Guideline

Scope of the guideline

The areas covered by the guideline are: the use of peak flow measurement in diagnosis and management, drug treatment, non-drug treatment and referral.

All recommendations are for primary health care professionals and apply to adult patients attending general practice with asthma. The development group assumes that health care professionals will use general medical knowledge and clinical judgement in applying the general practice principles and specific recommendations of this document to the management of individual patients. Recommendations may not be appropriate for use in all circumstances. Decisions to adopt any particular recommendation must be made by the practitioner in the light of available resources and circumstances presented by individual patients.

Peak flow: diagnosis

Recommendation:


Statement: diurnal peak flow variability of more than 19% is highly suggestive of asthma (II).

Higgins et al. (1989) studied a population which included those with chest disease. The 95th centile and above was defined by a 25% or greater variability in peak flow.

Quackenboss et al. (1991) studied 861 adults and children who were screened to exclude those with chest disease. In the remaining group peak flow was measured four times daily and used to define population centiles. The 95th centile and above was defined by a 19% or greater variability in peak flow.

References
Higgins, B.G., Britton, J.R., Chinn, S., Jones, T.D., Jenkinson, D., Burney, P.G.J. and Tattersfield, A.E. (1989) The distribution of peak expiratory flow variability in a population sample. American Review of Respiratory Disease 140:1368-1372.

Quackenboss, J.J., Lebowitz, M.D. and Krzyzanowski, M. (1991) Normal range of diurnal changes in peak expiratory flow rates: relationship to symptoms and respiratory disease. American Review of Respiratory Disease 143:323-330.

Peak flow: management

Recommendations:

Statement: the routine home use of peak flow meters does not alter patient outcomes (I).

GRASSIC (1994) studied 569 patients who were randomly allocated to routine care or to have a peak flow meter plus guidelines - they were followed for 12 months. There was no significant difference between the groups except those with peak flow meters used more oral steroids though this was within the more severe patients.

Comment:
the much cited paper by Charlton et al. (1990) addressing this issue was rejected on methodological grounds.

References
Charlton, I., Charlton, G., Broomfield, J. and Mullee, M.A. (1990) Evaluation of peak flow and symptoms only self management plans for control of asthma in general practice. British Medical Journal 301:1355-1359.

Grampian Asthma Study of Integrated Care (GRASSIC) (1994) Effectiveness of routine self monitoring of peak flow in patients with asthma. British Medical Journal 308: 564-567.


Statement: "morning dipping" reflects transient, rather than long term, poor control (II).

Bellia et al. (1985) showed in 38 patients with morning dips compared with controls and followed for 2 years that morning dipping is a transient phenomenon reflecting current control rather than long-term prognosis.

References
Bellia, V., Cibella, F., Migliara, G., Peralta, G. and Bonsignore, G. (1985) Characteristics and prognostic value of morning dipping of peak expiratory flow rate in stable asthmatic subjects. Chest 88:89-93.


Statement: in acute situations peak flow can be used to predict outcome (III).

Nowak et al. (1982) looked at 109 patients attending emergency rooms and measured pre-treatment and post-treatment peak flow, need for admission and followed up those patients discharged from the emergency room without admission. They defined poor outcome as having to be admitted or having poor control of their asthma in the 48 hours after leaving the emergency room. A pre-treatment peak flow of less than 100 l/min, a post-treatment peak flow of less than 300 l/min, and an improvement in peak flow of less than 60 l/min all predicted poor outcome.

References
Nowak, R.M., Pensier, M.I., Sarkar, D.D., Anderson, J.A., Kvale, P.A., Oritz, A.E. and Tomlanvich, M.C. (1992) Comparison of peak expiratory flow and FEV1 admission criteria for acute bronchial asthma. Annals of Emergency Medicine 11:64-69.

Research questions
Is there a learning effect from the use of peak flow meters on symptom perception and control?

What is the role of chest X-ray in patients newly presenting in primary care?

What is the role of peak flow in predicting outcome in acute situations in UK primary care?

Which patients should be monitored with regular peak expiratory flow rate measurements and when?

Aims of treatment

Comment:
The group did not define their own aims of treatment. The British Thoracic Society (British Thoracic Society) guidelines state the aims of treatment as patients having: the least possible symptoms; the least possible need for relieving bronchodilators; the least possible limitation of activity; the least possible circadian variation in peak flow; the best peak flow possible; and the least possible adverse effects from medicine.

A further general statement from the British Thoracic Society guidelines that is relevant at this point is that it is preferable to adjust treatment to cover exposure to day to day triggers, such as exercise and cold air, because avoidance imposes inappropriate restrictions on lifestyle. Specific comments about adjusting the dosages of drugs are made within the relevant sections on drug treatment.

References
British Thoracic Society, British Paediatric Association, Royal College of Physicians.

Kings Fund Centre, National Asthma Campaign, Royal College of General Practitioners, General Practitioners in Asthma Group, British Association of Accident and Emergency Medicine, and British Paediatric Respiratory Group (1993) Guidelines on the management of asthma. Thorax 48:s1-s24.

Drugs used in the treatment of recurrent wheeze

Comment:
The range of drugs considered in the treatment of recurrent wheeze, their dosages, contra-indications and side-effects are described in the British National Formulary (BNF) sections 3.1 (bronchodilators), 3.2 (corticosteroids) and 3.3 (cromoglycate and related therapy).

All recommendations for treatment apply only in the absence of recognised contra-indications, side-effects or interactions as documented in the BNF.

References
British Medical Associations RP. (1995). British National Formulary Bath: BMA, The Pharmaceutical Press.

Compliance

Recommendation:

Sequencing of treatment

Comment:
There is little evidence to answer the important clinical questions of appropriate sequencing of treatment and the relative places of various agents in drug management. The drugs are therefore considered in the order they are presented in the BNF: short acting bronchodilators, long acting bronchodilators, inhaled anti-inflammatory agents, oral drugs, intravenous drugs. A suggested sequencing is provided after consideration of the drugs.

Short acting beta2 agonists

Recommendations:

Statement: beta 2 agonists are effective as judged by an increase in PEFR (I).

Orgel et al. (1985) showed that salbutamol is effective when used as a Rotahaler.

References
Orgel, H.A., Meltzer, E.O., Welch, M.J. and Kemp, J.P. (1985) Inhaled albuterol powder for the treatment of asthma - a dose-response study. Journal of Allergy and Clinical Immunology 75:468-471.

Statement: there is conflicting evidence on the issue of p.r.n. versus regular dosage (I).

Comment:
If patients need four daily doses of a short acting beta2 agonist there is conflicting evidence on the issue of p.r.n. versus regular dosage. The two studies identified give contradictory findings; this may be due to any or all of the following: patient selection, drug selection and study design.

Taylor et al. (1993) studied 64 adults, taking either fenoterol 400 micro g four times daily or matching placebo in a double blind study of two 24 week periods . During each period they had a fenoterol inhaler to use as required. During the time they were on placebo, the subjects had fewer exacerbations of asthma, better FEV1 and morning peak flow, and less bronchial hyper-reactivity. The results suggest that doses of short acting beta 2 agonists should only be taken as required.

Chapman et al. (1994) studied 341 asthmatics (of whom 313 completed the trial) who took either 200 g of salbutamol four times daily or matching placebo for two weeks, then crossed over to the alternative. During each period they had a salbutamol inhaler to use as required. During regular salbutamol dosing, there were fewer "asthma episodes" and less requirement for supplemental salbutamol. There was no difference in morning or evening peak flow. This study appears to show that regular usage of beta 2 agonists is preferable to p.r.n..

References
Chapman, K.R., Kesten, S. and Szalai, J.P. (1994) Regular vs as-needed inhaled salbutamol in asthma control. Lancet 343:1379-1382.

Taylor, D.R., Sears, M.R., Herbison, G.P., Flannery, E.M., Print, C.G., Lake, D.C., Yates, D.M., Lucas, M.K. and Li, Q. (1993) Regular inhaled beta agonist in asthma: effects on exacerbations and lung function. Thorax 48:134-138.


Statement: salbutamol is effective in the treatment of exercise induced bronchospasm and is more effective than sodium cromoglycate (I).

Rohr et al. (1987) studied 80 patients with exercise induced bronchospasm in a randomised parallel group study comparing sodium cromoglycate with salbutamol. The sodium cromoglycate group took 20 mg four times daily for four weeks and then a single dose 15 minutes before a treadmill test; the salbutamol group took salbutamol p.r.n. for four weeks and a dose 15 minutes before the exercise test. The reduction in FEV1 was significantly smaller with salbutamol (17%) than sodium cromoglycate (27%).

References
Rohr, A.S., Siegel, S.C., Katz, R.M., Rachelefsky, G.S., Spector, S.L. and Lanier, R. (1987) A comparison of inhaled albuterol and cromolyn in the prophylaxis of exercise-induced bronchospasm. Annals of Allergy 59:107-109

Research questions
What is the relative place of regular and p.r.n. dosing with short acting beta 2 agonists?

What are the appropriate points at which to increase and decrease treatment with short acting beta 2 agonists?

Long acting inhaled beta 2 agonists

Comment:
We identified no evidence to suggest whether long acting beta 2 agonists should be used before or after inhaled anti-inflammatory drugs. At the time of writing the only prescribable long acting inhaled beta2 agonist is salmeterol.

Recommendations:

Comment:
If the introduction of salmeterol is based on frequency of short acting beta 2 agonist use, there is benefit in using it in line with the recommendation above. We identified no evidence on the use of salmeterol at lower frequencies of short acting beta 2 agonist use, nor any evidence in relation to frequency of inhaled anti-inflammatory use.

Statement: salmeterol produces significant bronchodilatation for 12 hours (I).

Statement: salmeterol produces no additional effect in dosages beyond 50 micro g twice daily but does produce more side-effects (I).

Fitzpatrick et al. (1990) compared salmeterol 50 micro g twice daily with salmeterol 100 micro g twice daily and with placebo in 20 asthmatics. Nocturnal peak flow fall was improved on both doses of salmeterol and sleep quality improved on 50 g twice daily.

Palmer et al. (1992) conducted a double blind parallel group study comparing salmeterol 50 micro g twice daily with salmeterol 100 micro g twice daily, with no placebo. Grouped data showed greater benefits in peak flow, symptoms, and rescue bronchodilator use with the larger dose of salmeterol, but this is partly due to baseline differences and there were also more side-effects on the bigger dose.

Bronsky et al. (1994) studied 154 subjects randomised to one of four doses of salmeterol or placebo for one week. The higher doses of salmeterol (50 micro g twice daily and 100 micro g twice daily) produced significant bronchodilatation (FEV1) for 12 hours; lesser doses did not. There were more side-effects on the 100 micro g twice daily dose.

References
Bronsky, E.A., Kemp, J.P., Orgel, H.A., Bierman, C.W., Tinkelman, D.G., van As, A. and Liddle, R.F. (1994) A 1-week dose-ranging study of inhaled salmeterol in patients with asthma. Chest 105:1032-1037.

Fitzpatrick, M.F., Mackay, T., Driver, H. and Douglas, N.J. (1990) Salmeterol in nocturnal asthma: a double blind, placebo controlled trial of a long acting inhaled beta 2 agonist. British Medical Journal 301:1365-1368.

Palmer, J.B., Stuart, A.M., Shepherd, G.L. and Viskum, K. (1992) Inhaled salmeterol in the treatment of patients with moderate to severe reversible obstructive airways disease: a 3-month comparison of the efficacy and safety of twice-daily salmeterol (100 micro g ) with salmeterol (50 micro g ). Respiratory Medicine 86:409-417.


Statement: salmeterol used twice daily is more effective than short acting inhaled beta 2 agonists used four times daily (as metered dose inhaler or a powder)(I).

Pearlman et al. (1992) studied 234 asthmatics randomised to three groups: placebo; salbutamol 180 micro g four times daily; salmeterol 42 micro g twice daily. Patients were followed for 12 weeks and approximately one third of each group were on inhaled steroids. In terms of symptoms and lung function measurements, salmeterol appeared superior to salbutamol which was superior to the placebo. There was no tolerance to the bronchodilating effects of salmeterol.

Britton et al. (1992) studied 534 subjects who completed a comparison of salmeterol 50 micro g twice daily with salbutamol 200 g four times daily for three months, and then a further nine months in which salmeterol was given with the same dosage and salbutamol was given 200 micro g twice daily; 37% were on high dose inhaled steroids and 26% on low dose. Most of the comparisons in the paper look at the first three months treatment and show that salmeterol was superior in terms of nocturnal asthma symptoms, morning and evening peak flow readings.

Lundback et al. (1993), in a study design the same as that of Britton et al. (1992) used dry powder inhalers instead of metered dose inhalers; 57% of patients were on inhaled steroids, 5% on oral steroids and 7% on both. 388 asthmatics were included in this study and again salmeterol was superior in terms of peak flow readings, nocturnal symptoms, and also rescue beta 2 agonist use.

References

Britton, M.G., Earnshaw, J.S. and Palmer, J.B. (1992) A twelve month comparison of salmeterol with salbutamol in asthmatic patients. European Study Group [published erratum appears in Eur Respir J 1993;6(1):150]. European Respiratory Journal 5:1062-1067.

Lundback, B., Rawlinson, D.W. and Palmer, J.B. (1993) Twelve month comparison of salmeterol and salbutamol as dry powder formulations in asthmatic patients. European Study Group. Thorax 48:148-153.

Pearlman, D.S., Chervinsky, P., LaForce, C., Seltzer, J.M., Southern, D.L., Kemp, J.P., Dockhorn, R.J., Grossman, J., Liddle, R.F., et al. (1992) A comparison of salmeterol with albuterol in the treatment of mild to moderate asthma. New England Journal of Medicine 327:1420-1425.


Statement: in one short term evaluation salmeterol was as safe as a short acting beta 2 agonist (I).

Castle et al. (1993) studied over 25,000 patients in general practice who were randomised to salmeterol 50 micro g twice daily or salbutamol 200 micro g four times daily for 16 weeks. The primary outcome was mortality; there were more deaths in the salmeterol group but this did not reach significance. Only 69% of the patients were on inhaled steroids.

Comment:
This is a negative study without a power calculation.

References
Castle, W., Fuller, R., Hall, J. and Palmer, J. (1993) Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment. British Medical Journal 306:1034-1037.