Introduction
Inhaled corticosteroids have been used in the management of childhood asthma since the early 1970s. Despite this, uncertainty remains about when to use them. There is overwhelming evidence of efficacy in the treatment of persistent asthma (including reduction in hospitalisation, reduced morbidity and improved quality of life). However, the evidence concerning risk is considered less clear, particularly regarding growth and adrenal suppression.1

This concern is surprising, given the available literature. A meta-analysis of paediatric asthma studies which included linear growth as an outcome measure, showed no evidence of growth suppression with doses of inhaled beclomethasone <800 microgram/day.2 Indeed, early clinical trials showed inhaled corticosteroids accelerated growth, since chronic asthma itself is a very potent growth suppressant. Although in high doses (>800 microgram/day) there is absorption of inhaled corticosteroids, clinically relevant suppression of the hypothalamic-pituitary-adrenal axis is extremely rare.3

Prescribing inhaled corticosteroids
The appropriate use of these drugs in paediatric asthma is clearly outlined in the Australian guidelines.4 Inhaled corticosteroids are the drugs of choice for managing children with persistent (daily) asthma symptoms, specifically:

– children with chronic night cough, night wheeze or waking due to asthma

– frequent (most days) need for bronchodilators

– major problems from exercise-induced asthma (not controlled with pre-exercise beta agonists)

– severe life-threatening attacks of asthma

The majority of children with asthma have infrequent, mild episodes and do not warrant any preventive therapy. Such children are best managed with beta agonists, as necessary, preferably by aerosol. For those with frequent (or more troublesome) episodes, cromoglycate or nedocromil are the drugs of choice. If a 4-6 week trial of cromoglycate fails to control the asthma, then inhaled corticosteroids should be commenced forthwith. The usual starting dose of budesonide or beclomethasone should be 400 microgram/day (fluticasone 200 microgram/day), with a plan to progressively reduce the dose ('back-titrate') to the minimum which keeps the child's asthma well controlled. Back titration can be done by halving the dose every 6-8 weeks and assessing the response. If there has been a prolonged remission (e.g. 6 months) from asthma symptoms on low-dose inhaled corticosteroids (200 microgram/day), then a trial on cromoglycate in place of the steroid may be appropriate.

Every attempt should be made to minimise the risks of adverse effects. This includes the use of spacer devices (or 'rinsing and spitting') to reduce topical adverse effects and oropharyngeal absorption. However, most of the absorption is pulmonary (via the airways and lung). Thus, the higher the inhaled dose, the more likely significant absorption will occur. To reduce respiratory tract absorption, there should be back titration of the dosage, once the child's asthma is in remission. Ideally, this should be done after approximately 3 months of good symptom control (see box).

Prevention of chronic disease
One of the present dilemmas is that, since inhaled corticosteroids are safe, they should be started earlier than current guidelines recommend. The rationale is that 'blitzing' the inflamed airways with a short-course, high-dose inhaled corticosteroid during the initial bout(s) of viral-induced childhood wheeze may prevent progression to (or development of) frank asthma. However, there is no evidence to support this hypothesis.

Signs of good control

– only occasional need for bronchodilators

– no significant asthma exacerbations

– no school absenteeism

– no night waking with asthma (cough or wheeze)

– easily controlled exercise-induced wheezing (e.g. with pre-exercise use of a beta agonist aerosol)

One widely quoted European cohort study suggests early use of inhaled corticosteroids results in improved long-term lung function, compared to children using other forms of preventive therapy (particularly cromoglycate).5 A more recent retrospective study from the U.S.A. found that the children who were not on any form of preventive therapy were at the greatest risk of long-term reduction in lung function.6 There was no difference in long-term lung function between those on cromoglycate and those on inhaled corticosteroids.

More evidence needed?
A large randomised controlled trial is needed to determine if early introduction of inhaled corticosteroids is the best option for long-term respiratory health in asthmatic children. One such study of both adults and children has begun.

Conclusion
Useful outcome measures from this long-term study will not be available for several years. In the meantime, it seems wise to use preventive therapy earlier rather than later and follow the current 'best practice' guidelines for appropriate selection of drugs. There should be no reluctance to prescribe inhaled corticosteroids when indicated, although the dose should be kept to a minimum.

 

Craig Mellis

Clinical Associate Professor and Consultant Respiratory Paediatrician, The New Children's Hospital, Sydney