Castilla y Leon is a large region in the centre of Spain (94 225km2). It has 2 550 000 inhabitants, of whom 12% are children under the age of 14. The prevalence of asthma in the paediatric population in 2010 was 7.4% (from doctor diagnoses), with grass pollen being the allergen most frequently implicated in allergic asthma.

The prescription data were obtained from the Pharmacy Information System of the Public Health Service of Castilla y Leon (SACYL), which covers 96% of the population. Data came from the total computerised official prescriptions written between January 1, 2005 and December 31, 2010 and dispensed in pharmacies. At the time of the study, only prescriptions from primary care were computerised (80% computerised and 20% issued manually). Prescriptions from primary care represented 94% of the total official requirements of Public Health System of this period, as hospital prescriptions only accounted for 6% of the total. Data correspond to the RO3 therapeutic subgroup (drugs for respiratory obstructive diseases) of the Anatomical Therapeutic Chemical Classification of WHO [ATC classification18]. The active ingredient and the age of the children were analysed for all prescriptions. Only electronic prescriptions were able to identify the patient's age. The patient identification data, the prescribing physician or the trademark used was not collected, in order to maintain the anonymity of those aspects.

The included population was children under 14 years old who had an individual health card (TSI) of Castilla y Leon between the years 2005 and 2010. The TSI identifies people who may personally receive national health care and official prescriptions. The paediatric population data for each age (0–13 years) were obtained from the Technical Department of the SACYL.

The main analysis unit was the prescribed daily dose (PDD), which is the usual recommended average daily dose of a given drug for its main indication. As there are no defined PDD for anti-asthmatic drugs in paediatric cases, they were elaborated taking into account the age or body weight dose recommended in the data sheet of each drug and the main guidelines for asthma in childhood. PDD was determined for 26 active ingredients with 59 different concentrations and pharmaceutical forms (inhaler, syrup, tablets, etc.). In cases where the PDD was calculated per kg body weight per day, tables were used representing the weight of the current Spanish child population.19 In other drugs, PDD was estimated by age sections. On the other hand, regarding inhaled corticosteroids, single or in combination, the PDD was calculated for each concentration of inhaler device and each age and it was concluded that the PDD was one inhalation every 12h, with the exception of formats of 50mcg of budesonide, beclomethasone and fluticasone, in which two inhalations every 12h was considered (usually the recommended dose). Online supplementary material for the calculation of the PDD is provided: Appendix I.

Results are shown in prescribed daily dose per thousand inhabitants per day (PDHD). The PDHD represents the average prescribed daily dose every day to 1000 people exposed. The PDHD was calculated for each active ingredient, raw and age-adjusted, by the direct adjust method [standard population20], using all children from Castilla y Leon with a TSI card and aged 0–13 years as the reference population.

The results in defined daily doses per 1000 inhabitants per day (DHD) have also been added to allow comparison of both units for all ages and to future comparisons with other studies. We have used the DDD values proposed by the WHO for each active ingredient.18

SPSSv15 and Excel sheets were used for statistical analyses.

This study analysed the paediatric prescription of anti-asthmatic agents by age in a relevant population sample and provided current information regarding use in a Spanish region. An excessive prescription was observed in younger children, with the significant use of systemic bronchodilators and some subgroups of maintenance therapy that are inconsistent with the recommendations of current asthma guidelines and treatment protocols of secondary wheezing to viral infections. The study also compared the intensity of consumption offered by PDHD and DHD units, showing that DHD underestimates the results at all ages, especially in young children.

The high prescription of anti-asthmatic drugs in young children has already been observed in other international studies conducted in the general paediatric population. In these, it also appears that children under two years received more anti-asthmatic agents,3–6,22,23 although the overall prevalence and age varied among countries. This fact is justified on the one hand by the high frequency of viral respiratory infections that occur with bronchial obstruction in younger children. On the other hand, because the differential diagnosis of asthma is not easy under four years, this could lead to the use of anti-asthmatic drugs as a therapeutic diagnostic test.

Regarding the type of drug used in this study, the bronchodilators were the most prescribed, and were highly consumed in children less than two years old. Also, other drugs were prescribed (in descending order): leukotriene receptor antagonists (ALT), single inhaled corticosteroids (ICS) and inhaled corticosteroids associated to long-acting beta-agonists (LABA-ICS). The use LABA-ICS in children under four years old was remarkable. This is an issue of concern due to the increased possibility of adverse effects in this age subgroup24,25 and because prescriptions were made outside the authorised conditions of use (off-label). The prescription pattern found does not fit the recommendations of current asthma guidelines or the therapeutic protocols of related diseases, and is also not justified given the severity of asthma that is currently reported in Spain.7,8,26

Regarding the type of drug used in other countries, the prescription of bronchodilators decreases with age. The consumption of inhaled corticosteroids is highest in pre-school and school children, except in Italy,3,6 with predominance in infants under one year. The prescription of LABA-ICS is not frequently measured, but also increases with age.6,12,16,22,23 In relation to maintenance treatment in other countries, inhaled corticosteroids as a single agent is generally the most prescribed subgroup, as recommended in the guidelines, followed by leukotriene receptor antagonists in second or third place. Although the prescription of montelukast is high in some countries2,9,11,23 and almost absent in others,6,12,17,27 which may be related to the differences at the time of the study, the population age or the prescription control has specific rules in each country.

The high prescription of montelukast that occurred in our study for all ages and which has been the most widely used drug controller, probably has a multifactorial explanation, but is closely related to the strong trade promotion and the influence of the article published by Bisgaard et al.28 claiming its beneficial effect on the post-bronchiolitis symptoms due to respiratory syncytial viruses. However, the findings were not confirmed by the author himself in a later and more extensive study.29 Other contributing factors may be related to the use of montelukast as a monotherapy controller or its use for other problems such as allergic rhinitis or atopic eczema. Also, the initiation of maintenance therapy with more than one drug (montelukast and other more), or the supposed absence of adverse effects [an issue questioned in post-marketing studies30], may have an influence.

Another contribution of our study has been the use of the prescribed daily dose (PDD) as a consumption unit and its comparison with defined daily dose (DDD) as it is recommended by the WHO to use in paediatric studies. We have not chosen the rate of prescriptions as unit of consumption because the size of the package and their contents vary between and within countries and although it is a unit widely used in other studies it is not very accurate. On the other hand the DDD is the consumer unit of measurement currently used in the Spanish Health Service, both in children and in general practice, to assess consumption and set targets for prescribing quality; thus, there are several recent publications in paediatric populations using DDD/DHD.31,32 We have decided to know the differences in the quantification of consumption between PDD and DDD. What we found was that the DDD/DHD underestimates the consumption in children, and more severely, the lower the age and/or the body weight: the systemic use of BD was four times lower in the first two years in DDD/DHD than in PDD/PDHD. In maintenance therapy, the use of the three major subgroups was half or almost half in DDD/DHD that in PDD/PDHD throughout the first 14 years of life (see Figs. 2 and 3). We cannot compare the information obtained in other studies, however, as no other has so far measured consumption using the two types of units.

The above comments highlight the difficulties and the limitations of using DDD/DHD units in children, since they underestimate drug consumption for almost all ages, except for inhaled bronchodilators, whose doses are independent of age or weight. Although the DDD/DHD is a technical unit of measurement that is often used for comparing consumption between countries or regions, at different periods of time, such comparisons could be made with data from PDD/PDHD, which would approximate more to actual consumption in childhood.

From the results obtained, we propose to use PDD as the consumption unit of the active agent and PDHD (prescribed daily doses per 1000 inhabitants per day) to compare figures in different paediatric populations at a determined time, or alternatively to apply a correction factor according to age to the adult DDD figures (see supplementary material online; Appendix I).

The authors declare that no patient data appear in this article.

The authors declare that no patient data appear in this article.

The authors declare that no experiments were performed on humans or animals for this investigation.