Heart failure: putting research into practice
Dr Dominic Cochran advises how to treat under-twos with persistent symptoms that are not necessarily asthma
A child under two with persistent lower respiratory tract symptoms is the single most common reason for a GP referral to a respiratory service. The question GPs ask is usually along the lines of 'Is this asthma and what drugs should I be prescribing?'. Unfortunately, the response from the hospital
clinician is unlikely to provide a clear answer.
The fundamental problem is that a substantial proportion of children under two presenting with recurrent cough and wheeze do not have asthma, or at least not the same form that affects older children and adults1. Therefore, many trials of steroids and bronchodilators in this age group have negative results suggesting this treatment is ineffective.
At the same time, we know some of these children do have typical asthma and will benefit from the appropriate treatment. We are
generally unable to discriminate between the
non-asthma wheezers and the asthmatic
After the age of two the clinical picture becomes much clearer with problems for non-asthmatic children becoming substantially less troublesome while those with asthma will be responding to treatment.
It is important to note that parents may use the term wheeze to describe a variety of respiratory noises including stridor, rattling or crackling. It is especially helpful to record if wheezing is heard in the chest during any consultation and to include this information if a referral is made to hospital.
Is this asthma?
Ideally, we would prefer to decide if the child was likely to have asthma on the basis of the history and examination and then to prescribe appropriately, but unfortunately it is rarely possible to be certain about the diagnosis in this age group. There are features that may give some idea about whether the child belongs to the asthma or non-asthma group.
lfamily history of asthma – obviously this increases the likelihood of asthma, but in view of the high prevalence of asthma it is likely that many of the non-asthma patients will have a close relative with asthma.
lsymptoms that occur in the absence of infection – one of the non-asthma syndromes is often described as virus-associated wheeze. If there is a strong history that wheezing exclusively occurs during viral episodes it is less likely that asthma is the diagnosis.
lage of onset – if the symptoms do not begin until well into the second year of life it is more likely that asthma is the correct diagnosis. Small airway diameter is one of the predisposing factors to non-asthma wheezing and therefore the non-asthma group is likely to be at its worst in the first year when the airways are smallest. Allergen sensitisation is thought to be one of the factors leading to asthma and is more likely to develop gradually over several years.
lcough but no wheeze – if the only symptom is chronic cough the diagnosis of asthma becomes less likely, although most clinicians would accept a diagnosis of asthma if a consistent response to
anti-inflammatory medication can be
lreported response to asthma drugs – in particular parents may report that symptoms are dramatically aborted by oral steroid treatment, making the diagnosis of asthma more likely.
None of these features is of enough significance to permit a definitive diagnosis and in many cases it will be necessary to proceed to a trial of treatment.
Are the symptoms actually unpleasant?
Before embarking on a trial of treatment it is important to determine if the symptoms are actually having a detrimental effect on the child's quality of life.
Parents who consult because of coughing and noisy breathing quite reasonably assume their child could be very ill.
If the GP then recommends medication the parents will assume the treatment is necessary and accept the prescription without pointing out that the symptoms do not trouble their child.
A proportion of children with these symptoms appear to experience no distress from them – often described as 'happy wheezers'. Given the diagnostic uncertainty it is difficult to justify administering drugs to children who may have noisy breathing but show no signs that they find the symptoms unpleasant.
I find it useful to ask the parents to put themselves in the child's position and describe in what specific ways the symptoms are unpleasant. It is not uncommon for them to report that the child is 'neither up nor down with them'.
Why do these children cough and wheeze if they don't have asthma?
The answer to this is complex but can be summarised in the box on page 55. Central is the fact that infants have relatively narrow bronchi combined with a relatively high oxygen requirement (for their size). In other words they are trying to shift a lot of air through narrow tubes. This means anything that reduces the airway diameter is much more likely to cause wheezing in an infant than in an older child or adult. Thus a high proportion of infants wheeze at some time, but only a minority of these have true 'childhood asthma'.
Trial of treatment
If the symptoms are distressing for the child, the presenting symptoms can usually be divided into two patterns that will determine the type of treatment.
Group 1 – recurrent, acute episodes of cough and/or wheeze: symptoms will probably be predominantly related to viral infection.
This type requires intermittent treatment with inhaled bronchodilator and short courses of oral steroid. In my experience it is relatively difficult to ascertain if there is a treatment response in this type of patient because of the fluctuating nature of the symptoms – did the symptoms get better because of a response to treatment or coincidental spontaneous improvement?
It may be necessary to continue this intermittent treatment for some months without being certain about the diagnosis or the benefit from treatment. But any child with these symptoms may be at risk of an exacerbation that could be severe and early intervention with bronchodilator and possibly oral steroid could be valuable in halting deterioration.
Explain to parents that there will be diagnostic uncertainty for months and that the treatment prescribed is not effective in all wheezy infants. But there is no reason to believe giving such treatment to unresponsive infants is detrimental. If it emerges that the treatment is clearly curtailing the exacerbations, this information may contribute to diagnosing asthma.
In those patients with intermittent symptoms it is difficult to justify a trial of asthma treatment if there is only recurrent cough and no wheeze. The diagnosis of asthma is unlikely to be correct in these patients and they are unlikely to benefit from asthma drugs.
Group 2 – more persistent cough and/or wheeze with symptoms on several days each week. There may also be periodic exacerbations when the symptoms become appreciably worse.
There is a good case for prescribing an inhaled steroid for a trial period in addition to the drugs suggested for group 1 patients. I find it is easier to evaluate the response to treatment in this group. For example, if a child wakes with coughing five nights a week, reducing to one night a week when treated with inhaled corticosteroid for four weeks, and then deteriorates when the medication is withdrawn, this suggests a good treatment response.
If there is no clear improvement this may not be because the underlying condition is not responsive. It can be difficult to ensure the parents are using the inhaler device effectively and the lack of improvement may be because of an inadequate dose reaching the airways rather than the drug being ineffective.
An alternative to an inhaled steroid trial is a moderately long course of prednisolone for around 10 days. This is only an option if the parents report consistent symptoms occurring almost every day for many weeks. If this is the case, a substantial improvement during a period of treatment with prednisolone makes it likely that continuing with an inhaled steroid is appropriate. If there is no improvement with prednisolone it is unlikely that less potent treatments such as inhaled steroid will be worthwhile.
Doses of inhaled drugs
The few studies that have examined drug delivery in very young children have suggested around 1-2 per cent of the drug released into the spacer reaches the airways2. At first sight this dose may seem excessively small but if the dose is corrected for the child's weight or surface area it is clear that, if one prescribes similar doses to those used for older children, the amount that reaches the airways will be in proportion to the child's size.
In other words, it is probably inappropriate to scale down the dose prescribed to young children but instead to prescribe a 'standard' dose and allow the child's small breath volumes to scale down the dose. This is particularly the case if intending to prescribe a drug on a trial basis and you do not want an insufficient dose to lead to a false negative.
Inhaled drugs should virtually always be delivered using a metred dose inhaler (MDI) with a spacer and face mask in this age group. Generally speaking large volume spacers (Volumatic, Nebuhaler) are recommended because of evidence that they have superior drug delivery.
There are points to be made in favour of small volume spacers. The Aerochamber is popular because it is less cumbersome and easier for a single operator to administer. The NebuChamber is a small volume stainless steel spacer which can be prescribed with a budesonide (Pulmicort) 200µg MDI.
Plastic spacers generate a static electricity charge that tends to cause aerosol particles to stick to the sides and reduces the proportion of drug available for inhalation – the metal NebuChamber does not have this problem and is therefore attractive if one wishes to use a small volume, portable spacer but avoid the difficulty of poorer particle delivery.
However, this device can only be prescribed in conjunction with a specific strength of a specific brand of steroid inhaler (although these devices can be obtained by direct request to AstraZeneca).
Advising on inhaler technique
Talking parents through potential problems of administering inhaled drugs is time well spent. A typical scenario is as follows. The parents start to administer the treatment regularly, applying the mask firmly to the child's face. The child is curious to see and hold this new object just under its eyes, so attempts to grip the device and pull it away so it can see it and manipulate it. The parent then forces the mask back on the face.
A battle ensues in which the parent and child pull and push the device in opposite directions until the child is screaming with frustration. After several days of this the child begins to cry at the first sight of the spacer and the parents conclude that their child is 'terrified of that thing'. Despite the child's agitation, some parents may continue to use the inhaler having been told that 'it's good if he cries, he'll take bigger breaths'.
Explain to the parents that the optimal inhaler technique is slow, steady inhalation and that when a child is crying, they are predominantly exhaling forcefully. The key is to draw the child's attention away from the inhaler as soon as it is applied to the face. My experience is that the best method is for the parent to play 'peek-a-boo', hiding behind the spacer chamber and intermittently popping out. The child usually becomes engaged waiting for the parent's face to emerge and forgets that the mask is firmly held on its face.
A further difficulty can occur in a child who was previously co-operating well. Sooner or later children will decide to experiment and find out what happens if they push the mask away. The parent then spends a few minutes trying to cajole the child into taking the device. The child learns it can double or triple the attention it receives by refusing to take the inhaler.
Understandably parents feel a child of this age cannot be allowed to decide when to take its treatment and are reluctant to give up. But the longer the parents plead with the child the more they reinforce the rewards for non-co-operation!
My advice is that if the child does not co-operate at the first or second attempt the inhaler dose should not be given and the parent should withdraw, demonstrating that non-co-operation leads to less attention rather than more.
Alternatives to inhaled steroid
There are some infants and toddlers who simply will not co-operate with an inhaler. For these there is the relatively new option of montelukast granules given directly orally or mixed with cool or room-temperature food. This preparation is licensed for children down to six months of age.
Montelukast could be administered on a trial basis for one to two months in the same way as I have described for inhaled steroid, attempting to draw cautious diagnostic conclusions from the response to daily treatment. The full role of montelukast in this young age group is still to be defined.
Reviewing the benefits of treatment
The latest set of asthma guidelines emphasise the reassessment of patients in this age group after a period of treatment (BTS/SIGN, British guideline on the management of asthma). In a sense this concept applies to all children with asthma but by giving emphasis to reassessment in this age group the authors are drawing our attention to the diagnostic and therapeutic uncertainties that are likely to dog parents and clinicians dealing with 'chesty infants'.
We cannot employ peak flow monitoring and other helpful diagnostic tools in these patients and ultimately the 'response to treatment' will be central in reaching a working diagnosis.
It is highly likely a large proportion of these infants gain little benefit from asthma drugs and clinicians must endeavour to withdraw treatment in those children in whom there has been no evidence of benefit. It is too easy to engage in prescribing a succession of drugs to unresponsive cases rather than advising their parents that no medication may be the most honest option.
Diagnosis and treatment of this group of patients remains difficult. My experience is that most clinicians advise parents correctly regarding the diagnostic uncertainty and engage in trials of treatment but I believe we often fail when it comes to avoiding unnecessary prescriptions in those who do not improve.
As much attention needs to be given to stopping ineffective treatment as to starting useful medication.
Dominic Cochran is consultant in paediatric respiratory medicine, Royal Hospital for Sick Children, Glasgow
1 Martinez FD et al. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. New England Journal of Medicine 1995; 332: 133-8
2 Tal A et al. Deposition pattern of radiolabeled (ll?)
salbutamol inhaled from a metered-dose inhaler by means of a spacer with mask in young children with airway obstruction. Journal of Pediatrics 1996; 128: 479-84