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The New Zealand Medical Journal

 Journal of the New Zealand Medical Association, 18-June-2004, Vol 117 No 1196

Inhaled corticosteroids in asthma action plans—double or quits?
Julian Crane
In this issue of the New Zealand Medical Journal, McNally et al re-explore the use of childhood asthma action plans by general practitioners and paediatricians. The authors asked whether these practitioners might have changed their practice in advocating a doubling step for inhaled corticosteroids (ICS) since 1995.1 They hypothesise that recent studies (suggesting that the doses of inhaled corticosteroid being prescribed are too high2 and are well above the top of the dose response curve) might have influenced whether such a step was included in children’s asthma action plans. The fact that no space exists in the current Asthma and Respiratory Foundation Child Asthma Plan released in 2000, and that there is no evidence supporting the doubling step, might also be significant factors leading to change.
McNally et al found that use of a doubling step has significantly decreased since 1995—from 95% to 86% amongst general practitioners, and from 57% to 32% amongst paediatricians. It is interesting, therefore, to revisit the issues surrounding the doubling of inhaled corticosteroids (ICS) for asthma exacerbations, and to ponder why general and specialist paediatric practice might differ.
One of the first studies to suggest doubling ICS at the onset of exacerbations (as part of asthma self management in adult asthmatics) showed a significant benefit in a before-and-after trial when PEFR fell below 30% of the best value.3 The idea was rapidly incorporated into adult asthma-management plans in New Zealand (in response to the asthma mortality epidemic).
The mortality survey showed that many patients who died from asthma were under-treated—both chronically and in the final acute episode. Furthermore, it was recognised that many patients failed to identify the severity of their disease, as did some of their doctors. Thus, the elements of asthma-management plans were a pragmatic response to an urgent need to improve asthma management.
The idea of doubling inhaled corticosteroids (in response to changing peak flow or increasing symptoms) was seen as an important part of patient education—encouraging them to use inhaled corticosteroids and reinforcing their role in asthma management. Indeed, the fact that doctors considered doubling a treatment that has no immediate palpable benefit (compared to bronchodilators) emphasised the importance they placed on it. Subsequently, at least in adults, studies of management plans (incorporating this doubling-step) have shown evidence for improved asthma management compared to usual care in adults.4
Lahdensuo et al4 suggested that the improvement was unrelated to increased ICS use, although ICS adherence was not formally measured. Indeed, it has been difficult to identify which elements of these plans are important: the increased doses or compliance with ICS, early treatment of an exacerbation, improved education and understanding, or simply a Hawthorne effect.
Only one study has formally examined the value of this ICS doubling step in children and it is discussed in the McNally paper.5 That study (Garrett et al), although underpowered, failed to find any evidence that doubling ICS (for 3 days following the onset of a mild exacerbation in children) had any effect on symptom scores or the time course of improvement in lung function.
Recently, the doubling-step has been specifically examined in adults.6 Again, that study (Harrison et al) was underpowered for the main outcome of preventing an oral steroid requiring exacerbation, but was sufficiently powered for changes in PEFR or symptom scores. In addition, it failed to show any benefit from doubling ICS—with PEF rates returning to normal over 2 weeks regardless of increased ICS use.
However we should probably not be surprised at this failure, given that there is little evidence that large doses of systemic corticosteroids improve an asthma exacerbation either. Morell et al compared 2 mg/kg and 10 mg/kg of methyl prednisolone 4-hourly with a placebo and were not able to show any clinically significant differences in the degree or rate of improvement in the first 48 hours following an emergency attendance for asthma.7
Bowler et al compared 50, 100, and 500 mg of hydrocortisone 6-hourly for 48 hours (followed by oral prednisone, 20, 40, or 60 mg daily) in a reducing regimen for 12 days, and could find no differences between the three groups at any time.8 In both these studies, initial FEV1 was around 20% of predicted.
Systemic corticosteroids appear to offer little additional benefit over high doses of bronchodilators in acute severe asthma. In a study of the effects of oral prednisone on preventing early relapse after an emergency department attendance, Chapman et al showed a significant reduction in early relapse with oral corticosteroids in a group of less severe patients after an emergency room visit while they were taking the steroid.9
These studies suggest that once an exacerbation has developed, corticosteroids do little to reduce its severity or time course—because although they prevent inflammatory lights from coming on, they cannot switch them off. Presumably this is a clinical reflection of their major action to inhibit the expression of inflammatory genes; once these genes are expressed, steroids have much less effect in reducing downstream inflammatory events. If large doses of systemic steroids don’t improve an exacerbation, it is perhaps not surprising that doubling ICS do not help either.
When doubling ICS is compared to placebo (in the context of an asthma management plan), they don’t have any measurable effect in adults or children.5,6 When an asthma management plan incorporating the ICS doubling-step is compared to ‘usual’ management, the plans lead to an improved outcome—particularly in reducing exacerbations. The key ingredient appears to be the adherence to regular ICS as a preventer, which a double-dose step may help to reinforce—as recently emphasised by Masoli and Beasley.10
Thus it might be argued that the diverging practices of general practitioners (using a double step) and paediatricians (not using a double step) are both correct for different reasons. Paediatricians have increasingly adopted an evidence-based approach—recognising that doubling ICS doesn’t work. Indeed, they feel able to convince the parents of their patients of the importance of regular ICS as an asthma preventer.
General practitioners, on the other hand, temper this evidence with pragmatism. They recognise the therapeutic frailties of human nature (especially frail when it comes to adherence to ICS) and hope to emphasise the importance they attach to regular ICS by suggesting a doubling when asthma deteriorates, thereby transmitting the subliminal message that in order to double the dose you must already be on one. . A follow-up study of why GPs and paediatricians do what they do with asthma plans would be of interest.
Author information: Julian Crane, Professor, Department of Medicine, Wellington School of Medicine, University of Otago, Wellington
Correspondence: Professor Julian Crane, Wellington School of Medicine, University of Otago, PO Box 7343, Wellington. Fax: (04) 389 5427; email: crane@wnmeds.ac.nz
References:
  1. Garrett J, Williams S, Wong C, Holdaway D. Application of asthma action plans to childhood asthma: a national survey. N Z Med J. 1997;110:308–10.
  2. Holt S, Suder A, Weatherall M, et al. Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis. BMJ. 2001;323:253–6.
  3. Beasley R, Cushley M, Holgate ST. A self management plan in the treatment of adult asthma. Thorax. 1989;44:200–4.
  4. Lahdensuo A, Haahtela T, Herrala J, et al. Randomised comparison of guided self management and traditional treatment of asthma over one year. BMJ. 1996;312:748–52.
  5. Garrett J, Williams S, Wong C, Holdaway D. Treatment of acute asthmatic exacerbations with an increased dose of inhaled steroid. Arch Dis Child. 1998;79:12–17.
  6. Harrison TW, Oborne J, Newton S, Tattersfield AE. Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. Lancet 2004;363:271–5.
  7. Morell F, Orriols R, de Gracia J, et al. Controlled trial of intravenous corticosteroids in severe acute asthma. Thorax. 1992;47:588–91.
  8. Bowler SD, Mitchell CA, Armstrong JG. Corticosteroids in acute severe asthma: effectiveness of low doses. Thorax. 1992;47:584–7.
  9. Chapman KR, Verbeek PR, White JG, Rebuck AS. Effect of a short course of prednisone in the prevention of early relapse after the emergency room treatment of acute asthma. N Engl J Med. 1991;324:788–94.
  10. Masoli M, Beasley R. Asthma exacerbations and inhaled corticosteroids (letter). Lancet 2004;363:1236.


     
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