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"