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Childhood wheeze are we getting it right?

Dr Mike Thomas questions whether the pressure to diagnose asthma in children has gone too far,and warns of the medicolegal risks of high-dose inhaled steroids

Dr Mike Thomas questions whether the pressure to diagnose asthma in children has gone too far,and warns of the medicolegal risks of high-dose inhaled steroids

A wheezing child is a bread-and-butter GP presentation that we and our nurses see nearly every day. We are all familiar with the BTS/SIGN asthma guidelines, which have been the basis of successful asthma management for many years. Asthma is the most common chronic disease of childhood, and there is no doubt that over the years GPs have taken it seriously and as a result have done well in providing good quality care and delivering good outcomes for this illness.

This is reflected in the falling asthma death and hospital admission rates during the 1990s, although there is now evidence that the improvements in outcomes have plateaued. Although we have made great headway, there is still a large burden of potentially avoidable morbidity arising from asthma and other wheezing illnesses.

More recently it has become clear from large cohort studies that wheezing illnesses in children are heterogeneous and cover a spectrum of conditions; all wheezes are not asthma. Also, although inhaled steroids are safe and effective treatment for asthma at standard doses, we now have good evidence that they are not effective for all the patterns of wheezing seen in childhood.

In addition, safety concerns have arisen over side-effects from high-dose inhaled steroids, with some evidence that inappropriately high doses may sometimes be putting children at risk. More than one in five UK children aged five to six years old were found to have active asthma-like symptoms in a survey in 2003. Even very young children may present with wheezing episodes, although we now recognise that not all wheezing in children is caused by asthma, and other conditions, some common, some rare, may also cause childhood wheeze (see box, right).

Other causes of wheeze

Transient infantile wheezing

Wheezing in very young children is most often transient infantile wheezing. This is a benign condition in which children are born with rather small airways, sometimes as a result of maternal smoking or some other intrauterine insult. It improves as the child grows and the airways mature, and needs no active treatment other than parental reassurance.

Recurrent viral wheeze

In toddlers and slightly older children, a common condition is recurrent viral associated wheezing, in which children wheeze when they pick up a respiratory viral illness but are fine at other times. This pattern of wheezing often follows a severe early viral respiratory infection, which if investigated is frequently found to be respiratory syncytial virus (RSV). It can, however, be difficult to decide at the time of presentation whether an individual child with wheezing has true asthma or viral-associated wheezing, particularly as viral illnesses can be a trigger for true asthma, which frequently gets worse when an asthmatic child picks up an upper respiratory tract virus.

Getting the diagnosis right

The BTS/SIGN asthma guidelines give pointers to a diagnosis of asthma in children, such as persistent symptoms and a personal or family history of other atopic illnesses (see box, bottom right), but recognise that the diagnosis is not always easy, as there is no straightforward gold-standard diagnostic test. Sometimes it takes time and trials of therapy before the diagnosis is clear, and we need to be wary of applying the label of asthma to children in whom the diagnosis is not clear.

Over the past 10 years, we have been under a lot of pressure not to miss asthma in children, as the treatment is so effective, but it is equally important not to apply the label of asthma to children whose wheeze is from some other cause. It is of more than academic interest, as the prognosis and implications for treatment are different for different wheezing conditions in children. Clearly rare illnesses need to be picked up, and we should have a low threshold for referral in very young children and those with atypical pictures.

But it's also important to distinguish between true asthma and the other common wheezing patterns in children. For one thing, a diagnosis of asthma can be upsetting for the family and the label tends to follow a child around once it is made. Also, whereas wheezing associated with viral infection tends to improve and disappear as childhood progresses, asthma tends to persist and may get worse as childhood progresses. The evidence for the effectiveness of inhaled steroids is also different.

Inhaled steroids in the treatment for childhood asthma

The BTS/SIGN guidelines lay out a clear stepwise management strategy for children under five, and separately for those aged five to 12 (see boxes, top right). The cornerstone of preventive treatment for persistent asthma is inhaled steroids, which in standard doses are an incredibly safe and effective treatment. Our increased use of inhaled steroids in childhood asthma has led to improvements in symptoms and quality of life and has prevented deaths and admissions for children with asthma. But in our enthusiasm we should be aware of some sobering facts and make sure that our use of inhaled steroids in childhood asthma is appropriate.

First, we need to recognise that these guidelines only apply to asthma, and not to other wheezing illnesses. There is, for instance, no evidence that inhaled steroids are useful in transient infantile wheeze (the 'happy wheezing baby'), and no evidence to support their use in recurrent viral associated wheeze. Viral wheeze is difficult to treat in an evidence-based way at the moment, but most authorities would agree that inhaled bronchodilators can help wheezing episodes, and high-dose oral or inhaled steroids may be necessary in severe episodes. A Cochrane review has shown that regular doses of inhaled steroids are not effective, however. There is some new evidence that leukotriene receptor antagonists may help in this condition, although more research is needed to confirm this.

Getting the dose right

If we are using inhaled steroids in childhood asthma it is crucial that we do not overdose our patients, and the BTS guidelines clearly state that the normal dose in children is up to 400µg/day of beclomethasone (equating to 400µg/day of budesonide and 200µg/day of fluticasone).

In the under-fives we should not go above 400µg/day, and if still uncontrolled we should review the diagnosis, add in a leukotriene receptor antagonist and if they remain symptomatic, refer to a specialist. There is no evidence or licence for the use of long-acting ß-agonists or combination inhalers in young children. In older children, add-on therapy with a long acting ß-agonist is recommended once 400µg/day is reached, but if this and other add-on trials are ineffective we can go up to a maximum of 800µg/day (400µg/day fluticasone) but no higher without a specialist opinion. This advice from the 2003 BTS guidelines remains valid, but is rather different from the older guidelines where higher doses of inhaled steroids (up to 2000µg/day) were advocated. Recent evidence has shown that for the vast majority of patients, there is no extra benefit from going up to high doses, and also that the dangers of doing so are greater than we believed in the past.

Dangers of high doses

Safety is always a major concern in prescribing, particularly in paediatric practice and chronic diseases such as asthma where long-term treatment is likely to be needed. The safety profile of inhaled steroids at standard doses is excellent, but there is some evidence that when used at higher doses over long periods of time, there is a small but detectable increase in steroid-related side effects such as cataract and osteopaenia.

As it is possible that children with asthma may have to use inhaled steroids for many years, we should always try to use the lowest effective dose. When we start using high doses (>800µg/day or >400µg/day fluticasone), some worrying signals emerge and there have been many documented cases of acute adrenal suppression and indeed at least one UK death associated with high-dose inhaled steroid use in children. Indeed, when detailed tests of adrenal function are performed on children receiving high doses, most show abnormal results. There are, therefore, real safety concerns about high-dose inhaled steroids, with associated medicolegal consequences.

If a child came to harm from taking unlicensed and unrecommended high-dose inhaled ster-oids, it would be hard for a GP issuing the prescriptions to defend himself against accusations of negligence. It may be that a small number of children with severe asthma genuinely do need high doses of inhaled steroids, but this should always occur after trials of add-on therapy, after assessment by a specialist and with full informed consent of the family. These children should carry a steroid alert card.

Our research on GP prescribing patterns for inhaled steroids has found that children are being prescribed such high doses. In a paper published in the British Journal of General Practice last year we reported that doses of >400µg/day were prescribed to 6% of under-fives and 10% of five- to 12-year-olds treated for asthma in 2003, and that doses of >800µg/day were prescribed to 4% of under-fives and 5% of five- to 12-year-olds, often without add-on therapy. We recommended that GPs should audit inhaled steroid prescribing in childhood asthma to identify these children, advice endorsed by the National Prescribing Centre in a recent MeReC Extra bulletin to GPs.

Inhaled steroids in childhood asthma – the way forward?

Inhaled steroids are the cornerstone of management of persistent childhood asthma and are likely to remain so for the foreseeable future. However, it is important that we use them safely and wisely.

•If children do not seem to be responding to standard doses, we should first review the diagnosis, and question whether giving more of a treatment that doesn't appear to be working at the usually effective dose is the right thing to do.

•Are we really treating asthma? Or could the wheezing be caused by some other (possible steroid non-responsive) cause?

•If further treatment is needed, we should consider add-on therapy before pushing the dose of steroids up. We should never be going above 400µg/day in under-fives or 800µg/day in five- to 12-year-olds without thinking carefully about a specialist review, and those on high doses should carry a steroid alert card.

•We should be thinking about doing an audit in our own practice to see if children are receiving such high doses; if they are, can they be stepped down, possibly by adding a second preventer therapy, and does the diagnosis (and the need for referral) need to be reviewed?

The treatment of childhood asthma with inhaled steroids has been a great medical success story, and we need to make stringent efforts to ensure that it continues to be.

Dr Mike Thomas is a GP and a member of the primary care respiratory research unit of the Department of General Practice and Primary Care, University of Aberdeen. He is a member of the BTS/SIGN asthma guideline group, working on the 'diagnosis' and 'difficult asthma' sections currently under review

Causes of wheeze

• Asthma • Transient infantile wheezing • Gastro-oesophageal reflux • Foreign body • Recurrent aspiration • Recurrent viral-associated wheezing • Cystic fibrosis • Ciliary dyskinesia • Developmental disorders • Immune deficiency states

Non-asthma wheezing

Factors that question a diagnosis of asthma • Symptoms from birth • Intermittent symptoms, particularly if only viral associated • Lack of personal or family history of atopy or asthma • Lack of response to standard management (especially to inhaled steroids at standard doses) • Isolated cough (rarely caused by asthma) • Excessive vomiting or posseting • Inspiratory stridor • Focal chest signs • Failure to thrive

Asthmatic wheezing

Factors supporting a diagnosis of asthma

Persistent symptoms • Wheeze • Breathlessness• Noisy breathingHistory of atopy • Eczema • Hay fever or rhinitisFamily history of atopy • Parental or sibling asthma, eczema or rhinitisResponse to usual treatment • Inhaled bronchodilators • Inhaled steroids

Causes of wheeze Non-asthma wheezing Asthmatic wheezing Inhaled steroids in asthma are a great general practice success, but few patients benefit from high doses Inhaled steroids in asthma are a great general practice success, but few patients benefit from high doses

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