ARLS 1 1997 Astra Respiratory Literature Service Experts comments

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màj : 17/06/99

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AstraZeneca Respiratory Literature Service
N°1 1997 (see also N° 2 1997)

For many years, AstraZeneca Draco laboratories have brought to the asthmolgist community an excellent "Respiratory Literature Service"(ARLS) with an alert to new references, selected summaries and comments by a group of experts. In 1997, AstraZeneca is extending this concrete service with Asmanet in order to take advantage of the Internet capabilities. The following comments have been edited ( HTML format) to smooth the reading with hypertext links to integrate the comment in the Asmanet server and the worldwide distributed library on asthma, such as : abstract of the commented paper, references as seen on Medline and others, author's e-mail ...

	Title	Authors	Journal	Reviewer
1	fluticasone propionate powder	Wasserman S.I., Gross G.N., Schoenwetter W.F.?, et al	J Asthma	Dr Duncan Geddes
2	oral corticosteroids & secondary osteoporosis	Walsh L.J., Wong C.A., Pringle M., Tattersfield A.E.	Br Med J	Dr Duncan Geddes
3	auranofin	Bernstein I.L., Bernstein D.I., Dubb J.W., et al	J Allergy Clin Immunol	Dr Duncan Geddes
4	theophylline	Finnerty J.P., Lee C., Wilson S., et al	Eur Respir J	Professor Philippe Godard
5	chronic obstructive airways disease	Grove A., Lipworth B.J., Reid P., et al	Thorax	Professor Philippe Godard
6	Asthma treatment in pregnancy	Wendel P.J., Ramin S.M., Barnett-Hamm C., et al	Am J Obstet Gynecol	Professor Philippe Godard

AstraZeneca Draco laboratories is also supporting the European Federation of Asthma and Allergy Associations which can be seen at http://www.efanet.org/

...

A 12-week dose-ranging study of fluticasone propionate powder
in the treatment of asthma

This study in 331 adult asthmatics adds valuable evidence to the debate about optimal dosing with inhaled corticosteroids. Yet again no dose response relationship was shown for a range of outcome measures over the range of 100-500 mg daily. These measures included FEV1, PEF, symptoms, rescue bronchodilator use and night awakenings. The evidence again favours the use of very low doses (100 mg/day of fluticasone or equivalent) for control of mild to moderate asthma.

There are only two arguments in favour of routine prescribing of higher doses in such patients:

Use of oral corticosteroids in the community and the
prevention of secondary osteoporosis: a cross sectional study

Respiratory physicians are major prescribers of corticosteroids and therefore need to know about osteoporosis and its prevention. This paper provides valuable data on chronic oral corticosteroid use in the UK as follows:

In the UK at least 250,000 people are at risk from oral corticosteroid induced osteoporosis and little is being done to prevent it

A placebo-controlled multicenter study of auranofin in the
treatment of patients with corticosteroid-dependent asthma

There remains a need for effective steroid-sparing agents for the treatment of asthma. Gold salts have a long history in this regard but have not yet been proved to work. In this study auranofin performed better than placebo as judged by the number of patients able to reduce their steroid dose by 50%. The benefit was most striking in those taking 10-19 mg/day of prednisolone and failed to reach significance in patients on 20 mg/day or more. Asthma control was the same in both groups throughout the 8-month trial.

These results look impressive but the study has two problems. First, the patients were not allowed to take high doses of inhaled corticosteroids ‘to prevent confounding effects in determination of the dependent dose’ and so the patients do not resemble those encountered in clinical practice. Second, there was a high incidence of gastro-intestinal (60%) and skin (30%) side effects in those taking gold which is likely to mean that the study was not truly blinded.

Steroid-sparing agents have, in the past, tended to perform better in clinical trials than in clinical practice. Auranofin looks promising but it is too early to celebrate yet.

Effects of theophylline on inflammatory cells and cytokines
in asthmatic subjects: a placebo-controlled parallel group study

Studies on theophylline have been reported in many previous ARLS issues, e.g. 96:6:24, 96:5:1, 95:6:24, 95:4:23. All these studies outlined effects of this old drug in bronchial asthma with new parameters in focus. In this placebo-controlled, 6-week study the authors demonstrate a positive clinical effect (asthma control) and an anti-inflammatory effect (bronchial biopsies) of theophylline; mean steady state concentration was 11.0 µg/mL.

This work has been well done and the results are interesting. However, it must be noted that 5 out of 12 subjects in the theophylline treated group were on inhaled steroids (low dose); the situation was similar (2 out of 9) in the placebo treated group. It is possible that this induced a decrease of the power of the study. This makes the results still more interesting.

The clinical control of asthmatics with theophylline improved significantly. PC20 (methacholine) was assessed at inclusion, but was not evaluated at the end. It would have been very interesting to have such a result. An interesting correlation between airway inflammation (bronchial biopsies) and PC20 in asthmatics treated with inhaled steroids has previously been observed (1).

Clinical research is very important. A link between bed and bench is always to be searched in order to give the patient the best medication, but also to select the patients who will have the best benefit.

Effects of regular salmeterol on lung function and exercise capacity
in patients with chronic obstructive airways disease

COPD is a frequent and disabling condition. The drugs which are available to relieve the symptoms are few. It is therefore useful to know the effect of a new drug, salmeterol, even if the results could be anticipated. The study design is very good including crossover comparisons.

From one point of view, you could be disappointed. The results with salmeterol were quite negative on exercise capacity. From another point of view, salmeterol disclosed some activity on lung function. So what?

The authors prospectively studied 84 pregnant women with asthma exacerbation. They performed a randomized open study on these women. In fact, the authors did two studies:

This paper rises a great deal of concern from many points of view: ethics, methodology, results, etc. It is very positive that gynecologists are interested in asthmology; that kind of work has been clearly recommended by the NHLBI committee. However, time, energy and money could have been saved if the NHLBI recommendations had been entirely followed.

Medications are now available to give the patients, also pregnant women, an excellent control of their asthma. This has to be done. However, the challenge now should concern the baby; foetal growth, weight at birth, in utero sensitisation, and other parameters have to be evaluated in cohorts with follow-up after birth.

Asmanet

Congrès Conçue et réalisée par: Michel Godard (at)

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Date de création: 1997 - Dernière mise à jour: 17/06/99
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Prevalence	0.5% for the whole population 1.4% for all aged over 55 years 1.7% for women over 55 years
Mean dose	8 mg/day prednisolone
Indications	rheumatoid arthritis 23% polymyalgia rheumatica 22% asthma + COPD 19%
Osteoporosis prevention	14% of those taking oral corticosteroids