For example, ten to twenty years ago, it was not uncommon for children to be given salbutamol in a liquid preparation. The decision to give this preparation (rather than via MDI and spacer) probably went something like this:
- A very small person is wheezy
- A parent wants a treatment for the wheezy small person
- It is difficult to give inhaled bronchodilators to small people
- There is a liquid preparation of salbutamol available
Ease of administration, acceptability of taste and lack of side effects all make a considerable difference to the effectiveness of medicines in children. One of the most common examples of this is phenoxymethypenicillin, often used for suspected streptococcal throat infections. It has a vile taste and is often rejected by the child after the first few doses. It can't work if the child won't take it. Fortunately it is often not needed, so it doesn't matter when the child votes with their feet.
By contrast, montelukast is one of the great success stories of child-friendly medicines of recent times. It comes in a chewy tablet or sprinkles. It's like being Dr Willy Wonka when you prescribe montelukast for children.
Acceptability is not the only factor when it comes to effectiveness. There has to be a proven clinical efficacy. Otherwise, montelukast becomes the salbutamol syrup of our generation. Just because it's a medication for wheezy children doesn't mean it will work in every clinical scenario. Just because it is easy to administer doesn't mean it should be the first line treatment.
A recent article in the Archives of Disease in Childhood (1) did an excellent job of exploring the evidence for montelukast as a treatment in the various phenotypes of childhood wheeze. This was no mean feat considering how many there are and that these phenotypes are variously defined and hotly debated.
Here is a summary of what they found:
Bronchiolitis* and montelukast
Unsurprisingly, montelukast can be added to the list of things that don't work when a child under the age of two has wet, inflamed airways (without bronchospasm). No doubt we will coninue to look for an effective treatment but so far nothing has worked. The management of bronchiolitis remains the art of doing as much nothing as possible, while knowing exactly when to do something.
* Bronchiolitis is defined slightly differently in the UK to the USA. In the UK, it is mainly infants under the age of 12 months with wet lungs of viral aetiology who are given the label bronchiolitis. In the USA, the definition includes young children with viral induced bronchospasm. This is why the UK guidelines recommend that bronchodilators are not used, while the guidance in the USA is that they an be tried.
Viral Wheeze (Viral Episodic Wheeze) and montelukast
There is some conflicting evidence for the use of montelukast both as prevention and as rescue treatment for pre-school children who develop bronchospasm only when they get a viral URTI (i.e. no other triggers and no chronic symptoms). However, a Cochrane review (2) did not find the evidence needed to support the use of montelukast as rescue therapy or as a preventative treatment for viral wheeze. So it seems that it's not really useful for these children either.
Multi-trigger Wheeze (aka asthma in the under 5 year olds) and montelukast
If you weren't already aware, there is debate about whether children under the age of five should be diagnosed as asthmatic even when they have interval symptoms and wheezy episodes which are not exclusively triggered by viral episodes. Some are calling this asthma and some call it viral wheeze. Arguably, it doesn't matter too much what it is called so long as we use evidence based treatment and we avoid mislabelling children who do not fit this phenotype. For example, it would be a mistake to say that viral episodic wheeze is the same as asthma since the latter benefits from inhaled corticosteroids (ICS) and the former does not. With multi-trigger wheeze and asthma in the under five year-olds, we essentially have two names for the same clinical scenario.
The article in ADC notes that the BTS/SIGN guidance recommends leukotrine receptor antagonists (LTRAs) as the next step after low dose inhaled corticosteroids or as first line treatment where the ICS is not tolerated.
The authors go on to note that while there is good evidence for benefit in this group of children, the effects of montelukast are moderate and clinically inferior to ICS. Also, there is no evidence to show that montelukast is effective above and beyond the benefit of ICS therapy. So, if there is a treatment with good evidence for superiority, how badly does a child have to not tolerate that treatment before you reach for the next option?
Since effect and tolerance are both important factors in the efficacy of a treatment, we need to consider both factors. Clearly if one factor is the same between two option, then the other is the deciding factor. In the case of the asthmatic/ MTW three year old, you may be faced with a difficult choice:
- Inhaled corticosteroids, which their parents are struggling to give
- Montelukast which is clinically inferior to inhaled corticosteroids but which the child might happily take
Although the formula is made up, the point is valid. Efficacy and concordance are the key factors in determining effectiveness. Since we can't change the efficacy of a treatment, we are only able to influence the concordance. In the example given above, if we could improve the concordance then this is a complete game changer. This is where a full team approach comes in. The prescribing clinician can emphasise the superiority of ICS over other treatments. The pharmacist can make a huge difference by a good explanation and demonstration. This can all be reinforced by a practice nurse who reviews technique and encourages the use of the inhaler, giving tips and tricks about how to get the child to take their inhalers.
Persistence counts for a lot with inhaler therapies. There are few (if any) children who immediately take to the idea of having a mask put on their face and few parents who find it easy to use the inhaler/ spacer combination well with a moving target to begin with. In time, children come to accept that the inhalers will be given and parents usually find that giving them becomes easier.
If the easy treatment was also the most effective, that would be brilliant wouldn't it? For some reason, that rarely seems to be the case. Is montelukast too easy? If it makes us choose it over trying everything possible to get the inhaled therapy to work, then the answer is yes.
So, choose the treatment with the biggest boom and maximise the sweetness of the delivery. It that way, the child who will benefit gets the best possible treatment in the most effective way.
Order of the Philosophers of Mathematics
Disclaimer - although a made up formula, there is good reason for applying a factor to the concordance. In very few cases does half the treatment have half the effect. Small moves away from the centre of the therapeutic window of a drug make a very big difference to the effect that it will have. I wanted to use a round number for simplicity but I would be willing to bet that the reality for most treatments lies somewhere between squared and cubed. Wouldn't it be great if the answer was really that the factor was pie?
- Haq et al, Should we use montelukast in wheezy children? Archives of Disease in Childhood, October 2017
- Brodie M et al, Leukotriene receptor antagonists as maintenance and intermittent therapy for episodic viral wheeze in children Cochrane Database Syst Rev. 2015 Oct 19