1960s: Did rescue medicine cause a spike in asthma deaths?

A spike in asthma related deaths forced physicians to take a closer look at this disease. Upon review of the available data, they began to surmise that the very medicines meant to make life better for asthmatics was responsible.

The spike in asthma rates correlated with the releases and increased advertising of the new metered dose inhaler that was introduced to the market in 1957.  The first to be released to the market were the Medihaler Epi (epinephrine) and Medihaler Iso (isoprenaline).  As word got out there were devices asthmatics could carry in their pockets or purse that would give instant relief from asthma, sales of the device skyrocketed.  (5, page 11)

This followed a rise in the death rate.  According to Speizer, Doll and Heaf in 1968:

It is evident that an increase in mortality began to occur in about 1961 and that all ages between 5 and 64 years of age have been affected.  The greatest increase in mortality has taken place at ages 10 and 14 years, the ages the rate has increased eight times, from 0.3 to 2.5 per 100,000 persons.  The increase has, however, been substantial at all ages from 5 to 34 years, and at these ages the annual number of deaths increased by 308 and the death rate trebled from 0.7 to 2.2 per 100,000 persons.  (7, page 336)

They further noted that that for the purposes of their study, the investigated only data obtained for the age group of 5-34, mainly because as asthmatics get older "mortality from bronchitis begins to exceed that from asthma."  (7, page 336)

Initial studies involved questioning the attending physicians of the patients who died from asthma.  F.E. Speizer, Doll,  Heaf and Strang  in 1968 reported their findings.  (9, page 342)

Excessive use of pressurized aerosols was reported by 29 general practitioners without specific inquiry having been made.  The reports ranged from  a vague implication, such as "tended to use aerosols too frequently" or "suspicion of excess aerosol at death," to direct observation such as "died clutching aerosol" and a detailed account of the amount consumed.  In extreme cases the use of as many as two canisters per day or two in two hours was reported. (9, page 342)

Investigators speculated that, perhaps, such asthmatic were victim of the false sense of security provided by the inhalers.  Instead of seeking help, they continued to puff on their inhalers.  By the time they called for help it was too late.  (5, page 12-13)

Upon further review of the data, they learned that asthma death rates remained stable in most nations where asthma death statistics were available. However, there were significant spikes in six Western countries: England and Wales, Scotland, Ireland, New Zealand, Australia, and Norway. (1, page 15) (2, pages 15-19)

In England, in particular, the asthma death rate was stunningly high.  According to Speizer, Doll and Heaf in 1968, the asthma death rate in England "accounted for 5.7% of all deaths at ages 10 to 14 years, it ranked sixth in the list of causes of death." (7, page 336)

Since the sharpest rise in asthma deaths was limited to six nations, investigators searched for something that was particular to these regions.  What they learned was reported by Beasley, Pierce and Crane. They noted that isoprenaline forte... contained a concentration of isoprenaline two to eight times greater than the standard isoprenaline metered dose inhaler available in other countries. Epidemics occurred only in countries where the high-dose preparation of isoprenaline was available; and in the two countries which marketed the high dose preparation and had no increase in mortality, it was introduced late into their markets per-capita sales were low." (1, page 16)

When the product was later pulled from these markets and the death rate declined, this proved to many researchers that this was probably the cause.

References; ???

1. "Asthma Statistics, "AAAI.org, http://www.aaaai.org/about-the-aaaai/newsroom/asthma-statistics.aspx, accessed 9/29/13
2. Beasley, Charles Richard William, Neil Edward Pearce, and Julian Crane, "Worldwide Trends in Asthma Mortality During the Twentieth Century," chapter two in the book "Fatal Asthma," edited by Albert L. Shefer, 1998, New York, Marcel Dekker, pages 13-29
3. Woolcock, Ann Janet, "Natural History of Fatal Asthma," chapter 14 of the book, "Fatal Asthma," edited by Albert L. Shefer, 1998, New York, Marcel Dekker, pages 179-196
4. 1940s: Why did asthma morbidity and mortality increase
5. Altman, Lawrence K., "The Public Perception of Asthma," Chapter one of the book "Fatal Asthma," edited by Albert L. Sheffer, New York, Marcel Dekker, Inc, pages 3 and 11

References:  See "1940-1970:  Asthma morbidity and mortality spikes"

1950s: The first peak flow meter

Wrights original peak flow meters (circa 1950s)

If you're an asthmatic you may not be familiar with Dr. Martin Wright, but you probably are familiar with an instrument he invented:  the peak flow meter.  It was a convenient, inexpensive, hand held tool that could be used by the patient at home to assess the effects of bronchitis and asthma.  

It was first introduced in the 1950s by London physician, Dr. Martin Wright, of the Clinical Research Center at Northwick Park Hospital.  It was an instrument specifically designed to measure 'peak flow,' or the amount of air that can be forced out of a patient's lungs after a maximum inhalation.  

The original Wright was a large, heavy, clock shaped device and was too expensive for the common person to have at home.  It was generally used in hospitals to assess patients.  It worked by the patient blowing air into the meter, and this air rotated a pointer on a dial against the resistance of a spring.   The device gave the first accurate readings of a peak flow.

Mini Wrights Peak Flow Meters (circa 1970s)

In the 1970s Dr. Wright invented a new device that was inexpensive and portable.  It's basically just a "tube with a spring inside and a calibrated scale along the outside.  The puff from the patient under test pushes the spring back.  A pointer registers the furthest point reached.  The meter comes complete with a set of cardboard mouthpieces.  Doctors recon that the instrument could be useful in home treatment. Patient's could monitor their own lung power in a simple and cheap way of determining recovery from lung ailments."

This instrument was called a "Mini Wright," although ultimately it became known as the peak flow meter.  The devices were ultimately manufactured by various companies, and now you can get an array of different types.  The first ones were not disposable, although they were soon thereafter manufactured for single patient use only, and the separate cardboard mouthpieces are no longer needed  

Many peak flow meters available today

I remember the "Mini Wright" from when I was an asthma patient back in the late 1970s and throughout the 1980s.  I also remember having one at Shoreline when I first started working there.  I believe at some point it simply became lost.  Gone are the days of the Mini Wright, replaced by the even cheaper plastic models.

Can you guess how many peak flow meter brands are on the market?  I couldn't even fathom a guess, although I've had over 20 in my grasp at one point or another.

Reference:

1. "Hot Air Invention," New Scientist, March 1, 1979, page 675

Further reading and another picture:

1. Check out: Wrights Peak Flow Meter, The Virtual Museum Library,  http://medicine.nus.edu.sg/anaesthesia/virtual_museum/airmed_spirometer.htm

1949-1969: The National Foundation for Asthmatic Children

One of the main reasons National Jewish Health was able to stay afloat through the years is that it recognized the changing health needs in America. While both National Jewish Hospital for Consumptives and Denver Sheltering Home for Jewish Children opened to provide opportunities for children and adults inflicted or affected by tuberculosis.

Between the 1940s and 1960s the number of tuberculosis patients declined, and the number of asthma patients increased. Plus there as a need for taking care of patients with other diseases, including emphysema, chronic bronchitis, cystic fibrosis, bronchiectasis, silicosis, sarcoidosis, and fungal infections (1)

Yet there was also an increased emphasis on research, hence the name change of the Sheltering home to Jewish National Home for Asthmatic Children at Denver in 1953, and in 1957 to Children's Asthma Research Institute & Hospital (CARIH). The hospital also performed research into immunity, and this was a major reason for the 1985 name change of National Jewish Hospital/ National Asthma Center to National Jewish Center for Immunology & Respiratory Medicine.

There was another institution in Tuscon, Ariona, that was similar to National Jewish. People with lung ailments flocked to Arizona due to its dry climate, which was perceived to better for adults and children with breathing difficulties. The National Foundation for Asthmatic Children (NFAC) was opened in Arizona in 1949. It was actually the first "diseased based organization to launch a national campaign on behalf of the asthmatic child. (2, page 115) During the 1950s National Jewish Home for Asthmatic Children started a similar educational campaign. (2, page 116)

Back then asthma was a little known disease, yet a massive advertising and public relations campaign by both National Jewish and NFAC increased awareness of the 2.5 million children in America with asthma. The campaigns increased awareness of the hospitals and research centers in both Denver and Tuscon. And the number of patients being referred to these hospitals increased. (2, page 116)

In 1973 CARIH changed its name to National Asthma Center, and admitted financial trouble by 1978, so it merged with National Jewish to create National Jewish Hospital/ National Asthma Center. This created the largest asthma hospital and research center in the world. Although there was an emphasis on patient care, the hospital continued to emphasize research.

While the school at NFAC closed in 1969, the hospital persisted. It was another option for children with hardluck asthma or other respiratory diseases. There was another such hospital in New York called Asthmatic Children's Foundation. In 1981 there were 15 similar residential treatment centers for asthmatics. (3)


In August of 2009 several former patients at NFAC met in Tuscon, Arizona to reminisce about their stay at the institution. The major emphasis back then about asthma was that medicine was used to treat acute symptoms, with included bronchospasm. Asthma was also a disease caused by a nervous disorder, or a suppressed cry for the mother. (4)

These kids were treated with a good course of education, exercise, and a good, healthy diet. They were also allowed to live a relatively normal life outside of that, by going on trips to town like normal kids, shopping, tours, amusement parks, parks, etc. They were also allowed to participate in games and other fun things kids do.

The kids "attend a boarding school for asthmatic children. These children can play out of doors year round and they become confident and competitive because they are competing with children on their own level," according A.B. Sieh, executive director for NFAC, in an article published in the Rotarian in August 1965. (5, page 51)

Boys and girls afflicted with bronchial asthma generally are admitted to the hospital for a one or two year stay, and this is at no charge, similar to the two asthma hospitals in Denver. The school the kids attend has a capacity of 72, and it's usually full (5, page 51)

Sieh notes that the "they come here pigeon chested with hollow eyes and sad faces... we have had children, who upon arrival, who could not walk up a single step without bringing on an asthma attack... the Arizona sun takes over and we have healthy looking children who can go home -- not cured, but rehabilitated to the point that they can cope with their asthma and live a normal life, attend public schools, and not be 'different.'

So while the main goal was to improve asthma, it wasn't like you were living in a hospital, at least not all the time. It allowed kids to get better, so they could go on to live normal lives.

References:

1. "Clinical History," NationalJewishHealth.org, http://www.nationaljewish.org/about/whynjh/history/clinical/clinical-history3/, accessed 11/7/12
2. Mitman, Gregg, "Breathing Space," 2007
3. Melvin, Tessa, "For 36 Children, Hope on Asthma," New York Times, September 26, 1982
4. Beal, Tom, "Tuscon asthmatic kids of reunite, view latest research," Arizona Daily Star, August 3, 2009
5. "These Rotarians: ABCs School," The Rotarian: An International Magazine, August, 1965

1960s: Spike in asthma death rate earns worldwide attention

A gradual rise in asthma deaths began during the 1940, although it gained little attention from the medical community, let along the general public.  However, a rising tide of asthma deaths in the 1960s not only gained the attention of the medical community, it resulted in an increase in research and studies into our disease.  This would have a significant impact on the millions of asthmatics around the world, and for the better.

The asthma death started to rise sharply in 1961.  Then, according to Beasly, Pearce and Crane:

In the mid-1960s, asthma mortality increased dramatically in at least six Western countries: England and Wales, Scotland, Ireland, New Zealand, Australia, and Norway.  In these countries, the mortality rates increased 2-10 fold within a 2-5 year period.  Other countries such as the United States, Denmark, Canada, and Germany did not experience epidemics, although in some countries such as Japan, significant increases in asthma mortality were noted within more narrowly defined age groups. (1, page 15)

It was the goal of researchers to discover the likely cause.  A variety of theories were postulated and investigated by the experts.

A.  Accuracy of physicians certifying the cause of death:  This was investigated and pretty much ruled out as a probable cause (7, page 337

B.   Changes in the way asthma was diagnosed:  While it was determined that asthma might be misdiagnosed or under diagnosed, this was ultimately ruled out as a likely cause in an increase in asthma fatalities (7, page 335)

C.  Increase in the number of cases of asthma:  This was actually considered as a likely cause noted by Speizer, Doll and Heaf in 1968.  They said, "In the absence of evidence t the contrary, it would seem that an increase in the case fatality rateis the most likely explanation of the increased mortality rate, and we have accepted this as a working hypothesis." ( 7, page 338),

D.  Environmental factors:  As noted by Speizer, Doll and Heaf in 1968:

"Certainly the increase could not be due to smoke pollution, which has decreased in English towns over the last decade, nor could it be attributed to pollution with sulphur gases, which has remained approximately constant (Ministry of Techology, 1967).  Motor traffic has increased considerably, and one of the constituents of motor fumes could perhaps have had a harmful effect.  If this were the case, however, a substantial difference in mortality would be expected between urban and rural areas, and we have failed to find any evidence of this in the national mortality data for 1966.  The death rate as 2.0 per 100,000 persons aged 5 to 34 in conurbations, 3.0 in urban areas of more than 100000 population, 2.2 in urban areas under 50,000 population, and 1.9 in rural districts. (7, page 338)

Similarly, Lawrence K. Altman said:

We often yearn for the "good old days." For instance, it is often said that there is more pollution today than before, but that statement i snot necessarily correct. Think back to those earlier eras.  Think of the stench from humans who found it dificult to keep clean when bathtubs were scarce. Imagine what it was like when horse manure constantly filled the streets.  It is said that in the 1920s asthma from horses was a common affliction. Dr. Sheffer told me about how a horse trotting along the street could trigger an asthma attack inDr. Robert Cook of Roosevelt Hospital in New York City.

Think also of the dust in the environment and pollution from wood-burning and coal-burning stoves.  Recall the inversions that caused so much sickness and death in Pennsylvania and London, England, a few decades ago. 

Many ofthe offending environmental hazards have been removed. Public health campaigns and legislation have reduced the amount of tobacco smoke and dangerous chemicals in the air.  Those changes have created a widespread impression that we live at a time when we breathe cleaner air (8, pages 5-6)

So, needless to say, environmental causes were ruled out as a factor. This is not to say that environmental factors are not likely factors in asthma morbidity in mortality.  It merely rules these out as likely culprits or the spike in morbidity and mortality during the 1940s and 1960s.

E.   Aging population:  This was not considered an adequate reason because a majority of the data collected by the experts is generally collected for asthmatics between the ages of 5 and 35 years of age, or some similar range.  The reason for this is because the older a person gets the greater the chance asthma will be complicated, or confused with, other medical conditions people normally get as they get older.  Asthma under the age of 5 is difficult to diagnose.  (1, page 13)

F.  Improved ability to recognize and diagnose asthma: This may result in an increase in the number of people diagnosed, but it would not explain the increase in morbidity and mortality.   (1, page 18)

G.  Change in mode of treatment.  There were actually two new modes of treatment on the market during the 1960.  They were:

1. Systemic Corticosteroids
2. Metered Dose Inhaler (MDI).  This was often referred to as pressurized aerosol (asthma rescue inhaler)

Systemic corticosteroids were never ruled out as a culprit.  However, Speizer, Doll and Heaf note the following: 

Corticosteroids were introduced into the management of the disease in 1952, but the increase in mortality did not begin until nine years later.  This discrepancy, however, is not sufficient to exculpate them entirely.  The frequent and prolonged use of corticosteroids spread slowly, and the risk of harmful effects may be at a maximum only after patients have been under treatment for several years.  

If patients were on a high dose of steroids and the patient suddenly stopped taking the medicine, this would result in adrenal gland suppression, which may result in death.

The asthma rescue inhaler was introduced between 1957 and 1960:  According to Speizer, Doll and Heaf:

These were introduced in England and Wales in 1960 and began to gain wide acceptance in 1961; and in the next five years their consumption is estimated to have increased more than fourfold (Ministry of Health, unpublished data).  The closeness of the correlation justifies inquiry into the possible harmful effect of the preparations, but a temporal correlatoin of this sort, taken by itself, is a poor basis for drawing conclusions about cause and effect." (7, page 335)

Ultimately, while there were many likely causes for the spike in asthma deaths during the 1940s and 1960s, the finger was pointing at beta adrenergic medicine as the likely culprit.  Whether this was the actual cause was never fully determined.

References.

1. Beasley, Charles Richard William Beasley, Neil Edward Pearce, Julian Crane, authors of chapter two in the book "Fatal Asthma" edited by Albert L. Sheffer, 1998, New York, Hong Kong, Marcel Dekker, Inc. Chapter two is titled "Worldwide trends in asthma mortality during the twentieth century."
2. Woolcock, Ann Janet, author of chapter 14 of the book, "Fatal Asthma," edited by Albert L. Sheffer, 1998, New York and Hong Kong, Marcel Dekker, Inc. Chapter 14 is titled "Natural Histor of Fatal Asthma."
3. Sears, Malcolm R., "author of chapter 29 in the book "Fatal Asthma," edited by Albert L. Sheffer, 1998, New York and Hong Kong, Marcel Dekker, Inc.  Chapter 29 is titled "Role of B-Agonists in Asthma Fatalities."
4. Jackson, Mark, "Asthma: The Biography," 2009, New York, Oxford University Press
5. Bisgaard, Hans, Chris O'Callaghan, Gerald S. Smaldone, editors, "Drug Delivery to the Lung," 2001, New York, Marcel Dekker, Inc
6. Mittman, Gregg, "Breathing Space," 
7. Speizer, F.E., R. Doll, P. Heaf, "Observations on Recent Increase in Mortality from Asthma," British Medical Journal, February 10, 1968, 1, pages 335-339
8. Altman, Lawrence K., "The Public Perception of Asthma," Chapter one of the book "Fatal Asthma," edited by Albert L. Sheffer, New York, Marcel Dekker, Inc, pages 3 and 11
9. Speizer, F.E., R. Doll, P. Heaf, and B. Strang, "Investigation into use of drugs preceding death from asthma," British Medical Journal, 1968, 1, 339-343Sheffer, Albert L, "Partner Asthma Center's Grand Rounds," asthma.partners.org, http://www.asthma.partners.org/newfiles/ShefferFatalAsthma.html, accessed 10/5/13
10. Bendy, Christine J., E.L-Fellah, R. Schneider, "Tolerance to sympathomimetic bronchodilators in guinea-pig isolated lungs following chronic administration in vivo," 1975, British Journal of Pharmacology, 55, pages 547-554
11. Yarbrough, J.,  L.E. Lansfield, and S. Ting, "Metered dose inhaler induced bronchospasm in asthma patients," , Annals of Allergy, Asthma and Immunology," July, 1985, (55)1, pages 25-27
12. Grant, Evalyn N., Kevin B. Weiss, "Socioeconomic risk factors for asthma mortality," chapter 17 of the book, Fatal Asthma," edited by Albert L. Sheffer, 1998, New York, Hong Kong, Marcel Dekker, Inc.

1940: Asthma death rate begins a gradual rise

The 1940's was a significant decade in the history of medicine, as advances in medicine resulted in declines of morbidity and mortality from some of histories deadliest diseases, such as consumption and influenza.  Our asthma history saw an opposite trend.  While asthma morbidity and mortality were negligible through the 1930, they started to gradually climb during the fourth decade of the 20th century.

Considering these other diseases were in the forefront of the general public, the spike in asthma deaths nearly went unnoticed. Some experts may have seen what was going on, although they had no way of even guessing at the cause.  The reason was because most of the public's attention remained on other diseases, with all public funds, therefore, not going for asthma research.  For this reason there was very limited data regarding asthma available to review.

That left researchers to reviewing death certificates.  However, many experts wondered if methods of certifying death certificates were even accurate.  There were probably times when asthma was misdiagnosed and under diagnosed.  A middle aged man with bronchitis may have been misdiagnosed with asthma.  A child with asthma may have been misdiagnosed with asthma. Likewise, a child with asthma may have gone unrecognized, and therefore un-diagnosed.

It actually wasn't until the 1960s when all eyes were opened to the rising death rates that death certificates were reviewed.  The experts decided to limit their research to asthmatics between the ages of 5 and 35.  The reason was that the likelihood of having pure asthma was greatest among this age group.  Those under five were hard to diagnose, and those over 35 had a a greater likelihood of having some other disease combined with asthma.  Figuring out which one resulted in death could sometimes be difficult to determine.

Data was collected from as far as 1900 for this age group.  According to Beasley, Pearce and Crane in 1968, here is what was learned:

Those Western countries in which relevant data have been published indicate that asthma mortality was uniformly low and relatively stable between 1900 and 1940.  The death rate began to increase gradually in the 1940s in a number of countries including New Zealand and Australia, in which a threefold increase over a 15-year period was observed.  Mortality declined again in the late 1950s in New Zealand, England, and Wales, but not Australia.  In contrast, little change in asthma mortality rates was observed in the United States during this period.  Although the interpretation of death rates over such an extended period is difficult, the historical data are likely to be acceptable accuracy in this age group." (1, page 14)

They also made one other observation:

It is interesting to note that isoprenaline was introduced in a nebulizer formulation during the 1940s when mortality began to increase, but whether this had a role in the increase in mortality was not examined in detail at the time. (1, page 14)

Trends in asthma related deaths were not significantly studied until the 1960s.  When this was done, one of the theories that arose for the rise of asthma deaths in the 1940s was the availability of nebulized isoprenaline at home.  Theorists sense this may have created a false sense of security among asthmatics, particularly children.  Where they once would have sought help, they now simply resorted to their rescue medicine.

Isoprenaline was a new line of sympaththeomimetic medicines, also known as beta adrenergic medicine, more recently as asthma rescue medicine.  Regardless of what it is called, it has the tendency to provide immediate relief from an asthma attack.  Having access to such medicine was a godsend for asthmatics, because it meant that they could get immediate relief in the convenience of their own homes.

While physicians were happy to provide such an opportunity to asthmatics, they were not ready for the potential consequences.  Allowing asthmatics to have quick access to such rescue medicine resulted in two things.

1. Overuse of isoprenaline may have resulted in cardiac arrest. This would have resulted in suden death from isoprenaline overdose secondary to asthma. 
2. Overuse of isoprenaline may have resulted in tolerence to the medicine. This would have made the asthma refractory to the isoprenaline, resulting in increased dosing. By the time the asthmatic gave up on the isoprenaline, it was too late. 

These were simply theories that were never proven.  It as impossible for researchers to question these asthmatics after they died, and therefore it was impossible to know how much isoprenaline they used, if any.  

However, in many instances, there were reports from family members and friends of these asthmatics using their rescue medicine prior to death.  

For these asthmatics, however, such theories were trivial and too late. Although data obtained from studying how they died may have resulted in safety precautions that saved the lives of many future asthmatics.  In this way, the experts made sure these asthmatics did not die in vane. 

Another good thing that came out of the rise in asthma deaths during the 1940s, and later in the 1960s, was better recognition of our disease by the medical community.  This ultimately resulted in better recognition by the public, and therefore better funding for future research.  

However, as morbidity and mortality from asthma still remained low in comparison to other diseases, the rise in public awareness continued to pale in comparison.  While it's sad to say, many asthmatics continued to suffer from their disease because the general public simply was not paying attention.  

References.

1. Beasley, Charles Richard William Beasley, Neil Edward Pearce, Julian Crane, authors of chapter two in the book "Fatal Asthma" edited by Albert L. Sheffer, 1998, New York, Hong Kong, Marcel Dekker, Inc. Chapter two is titled "Worldwide trends in asthma mortality during the twentieth century." 
2. Woolcock, Ann Janet, author of chapter 14 of the book, "Fatal Asthma," edited by Albert L. Sheffer, 1998, New York and Hong Kong, Marcel Dekker, Inc. Chapter 14 is titled "Natural Histor of Fatal Asthma." 
3. Sears, Malcolm R., "author of chapter 29 in the book "Fatal Asthma," edited by Albert L. Sheffer, 1998, New York and Hong Kong, Marcel Dekker, Inc. Chapter 29 is titled "Role of B-Agonists in Asthma Fatalities." 
4. Jackson, Mark, "Asthma: The Biography," 2009, New York, Oxford University Press 
5. Bisgaard, Hans, Chris O'Callaghan, Gerald S. Smaldone, editors, "Drug Delivery to the Lung," 2001, New York, Marcel Dekker, Inc 
6. Mittman, Gregg, "Breathing Space," 
7. Speizer, F.E., R. Doll, P. Heaf, "Observations on Recent Increase in Mortality from Asthma," British Medical Journal, February 10, 1968, 1, pages 335-339 
8. Altman, Lawrence K., "The Public Perception of Asthma," Chapter one of the book "Fatal Asthma," edited by Albert L. Sheffer, New York, Marcel Dekker, Inc, pages 3 and 11 
9. Speizer, F.E., R. Doll, P. Heaf, and B. Strang, "Investigation into use of drugs preceding death from asthma," British Medical Journal, 1968, 1, 339-343Sheffer, Albert L, "Partner Asthma Center's Grand Rounds," asthma.partners.org, http://www.asthma.partners.org/newfiles/ShefferFatalAsthma.html, accessed 10/5/13 
10. Bendy, Christine J., E.L-Fellah, R. Schneider, "Tolerance to sympathomimetic bronchodilators in guinea-pig isolated lungs following chronic administration in vivo," 1975, British Journal of Pharmacology, 55, pages 547-554 
11. Yarbrough, J., L.E. Lansfield, and S. Ting, "Metered dose inhaler induced bronchospasm in asthma patients," , Annals of Allergy, Asthma and Immunology," July, 1985, (55)1, pages 25-27 
12. Grant, Evalyn N., Kevin B. Weiss, "Socioeconomic risk factors for asthma mortality," chapter 17 of the book, Fatal Asthma," edited by Albert L. Sheffer, 1998, New York, Hong Kong, Marcel Dekker, Inc.

1913: Cauterize your nose, cure your asthma

Another interesting concept of Adams is that he denied that most asthmatics had allergies, although he associated abnormalities in the nasal cavity with asthma.  He noted that Henry Hyde Salter cursorily mentioned the relevance of the nose in cases of asthma, when such knowledge was known since 1844 when Herck of Freiburg noted the association of sneezing and asthma. (1, page 89)

Later, Adams noted, Voltolini, in 1872, claimed to have "relieved eleven cases of asthma by removal of nasal polypi.  This idea received further impetus when Lazarus, Brodie and Dixon and others showed that electrical stimulation of the nasal mucosa caused bronchial spasm."

Ernst Schmiegelow explained that Voltini noted that no other asthma physicians prior to him noted the link between nasal polypi and asthma.  And while polypi are not always associated with asthma, there are noted cases where, upon removal of the polypi, the asthma disappeared. Although, if asthma has existed long enough so that it is chronic, removal of the polypi will not make the asthma disappear. Schmiegelow notes that Voltini's opinions were confirmed by Hanisch. (2, page 14)

Schmiegelow notes that "Hanisch thinks that as not all nasal polypes cause asthma, there must be a certain debility of the whole organisation or at least of the organs of breathing. In the nasal polypes themselves he finds sufficient ground for the weakened state of the organisms and lungs, as the insufficient breathing, the restless sleep, the buccal respiration, etc., must be considered capable of causing the general weakness."  (2, page 14)

B. Frankel and Weber also confirmed the findings of Voltini, and they also believed that chronic catarrh could also cause asthma. They believed irritation of the nasal mucous membrane passed a message down the pneumogastric to the pulmonary fibres, causing asthma, and "the result of the reflex was always a bronchospasm.". (2, page 15) Henry Hyde Salter previously mentioned this, and referred to is as reflex asthma.  

Schmiegelow also mentions a Dr. Wilhelm Hack, who "supported by casuistic observations, considered a number of different nervous diseases from the same point of view. Hack's principal object was to show that in the swollen cavernous mucous membrane in the foremost end of the inferior turbinated bones, different nervous states of irritation originate, and these reflex neuroses can be caused experimentally, and they disappear entirely as soon as the places in question are operatively removed. The filling of the cavernous membrane is, according to Hack, the essential in the pathogenesis of these reflex neuroses."

Adams notes that other physicians were so focused on the other theories of asthma, particularly that asthma was neurotic, that they were overlooking the true cause: that there was a problem with the patient's nasal passage causing the asthma, or that there was a toxaemia in the blood causing asthma as I discussed in this post.

Adams emphasises the following: (1, page 89-90)

"I have seen patients with noses absolutely ruined, mere shells of what they should have been—their asthma remaining the same, but promptly clearing up on simple antitoxaemic treatment, except in the case of a poor woman who owed an opium habit to her doctor. Francis cauterises the septal tubercle of all asthmatics—sometimes a valuable temporary procedure; others would also cauterise the lower turbinals—an unnecessary addition. The value of proper nasal treatment cannot be gainsaid; but that it should be subsidiary and ancillary to treatment of the toxaemia I have, where mouth breathing was absent, occasionally and successfully proved by the experiment of carrying out the latter treatment and leaving the nose alone. Apart from the experimental and therapeutical evidence just mentioned, the importance of a nasal factor in asthma can be gauged from several considerations."

Some of the ailments he observed on asthmatics, were:

• Nasal polypi
• Deviated Septum
• Hypertrophied areas in nasal passages
• Pigeon chest (due to laboring for air so frequently)
• Mouth breather
• Expanded shoulders (due to years of laboring for air)
• Expanded chest (due to emphysema if chronic)

References:

1. Adam, James, "Asthma and it's radical treatment," 1913, 
2. Schmiegelow, Ernest, "Asthma, considered specially in relation to nasal disease," 

1913: Adam: A perfect description of an asthma attack

Consider the following description of an asthma attack:

"In marked attacks not only is the struggle for breath so severe as to make the patient sit or kneel in bed, but he may even get out of bed and stand gasping at an open window, or clutching at any support that will aid the respiratory muscles of respiration. many will not go to bed at all, but sit in a chair all night, dozing when they can." (1, page 9)

If that doesn't describe one of my typical asthma attack when I was a kid I don't know what does. 

References

1. Adam, James, "Asthma and it's radical treatment," 1913, London, Gasgow: Alexander Stenhouse