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.