Thursday, October 6, 2016

1950: Seroids for asthma

In 1949, a report was published noting the benefits of steroids for rheumatoid arthritis. This inspired researchers to experiment with cortisol and ACTH for other diseases, including asthma and allergies. By 1950, the results of the first studies using steroids for asthma came back positive. (1, 2)

The first study showing the benefits of steroids for asthma and allergies was published in 1950 by Carryer and company. They showed that oral cortisone benefited patients with allergies and asthma induced by ragweed pollen. (1, 3)

In 1951, Maxwell F. Gelfand reported on the benefits of inhaling aerosolized cortisol on the treatment of allergic asthma. This was the first study showing the benefits of inhaled corticosteroids for asthma. (3, 4)

In 1955, the first synthetic version of cortisol was approved by the FDA and entered the market as prednisone under the brand name Meticorten by Schering.
That same year, the first synthetic version of ACTH entered the market as prednisolone under the brand name Delta-Cortef by Upjohn. Subsequent studies confirmed the efficacy of these synthetic steroids for the treatment of asthma. (1, page 18) (need more references)

In 1959, methylprednisolone was approved by the FDA and entered the market as Depo-Medrol. Dexamethasone also entered the market in the 1950s as Decadron by Merck. It was shown to produce greater anti-inflammatory effect with less side effects as the other corticosteroids. (9, 10)

Dexamethasone was actually the first corticosteroid to be marketed as a solution to be nebulized, and this was shown to benefit asthmatics in studies performed in the 1960s.  (8)

In 1956, another study was performed by the Medical Research Council in Britain confirming the benefits of cortisol for the treatment of acute and severe asthma episodes. This and other similar studies showed how well oral or intramuscular cortisol worked to end severe asthma exacerbations.  (3, 5)

These and other similar studies confirmed the benefits of steroids for moderate to severe asthma, and they were prescribed generously, mainly because doctors and patients alike could see their benefits.  Sales of systemic corticosteroids boomed during the late 1950s and early 1960s.

However, it did not take long for the harsh side effects of long-term use to become a concern.

Steroids were learned to cause fluid retention, which results in a moon-face, thinning skin that easily bruises, acne, hypertension and diabetes. It also causes weakened bones, osteoporosis, and increased risk for bone fractions. It was also shown to stunt growth, obesity, and glaucoma.

It also became apparent that the diminished immune response responsible for reducing airway inflammation and controlling asthma also slowed healing, which was particularly concerning for those requiring surgery.

Various subjects died as a result of steroids use, some dying as a result of rapid cessation of the medicine. It was soon learned that when a person was taking steroids, their adrenal cortex stopped making natural cortisol.

By 1960, the systemic side effects were such a grave concern that the medical profession all but shunned the use of them. They went from "miracle cure" to condemnation after less than a decade of use. (6)

In the early 1970s, steroids were prescribed for people with moderate to severe asthma to control moderate to severe asthma. These were still only prescribed when oral and inhaled bronchodilators failed to work. (1)

By the 1980s, low dose steroids were used with regularity to control moderate to severe asthma, although they were used only when absolutely necessary. Inhaled corticosteroids were also an option, and even these were used sparingly due to fears of side effects.

References:
  1. Brenner, Barry E, editor, "Emergency Asthma," 1999, New York, Marcel Dekker Inc., page 18
  2. Cromptom, Graham K, "A Brief History of Inhaled Asthma Therapy," Primary Care Respiratory Journal, 2006, 15, pages 326-331, https://www.researchgate.net/publication/6704067_A_brief_history_of_inhaled_asthma_therapy_over_the_last_fifty_years
  3. Byrne, Paul M., "Future Trends in the Use of Corticosteroids in Asthma," 2000, pages 120-140, http://link.springer.com/chapter/10.1007%2F978-3-0348-8480-8_7, in the book "Asthma: Epidemiology, Anti-Inflammatory Therapy and Future Trends," edited by Mark A. Giembycz and Brian J. O'Conner, 2000
  4. Gelfand, Maxwell L, "Administration of Cortisone by the Aerosol Method in the Treatment of Bronchial Asthma," New England Journal of Medicine, 1951, August 23, 245: 293-294, http://www.nejm.org/doi/pdf/10.1056/
  5. Jackson, Mark, Asthma: The Biography," 2009, New York, Oxford University Press, page 136
  6. Buer, Jonas Kure, "Origins and Impact of the Term "NSAIDs," inflammopharmacology," July, 2014, file:///home/chronos/u-48b0af7d8a6e832f841243beb1bf56db699d3e12/Downloads/NSAID%20accepted%20version%20for%20self-arch.pdf
  7. Pfeiffer, John E., "How Hormone Team is Saving Lives," Popular Mechanics, pages 97-99, 
  8. Schleimer, Robert P., et el, "Inhaled Steroids in Asthma," vol. 163, 2005, New York, page 5
  9. http://pmj.bmj.com/content/36/411/26.full.pdf
  10. http://archderm.jamanetwork.com/article.aspx?articleid=525922



file:///home/chronos/u-48b0af7d8a6e832f841243beb1bf56db699d3e12/Downloads/NSAID%20accepted%20version%20for%20self-arch.pdf

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