Thursday, January 26, 2012

1968-2010: Mast Cell Stabilizers for asthma

Intal Spinhaler used by asthmatics in the 1970s, 80s and 90s
In the early 1980s my doctor introduced me to the Intal Spinhaler that crushed a capsule with a medicine called disodium cromoglycate or chromolyn.  It was a white powder that was proven to improve lung function by decreasing inflammation. 

It was also proven to improve exercise related asthma. 
Each month you'll pick up a small white and yellow box from your pharmacist that contained a bunch of small capsules called Spincaps wrapped in tinfoil.  You unwrapped one and set it aside. 

Now you grab the inhaler and hold it so the mouthpiece is facing down.  You unscrew the cap and place  it onto a cup on the propeller, screw the body back on the mouthpiece, and slide the outer sleeve (the blue part in the picture) down as far as it will go and then back up again.  This pierces the capsule and makes the spinhaler ready for use. (1)

You exhale as much air as you can, place your mouth over the mouthpiece, and inhale.  As you inhale the powder will enter your airway, with a good portion going to your air passages.  You can feel the powder as it enters, and taste it.  This is how you know you did it right. 

This was the first dry powder inhaler that hit the market.  It was a great medicine, and when used with an inhaled corticosteroid it worked great to prevent asthma.

When I was a kid I had what my doctors referred to as high risk asthma. I was allergic to pretty much everything outdoors, and had exercise induced asthma (EIA).  Unless I was in an allergy proof bubble my asthma was usually acting up.  By the time I entered the 9th grade in September of 1984 I pretty much stopped going to gym class per my doctor's instructions.

By January of 1985 I had made so many trips to the ER I was admitted to NJH/NAC in Denver.  Once they managed to get my asthma under control they did some pulmonary function testing (PFT) on me to see what medicine might help me with my EIA. 

In one test I took no medicine and ran on the treadmill.  My lung function dropped significantly.  A week later I did another PFT, this time taking two puffs of Alupent before I ran on the treadmill.  My lung function once again dropped significantly, indicating Alupent had no effect. 

A week later I used my Intal Spinhaler before exercise, and while my lung function declined it wasn't as steep of a decline, indicating that disodium cromoglycate prevented EIA. (You can see my PFT tests here).

Intal Inhaler
I was using this inhaler four times a day (which was a pain in the butt anyway), so there was no need for me to use it prior to every time I exercised.  Yet the medicine was proven to reduce inflammation in your air passages so your asthma triggers don't irritate you as much, and don't constrict your air passages as much.

In a way, it worked the same way inhaled steroids worked, yet apparently not as well.  Prior to being at NJH/NAC my doctors had me using my Intal every day all the time, and only using my inhaled steroids as needed.  Yet by the time I left NJH/NAC in July of 1985 I was using both medicines four times every day, along with a ton of other medicines as you can see here.  Yes, this was a lot of medicine.

Yet the Intal Spinhaler was a good medicine for asthmatics since it was introduced to the market in 1968.  The medicine disodium cromoglycate was isolated by Roger Altounyan who had bad asthma himself and decided to test a variety of substances that were already proven to benefit asthma. He was working at Bengers Research Laboratories.  (2)

Cromolyn Nebulizer Solution
Khella was used by local natives living in Eastern Mediterranean countries for quite a few years to treat asthma with some success.  They made various "concoctions" from the seeds of the plant Amni Vasnaga, from which the substance Khellin was extracted in 1879.  (3)

Various studies in the 1940s and 50s showed the medicine relaxed smooth muscles throughout the body, including the muscles surrounding air passages in the lungs.  Yet the bronchodilating effect was less than epinephrine.  The various studies showed the medicine accumulated in your system if used regularly, and was proven effective for both asthma and other lung diseases. (4)

In 1953 The American Journal of Physical Medicine published the results of a study that showed inhaling aerosols of  7mg of Khellin improved lung function.  Perhaps it was studies like this that inspired Altounyan to study this extract.  (5)

Amps of Cromolyn solution
By experiments in the lab Altounyan produced a safer version of khellin called disodium chromoglycate.  While his goal was to improve his own asthma, what he ended up with was a new product.  It was marketed by Fisons and sold as the Intal Spincaps and Intal Spinhaler.  It became yet another option for many asthmatics worldwide suffering from asthma and allergies. 

Along with being the first dry powder inhaler, it was also the first mast cell stabilizer.  It prevented inflammation by preventing mast cells from releasing the mediators of inflammation (like histamine) which ultimately cause the inflammatory response. 

A problem with the spinhaler was that it couldn't be used during an asthma attack, and the dry powder entered your airway at such a force it was known to cause a fit of coughing and, thus, cause some asthma attacks.  I never experienced this problem however.  It was a nice option for me until modern inhaled steroids made it unnecessary.

Tilade inhaler
Nedicromil Sodium was approved by the FDA in 1992 as an alternative to Intal, and was marketed as the Tilate inhaler. (6) It was equally effective in treating inflammation and reducing allergy and asthma symptoms.  I never used Tilade, and I have little clinical experience educating it to patients either.

By 1995 Chromolyn was available as a solution to be nebulized, and this was ultimately a good option for pediatricians to prescribe for kids with asthma.  I have no recollection of ever giving this via aerosol to an adult, and rarely gave it to kids either for that matter.  I believe we no longer carry it in our stock. 

The Intal Spinhaler was ultimately phased out in the U.S. and Europe in favor of an inhaler, and the inhaler was ultimately phased out on December 31, 2010.  I imagine by information I've read on the Internet it's still a viable and cheap option for some asthmatics in 3rd world nations.  Yet here in the U.S. it's an antique. 

Tilate was phased out on June 14, 2010.  Altounyan's product was a great option for many asthmatics for many years, and for that we owe him thanks.  Perhaps some form of this product will make a comeback someday and replace the need for inhaled corticosteroids. 

References: 
  1. "Intal Spincaps Powder for Inhalation, Sodium cromoglycate, Consumer Medicine Information, " package insert for the Intal Spinhaler and Intal Spincaps, 2005
  2. Jackson, Mark, "Asthma: A biography," 2009, New York, page 187
  3.  Kennedy, M.C.S, J.P.P. Stock, "The Bronchodilator Action of Khellin," Thorax, 1952, 7, 43, pages 43-65
  4. Kennedy, ibid, page 43
  5. Braun, K, E. Eilender, "Khellin Aerosol in Bronchial Asthma," American Journal of Physical Medicine, Dec., 1953, Vol. 32, Issue 6,
  6. "Tilade approved by FDA; Fisons Announces Co-Promotion Agreement with Rhone-Poulenc Rorer," Press Release, TheFreeLibrary.com, http://www.thefreelibrary.com/TILADE+APPROVED+BY+FDA%3B+FISONS+ANNOUNCES+CO-PROMOTION+AGREEMENT+WITH...-a013101159

1 comment:

  1. The INTAL inhaler is available in the UK, albeit usually with a little difficulty. Pharmacies seldom have it in store. This is just as well for me, because the supposedly better inhalers don't do a thing against my hayfever-induced asthma. However, the INTAL inhaler is nothing like as effective as the spincaps used to be. They were messy, but they did such a good job of preventing asthma in me that I stopped bothering to get the Salbutamol reliever. But now I need both the INTAL inhaler and the reliever, and I wish the Spincaps were still available.
    James Brown

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