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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:
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