Discussion
We investigated adherence to ICS in children aged 1-5 years with
moderate to severe wheezing attending a tertiary respiratory centre.
One-quarter of families did not return the electronic monitor, which
meant an objective assessment of adherence could not be made, but
suggests adherence was likely sub-optimal in that group. Of those who
did return the monitor, adherence was sub-optimal (<80%) in
two-thirds.
Preschool children aged 2-6 years from a Dutch cohort with milder
wheezing monitored for 12 months had median adherence of 87%[10].
Only 33% of children in our study had good adherence
(>80% of prescribed doses), compared with 63% reported in
the Dutch study. However, poor adherence to treatment may be rational,
especially if the therapy prescribed is identified as ineffective by
parents[18]. Hence parents of children with episodic viral wheeze, a
group which may be less likely to be steroid responsive, may be right
not to give the treatment. We therefore investigated the relationship
between clinical phenotype, adherence and symptom control. However,
there was no relationship between adherence to ICS and episodic viral or
multiple trigger wheeze. In a randomised controlled trial (INFANT
trial), children with aeroallergen sensitisation and an elevated
peripheral blood eosinophil count responded best to ICS[7]. We did
not have contemporaneous blood eosinophil counts in this study, but we
were able to investigate whether atopic status influenced the
relationship between adherence and response to ICS. Overall, only atopic
wheezers had an improvement in TRACK score from baseline to follow-up.
But importantly, only those atopic wheezers with> 60% adherence to ICS during the monitoring period
had a significant and clinically meaningful improvement in symptom
score. This suggests that this is indeed a steroid-sensitive group. In
summary, even in those with troublesome wheezing, an improvement in
symptom control is only apparent in atopic wheezers with moderate-good
adherence to ICS.
There are other potential reasons for poor adherence, which we tried to
exclude. We ensured the recruiting nurse provided education about the
technique, need for the inhaler and a clear personalised wheeze plan. We
had considered parental commitment to administering medication would be
high in this group since most children had suffered frequent attacks
requiring hospitalisation and the median dose of prescribed ICS was
high[17]. A previous study in preschool children investigated
reasons for poor adherence and found the most common reasons were
parental forgetfulness and their child’s reaction when the medication
was given[11]. Administering inhaled therapy to children in this
age-group is a challenge and lack of cooperation from the child may also
be a reason for missed doses. Another contributory factor in this age
group may be parental anxiety about the adverse effects of
steroids[19].
Limitations of the study include the large number of families that did
not return the monitoring device, but this was a pragmatic study
undertaken in the clinic and this rate reflects our experience in
school-age children[9], and highlights the potential costs incurred
of lost devices (£150 per device), especially if they are given
indiscriminately to children unlikely to improve with ICS therapy. In
addition, we did not assess change in TRACK score, or FeNO in children
according to blood eosinophils as this had not been measured in the
clinic. FeNO may have been influenced more by adherence to ICS in those
with peripheral eosinophilia as is seen in older children and
adults[20].
The implication of this and the previously published INFANT study[7]
is that firstly, prescription of maintenance ICS should be limited to
atopic preschool wheezers. We accept that when children have recurrent
and severe symptoms, it is often easier to prescribe treatment, than do
nothing, even if there is little evidence of efficacy. The ERS Task
Force has stated (not on the basis of any evidence) that children with
frequent and severe attacks may respond to ICS and so should be given a
trial[21]. If this is to be done, the second implication of our
study is that adherence needs to be assessed objectively. If ICS have
been administered to the child, and there is no benefit, rather than
escalating the dose, they should be discontinued.
We had hypothesised that adherence to ICS in this age group would be
higher than in school-age children as parents would be committed to give
the medication. However, adherence to ICS was sub-optimal in
approximately half of children despite recurrent troublesome wheeze and
being seen at a tertiary centre. Good adherence must not be assumed in
this age group, and just as for older children with difficult asthma, if
a preschool wheezer with a steroid responsive phenotype is not improving
on high-dose ICS, then it is essential to ensure adequate adherence
using objective monitoring prior to continued escalation of therapy.
Getting the basics of management right is as important for preschool
wheezers as for older children with asthma, especially as biologics may
soon be considered for young children.