05 - The Becotide Story ( Beclomethasone Dipropionate)
Becotide Results 1970-1980 - Qvar

Today it is taken for granted that asthma is treated with inhaled steroids, and nowadays very few are dependent on oral steroids. Some account of the early days of the first trials may be of interest, for this was really an exciting time. These open trials from 1970 to 1972 would never have been accepted for publication today, but the results, especially in children, were so obvious that double blind trials would really have been unnecessary and unethical. Although Becotide and other inhaled steroids have had a tremendous impact on the treatment of asthma affecting both children and adults, I feel that the very effectiveness of this therapy may have made it seem less important to find out the causes of asthma or rhinitis, and may even have made the development of clinical allergy as a speciality appear less urgent and important.

The first trials of beclomethasone dipropionate aerosols, or “Becotide”, in 1970-71 were monitored by using individual peak flow meters for each patient. This was possible because I had obtained a supply of these meters, which had been invented only a few years before, for previous drug trials. In fact, the Becotide trials were among the first in the world to be individually monitored in this way. The essential criterion for entry was finding eosinophil cells in the sputum or nasal smears, and many of the earliest cases were children who had very unstable asthma or were already steroid dependent.

Before 1970 quite gross chest deformities in children were not uncommon, and photographs were taken before and at intervals after the introduction of Becotide show their disappearance. In adults dependent on oral steroids the photographs show the remarkable changes in their appearance on transfer to inhaled steroids. accompanied by improvements which lasted indefinitely. A selection of unpublished pictures and peak flow charts showing dramatic improvements are shown here as a matter of historical interest.

This boy aged 14 had such unstable asthma that he had to have frequent courses of oral steroids

When he was started on Becotide he rapidly came under control but is dependent on inhaled steroid to this day. He was repeatedly skin test negative, but a retest aged 20 produced a +++++ reaction to mites

This 50 year old patient had severe unstable asthma frequently requiring emergency oral steroids. He had perfect control for the next 34 years, and died of unrelated causes aged 84

Pauline was aged 8 in 1971, and was a very unstable multiple allergic living on a farm as shown above by peak flow records. The black areas at the bottom represent short courses of oral steroids

It was finally decided to try her on Becotide at the end of 1971, and her peak flow stabilised at once. She is now 43 and still maintained on Becotide. Serial photographs were taken over the next few years, as shown below.

On the left is a picture of Pauline aged 7, showing a very unhappy child breathing through her mouth because the nose is blocked by rhinitis, with the beginning of a pigeon chest, which is developed further in the middle photo taken before she began Becotide. On the right she is now aged 12, and the deformity has almost disappeared after 30 months on Becotide with complete control of the asthma

This boy aged 14 had developed a chest deformity from chronic asthma. After a year on Becotide with complete control of his asthma, and being able to take normal exercise and sport for the first time the shape of the chest has become normal. He is now aged 47 and still requires Becotide daily

John was only two and a half when the photo on the left was taken. He had been treated elsewhere with oral steroids for some time, with obvious side-effects and retardation of growth. I doubted if we could get him to use an inhaler at his age, but with his mother’s persistence he learnt to use an inhaler properly. Oral steroids were stopped and he did very well as shown by the second picture taken only a year later showing rapid growth and disappearance of the steroid side-effects . He developed normally into a healthy young man, except for the asthma for which he still has to take Becotide daily. He has been a game keeper for some years and is now aged thirty-six.

This girl began to wheeze as a baby, and was, treated elsewhere with oral steroids from about age five. She had been on continuous steroids for five years when the first photo was taken, showing the stunted growth, moon face, and obesity typical of steroid dependency. She was successfully transferred to Becotide, and her average peak flow rose from an average 60 L/min to 140, (predicted peak flow was 230). The picture 14 months later shows rapid growth of 8cms and disappearance of the side-effects. She was eventually able to do cross-country running and swimming, but some years later she had to have oral steroids again. All contact has been lost with this case.

Rachel was aged 6, and a very unstable asthmatic when the photo on the left was taken.  The photo on the right was taken after she had been perfectly controlled with becotide for nearly two years. The difference in every way is quite remarkable.

Becotide Results 1970-1980

The graphic presentation on the left shows how the steroid dependent children were much more likely to be able to transfer to Becotide, and how the older the patients were the less likely was transfer to becotide to be successful

This group were less severe asthmatics who had not had to be treated with oral steroids except for a flare-up. Older patients were only slightly more likely to have problems in becoming stabilised on Becotide.

Comments

Patients treated with Becotide were all monitored using peak flow meters, and the last reviews being in 1980. Obviously the cases illustrated here were carefully selected to show dramatic results, but are by no means exceptional. A series of papers from Derby were published from 1971 to 1980, and thousands of studies from investigators all over the world on various aspects of inhaled steroids have been published over the years. The use of aerosol steroids for rhinitis has also been studied in Derby and a survey over a five year period, in which Beconase had been used in 223 patients, showed no long-term side-effects in 534 patient/years of use.

Anxiety has lingered over the possibility that long term use would result in adrenal suppression or osteoporosis, especially in post-menopausal women. Several negative studies on this aspect have been published, but have usually been for a few years only. Many patients in the Derby group have been using Becotide for up to thirty-five years. No reports of long-term side-effects have surfaced so far, so it seems most likely that no significant side-effects occur even after so many years, but I have consistently failed to persuade anyone to recall and carry out a comprehensive survey to settle the matter.

From about 1968 onwards all allergic patients attending the Derby Chest Clinic had not only the usual case records, but also a punch card system on which brief notes of each consultation were made. Furthermore, all case notes were dictated while the patient was seen and typed, so there is a unique legible record of each case is in existence. When I retired from the NHS in 1982 I was not replaced by anyone with an interest in allergy, and as a result one of the largest allergy clinics in the UK was disbanded and most of the patients referred back to their GP’s . Some continuity was preserved by the nurse specialist, and the punch card records of the trials carefully preserved, but she has now retired also . These punch card records have now been taken over by Nottingham University and it is hoped that the group of patients who were the first in the world to receive inhaled steroids and have been taking them every single day ever since will be reviewed This would finally demonstrate if inhaled steroids can be used for life without fear of side-effects or not.

Qvar--- A Significant Breakthrough in Steroid Aerosol Technology

Recent developments in aerosol technology to find an alternative to ‘CFC’ aerosols containing chemicals which are destroying the ozone layer have resulted in dissolving the steroid drug in a new Hydro-flouro-alkane propellant gas in the aerosol can, instead of drug particles being suspended in the liquid CFC gas, which explains why the aerosol has to be shaken before use. The result is that the new aerosol produces really tiny particles of the steroid drug as small as one micron which have been positively demonstrated by radio-active studies to penetrate right down to the smallest bronchial tubes.

The importance of this development is that up to the present time the particles of steroid drug produced by CFC aerosols have been comparatively large, therefore able to reach only the larger bronchial tubes, but now these micro-aerosols have been shown to reach the smaller bronchi. This is of great potential importance because it means that for the very first time the whole lung can be being treated by inhaled steroid aerosols. In my opinion this development is a real breakthrough which was not noticed even by some experts in the field. This was pointed out in a letter from me to the Editor of the Lancet published in February 2003.

Unfortunately these aerosols are not yet in general use because most doctors in the UK have never heard of this important development in treatment, although Qvar has actually been prescribable on the NHS for at least four years and is not expensive. Unfortunately some NHS Pharmacy Advisers are advising GP’s not to prescribe Qvar for some ill-defined reason. In any event CFC aerosols are all being phased out, so all aerosols for asthma are changing to this system. This change is not because this development enables the smallest bronchi to be treated for the first time, but because of the possible effect of tiny medical aerosols containing CFCs on the ozone layer!

Appearance in 1971, after 5 years on oral steroids for asthma		One year after transfer to Becotide. 'Slimmer of the year' 1972. Still taking Becotide 2005.