Sunday, October 9, 2016

1980s: The first corticosteroid inhalers

By the 1980s, it was evident that corticosteroids helped asthmatics gain control of their disease, although it was also evident that prolonged use of high doses resulted in severe and unwanted side effects. Despite this setback, efforts were ongoing to refine the chemical composition of steroids and to develop a method of delivery suitable and safe for asthmatics. This lead to the introduction of inhaled corticosteroids to the market in 1972.  (7)

This was the year that Allen & Hanbury introduced beclomethasone to the market as Becotide, with the recommended dose of 4 puffs daily of 100 μg per puff, a total of 400 μg per day.  (7)

Ten years later, in 1982, the FDA approved two beclomethasone inhalers in the United States: GlaxoSmithKline's Vanceril and Schering-Plough's Beclovent. Other oversease brand names were Becloforte, and Beconaise.  (You can see a 1979 ad for Beclovent and Ventolin from the Canadian Medical Association Journal here. )

Initial studies confirmed the benefits of daily use of this medicine, although it was usually only initiated by hospital physicians due to ongoing fears that even low dose steroids from inhalers could produce unwanted side effects.  (7)

I can use myself as evidence here. I actually have my discharge instructions from a hospital admission in 1984. A note to my mother says, "Have this boy take 2 puffs of Vanceril 4 times daily until he starts to feel better, then only use it when he feels symptoms."

Taking an inhaler four times daily was not easy for an eleven-year old. I would take it to school with me, and then I'd forget to use it. Or, worse, I would hesitate to use it because I didn't want to use it in front of my peers at school. Either way, for one reason or another, taking it compliantly was not easy.

Of course, when I left the hospital I was probably either recently removed from steroids or still on a Medrol pack. And as soon as I was weaned off of them, I was susceptible to the effects of whatever triggered my symptoms in the first place, which was probably dust mites. Sure I tried to avoid them, but the ubiquitous nature of dust mites makes them very difficult to avoid.

So, at some point, I'd be weaned off systemic steroids, would quit using my inhaled steroid, my symptoms would come back, and I'd end up using my Alupent inhaler with increased frequency. Actually, my asthma was so severe that even if I was taking my Vanceril compliantly I might still have symptoms.

During moderate to severe episodes, which was usually the case with me, I'd go through an Alupent inhaler pretty fast. Sometimes it would last a month, and those were the good times. More likely, it lasted a few weeks, or one week, or a matter of days. I know there were times I'd puff through an inhaler in one day.

And, when you're a boy with anxiety, and a boy who is shy like I was, and a boy who is self conscious and who doesn't like to ask for help, you don't seek help when you need it. So I'd suffer from asthma all day, sometimes praying it would go away and knowing it wouldn't. Usually, by the time I sought help I was beyond quick repair, and required a six day admission in a hospital.

For those of you who are wondering why my parents didn't recognize I was having trouble breathing, they probably did. You have to realize that this was back in the early 1980s, when there wasn't a whole lot of parental education about asthma. And even if my parents did know I was having trouble, I developed quite the skill of staying calm and not giving off the appearance that I was having trouble. So, my parents are off the hook.

And it's not that I didn't know better, because I did. I was very much aware that I needed help. It's just that I knew my parents were busy, and I didn't want to bother them. This was especially true when I had only recently visited the emergency room with one of my parents, and had felt guilty that I was overusing my rescue inhaler.

A side story here, and one for another post, is that I also felt guilty asking my mom to buy me another Alupent inhaler. This was especially true when she JUST bougth me one and it was empty already. So, by the time I got the nerve to tell mom I needed help, I was also nervous that they'd be able to tell I was abusing my Alupent.

However, in retrospect, they never said a word about this; they were just happy that I came in to get help, and they did a very good job of making me aware that they were happy I came in to seek help. The good folks at West Shore Hospital got to know "Little Johnny" really well, and the boy really like them, got to know some of them personally.

But I digress. As far as I knew, I was the only asthmatic who had it this bad in the entire world. Little did I know that I was not alone, and studies showed this. So, perhaps this was why my doctors never bothered me about my high frequency of Alupent use.

In 1982, Flunisolide was introduced to the market by Forest Laboratories as Aerobid. Aerobid was supposedly stronger than Azmacort, requiring fewer puffs daily. Many physicians were prescribing it for their patients, and mine was no exception. I, however, could not stand the taste, and was quick to complain about this to my doctor so I could get back to the better tasting Vanceril. Like beclomethasone, the standard dose was four puffs daily.

In 1973, budesonide (Pulmicort) was patentted, although it was not used clinically to treat asthma until 1981. A landmark study in 1982 by Wiley and company showed that two puffs daily (once in the morning and once before bed) of budesonide was as effective as four puffs daily of beclomethasone.


In 1984, Triamcinolome (package insert here) was introduced to the market by Abbott Laboratories as Azmacort. It's formula was slightly stronger than beclamethasone. It was a bulky white inhaler that had its own built in spacer. This was nice in that it required use of spacer with the medicine, improving coordination and increasing airway deposition to assure that the ideal dose was inhaled. Like beclomethasone, the standard dose was four puffs daily.

I was introduced to this inhaler in 1984. It was nice in that physicians for years had recommended I use my spacer when taking my inhalers, although spacers were large, bulky, and inconvenient to carry around with you. This made them less than ideal, as it was easier to pick up an inhaler and use it without a spacer. The Azmacort built in spacer was nice, although made it impossible to put into your pocket, pretty much assuring that any dose required during school hours would be missed.

At some point my dose of Azmacort was upped to 4 puffs 4 times a day, and, as you might imagine, this was very difficult to be compliant with, even for the most gallant of asthmatics.

I like to think of asthma similar to doing homework and getting good grades. Every semester I would work hard and try to get all A's. However, as time went by, it became harder and harder to study at night. For instance, there was other things to do, funner things to do, like playing football with my brothers. They would bug me until I gave in and played. Being compliant with my Azmacort was the same. I would get a new one and promise myself to take all my puffs, to be a gallant asthmatic. But soon enough I'd get busy, and forget, and puffs would get missed.

Through all of this I thought my doctor would say something. Through all of the extra puffs of albuterol and missed puffs of my corticosteroid inhaler, I thought my doctors would find out and lecture me. But they never did. Now, as an adult, I understand that they were probably aware of all this, and probably didn't say anything because they knew that they would have a difficult time with it, let alone a boy trying to get through life with severe asthma.

My doctor would review all my medicines with me at each appointment, and he would remind me of when I was supposed to take them. Actually, that didn't happen very often. Still,under it all, I'm sure he was aware that such a task was daunting. I know he empathized with me, otherwise he wouldn't have met mom and me at his office after hours. He did this more than once.

Noting the difficulty of taking four puffs daily, studies, studies, such as one conducted by Williams and company in 1986,  purported to show that 2 daily puffs of 200 μg was as effective as four puffs of 100 μg per dose, with a daily dose of 400 μg either way. 

Such studies were neat, in that during the 1990s most asthmatics were changed to a regular routine of 2 puffs daily for maintenance medicines, and this worked to greatly improve compliance with such inhalers. I know this to be true from personal experience. 

  1. Primary Care Respiratory Journal,"A brief history of inhaled asthma therapy over the last fifty years," Volume 15, Issue 6, December 2006, Pages 326-331
  2. Williams, Hywel, et al., "Twice daily versus four times daily with beclomethasone dipropionate in the control of mild childhood asthma," Thorax, 1986, 41, pages 602-605

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