Inhaled corticosteroids use in childhood respiratory diseases: an italian survey on pediatricians’ prescription habits

Respiratory allergic diseases represent a significant health problem in childhood. Epidemiological data show that in Italy the prevalence of allergic rhinitis (AR) varies from 5 to 15% in children aged 6–14 years, while the prevalence of asthma varies from 9.3% in children to 10.3% in adolescents. Severe asthma is reported in 1.6% of children and 12.3% of adolescents [1]. Asthma and AR have a huge impact on health care systems in terms of costs: as far as AR, it has been calculated that in Europe between 55 and 151 million euros are lost each year, including parents’ absence from work and reduced productivity [2]. In Italy, direct costs of bronchial asthma, which has been included in the Italian list of chronic and invalidating diseases in 1999 [3], are estimated to be between 1 and 2% of overall health care system costs. The frequency of hospitalization is also remarkable, as recently confirmed by the OSMED report [4]. Therefore, it is not surprising that the most prescribed categories of drugs in children are those related to the treatment of the airways (35.6%): as a matter of fact, in the list of the first 20 most prescribed drugs in Italy there are five inhaled corticosteroids (ICS) [4]. ICS are widely used in respiratory diseases treatment also in adults because they are highly effective and allow to choose whether to treat upper and/or lower airways on the basis of the dimensions and rheological properties of the particles aerosolized by different devices using different molecules. Moreover, administration of corticosteroids by inhalation avoids the use of the systemic route, with consequent advantages in terms of safety [5]. However, the fact that ICS are commonly prescribed in our country implies cost issues and potential health risks for children related to recurrent and / or prolonged corticosteroids exposition [6‐9]. Consequently, in 2019 the representatives of the main Italian pediatric scientific societies and professional associations (Additional file 1) released a national consensus document to provide a valid reference paper to promote the appropriate use of ICS [10]. Moreover, in order to obtain an updated and reliable picture on the current ICS prescription habits in Italy, they carried out a web-based survey involving pediatricians from every part of the country. Here, we report the main results from this survey.

To our knowledge, our study is the first having gathered information on pediatricians’ ICS prescription habits in Italy for the management of the most common pediatric respiratory diseases. The pediatricians who participated to the survey left very good feedbacks, supporting the importance of the topic for pediatricians and the usefulness of surveys as tools to investigate clinical practices. We collected data from almost 10% of SIP members: as expected, most of the questionnaires were filled out by primary care and hospital pediatricians who are usually keener to analyze clinical practice issues rather than research issues. We found that in our country the treatment of AR is in agreement with international guidelines, with a greater use of antihistamine in AR with prevalent secretive component, and of nasal ICS in AR with prevalent obstructive component [2]. We chose this definition of AR phenotypes not including the recent classification of intermittent and persistent AR and non-allergic rhinitis to reduce the difficulty and time required to fill the questionnaire. As far as asthma is concerned, the aims of the survey were to evaluate the approach to a child with asthma exacerbation as well as the management of patients with persistent asthma. We found that even if 53.4% of the pediatricians avoid the use of ICS in asthma exacerbations, the remaining 46.6% prefer to use ICS both at high dose and at low dose in spite of the fact the main national and international guidelines agree in recommending not to use ICS to treat asthma exacerbations [11‐15]. Nevertheless, some good methodological quality systematic reviews and meta-analysis have shown a possible role of ICS in the treatment of exacerbations [16], but these works have been carried out in the setting of emergency departments, using very high dose of ICS mostly administered by nebulizers, with conflicting results [17, 18]. As far as maintenance therapy, more than 67% of the participants used to prescribe low dose ICS in persistent asthma, in agreement with the guidelines. Conversely, 31% of the participants used to prescribe high dose ICS in these patients. Less than half of the responders started a maintenance treatment in intermittent asthma. However, high doses were suggested also in these cases, demonstrating that pediatricians show an excessive concern on the influence of the single episodes on the functional integrity of the airways and on the quality of life of the children. It is not possible to understand whether all these treatments were recommended in the contest of a step-down or step- up strategy, since the assessment of the behavior of pediatricians in the management of the long-term therapies was beyond the aims of our study. Notably, even if most of the guidelines suggest to reassess the patients after 3 months of therapy, more than 45% of the responders re-evaluated their patients after 1 month of maintenance treatment: this data may be influenced by the high response rate of primary care pediatricians, since they are particularly keen to follow up their children more closely. As for preschool wheezing, the optimal therapeutic strategy is far from been identified: a maintenance therapy should be recommended in children with recurrent episodes and/or risk factors for recurrence such as family and personal history of allergy/atopy, in order to reduce the number of hospitalizations and the burden for the children and their family. Early schooling, the presence of associated diseases, tobacco exposure, siblings going to school and overcrowding at home should be evaluated too. However, when long-term treatment is needed, pediatricians should always look for the lowest effective dose to avoid an excessive use of drugs [19, 20]. We must admit that a definition of wheezing and its recurrence as well as the related risk factors should have been included in the survey in order to obtain more realistic answers. We didn’t find a clear preference for a single drug in the prevention of wheezing recurrence, confirming a well-known difficulty in phenotyping wheezing [21‐24]. Nevertheless, ICS were the most prescribed drugs in these patients (38.9%), but also antileukotrienes were commonly used both alone (24.3%) or in association with ICS (32.5%). As far as the choice of a device to treat the lower airways, only 50.9% of the pediatricians follows the guidelines choosing a pMDI + spacer. However, 30.9% of the pediatricians declared to choose the device on the basis of the family and patient’s preferences. Regarding this latter point, responses on the item related to the influence of the parents’ opinion are not easy to evaluate, since most of the participants answered that they were “a little” or “much” influenced by them: whether these answers are related to real needs of the family or the doctor’s need to obtain adherence, is not known [7, 25‐28]. Our study results show that Italian pediatricians use to prescribe some corticosteroid molecules more than others to treat different diseases: as far as budesonide for the treatment of laryngitis, this strategy is supported by its well-known vasoconstrictive effect [29, 30]. As for asthma, AR and preschool wheezing, all the most prescribed ICS are effective, but physicians should know devices and drugs doses in order to obtain an equivalence in terms of efficacy and safety issues when using each of the available molecules. Therefore, pharmacodynamics and pharmacokinetics of corticosteroids knowledge should be improved, and these aspects have been fully examined in the recently published Italian consensus document [10]. Our study has some limitations. First of all, even if university pediatricians are far less numerous than primary care and hospital pediatricians in our country, their response rate was particularly low, so that the subgroups division of the participants on the basis of work settings could not be completely representative of the national situation. Moreover, pediatric pulmonologists are almost exclusively university professionals in Italy, so that, since their responses may be missing, our results may underestimate good clinical practice in our country in terms of ICS prescription. Another limit is that we couldn’t check diagnostic criteria in our sample. However, we are confident that diagnoses were correct, since the diseases included in the questionnaire are extremely common in childhood, so that every pediatrician should be able to recognize and treat them, considering also a similar background training across the country. Moreover, regarding the geographical distribution of the responders, the number of responses from the various Regions reliably reflects the number of pediatricians and inhabitants from each Region. However, we recognize that in the smallest regions response rates are particularly low and this could represent another limitation to our study. Last but not least, our questionnaire was not validated and was very simple, in order to obtain higher response rates. Regarding drugs, it was not possible to include all the available treatments for the different diseases and we had to choose to narrow the field on the most used ones in childhood (nasal ICS and antihistamine in AR, ICS in asthma and laryngitis, ICS and antileukotrienes in preschool wheezing).

To our knowledge, this is the first survey on pediatricians’ ICS prescription habits performed in Italy and it should be considered as a pilot study. Our study confirmed that AR is mainly treated following guidelines, while ICS are still too much used in the management of acute asthma, even at high doses. Unfortunately, high doses are commonly used also in the long-term management of these patients. Data emerging from our survey suggest that ICS prescription habits and good clinical practices in Italy should be improved, especially in the treatment of asthma. Moreover, further and more detailed surveys should be performed on this subject, to shed more light on differences in prescription habits on the basis of pediatricians’ work settings and geographical distribution.