Tuesday, February 19, 2013

1870-1900: What asthma theory won the era?

History 2700 B.C.
Time 1 A.D.
Scientific revolution 1543-1899
Age of Reflection 1900-

As we travel into the middle of the 18th century we enter the scientific revolution, and it's at this time when physicians start to wonder about the definition of asthma. Various theories are formed and debated over the next

The following post is presently being edited: Rick Frea 1/9/13

The 18th century is over, and we are now headed into the 19th century.  It is in this century that the definition of asthma would change and change for the better.  It would evolve from one based on speculation to one based on scientific fact.  Yet, as we all know, change never comes without a fight.

In my last post I listed the eleven theories about asthma that were debated in the 19th century.  Below is a chronology of the most important physicians of this era, and how that person influenced the evolution of the term "Asthma."   

xAlbrecht von Haller: (1708-1777) He studied at the university of Tubingen and then in 1725 at Leyden where his professor was Herman Boerhaave.  Medical historian Thomas Bradford said he had such a zeal for anatomy that while at Tubingen he dissected dogs, and at Leyden he purchased half a body for dissection.  He also "engaged in grave robbing, and betrayed by the stench that arose, was obliged to flee." (20, page 143)

He received his medical degree at 19 and went to London where he taught anatomy. At 26 he became professor of anatomy and director of the hospital at Berne. In 1736 he became professor of anatomy, surgery, chemistry and botany at Goettingen.  He wrote many books, and some say he was so busy that he slept in a library, said Bradford. (20, page 143)

He is often given credit as the physician to revive experimental physiology, or the study of the functions of living organism. (20, page 143)

He believed that "the normal act of expiration hindered the flow of blood through the lungs," and "demonstrated that the lungs contracted when concentrated acid was applied to it."  (16, page 27)

He also performed experiments that would verify the spasmotic theoery of asthma. (15, page 4)

xWilliam Herberden: (1710-1801) defined "convulsive asthma" the way angina pectoris was later defined: as chest pain or discomfort due to activity or stress.  (16, page 27)

x (compare)Dr. Robert Bree:  (1759-1839)  He was an English physician and asthmatic who believed modern theories such the nervous theory of asthma and the spasmotic theory of asthma were the subject of quackery.   He set out to prove William Cullen wrong and Hippocrates and Galen closer to the truth in a book about asthma he published in 1797.  He was an ardent supporter of the bronchitic theory of asthma.  (1)

He wrote that no science proves the nervous or spasmotic theory of asthma, especially considering those two conditions cannot even be observed in autopsy.  He said you can see phlegm on autopsy but no evidence of spasms, so science supports his theories and those of Galen and Celsus more so than Cullen.

A problem we run into with Bree is he tried to prove his theories by dissecting the lungs of asthmatics who died, yet asthmatics, as he duly noted in his book, rarely died. So he often had to rely on autopsies performed on the lungs of people who died of other lung diseases. (3, page 85)
Ernest Schmiegelow explained in his 1890 book that:
"Bree does not actually deny the possibility of bronchial spasms taking some part in the cause of asthma, but it is only secondary; the primary cause is an exudation in the bronchial tubes, by which the lungs (specially the muscles of respiration) are stimulated to contraction, in order to expel the mucus which they contain." (2)
Bree believed that mucus was the cause of most diseases, including asthma.  He believed the contraction of the lungs was a defense mechanism to expel mucus from the lungs. Bree's ideas about asthma are important to our 19th century history because he is considered by many the preeminent asthma expert of the first half of that century.  You can read more about Dr. Bree by clicking here.  A thorough review of Dr. Brees book was written by Ralph Griffiths of The Monthly Review and can be found by clicking here.

(x) Georgy Lipscomb:  (1773-1846) He's a fellow asthma expert of Bree from England, and he sets out to prove Bree wrong.  Around the year 1800 his goal was to "elucidate the history of a very prevalent and distressing disease, which has been hitherto but ill explained, and very unsuccessfully treated,' according to Mark Jackson in his 2009 book. (3, pages 86-8)

Lipscomb published his own theories in a book published in 1800 called "Observations on the history and Cause of Asthma."  Lipscomb argued that Bree could no more prove Cullen's theories were wrong than Cullen could prove them right because upon death the lungs automatically relax." (3, pages 86-88)

Lipscomb was reviewed in an 1800 edition of Monthly Review:  (17, page 310)
This publication, notwithstanding its promise, contains merely an attack on Dr. Bree's Enquiry. Some of the observations may be just, but they are so minute as to assume a captious appearance; and the strictures on Dr. Bree's language are certainly conveyed with an unnecessary degree of severity. After our large account of the Doctor's work in the Review for May last, it is needless to repeat our opinion concerning the style and arrangement of it: but we, should not have expressed ourselves in the manner of Mr. Lipscomb. In p. 89, Mr. L. sneers at Dr. Bree's account of acid perspirationbut, if he will consult Dr. Wilson's book on febrile diseases on the subject of sediment in the urine, he will find ample proof of the fact. It is not indeed peculiar to asthma, nor to any morbid state of the body.  We are sorry to learn, from Mr. Lipscomb's preface, that he has enemies, who have succeeded in lessening his professional engagements. Lest we should be deemed desirous of adding to his uneasiness, we shall decline any farther examination of his criticisms. (17, page 310)
You can read another criticism of Lipscomb's criticism in the British Critic by clicking here. You can learn more about Dr. Lipscomb by reading his obituary here.

xJean Nicolas Corvisant: (1755-1821)  In 1808 he introduced to the medical community an old technique called percussion, or tapping on the chest, to hear the different sounds emitted by different diseases. "It is only after percussion began to be practiced that asthma can more clearly be discerned in history," wrote Berkart. (4, page 13)

This allowed physicians to distinguish dypsnea from heart disease and pneumonia from asthma.  Once this occurred, physicians could accurately observe that there are no organic lesions from pure asthma, and that it was nervous in origin.  While his theories were later proven by later physicians, "his means of diagnosis were yet too limited to prove that supposition." The next person to take up that task was Laennec, a student of Corvisant. (4, page 13)

You can read about Dr. Corvisant and chest percussion by clicking here.

xSamuel Thomas von Sommering: (1755-1830) Like Reissisen below, he discovered fine muscles that wrap around the air passages of the lungs. (15, page 4)

xRene Laennec:  (1781-1926) In 1816 he invents the stethoscope, and, according to Dr. J.B. Berkart, by using this tool Bree's theories are pretty much wasted, as it's easily to prove by auscultation that an attack of bronchitis does not precede asthma, and that rhales, a lung sound Rene Laennec used to describe secretions in the lungs, are heard later during the attack. (4, pages 13-)

By use of his new tool, Laennec (an asthmatic) sets out to study disease symptoms and signs, and compare them to what he sees on autopsy. He soon realizes that asthma is a very abused term by the medical community, as it is used to describe any disease that causes dyspnea. He realizes that some cases of asthma are caused by the heart, and he refers to this as cardiac asthma.
He defined asthma as either:
  • Dry: This is basically asthma that was not associated with copious amounts of sputum.  This type of asthma is generally periodic, with periods of no symptoms between attacks. 
  • Humid: This is basically asthma associated with copious amounts of sputum with chronic catarrh (inflammation) of the air passages.  This is in line with the bronchitic theory of asthma.  This type of asthma is generally chronic. 
  • Cardiac asthma:  This is dyspnea caused because the heart becomes a weak pump (heart failure)
By listening to the lung sounds of his patients, he heard sibilant and sonorous wheezes, and he associated these as probable proof that asthma was caused by spasming of the air passages, and in this way he becomes a supporter of the spasmotic theory of asthma. By observing no organic lesions in cases of paroxysmal asthma, he believed supported nervous theory of asthma. For more on Laennec click here.

Yet while Laennec believed spasms were a component of asthma, he believed the most common form was his "catarrhal asthma," which was essentially bronchitic asthma. (15, page 4)

Corvisant and Laennec set the ground work for other physicians to work from in further defining asthma and distinguishing it from other diseases.

xDr. Franz Daniel Reisseissen:  (1773-1828) He was a German physician who studied the lungs. He performed experiments in 1808 (13, page 8), that were published in 1820, that were "the first step toward a ruly scientific theory of the pathology of asthma. He discovered "smooth muscle fibres of teh bronchial tubes. These fibres are found not only in the large and medium-sized bronchi, but even in thoses of the smallest calibre." (10, page 185, 193)

He is quoted as writing: "there is another apparatus appointed for contracting the bronchi, which consists of transverse muscular fibres. As far as the cartilaginous rows extend, these fibres are inserted...." (5, page 186).
He found these smooth muscular fibres to exist in "the large and medium-sized bronchi, but even in those of the smallest calibre." Berkart notes that Reisseissen had no idea their function at the time they were discovered. (4, page 17) You can read the 1835 edition of his book by clicking here

M. Varnier: (Name and lifespan unknown to me) believed "irritating fluids or fumes forced into the lungs cause contraction therof." Varnier: , however, was also among the first physicians to prove by his experiments that muscles that wrap around the bronchial tubes contract, and this is the cause for the symptoms of asthma. He basically offered proof that confirmed the studies of Dr. Franz Daniel Reisseissen (see above). (15, page 4)(16, page 27)

xFrancis Hopkins Ramadge:  (1793-1867) In 1835 he described food as an asthma trigger, recommends moving from the city to country, and of asthma being mostly a nocturnal disease. He discourages use of opiates because they impede respirations that are already impeded. He mainly recommends strammonium because it "produces a grateful forgetfulness and a balmy oblivion like opiates." (8, page 7) He regarded asthma as a neurosis of the respiratory organs. (You can read his 1835 book "Asthma, its species and comications" by clicking here)

Prize essays of Bergson and Lefevre: This occurred in 1836. They regarded, as did Ramadge, asthma as a neurosis of the respiratory organs (7). (need to write about his remedies, see his book).

x Amedee Lefevre: Around 1835, Lefevre (an asthmatic) observed in his own asthma and that of a friend and concluded asthma could only be caused by bronchospasm, and that this bronchospasm was caused by the mind, according to Berkart. While he believed asthma was nervous, "he still was not prepared to deny the possible existence or organic lesions; adding, however, that if they were present, they were of so fleeting a nature as to elude detection. " (4, page 23-24)
Berkart further explains that "in essence of the disease he (Lefevre) considered to be an increased irritability of the nerves of the lungs, in consequence of which the slightest irritation applies to the bronchial surface induced spasm of the bronchial tubes."(4, page 23-24)

Berkart also notes that Lefevre's reports prove nothing: "The cases, however, which he himself reported, do not confirm his views. It is difficult to recognise a nervous affection, much less a bronchial spasm, in the dyspnoeal attacks, which terminated always with the expectoration of thick masses of mucus. The expectoration was of a grey colour, very viscid, in consistency like boiled maccaroni, filamentous in shape, and, when disentangled, appeared as if moulded to the bronchi. Sputa of that kind sufficiently distinguish the preceding dyspnoea as the symptom of a fibrinous (croupous) bronchitis, and there can be no doubt that Lefevre and his friend were s     ubject to that disease.

xRobley Dunglison:  (1798-1869) He had doubts about the nervous theory of asthma, believing instead that there is some organic cause to the affection.  

xDr. William Budd:  (1811-1880) In 1840 Budd disproved the convulsive theory of asthma. Berkart explains that Budd repeated experiments previous authors wrote would produce bronchospasm and he didn't produce the same results. In fact, as Berkart explains, Budd flat out "rejected the theory of a bronchial spasm, and even doubted whether the circular fibres were muscular, as alleged." (4, page 25)

It's also interesting to note, as Shmiegelow explains, that one thing that helped him verify his proof that asthma was not spasmotic was that "He has found by experiments that only one-fifth of the vital tonus of the lungs is due to organic muscular fibres in the bronchial tubes, while the remaining four-fifths depend upon the elastic fibres in the tissue of the lung. A spasm of these muscles can, therefore, only be of small and insignificant influence, and does not give a satisfactory explanation of the nature of asthma, for both the expiratory and inspiratory muscles exceed in strength all the bronchial muscles put together." (15, page 4)

Budd, thus, did not believe the fibres discovered to be wrapped around the air passages of the lungs were muscular, let alone that they spasmed and caused narrowing of the air passages that resulted in asthma. He believed asthma was more so caused by heart disease and emphysema than spsasm. Yet some cases of asthma are nervous, although most cases considered nervous are probably caused by some "organic change which has yet escaped our observation." He believed all the tissues of the lungs contracted, not just the bronhioles. (16, page 32)

So now we had proof the bronchospasm theory of asthma was fallacious. Or did we? Budd was proven wrong that same year by Dr. Charles J. B. Williams.

xDr. Charles James Blasius Williams:  (1805-1889) He is the same brilliant physician who came up with the term lub dub to describe the sounds emitted by the beating of the two chambers of the heart.  He also studied asthma, and for that we are fortunate, as he's the person who ultimately proved in 1840  the spasmotic theory of asthma.  Geddings explains that William's "ascertained" that by "irritating the lung he could cause contraction" of the muscular fibres that were discoverred by Reisseissen to wrap around the lungs.  (10, page 94)

J.B. Berkart explained that Williams performed experiments that proved without a doubt "that mechanical and electrical stimuli do produce contraction of the air-tubes. Thus the theory of a bronchial spasm obtained the support of experimental physiology. And even those who until then wavered in their opinions as to the possibility of such a spasm saw now no reason for doubting, but readily accepted that doctrine."  (4, page 26)

John Charles Thorowgood, in his 1878 book "Notes on Asthma," explains: (9, page?)
"The larger bronchial tubes have their cartilaginous rings as elastic spring-openers; the smaller tubes, lying nearest to the vesicular parts of the lung, have no cartilaginous rings, but are entirely muscular; and (Rene) Laennec and (Daniel) Reisseissen, and more recently Louis Pierre Gratiolet (1815-1865) , have detected muscular fibres in air-tubes less than one line in transverse diameter. The contractility of these fibres under the influence of electrical, chemical, and mechanical stimuli was proved in a series of ingenious and conclusive experiments by Dr. Williams many years ago."
Williams became the first to break asthma into two types: spasmodic and paralytic. Berkart wrote that as of the writing of his (Berkart's) book in 1878, the two terms described by Williams were the ones accepted by most experts.  However, other doctors would continue to reclassify asthma to their own content and amusement.

He also proved that certain irritants cause contraction of the muscular fibres that Reisseissen proved wrap around the air passages in the lungs

xDr. Francois Achille Longet: (1811-1871) Shortly after Charles J.B. Williams performed his experiments and published them in 1840 that proved that asthma was caused by contraction of the smooth muscles lining the air passages, Longett performed experiments of his own that confirmed William's findings.

According to William Pepper and Louis Star, "It was ascertained by (Charles J.B.) Williams that by irritating the lung he could cause contraction of these fibres, and Longet subsequently proved that the same effect could be produced by galvanizing the pneumogastric nerve."  (10)

Berkart explains that in 1842 Longet performed experiments to prove "irritation of the pneumogastric nerve always produced spasmodic contraction of the bronchi, whereas section of the nerve led to emphysema, which was described as distention of the air vesicles."  (4, page 27) Longet also believed bronchospasm and emphysema were both parts of asthma.

xMoritz Heinrich Romberg:  (1795-1873)  In 1841 he described asthma as two different affections of the vagus nerve, and he called them bronchospasm (spasms) and paralysis (emphysema). (4, page ?)(16, page 34)

By this he further established the view of asthma as a nervous disorder, and "based his conception of the disease as a spasmus bronchialis, upon the discovery by Reiseissen (1808) of muscular tissue in the finer bronchial tubes, and the contraction of these tubes under galvanization of the lungs by Charles J.B. Williams (1840), and irritation of the vagus (nerve) by Dr. Francois Achille Longet (1842)." (7, page 506)

Romberg basically referred to spasms as "bronchial cramp," or spasmus bronhialis. (15, page 4)  He therefore was an obvious supporter of the spasmotic theory of asthma.  (20, page 13-14)(25, page 11)

George Hirsh: He published a book called "Spinal Irritation" in 1843.  Berkart gives a pithy summary of his thoughts on asthma.  Berkart said:
Only George Hirsch urged that, among a large number of cases that had come under his notice, he had never met with one in which the dyspnoeal paroxysm seemed independent of structural lesions. If asthma were a nervous affection, its frequent occurrence in the male would be unintelligible, because functional derangements of the nervous system are almost exclusively met with in the female.  (Berkart, page 30)
( Berkart's Referene: Spinal Irritation. Kbnigsberg, 1843, p. 248. )

xCaleb Hillier Parry?:  Believes "engorgement of the mucous membrane of the bronchi... (can) interfere with the passage of the air." (16, page 32) In other words, he believes in the bronchitic theory. He wrote "Elements of Pathology," in 1815.

xNathaniel Chapman:  He believes a "caharrhal condition of the respiratory passages and cough" as preceding the spasming of the air passagis, and therefore believes in the bronchitic theory of asthma and the spasmotic theory of asthma. He believed that "holding your breath and talking quietly and calmly decreases the intensity of the attack." (16, page 33)

Friedrich Gustav Jakob Henle:  (1809-1885) He believed "imperfect expiration and stenotic sounds as evidence of a paralysis of bronchial muscle." (16, page 33)

xCarl von Rotikansky:  (1804-1878) In 1844 he wrote about emphysema being the basic cause of nervous asthma.  (15, page 4)(brief mention in Traube post)

x Rudolph A. von Killiker: (1817-1905) In the 18th century William Cullen believed the muscle was just a continuation of a nerve.  In 1848 von Killiker was a histologist who proved this was not true.  He basically confirmed the works of Williams and Reisseissen as he isolated smooth muscles in the lungs. Yet since nerves still connected to muscles, van Killiker's discovery was unable to stop the fallacy of the nervous theory of asthma.  (11, page 422)  He "demonstrated them in bronchioles 0.18 milimeters in diameter." (10, page 194)

xJoseph Bergson:   In 1851 Bergson denied paralytic asthma existed and he did experiments to prove asthma was only spasmotic. Actually, John Reid performed these experiments, Bergson just applied Reid's experiments and theories to the understanding of asthma.  While Bergson believed asthma was spasmotic in nature, he believed the cause was nervous and he performed studies with Dr. Lefever (as noted above) to prove this. (3, page 17) (20, pages 13-14) (25, page 11) His studies, along with the studies of Romberg and  Dr. Lefevre pretty much proved the nervous theory of asthma. His book was Das Krampfhafte Asthma Der Erwachsenen (The 1889 edition here).  (7, page 506)

The following was also learned by Bergson's book: (5, page 4)
It was especially after the publication of Bergson's prize work that a decided separation was made between the idiopathic nervous asthma, characterized by its periodical attacks, which are separated by perfectly free intervals, and the numerous forms of difficulty in breathing, which appear purely symptomatic in many different complaints of the chest. ToBergson the idiopathic nervous asthma is an independent neurosis of the organs of the chest, whose origin is a cramp or spasm which like all other neuroses can be caused by a central or peripheral irritation of the nervous centre.
x  Dr. M. Beau and his pupil Crozant:  In 1851 they devised theories that  rejected the spasmotic and nervous theory of asthma.  They insisted asthma was caused by increased sputum in the lungs that was capable of blocking the air passages with mucus plugs. (read more about their theories here) (4, page 30-31)

In his "A distinction of two forms of bronchitis" that was published in "He (Beau) considers asthma to be a phenomenon of a particular form of bronchitis which he calls 'bronchite a rales vibrants," according to Dr. Henry Hyde Salter, "and that the wheezing and the dyspnoea alike depend on the obstruction of the air tubes by the inflammatory products of this bronchitis.  (12, page 24)

Of the Spasmotic theory of asthma, Salter quotes Beau as writing: (12, page 24)
This opinion, adopted by many conscientious physicians from respect for medical traditions, is no longer capable of being maintained, since auscultation and percussion have given us the means of seeing (so to speak) what occurs in the chest. It has, in fact, been ascertained, with the assistance of these two methods of inquiry, and in a manner the most positive, that there is no asthmatic dyspnoea without an obstruction of the bronchial tubes, which causes vibrating rales (the sound of secretions moving through air passages)and which, producing an obstacle to the exit of the inspired air, forces it to react on the vesicles and to dilate them. (12, page 24)
Essentially Beau and Crozant performed experiments that confirmed that contractility of the muscular fibres that wrap around the air passages spasm during an asthma attack.

xWilliam Tennant Gairdner:  (1824-1907)  He graduated from medical degree in 1845 (24) and became a physicain at Edinburgh who was mentioned by a variety of sources as being an ardent supporter of the spasmotic theory of asthma. (12, page 12, 24)(23, page 66)  Salter has written about him.  He rejected J.S.H. Beau's bronchitic theory of asthma, and wrote some nice articles on it.  You can also find some by surfing the net.

xM. Alton Wintrich:  After Salter wrote of his support for the spasmotic theory of asthma "it met with but little opposition until 1854, when Wintrich, after a series of experiments, arrived at conclusions directly opposed to those of Williams and Longet in regard to the contractility of the muscular fibres of the bronchi, and refused to accept the spasm theory on the grounds that it afforded no rational explanation of the phenomena of asthma.  He believed that the various symptoms of that disease were due to tonic spasm either of the diaphragm alone or of the diaphragm and the other muscles of respiration (which was an idea first introduced by Thomas Wilson in the 17th century)." (10, page 194) (16, page 34)

Berkart explained the Wintrich didn't deny bronchospasm altogether, although when it occurred it was a result of "disturbance of intervention." This is when irritation of one area of the body (such as the diaphragm) effects the nerves that lead to another organ (such as the lungs or glottis). (4, page?) (also see 15, page 4)  As noted by Shmiegelow, both Thomas Willis (1621-1675) and Neumaun (?) both mentioned the diaphragm as the cause of asthma. (5, page 4)

xDr. Ludwig Traube (1818-1876) In 1855 denied nervous asthma but believed asthma was rare and the dyspnea that resulted was caused by "fluxionary hyperaemia of the bronchial mucous membrane." What he is referring to here is "swelling of the bronchial mucus membrane," wrote Berkart. This is probably what we now refer to as inflammation of the bronchial tu es. This is one again a version of the bronchitic theory of asthma.(4, page 32-33) 

Traube also believed asthma was caused by sputum in the air passages of the lungs, according to Jackson  He also wrote that this inflammation cannot be diagnosed during a person's lifetime, and can only be diagnosed by the symptoms it presents with, such as dyspnea and wheezing. ( 3 Jackson?)

He also "demonstrated how respiration can be arrested by irritation of the pneumogastri or laryngeal nerves or the Schneiderian membrane of the nose (membrane lining the maxillary sinus cavity)." The nerve is much more to be irritated during expiration, and this might explain why asthmatics go into a fit after a strong cough or laughing fit. (9, page 5)

xGuillaume Benjamin Amand Duchenne (1806-1875) He was a French neurologist, who, unaware of the works of Budd and Wintrich, proved Budd right in 1855 --or so he thought. As Berkart wrote, Duchenn proved "faradisation of the phrenic nerve caused tetanus of the diaphragm. He initially thought this was no big deal until he talked to Dr. Vallette, who convinced him that "tonic spasm of this muscle was the main cause of the asthmatic paroxysm." (4, page 35)

He demonstrated that "faradisation of the phrenic nerve caused tetanus of the diaphragm," and this proved the diaphragmatic theory of asthma. He, along with Budd, Banberger, and Wintrich supported this theory. (4, page 35)
(You can view Duchen's book here) (4, page ?) (also see 16, page 34)

xCarl Friedrich Cannstatt(1807-1850) He was a pioneer of modern medicine in Germany. In 1855 he wrote that a differential diagnosis of asthma didn't matter because anti spasmotics were equally beneficially for both diseases. (4, page 32) He believed asthma was a "spasm of the breathing organs" as opposed to accepting the spasm theory of asthma. (16, page 32)

x? Armand Trousseau:  (1801-1867) He believed in the nervous theory of asthma, that asthma lead to emphysema, and that it was often associated with consumption.  (9, page 37)

Ironically, other physicians believed asthma was the opposite of consumption.

He also supported the spasmotic theory of asthma.  (20, page 13)(25, page 11)

I believe I already wrote an article about him.

Gabriel Andral:  In the 1857 edition (the 4th edition) of his book, "Clinique Medicale," he describes asthma as nervous. (16, page 34)  He also supported the spasmotic theory of asthma. (20, page 14)

You can read more about Andral's views on asthma by clicking here.

For more on him see his book, and also see Rene Laennec's book, because Andral wrote the notes in the margins.

Sir Thomas Watson:  (1792-1882) According to John Thorowgood, he said in his lectures:
"The bodies of asthmatics have often, on being examined after death, presented no vestige whatever of disease, either in the lungs or in the heart; evidence that the phenomena attending a fit of asthma may be the result of pure spasm." (9, page 2)
He wrote about asthma in his 1857 book "Lectures on the Principles and Practice of Physic."  In this book he explains that asthma is sometimes "purely spasmotic," and sometimes the result of "congestion of blood in the lungs." (29, page 130)

Charles Radclyffe Hall:  (1819-1879) He believed in the spasmotic theory of asthma. (20,page 14) (25, page 11) He was from Edinburgh, was a member of the College of Chest Physicians in 1859, and was physician to the Western Hospital for Consumptives at Torquay and author of Essays on Pulmonary Tubercle.

xDr. Jean-Pierre Thery:  He believed in the spasmotic theory of asthma. 20, page 14)(25, page 11)  He supported the idea that "spasm of the bronchi for the purpose of getting rid of irritating material."  (16, page 34) This idea sounds eerily similar to that of Dr. Bree. (published in Bree Post)

He published his asthma wisdom in his 1859 book "De l'Asthma."

xMoise Bervenisti In 1859 he brought attention once again to the differentiation of the different causes of lung diseases that he believed were probably unrelated to asthma. He (Bervenisti) believed that a doctor could not possibly diagnose bronchospasm by listening to lung sounds alone. That sonorouis and sibilant rhonchi are also present with a pulmonary embolism, which also causes dyspnea. (4, page ?) He also believed that "there was a definite pathological process at the bottom of asthma even though often undiscoverable." (16, page 34)

Smith: Notes that asthma (dyspnea) is caused by congestion in the lungs," and that, according to Thorowgood, blood is inspired into the chest and hence, if the air tract is obstructed, proportionately more blood is taken in." (9, page 35) It is this blogger's belief that Smith is referring to cardiac asthma, which was later taken out from under the umbrella of asthma and referred to as heart failure.

L. Merkel:  He studied the various studies on asthma and by 1861 concluded that spasm of the lung must be caused by some nervous stimulation. Of interest, he was one of many physicians who believed the purpose of bronchial muscles was to cramp in order to prevent irritating matter from getting into the lungs. In asthma, he believed the bronchial muscles "may be exercised when it is of no benefit or use." (9, page 35)

He believed asthma was often complicated with bronchitis, catarrh, emphysema and heart disease. He believed "treatment should be directed at the nervous system," and that "inhalations are the most efficacious treatment." (9, page 35)

xJean Antoine Villemin: He gained fame as the person to prove tuberculosis was contagious after rabbits he injected with tuberculosis from humans contracted the disease. In 1860, while studying asthma, he tried to disprove the nervous theory with his own scientific experiments, yet once again the nervous theories were so popular Villemin's approach was ignored by the medical community.

His theory, however, was quite interesting.  Here it's described by Berkart:
Villemin professed to have demonstrated the pathological changes that deprived the pulmonary tissue of its elasticity, and predisposed the bronchial mucous membrane to hypersemia. He stated that emphysema originated in a proliferation of the inter-capillary nuclei, whose advancing growth tended to compress the alveolar vessels. As the nutrition of the air-vesicles became impaired, they were unable to efficiently perform expiration. At the same time, the respiratory surface was reduced, and the blood accumulated in the bronchi to such extent as to convert their mucous membrane into a kind of erectile tissue. This condition gave rise to no symptoms, either subjective or objective. Its existence became manifest only by the readiness with which trifling incidents produced their effect. Hyperaemia (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 recognised by other observers
Ironically, 130 years later, asthma was found to be a disease of chronic inflammation.  Should we go back now and give Villemin cretic in retrospect?

Leo Gerlach:  In 1876 he wrote of his supporter of the spasmotic theory of asthma.   (25, page 10-11)(20, page 14)(25, page 15)  He was among five physicians who proved that stimulation of the vagi resulted in spasms of the bronchi. The others being Horvath, Willem Einthoven, T. G. Brodie, Dixon and Beer.  (16, page 163)

He was Professor of Anatomy and Director of Anatomical Institute of Evlangen, according to The Lancet in 1861. (27, page 162)

x Alfred Wilhelm Volkman: (1801-1877) He proved that irritation of the pneumogastric nerve caused "contractions of the air tubes."  (?)  Traube, Bernard (?) and Paul Bert verified these results. (9, page 5)  Of interest to note is one of the experiments he performed: "(He) tied a tube into the trachea of an animal and set a candle before the opening and then stimulated the vagus and the flame showed that air was thereby caused to come from the lungs." (16, page 33)

xGermain See:  (1818-1896) In 1865 he supported the ideas of Wintrich and Bamberger that asthma was not caused by  spasms of the muscular fibres in the lungs. (15, page 5)  (4, page 2) See reviewed all the theories of the day, and concluded: 
"Asthma is a neurosis in the medulla oblongata, that is to say in the centre of respiration, caused by an acquired or native elevated reflex irritability in this organ. The cause of the attacks must be sought for in irritations, which originate in pneumogastric nerves or other peripheral nerves. The effect of the reflex exhibits itself in the motory nerves of the inspiratory muscles, specially those of the diaphragm. We have, therefore, before us a permanent neurosis, whose attacks are caused by an irritation especially of the pneumogastric nerves, and which is always concluded by a tetaniform contraction of diaphragm, this theory only (in contrast to the bronchial spasm) can explain the dilatation of the lungs... The principal factor in the asthmatic attacks is therefore not (as in the bronchial spasm) a direct motor effect of the pneumogastric nerve, only the sensitive pneumogastric fibres take a part in this respect as they lead the irritation up to the noeud vital of the spine, whence the irritation spreads through the nervi phrenici to the diaphragm. " (15, page 9)
See divided asthma into three elements: (4,page 2)
  1. Dyspnoea
  2. Bronchial exudation
  3. Emphysema of the lungs  (4, page 2) 
J.B. Berkart explains that German experts, such as See was, to "maintain that, to warrant a diagnosis of pure bronchial asthma the bronchial mucous membrane should appear healthy, nor should any other cause for the dyspnoea be discoverable.  Still, not all supporters of this definition adhere to it throughout.  They admit that asthma may be complicated 'with' or 'grafted on' other cardiac and pulmonary affections. But, as these affections are themselves capable of producing asthmatic seizures, the distinction in a given case between this symptom and the supposed complication would be purely arbitrary." (4, page 3)

In other words, pure bronchial asthma was only diagnosed when there were no other scars found upon the lungs or the heart, at least according to the Germans, says Berkart.  (4, page 3)

Lehman:  In 1866 he also supported the ideas of Wintrich and Bamberger that asthma  not caused by spasms of the muscular fibres in the lungs.  He believed most cases were causes by "spastic affection of the respiratory muscles." (15, page 5)

CrozantHe, along with his teacher, Beau, believed "bronchial catarrh with a very viscid secretion as the cause of asthma." (18, page 30) (16, page 33)

Walter Hayle Walshe:  Orville Brown said he suggested "that the easy inspiration and difficult expiration are good reasons for assuming a paralysis of the bronchial musculature in at least certain types oasthma. He adhered, however, to the bronchiolar muscle spasm theory to explain most cases of the disease." (16, page 33)(19, page 555-556) (20, pages 13-14) (25, page 11)

Walshe published his studies and opinions regarding lung diseases in the 1871 publication "A practical treaties on the diseases of the lungs."  In this book Walshe said his idea was opposed by Dr. Salter, who did "refuse to admit the paralytic variety of asthma... it seems by law of nature, that, where circular fibres embrace a tube, they are designed to influence the movements of its contents.  Why should the bronchial muscles have been created on a different principle?   Experimenta Fallax!  Dr. Salter may urge. True; but experimenta fallaciora (19, pages 555-556)

xEmanuel Aufrecht:  (1844-1903)  He attended medical school in Berlin, and was a student of Ludwig Traube and Rudolf Virchow (1821-1902). He graduated from medical school in 1866.  He became a physician at Magdeburg-Alstadt City Hospital in 1868, and physician in chief of Internal Medicine at Magdeburg in 1879.

He worked out the arrangement of the bronchial muscle fibres. (16, page 163)  While chief of clinical medicine Magdeburg he published a book with his colleagues in 1902 called "Diseases of the Bronchi, Lungs and Pleura," (28, title page)

xRobert Bentley Todd:  (1816-92) "Todd believes asthma to be the result of a humor and compares the disease to gout and rheumatism, the difference being that in asthma the materia morbi affects the respiratory center." (16, page 33)

xDr. Henry Hyde Salter:  (1823-1871) Salter (an asthmatic) started his career as an assistant to Dr. Todd (see above). He wrote articles during the 1850s that were compiled in his 1869 book "Asthma: Its Pathology and Treatment."
He quoted  Dr. W. T. Gairdner as writing that the experiments of Williams, Longet and Volkmann "might have saved the spasm-theory of asthma from being consigned so very coolly... to the limbo of medical tradition; more especially as there never has been any doubt, even among the most hazy and 'traditional' of the spasm theorists, as to the experience of an obstruction in the bronchial tubes."(12, page 24)
Gairdner says, as quoted by Salter, that the bronchitic theory of asthma cannot be legit simply by the fact that  bronchitis usually produces a lot more sputum production than just at the end of the fit, and this appears with little signs of obstruction. (12, page 24)

Salter had great respect for all the above physicians and their theories, although he was an ardent supporter of both the nervous theory of asthma (you can see his proof of it here) and the spasmotic theory of asthma.

He also mentions "pulmonary venous congestion, distended right heart, large veins full and scant supply scant supply of arterialized blood finding its way to the left ventricle." (9, page 35) (12, page?)

He is basically recognizing cardiac asthma or heart failure, and associates it mainly with adult asthma where the fits are more frequent and less severe.  He believed some exciting factor excited the nervous system, and this caused the bronchospasms.

His book was so well researched and written that many physicians just assumed asthma was nervous from this time on.  While Bree was the preeminent asthma expert of the 1st half of the 19th century, Salter was the same for the second half. You can read more about Dr. Salter by clicking here.

xHeinrich von Bamberger:  (1822-1888) He supported the theories of Wintrich in 1870. He saw "tetanus of the diaphragm, and to convince himself by post mortem examy no means resembled those usually assigned to asthma, he, nevertheless, regarded them as characteristic of the disease. " (4, page 36)

Duchenne and Biermer proved the diaphragm was the main muscle used during inspiration, and is probably therefore not a cause of asthma but a cause of dyspnea due to weak inspiratory abilities (such as in Duchenne's disease. (9, page 7-8)

You can view his 1865 book, "Ueber asthma nervosum" by clicking here.ination of the absence also of structural lesions. Although the symptoms of that case b

xPaul Bert:  (1833-1886) Alton Wintrich was so well respected as a respiratory physician that his ideas supporting the diaphragmatic theory of asthma were held to high esteem until Paul Bert performed experiments with improved equipment in 1870.  He once again reaffirmed the experiments of Williams and Longet.   (10, page 194)

However, Berkart explained that he had a difficult time getting the air passages to contract until he realized that he had been over inflating the lungs.  It was only when he provided less inflation that he was finally able to induce the air passages to "contract... upon electrical irritation, applied either directly to it or to the pneumogastric nerve.  But the contractions were so feeble and slow as to induce Bert to think that they had no active share in the mechanism of respiration," said Berkart.  "Moreover, the paralysis of the bronchial muscles, following the section of the vagus, did not appear to influence in that least the function of nutrition of the lungs.  Thus the integrity of those muscles, not being indispensable to an efficient ventilation of the lungs, it seemed not unreasonable to conclude that their spasmodic contractions could hardly have the effect generally assigned to them."  (4, page 42-43)(9,page 5)

He therefore concluded that his experiments did not initially demonstrate contraction of the lungs because he over inflated them.  It was this observation that would later be used by J.B. Berkart as proof that the air passages may constrict as Williams proved, but that this does not, and cannot, occur in asthma, because most asthmatics also present with emphysema, which is, essentially, over inflation of the lungs.  (4, page 103)

He, like Traube, also "demonstrated how respiration can be arrested by irritation of the pneumogastri or laryngeal nerves or the Schneiderian membrane of the nose (membrane lining the maxillary sinus cavity)." (10, page 194)
 You can read his 1870 book "Ueber bronhialasthma" by clicking here.

xMichael Anton Biermer:  (1827-1892) After Bert performed his experiments, he ardently supported the spasmotic theory of asthma in a series of lectures in 1870.  (10, page 194) (4, page 43)(20, page 14) (25, page 11)

He believed the objections to the spasmotic theory of asthma based on the experiments of Bert "irrelevant," said Berkart, "for contraction of the thorax and the deficient resonance on percussion... could take place only if asthma were a spasm of the alveoli.

Along with the theories put forth by Bert, he proved that irritation of the vagus nerve caused contraction of bronchial musccles.(15, page 4)

According to Orville Brown he also "says that asthma is the result of swelling of the bronchial mucosa and a consequent obstruction of the smaller bronchi; the residual air in the alveoli then develop a greater tension and causes thereby a reflex spasm of the bronchial musculature. He reports a patient whose asthmatic seizures ended after the expectoration of a small feather." (16, page 34)

Thorowgood said:
Biermer observes that the bronchial muscles antagonise the muscles of inspiration, and so prevent over distension of lung. When, by frequent attacks of spasm, the nutrition of the bronchial muscles begins to fail, they no longer are able to antagonise the force of inspiration; or, by their contraction, to assist expiration, and thus that permanent condition of lung distension known as emphysema is brought about. (9, page 7)
Biermer published his wisdom on asthma in his 1870 book "Ueber Bronchioalasthma, and with Joseph Coats in the 1876 book "On bronchial Asthma."

xErnst Victor von Leyden:  In 1871 he found crystals in asthmatic sputum and he believed these caused asthma.  During his era he was the closest supporter of Bree's theories, and therefore he was more of a supporter in the bronchitic theory that the spasmotic and nervous theories.   (9, page 14-15)

Leyden believed that these crystals somehow irritated the "vagus in the mucus membrane of the bronchials, and hereby caused by reflex action a spasm of the muscles of the small bronchial tubes. (15, page 8)

You can read more about Leyden and asthma sputum in this post

Weber:  In 1872 he disagrees with the spasmotic theory of asthma and the diaphragmatic theory of asthma.  He says neither of these can explain all the symptoms of asthma. Instead, he believes asthma is caused by "vaso-motor influences."  (15, pages 7,8)

He believed "A vaso-motor neurosis to be the cause of the attack, by which the vessels of the mucus membrane are abnormally filled and swollen. A swelling of the mucus membrane of the nose has often been directly observed in cases of asthma in which the attack is immediately preceded by an obstruction of the nasal passages, and as the mucus membrane of the bronchials is anatomically very like that of the nose, there is nothing to prevent the supposition that something of the same kind takes place in the bronchial tubes." (15, pages 7,8)

xHerman Lebert:  In 1873 supported both the spasmotic theory of asthma and the diaphragmatic theory of asthma. He  believed asthma was caused by dilation of the blood vessels in the lungs. (4, page 45)

In fact, this theory was still believed to be true when epinephrine was later invented in 1900, as the vasoconstricting component of epinephrine was believed to increase blood flow to the lungs and thus make breathing easier that way. (9, page 38)

Orville provides us with the interesting observation that "On the findings of Laennec that a patient had asthma in the dark, Lebert advised the use of as many candles as possible in the rooms of asthmatics. (9, page 38)

Charles Harrison Blackley:  (1820-1900) In 1873 he provided scientific evidence  that pollen, when introduced to the mucus lining of the respiratory tract, caused swelling and redness, and this lead to asthma. (9, page 38)

Blackley and other hay fever experts were proponents of the hay fever theory of asthma.  You can read more about Dr. Blackley by clicking here (to be published on 10/24/13)

Franz Riegel:  After studying the various literature, in 1875 he supported the views of Biermer, although he thinks that after spasms of the bronchioles there could also be a secondary spasm of the diaphragm. In this respect he agrees with Lebert. (15, page 7)(9, page 38)

Ringer:  He observed "diminution of urea and chlorides in the urine, indicating he believed, some profound disturbance in metabolism." (9, page 36)

Popoff: Believed fungi only caused asthma when there was previously existing inflammation of the air passages. He believed this inflammation was "rarely lacking in an asthmatic," according to Orville. (9, page 37)

Aitken:  In 1864 he noted that asthma leads to dilated right heart and emphysema.(9, page 26)

H. W. Fuller:  Supported the spasmotic theory of asthma, the nervous theory of asthma, and the paralytic theory of asthma.  (9, page 37)(20, pages 13-14)(25, page 11)

xJohn Thorowgood:  (1833-1919) In his 1878 book he basically supports the ideas of Henry Hyde Salter, therefore supporting the nervous theory of asthma and the spasmotic theory of asthma. He was also a supporter of hay asthma. He gained his experience at Victoria Park Hospital for Diseases of the Chest. (9, pages 16)(9, preface, 5, 11)

He said that the studies of "Duchenne, Biermer, and others tends to throw doubt on Bamberger as to diaphragmatic spasm being the most frequent cause of the asthmatic paroxysm." (9, page 7)

xJoseph Isidor Bernard Berkart:  While Thorowgood basically supports the theories of Henry Hyde Salter that the main theories regarding asthma are the nervous and spasmotic theories, (4) Berkart believed those two theories were simply not true.

He believed that Paul Bert, by his experiments, proved bronchospasm did not occur in asthmatic lungs.  As quoted by Berkart (4, age 103):
He (Bert) discovered that the failure of his numerous experiments was attributable alone to the inflation of the lungs.  Hence, as this obstacle exists normally, and in a still greater degree in emphysema, with which, by necessity or by accident, asthma is almost always associated, there can consequently be no bronchial stricture. -- Moreover, the clinical features of the asthmatic paroxysms afford abundant evidence against that theory.  Aart from the imporbability that muscles could remain uninterruptedly contracted for days and weeks together, there are the physical signs during an attack, which are quite inconsistent with the assumption of a bronchial spasm." (4, pages 103 and 104)
Instead believed that asthma was a mere symptoms that  "accompanies the idioppathic forms of bronchitis and emphysema, as well as those that complicate the various cardiac and pulmonary affections."  (4, page 110) (18, page 537-539)

x?F.H. Bosworth:  In 1889 he believed hay fever was a "vasomotor rhinitus (inflammation of the nasal passages)" and asthma was based on three things: it's a neurosis (proven by Salter),  a "diseased condition of nasal mucus membrane," and "some obscure substance of the atmosphere exciting the paroxysm. He believes the cause is not bronchospasm, but "a vasomotor paralysis of the blood vessels supplying bronchial mucus membrane." He likewise believed that if nasal disease was cured, so too would asthma.  The reason is because he believed the "nasal obstruction causes a diminished air pressure of the lower respiratory passages which leads to dilation of the blood vessels of the mucosa and lessoned vasomotor control, producing in the nose, hay fever; and in the bronchi, asthma," per Orville.(16, page 41-42)  You can read an article written by him here.

Dr. H. MacGillivray:  He was a supporter of the spasmotic theory of asthma, and provided evidence that stimulation of the vagi caused contraction of the bronchial muscles. (25, page 10-11)(20, page 14)

Dr. P. Watson Williams: He also believed that intra nasal irritation may cause asthma.  He didn't believe asthma was due to vascular dilation.  (4, page 94)  He believed the "'tonus' to counteract the affect of coughing." (22, page 349)

According to the July, 1899, edition of the journal of Opthalmology and Laryngology, he said:
"We do not know for certain what is the actual condition of the bronchi in asthma" nor how nasal abnormalities caused asthma, still he believed in treating intranasal defects in asthmatics, since the removal of any contributory factors toward the occurrence of the paroxysms, although they might not be the essential cause, will often materially aid our efforts in other directions to combat the disease, while occasionally the happy results that follow the intranasal treatment seem conclusive proof that therein lay the essential cause." (25, page 344)
He was among the many physicians who believed there might be a link between the nasal passages and asthma.  He was a physician from Bristol, England.

Interesting notes:  Dr. Williams must have agreed with Dr. Laennec and J.B. Berkart that asthma was an abused term.  James Thomas Whitaker noted that in 1768 there were 17 different types of asthma (as described by Savage) and in 1822 this was reduced to 11 (by Richter). This was confusing.  Williams wanted to simplify the definition of asthma. (7)

The thing to note about most of these experts is that even while they believed in the bronchospasm theory of asthma, they continued to believe in the nervouse theory of asthma, and their experiments proved the two co-existed  -- or so they though.

Conclusion: Most physicians of this era had an opinion regarding one or another of the eleven asthma theories,  although few offered. I could expound ad nauseum listing all these physicians, although I see no point going on further.  I think I've made my point that asthma was a hot topic amid many 19th century physicians.

While the various physicians of the 19th century did not often agree on the causes of asthma, the knowledge obtained from their investigations allowed 20th century asthma experts to further fine tune the definition of asthma.  All of this, of course, was done to the benefit of every asthmatic.

I will end the decade with a few quotes from three of our references from the 19th century.
  1. W.H. Gedding:  By 1885 "most modern pathologists have arrived at the conclusion that bronchial asthma is a spasmotic contraction of the middle and finer bronchi dependent on some derangement in the function of the pneumogastric nerve." (10, page 194)
  2. James Thomas Whitaker:  "Whatever doubt still hung about the contraction of the bronchial tubes themselves would seem to have finally been dissipated by Lazarus (1891), who devised an ingenious apparatus wherewith he could, with the aid of curare and tracheotomy, experiment on animals in life, and whereby he produced the characteristic dyspnea of the disease by irritation of the vagus nerve." (7, page 506)
  3. "Willem Einthoven (1860-1927), the inventor of the electrocardiograph (EKG) evaluated three theories of pathogenisis of asthma popular at the time: bronchospasm vs. spasm of the diaphragm.  vs. capillary leak.  He demonstrated experimentally that spasm of the bronchi was the etiology." (14, page 13)
(Names to look up:  Bernard)

  1. Bree, Robert, "A Practical Inquiry into Disordered Respiration, distinguishing the Species of Convulsive Asthma, their Causes, and Indications of Cure, London, 1810.  I could not find the 1790 edition online, yet this one serves our purpose.
  2. Schmiegelow, Ernest, "Asthma, considered specially in relation to nasal disease," 1890, London, H. K. Lewis
  3. Jackson, Mark, "Asthma: The biography," 2009, London
  4. Berkart, J.B., "On Asthma: It's pathology and treatment," 1878, London, J. & A. Churchill
  5. Forbes, John, ed., "The Cyclopaedia of practical medicine," 1833, volume 1, page 186
  6. Brenner, Barry E, ed, "Emergency Asthma" 1998, page 7 (chapter one is a history of asthma written by Brenner)
  7. Whitaker, James Thomas, "The theory and practice of medicine," 1893
  8. Daintith, John, editor, "Biographical encyclopedia of scientists." 2009, 3rd edition, Florida, CRC Press
  9. Thorowgood, John Charles, "Notes on Asthma," 1878, 3rd edition, London, J and A Churchill
  10. Geddings, W.H., author of the chapter on "Bronchial Asthma," in the book  "A System of Practical Medicine," edited by William Pepper and Louis Star,Volume 3, 1885, Philadelphia, Lea Brothers and Co.
  11. Daintith, John, editor, "Biographical encyclopedia of scientists." 2009, 3rd edition, Florida, CRC Press
  12. Salter, Henry Hyde, "On Asthma: It's Pathology and Treatment," 1864, 
  13. Bryan, Jenny, "Asthma," 2008, page 8
  14. Brenner, Barry E, "Emergency Asthma," 1999, New York, Marcell Dekker Inc.
  15. Shmiegelow, Ernst, "Asthma, considered specially in relation to nasal disease," 1890, London, H.K. Lewis
  16. Brown, Orville Harry, "Asthma, presenting an exposition of nonpassive expiration theory," 1917, St. Louis, C.V. Mosby Company
  17. Grifiths, Ralph, "The Monthly Review, 1800, Volume XXXII, London, Printed by A. Strahan, the reference notes to a review of the following: "Article 25:  Observations on the history and cause of asthma; and a brief review of  'A practical enquiry on disordered respiration:' in a letter to Robert Bree, M.D., the author of that work. By George Lipscomb, surgeon, at Birmingham." 
  18. Berkart, J.B., "On the Nature of the so-called bronchial asthma," British Medical Journal, November 8, 1873, 2 (671), pages 537-539
  19. Walshe, Walter Hyde," A Practical Treaties on the Diseases of the Lungs," 1871, London, Smith, Elder & Company
  20. Thorowgood, John C., "Asthma and Chronic Bronchitis: A New Edition of Notes on Asthma and Bronchial Asthma," 1894, London, Bailliere, Tyndall, & Cox
  21. Andral, Gabriel, "Medical Clinic: Diseases of the Chest," Volume II, Diseases of the Chest, 1843, Philadelphia, Ed Barrington and Geo D. Haswell
  22. Macintyre, John, et al, editors, The Journal of Laryngology, Rhinology, and Otology,"  volume XIV, 1899, London, Regman, Limited
  23. Hamilton, David James, "A Textbook of Pathology: Systemic and Practical," Volume II, 1894, London, Macmillan and Co.
  24. "Obituary: Sir W. Gairdner," The Times, Monday, July 1, 1907, Issue 38373, page 7, column D,
  25.  Dobell, Horace, "On Asthma; Its Nature and Treatment," 1886, London, Smith, Elder & Co.
  26. Berkart, J.B., "On Bronchial Asthma: Its Pathology and Treatment," 1889, 2nd edition, London, J&A Churchill
  27. Wackley, Thomas H., Thomas Wackley, editors, "The Lancet," Volume I for 1891, London, "The Registrar-General's Fifty-Second Annual Report: Foreign University Intelligence," The Lancet," January 17, 1891, edition
  28. Hoffman, Friedrich Albin, Ottomar Rosenbach, Emanuel Aufrecht, writers, John H. Musser, editor, Alfred Stengel, translator, "Diseases of the Bronchi, Lungs and Pleura," 1902, Philadelphia, New York and London, W.B. Saunders and Company. 
  29. Watson, Thomas, "Lectures on the principles and practice of physic; delivered at King's College, London, by Thomas Watson, M.D.," 1857, 4th edition, London, John W. Parker
  30. Bradford, Thomas Lindsley, writer, Robert Ray Roth, editor, “Quiz questions on the history of medicine from the lectures of Thomas Lindley Bradford M.D.,” 1898, Philadelphia, Hohn Joseph McVey

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