Recommendations:
Statement: metered dose inhalers are as effective as powder devices (I).
Blumenthal et al. (1988) showed that sodium cromoglycate works equally well with a metered dose inhaler when compared with spinhaler.
Lundback et al. (1993) (as above) studied 585 patients in a randomised, double blind three parallel group study comparing 500 micro g of fluticasone via diskhaler, 500 micro g of fluticasone via metered dose inhaler, and 100 micro g of beclomethasone via a metered dose inhaler. There were no significant differences between fluticasone metered dose inhaler and diskhaler groups.
Lundback, B., Alexander, M., Day, J., Hebert, J., Holzer, R., Van Uffelen, R., Kesten, S. and Jones, A.L. (1993) Evaluation of fluticasone propionate (500 micro g day-1) administered either as dry powder via a Diskhaler inhaler or pressurized inhaler and compared with beclomethasone dipropionate (1000 micro g day-1) administered by pressurized inhaler. Respiratory Medicine 87:609-620.
Comparing metered dose inhaler with autohaler Woodman et al. studied 36 patients who were currently taking 400-1000 g of beclomethasone daily. In a four week double blind randomised crossover design they compared the effectiveness of drug delivery via a metered dose inhaler or an autohaler. Lung function and symptoms were equivalent in the two groups.
Toogood et al. (1984) studied 35 patients taking two doses of budesonide (400 micro g, 1600 micro g) by three different delivery devices (metered dose inhaler, metered dose inhaler and tube extension, and metered dose inhaler and nebuhaler). Patients took each of the six possible combinations for a period of two weeks. Both spacer devices produced a relatively small (~10 l/min) but statistically significant increase in lung function which tended to be better with the nebuhaler. The mouth was swabbed for candida and there was a marked decrease in colony count with the spacers.
Colacone et al. (1993) studied 80 asthmatics treated in the emergency room with either 400 g of salbutamol from a metered dose inhaler via a spacer at 30 minutes intervals, or 2.5 mg of salbutamol via a nebuliser at 30 minute intervals. There was no significant difference between the groups in the eventual maximum FEV1 or in the time taken to get there.
Recommendations:
De Blaquirere et al. (1989) studied subjects who had difficulty using a metered dose inhaler; they were randomised to receive verbal instruction plus an electronic meter which registers correct technique with a green light. There was no difference in improvement in technique in those using the meter.
Recommendation:
Neville et al. (1991) studied 29 patients in a randomised double blind crossover study. They received either twice daily theophylline or a placebo for two months, and then crossed over. There were significant benefits from theophylline in terms of peak flow and symptoms.
Pierson et al. (1990) studied 124 patients; all had their theophylline dose titrated to achieve a desirable serum level but then half of them were treated with theophylline and the other half with controlled release salbutamol, 8 mg twice daily. Both treatments produced improvement compared with pre-treatment values but there was no significant difference between the two.
Billing et al. (1987) studied 20 patients with reversible air flow obstruction, all taking oral beta 2 agonists. The effects of adding theophylline in high dose, low dose, or a placebo were compared. There was a significant benefit from the addition of theophylline.
Beskow et al. (1984) studied 25 patients in a double blind double dummy crossover trial comparing sustained release terbutaline 7.5 mg twice daily with salbutamol 4 mg three times daily. Morning PEFR were significantly better on terbutaline by 18 litres per minute. There were no other differences in PEFR or symptoms.
Dahl et al. (1989) studied 37 patients in a double blind crossover study of sustained release terbutaline 10 mg twice daily, budesonide 400 micro g twice daily, or the combination. There was a significantly lower fall in PEFR with the combined treatment; there was no difference between the two drugs given as single treatments. There was no power calculation.
Vilsvik et al. (1991) studied 72 subjects; placebo was compared with bambuterol 5 mg, 10 mg, or 20 mg, each treatment for one week. Lung function tests improved on the highest dose of bambuterol but there was no significant improvement in symptoms or in use of rescue bronchodilators.
Fugleholm et al. (1993) studied 70 patients taking 10 mg of bambuterol compared with 5 mg twice daily of controlled release terbutaline for two weeks (crossover). There was no significant difference between the two treatments in any parameter.
Persson et al. (1988) studied 25 patients taking bambuterol 30 mg a day for 14 days, or slow release terbutaline 10 mg twice daily (crossover). Bambuterol produced significantly better evening peak flow readings, and less rescue bronchodilator use was necessary with bambuterol. However, the two preparations have not been compared in equal doses of terbutaline.
Persson, G., Gnosspelius, Y. and Anehus, S. (1988) Comparison between a new once-daily, bronchodilating drug, bambuterol, and terbutaline sustained-release, twice daily. European Respiratory Journal 1: 223-226.
Vilsvik, J.S., Langaker, O., Persson, G., Ringdal, N., Schaanning, J., Kvelstad, G., Svensson, K., Holthe, S. and Soliman, S. (1991) Bambuterol: a new long acting bronchodilating prodrug. Annals of Allergy 66:315-319.
Recommendations:
From a meta-analysis of 30 relevant randomised controlled trials looking at the effectiveness of steroid therapy in acute exacerbations of asthma Rowe et al. (1992) concluded that: the use of steroids early in the treatment of asthmatic exacerbations reduces subsequent admissions in adults (Odds Ratio 0.47; 95% confidence interval 0.27, 0.79); steroids are effective in preventing relapse in the outpatient treatment of asthmatic exacerbations (Odds Ratio 0.15; 95% confidence interval 0.05, 0.44); and oral and intravenous steroids appear to have equivalent effects on pulmonary function in acute exacerbations (Effect Size -0.07; 95% confidence interval -0.39, 0.25). They could not produce any summary conclusions about dose and dosing, though "low" doses were not as effective as "medium and high doses".
Carson et al. (1991) reported a descriptive analysis of the records of 90,880 patients who received oral steroids (for dermatitis as well as asthma). They show a very low incidence of gastrointestinal bleeding and conclude that prophylaxis against bleeding is not generally necessary. In sub-group analysis the biggest risk was in people who had upper GI bleeding in the past and in subjects also taking oral anticoagulants but even here the incidence was low.
Recommendation:
Statement: intravenous aminophylline offers little benefit over 2 agonists in the treatment of acute asthma (I).
Littenberg (1988) conducted a meta-analysis on the use of aminophylline in acute asthma. He looked at 347 papers and for various reasons rejected all but 13 of them. From these papers the conclusions were: (a) in five comparisons of intravenous aminophylline against parenteral beta 2 agonists, the beta 2 agonists did marginally better; (b) in three papers in which beta 2 agonist plus steroid were compared to aminophylline plus steroid there was no obvious advantage to either; (c) in five trials of beta 2 agonists compared to beta 2 agonists plus aminophylline, there was a trend towards an increased effect with the addition of aminophylline but this was not significant.
Wrenn et al. (1991) studied 133 subjects presenting to a hospital emergency room. Some had asthma, some COPD, though the numbers are unclear. They were given inhaled beta 2 agonists at 20 minute intervals, methylprednisolone 80 mg intravenously, and either aminophylline infusion or a placebo. There were no significant differences in any lung function measurements or in side-effects. Significantly fewer patients were admitted from the emergency room to hospital after aminophylline (6% v 21%).
Murphy et al. (1993) studied 44 asthmatics who were treated with nebulised beta 2 agonist then, if their peak flow did not improve to above 40% predicted, treated with an infusion of aminophylline or placebo. Nebulised beta 2 agonist was continued and they were given intravenous methylprednisolone. There was no difference in improvement between the two groups and more side-effects in the aminophylline group. Serum levels of aminophylline were not measured.
Murphy, D.G., McDermott, M.F., Rydman, R.J., Sloan, E.P. and Zalenski, R.J. (1993) Aminophylline in the treatment of acute asthma when beta 2-adrenergics and steroids are provided. Archives of Internal Medicine 153:1784-1788.
Wrenn, K., Slovis, C.M., Murphy, F. and Greenberg, R.S. (1991) Aminophylline therapy for acute bronchospastic disease in the emergency room [see comments]. Annals of Internal Medicine 115:241-247.
Salmeron et al. (1994) studied 47 patients admitted to hospital with severe acute asthma (PEFR <150 l/min and Pa CO2 40 mm Hg) in a multi-centre parallel group study. The patients received either nebulised salbutamol 5 mg twice or an intravenous salbutamol infusion 5 mg over one hour. The increase in PEFR was greater in the nebulised group (by over 60 l/min) as was the decrease in Pa CO2. The percentage judged, by pre-defined criteria, to have been treated successfully at one hour was greater in the nebuliser group (86% v 40%).