the first to link allergies to asthma. We now know 75% of asthmatics have allergies.

1907 it's discovered epinephrine is a bronchodilator.

1909 Park, Davis & Co. introduced it's own line of ampoules of which it provided its soluble medicine in. It marketed the products as the Glaseptic Ampoule, which was supposed to prevent the need to worry about waiting for the solution to be sterilized and cooled, and guarantee proper dosing. The top of the ampoule was snapped off and the medicine drawn up with a hypodermic needle.

1910: Epinepherine was first given by nebulizer (probably by squeeze bulb syringe).

1910: Samuel James Meltzer performed studies in his lab and determined the symptoms of anaphylactic shock were similar to the symptoms of asthma. Both conditions result in shortness of breath due to spasms of the air passages in the lungs. He therefore postulated that asthma was not a nervous disorder, that it was an allergic disorder. He described how an asthmatic can become sensitized to certain substances, and then when exposed to those certain substances the air passages become hyper-reactive. This response is what results in an asthma attack.

1910: British scientists (Henry H. Dale and P.P. Laidlaw) discovered a chemical later called histamine (then called β-iminazolylethylamine) that was released during an allergic reaction, and determined it was this substance that was responsible for causing tissues to become inflamed. Dr. Brian Melland wrote an article for Lancet (May 21, 2010) discussing his successful experiments with hypodermic use of epinephrine for asthmatics. He also suggested the medicine worked because of its relaxing effect on smooth muscles lining the air passages in the lungs.

1911 Henry Dale discovered that histamine causes symptoms similar to aniphylactic shock. They later discovered it was elevated in allergic patients. Henry Dale proved that injecting histamine into guinea pigs and dogs would instigate the allergic response. Dr. John Freeman and Dr. Leonard Noon wrote about desensitization in the Lancet. The physicians "inoculated" a variety of patients with increasingly large doses of "pollen extract. It turned out others had already started using this method before 1911.

1916 several pharmaceuticals were marketing pollen extracts that could be used to do allergy testing, or as desensitization

1921 Carl Prausnitz discovered the antibody to be present in the serum of allergic patients. It could be transferred to nonallergic patients and was involved in the allergic process.

1918 Frances M. Rackemman publishes his report, " "A Clinical Study of One Hundred and Fifty Cases of Bronchial Asthma." He recommended asthma not be treated as just nervous or just allergic. He classified most cases of asthma as either extrinsic or intrinsic asthma. These two terms are still used to this day. He wrote over 175 writings about asthma and allergies.

1927 a Norwegian man named Erik Rotheim patented the first spray can that was capable of holding pressurized contents and spraying them. It's now considered the forerunner of modern spray cans, and ultimately the metered dose inhaler (MDI)

1929 the first glass nebulizers with bulb syringes for self nebulizing solutions of epinephrine are available.

1930s physicians stopped making house calls during this decade. However, when they did the homes of asthmatics were obvious by the strong odors of asthma cigarettes and incense and burnt niter paper. Aminophyllin and theophyllin (mild bronchodilators) production began. They would become a top line therapy for asthma and COPD through the 1990s when combination inhalers like Advair and Symbicort hit the market. It was also in this decate the electric nebulizer is invented and it becomes the first mass producible nebulizer for asthmatics to inhale the solution forms of various medicines like epinephrine and Isuprel.

1936 Iseotharine was introduced to the market as Bronkosol and marketed as a bronchodilator with fewer cardiac side effects as epinepherine. It's the first successful synthesized modification of epinephrine.

1937 Thanks to the works of Leonard Noon and John Freeman the first allergy shots were introduced to the market. They believed this would ultimately make the allergic person getting this treatment less sensitive to that substance over time. Daniel Bovet introduced to the world the first medicine to treat allergies, and he called his new medicine an antihistamine because it blocked the effects of histamine, and thus prevented an allergen from causing a stuffy and runny nose, itchy eyes and throat, and sneezing.

1939 Clark patents a DPI that resembles the ones we use today. It was used to inhale aluminum dust for those exposed to certain chemicals. It was never marketed.

1941 George Rieveschl discovered a drug called Benadryl that was useful in treating allergies

1944 Cortisol (steroid) was discovered to reduce inflammation in asthmatics lungs. Penicillin hit the market

1946 Antihystamines his the market (Benadryl and Pryibenzamine). In less than a decade they'd become the third most commonly prescribed medication behind antibiotics and barbituates. The first antihistamines were benadryl and pryibenzamine

1947 Hydrillin was introduced to the market. It was a combination of Benadryl and Aminophyllin.

1948 The terms beta adrenergic and alpha adrenergic were described by Raymond Ahlquis. Corticosteroids were discovered to benefit both asthmatics and allergy sufferers by treating inflammation.

1949 the Aerohaler was introduced as the first marketable DPI, and also the first rescue inhaler.

1949 Neohetramine was approved by FDA as the first over the counter antihistamine. Anahist and Inhiston were also available. Other antihistamines soon followed.

1951 Iseotharine (Bronkosol) approved by the FDA

1953 Mast cell is discovered. It's a cell that holds the mediators of inflammation that are released during an allergic reaction and cause all those nasty allergy symptoms.

1955 The first inhalers hit the market by Riker Laboratories to dispense perfume. Prednisone approved by the FDA for use in asthma and marketed as an effective treatment for acute asthma symptoms. It could be given in emergency rooms, or it could be given by pill form for patients to use at home. .

1956 Riker created the asthma inhaler market with a Medihaler-Epi that contained epinephrine and Medihaler-Iso that contained Isophrenaline.

1957 The Riker inhalers enter the market.

1958 Varaious steroids hit the market that were ultimately marketed under various brand names such as Dexamethasone (Decadron), Methylprednisolone (Medrol), and prednisolone. All were eventually available as a variety of brand names.

1960 Susphrine was introduced to the market as a longer acting version of epinephrine, lasting 6-8 hours

1960s Triamcinolone enters market as Azmacort

1961 Metaprateronol (Alupent) enters the market as Metaprel and Oriprenaline overseas. It was the first B2 specific rescue medicine that lasted more than 3-4 hours.

1960s Allen and hanbury introduced the Ventolin Rotacap to go along with the Ventolin Rotahaler as the first DPI albuterol product. 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.

1960 Allen & Hanbury marketed as Becotide as the first beclomethasone inhaler. It was only available outside the U.S. The recommended frequency was two puffs four times daily.

1963 the definition of allergy was refined by immunologist Phillip Gell and researcher Robin Coombs to refer to hypersensitivities to substances that result in immediate symptoms, such as hives, dyspnea, runny nose, sneezing, stuffiness, etc. Metaprateronol (Alupent) approved by FDA

1964 The first successful DPI is patented by Newton. The medicine he used was potassium chorate, a medicine that was more of an irritant than benefit to asthmatics. The device was never a marketing success, although Newton established the need for inhaled powders to be pulverized and kept dry.

1967 IgE antibodies are discovered, and later found to have a significant role in the allergic response.

1968 the Intal Spinhaler was introduced to the market. Albuterol inhaler enters the market as the first B2 selective agonist with minimal side effects that lasted 4-6 hours.

1976 Immunoglobulin E antibodies (IgE) antibodies were discovered.

1968 reports of patient abuse were made. Asthma deaths had risen, and the debate began whether deaths were due to the medicine or asthmatics over relying on their inhalers instead of seeking help. The debate continues to this day. IgE was discovered. The medicine disodium cromoglycate was isolated by Roger Altounyan marketed in the 1960s as the Intal Spinhaler.

1969 FDA decided to limit over the counter bronchodilators due to fears they were being abused. Epinepherine inhalers were grandfathered in and remained as over the counter medicines (primitine mist). Prescription refills for Epi-Iso plummeted 40 percent. The first successful dry powder inhalation system (Spinhaler) was introduced. The medicine was Chromolyn (Intal) and was an anti-inflammatory medicine that was not a steroid.

1970 terbutaline was introduced to the market. It was stronger than Iseotharine and lasted 4-6 hours. It was later available as an inhaler called Brethine or Bricanyl or Brethaire. It was learned (during this decade) that leukotrienes were the main culprits in causing inflammation of the bronchioles. Dr. Martin Wright invents peak flow meter that is inexpensive and portable

1971 Fison's Intal Spinhaler was approved by the FDA for the dispensing of disodium cromoglycate (cromolyn). The spinhaler was popular for asthma during the 1970s and 80s and even 1990s.

1972 inhaled corticosteroids almost written off as useful medicine until a study reported in The British Medical Journal in 1971 and 1972 showed the medicine was effective in controlling asthma

1975 a synthetic form of atropine, ipatropium bromide, was introduced to the market in Germany. It had fewer side effects than atropine.

1976 Metaproterenol was approved for use by asthmatics and was marketed as Alupent and Metaprel or sometimes oriprenaline. Fenoterol was marketed in New Zealand as the first long acting beta adrenergic (LABA). It was later determined to be responsible for a spike in asthma related deaths, although many suspect this was due to poor education and not so much the medicine itself.

1978 Chomolyn (Intal) hits the market as a nonsteroidal anti-inflammatory medicine (mast cell stabilizer). It was available as a dry powder inhaler given via the spinhaler. Ipatropium bromide is approved by the FDA and marketed as an inhaler and solution. Oxitropium bromide is likewise released as a longer acting anticholinergic, but not approved by the FDA.

1980s Pirbuterol (Maxair) autohaler was introduced as first breath actuated inhaler. It works in 5 minutes compared to Albuterols 15. Nervous theory of asthma was disproved. Growing concerns about the manner in which young people were inhaling or ingesting asthma cigarettes for their hallucinogenic properties led to their eventual disappearance from the market. Leukotriene antagonists were discovered and proven to block the effects of leukotrienes, which are believed to cause inflammation of the air passages of the lungs.

1981 Allen & Hansbury's Ventolin and Schering-Ploughs Proventil were approved by the the FDA

Fenoterol was repackaged in New Zealand with warnings and information about proper use, and the asthma death rate in the country subsided. Three brand names of terbutaline were approved by the FDA: Bricanyl, Brethaire, and Brethine. A DPI was available but not in the U.S.

1982 Albuterol (Salbutamol in some countries) was approved for use as a nebulizer solution and as an inhaler. It became the most popular asthma medicine of the 1980s and 1990. Azmacort was on the market. 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

1982 Alupent became the only prescription drug switched to an over the counter drug because it was deemed safer and more effective than primitine mist. Due to risk of abuse and disputes with lawyers the drug was taken off the shelves within the same year. Aerobid (flunisolide) approved by FDA.

1984 Flunisolide (Aerobid) enters market as another inhaled corticosteroid (that tastes like rotten mints). Triamcinolome was approved by the FDA and marketed as Azmacort. The recommended frequency was 2-4 puffs four times daily.

1985? Theochron hit the market as the first slow release theophylline medicine. It was hard pressed to top the market for Theodur, the popular brand of theophylline on the market. In fact, my home doctor put me on Theochron, and my doctor at NJH/NAC took me off this medicine saying long acting bronchodilators are not for asthma.

1985 The inhalator DPI is on the market in Europe but is never approved by the FDA until it was later refined and marketed as the Foradil Centihaler in 2006. Inhalers, both rescue inhalers and inhaled corticosteroids, accounted for 25 percent of all prescriptions dispensed for the treatment of asthma

1986 Alupent patent ran out opening the door for generic and cheaper metaproterenol products.

1987 the chemical composition of Atropine was refined and Ipatropium Bromide (Atrovent) was introduced to the market. It was marketed as a medicine that dilated the lungs without the side effects of Atropine. Albuterol solution approved by FDA.

1987 Montreal protocol signed to phase out chlorofluorocarbons (CFC) as a propellant in asthma inhalers by 2000 because theory had it CFCs were damaging to the ozone.

1989 The patent on Albuterol ran out opening the door for cheaper generic Albuterol inhalers. National Heart Blood and Lung Institute created the first Asthma Guidelines for the diagnosis and management of asthma. For the first time all asthma experts would be on the same page, and all the latest evidence would be analyzed. A recommendation made by these guidelines was that inhaled corticosteroids should be a top line treatment to prevent and control asthma. As a result, sales of Aerobid (flunisolide) skyrocketed.

1990s Bitolterol (Tornalate) was introduced to market as having fast onset. Because it was simiilar to epinepherine, isoproterenol, and esoetharine it never caught on. Salmeterol (Serevent) was introduced to the market as the latest version of a long acting bronchodilator (similar to Albuterol).

1990s inhaled corticosteroids proven to be relatively safe for asthmatics. It was also proven that asthma is a disease of chronic inflammation. Studies verified that the small amount of steroid inhaled every day is much better and much safer than starting and stopping the medicine based on asthma symptoms. Inhaled corticosteroids became a front line treatment for asthma. For the first time asthma was treated as a preventable illness as opposed to simply treating acute symptoms.

1990s Combivent was introduced to the market as first combination inhaler (Albuterol and Atrovent). The cyclohaler DPI is made available in Europe and marketed as Salbutamol Cyclohaler and Salbutamol Cyclocaps.

1991 Aerochamber spacer device became the top selling spacer device on the market. In the first three months of this year sales of Aerobid sales double sales from previous year, and credit is given to the new asthma guidelines.

1992 GlaxoSmithKline's diskhaler was approved by the FDA. The original discus contained 4-8 blisters per cartridge, which made it so the patient didn't have to worry about handling each dose. Today's diskus contains a month supply of capsules that are made available to the patient by clicking a lever (i.e. Advair Diskuss). Nedicromil Sodium was approved by the FDA as the main alternative to the Intal Spinhaler. Purbuterol (Maxair) approved by FDA as first breath actuated rescue inhaler on the market.

1994 Salmeterol (Serevent) approved by the FDA as a safe LABA to be used to control asthma.

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.Salbumin was the first HFA albuterol inhaler

1996 Duoneb and Combivent approved by the FDA. Fluticasone (Flovent) approved by the FDA. Proventil HFA was approved by the FDA

1997 Fluticasone Propionate (Flovent) on the market. It's a stronger and longer lasting inhaled corticosteroid as compared to beclomethasone dipropionate (Vanceril ) and Azmacort.

1997 Astra Zeneca's turbohaler was approved by the FDA and marketed as Pulmicort Turbohaler.

1998 Advair introduced to market. It contains a long acting bronchodilator salmeterol and inhaled corticosteroid fluticasone. Budesonide (Pulmicort) turbohaler introduced to market. Montelukast sodium approved by the FDA as the first leukotriene antagonist to prevent the allergic reaction in asthmatics. It's marketed as Singulair.

1999 Levalbuterol was introduced to the market as Xopenex. It was the first bronchodilator since epinepherine to have only the r-isomer. Zafirlocast (Accolate) approved by FDA as a a leukotriene antagonist to compete with Singulaiir. 17 unique brand names for ventolin are on the market including ProAirr, AccuNeb and Vospire.

2000 Symbicort released in Sweden. Flovent Diskus approved by FDA. Advair approved by the FDA. Pulmicort respules approved by the FDA as the first approved solution version of an inhaled corticosteroid. It's presently marketed for kids. The first HFA beclomethasone is approved by the FDA as Qvar. The inhaled particles are later realized to be finer and generate better lung distribution than CFC inhalers and DPIs. Liekotriene antagonists like Singulair on the market.

2001 terbutaline inhalers brethine and brethair were taken off the market, and so to was bitolterol. Symbicort available in Europe. Foradil Aerolizer was approved by the FDA and introduced to U.S. market. Formoterol was marketed in the U.S. Oxeze, Atock, Atimos and Performist were common names used overseas. A Ventolin HFA was approved by the FDA.

2002 Xopenex inhaler introduced. Spiriva introduced to the market as long acting version of Atrovent with even fewer side effects. It was later proven to improve lung function in COPD patients. All Ephedrine products were discontinued and the product line was phased out mainly due to fear people were abusing the medicine.

2002 QVAR patented as the first beclomethasone hfa inhaler. QVAR is proven to have smaller particle size than other inhaled corticosteroids fore deeper and more equal lung distribution, and it generally costs less than its competitors.

2003 Mometasone (Azmanex) dry powdered Twishaler introduced to market. A black box warning is placed on all long acting beta adrenergic products (LABA), which would ultimately include Foradil, Serevent, Advair, Symbicort, and Dulera. Tiatropium bromide (Spiriva) approved by the FDA and released in Europe and the U.S. Omalizumab is approved by the FDA as the first anti-IgE medication, and marketed as Xolair. It costs $10,000- 30,000 per dose. Purbuterol (Maxair) removed from market to to lack of acceptance.

2004 Ciclesonide (Alvesco) approved for sale in the U.S.and Australia. Flovent HFA inhaler approved by FDA

2005, the FDA released a health advisory warning of dangers of long acting beta adrenergics like Serevent, Formoterol (Foradil), Advair, Symbicort and later Dulera. Alvesco launched in the U.K and Germany.

2006 Serevent Discuss (salmeterol xinafoate)approved by FDA. The FDA approved the Foradil Centihaler which will be under patent until 2019. The recommended dose is two puffs of the inhaler twice daily or one puff on the DPI. Symbicort is marketed by AstraZeneca and approved by the FDA. Foradil centihaler approved by the FDA.

2007 Symbicort hits the market as competition to Advair. It contains formoterol (a quick acting and long acting bronchodilator) and inhaled corticosteroid budesonide. Zileuton approved by the FDA as another anti-leukotriene antagonist and marketed as Ziflo.

2008 there would be over 20 different DPIs on the market. Azmanex (mometasone furoate) approved by the FDA as the longest acting inhaled corticosteroid. It was marketed as the Azmanex Twisthaler (DPI). Salmeterol was linked with asthma related deaths and a black box warning was added to the labeling. Ziflo taken off the market.

2010 Metaproteronol was phased out as an option for asthma. Tilade, Alupent, Azmacort, Intal, Aerobid and Combivent are all phased out. A new corticosteroid/ long acting beta adrenergic combination inahler containing mometasone furoate and formoterol fumarate dihydrate is introduced to the market as a new competitor against Advair and Symbicort. Dulera approved by the FDA as a combination inhaler to compete with Advair and Symbicort. It contains mometasone furoate and formoterol. The patent for Advair expires.

2011 Primitine Mist, the last remaining over the counter bronchodilator, was removed from stores. The medicine used a CFC propellant and this gave the FDA an excuse to do what it was try ing to do for years, get bronchodilators off the shelves. The Pulmicort Turbohaler is phased out. In December 2011 the last remaining brand of the epinephrine inhaler is taken off the market, which means there are no longer any approved over the counter asthma rescue inhalers.

2012: The most popular inhaled corticosteroids are Aerobid, Azmacort, Qvar, Flovent and Azmanex. The two main bronchodilators are Albuterol and Levalbuterol. There are over 35 DPIs on the market. The Combivent Respimat approved by the FDA.

2013 Maxair set to be phased out
References:

*Baas, Johann Herman, author, Henry Ebenezer Sanderson, translator, "Outlines of the history of medicine and the medical profession," 1889, New York.  all other references can be found in the posts. 

1 comment:

  1. Great post. You have great knowledge. Thank you for sharing the historic info. It has also some info about ephedrine.

    ReplyDelete