The main result of this study is that two kinds of risk factors of ED visit are observed: early (before two years of age) risk factors such as multiple sensitization and atopic dermatitis, and a posteriori risk factors observed at the last follow-up: younger age, more inhaled treatment and more severe exacerbation in the previous months, suggesting more severe asthma. The independent contributors for ED visit were age, the dose of ICS and post-bronchodilator FEV1, whereas the independent contributors for ED hospitalization were the number of specialist visits and post-bronchodilator FEV1. From a practical point of view, the absence of hospitalizations and atopic dermatitis before two years of age decreased the risk of ED visits after two years by approximately one third. These two risk factors are not modifiable.
The first issue deals with whether an ED visit is a marker of severe exacerbation in children. ED visits and hospitalizations were supposed to be related to severe exacerbations in the TENOR study . Nevertheless, this could be a shortcut. A prospective study in French ED assessed the number of ED visits for asthma exacerbation that would be avoidable . An ED visit was deemed potentially avoidable when a child who had not received adequate pre-hospital treatment left the ED after a maximum of 3 nebulisations with a bronchodilator with no relapse within 48 hours; in total, 38% of children had an avoidable ED visit, suggesting that some of the ED visits are not related to severe exacerbation in children. Feelings of fear/anxiety were the only independent risk factor for avoidable visits . Thus, parents of younger children may be more prone to visiting the ED, explaining why younger asthmatic children had more ED visits. This increased frequency of ED visits in younger children was expected since it has previously been demonstrated a decrease in severe exacerbations with increasing age [15, 16].
Children with high respiratory resource use in early childhood are characterized by more frequent wheezing in infancy and continue to incur healthcare costs from 3 to 5 years of age . Compared to older children with persistent asthma, preschool children with recurrent wheezing have nearly twice the rate of outpatient physician visits and ED visits for wheezing exacerbations and more than five times the rate of hospitalizations . Accordingly, in our study, preschool children had nearly twice the rate of ED visits than school children.
The mean annualized rate of ED visits in our study was 0.194, which is quite similar to that observed in the USA in an older asthmatic population (6 to 21 years: 0.171) . The mean annualized rate of ED hospitalizations (0.055) was nearly twice that observed in France in 2010 (30.1/10,000 children with ~ 10% asthmatics) , which may be related to the better hospital proximity in the suburbs of Paris or recruitment bias of a specialized pediatrician.
ED visits are mostly related to severe exacerbations, and these children remain symptomatic at their last visit despite increased ICS. This result is in agreement with that of the multicenter INSPIRERS study, showing that a phenotype was comprised of highly symptomatic asthmatic adolescents at baseline who presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up . Lenhardt et al. showed that patients with asthma exacerbations most often had uncontrolled asthma before the ED visit that subsequently deteriorated, temporarily improved with ED treatment, and continued as uncontrolled asthma after the ED visit . Thus, increased ED visits is a marker of severity of asthma, which was not related to the level of health insurance coverage in French children. Asthma exacerbation frequency in adults did not differ significantly between low and medium/high socioeconomic status patients in France, but differences were found in the management of asthma exacerbations since patients with a medium/high socioeconomic status were less likely to visit an ED or be hospitalized .
The main unexpected finding was that a higher post-bronchodilator FEV1 was related to increased ED visit and hospitalization rates. Low pre-bronchodilator FEV1 is a strong independent predictor of risk of exacerbations . Nevertheless, in the TENOR study, a lower post-bronchodilator FVC and lower post-bronchodilator FEV1/FVC were associated with a decreased risk of future severe exacerbations or steroid bursts, respectively . Thus, our result may be in agreement with the results of the TENOR study.
In a patient with multiple sensitizations and early-onset disease, the prognosis of asthma is poor with a high risk of persistence and severity of disease during childhood . Thus, our results are in agreement with this statement, further showing that the absence of atopic dermatitis decreased the rate of ED visits. The results of the logistic model that show that atopic dermatitis but not atopic status remains an independent predictor of ED visits, which is in agreement with the concept of atopic march . Interestingly, Yoon et al., in a cluster analysis of the Korean childhood asthma study cohort, found a specific cluster of children (36.6%; mean age, 8.9 ± 2.1 years) that was characterized as having early-onset atopic asthma with atopic dermatitis and the least severe type of asthma . Contrarily to our findings, the proportion of these patients requiring hospitalization or ED visit was the lowest among their four clusters, although the differences were not statistically significant among the clusters .
Unexpected ED visits and hospitalization rates were weakly related and their independent contributors were different, except for post-bronchodilator FEV1. This may be related to the fact that a lot of ED visits are avoidable . Visits to asthma specialists were associated with a decreased rate of hospitalization, which may be related to the increased ability of these families to manage exacerbations at home after the initial treatment.
Overall, our study shows that the absence of hospitalization before two years of age and of atopic dermatitis decreased the risk for further ED visits or hospitalizations by 28%, which should be taken into account when selecting candidates for a written action plan. It has been shown that the delivery of a comprehensive asthma education program after an ED visit may be effective in children . Nevertheless, all children in our study had a written action plan. Finally, it has to be stated that the level of explained variance of the risk of ED visit was low and that the risk factors identified are non-modifiable. Overall, our study confirms in an out-of-hospital setting that younger age, increased asthma severity and early hospitalization are risk factors of subsequent ED visit.
Our study has some limitations. The interval between two visits to the specialised pediatrician was not standardized, thus it could be questioned whether the recall for ED visits may vary to some extent. Nevertheless, visits to the ED are undoubtedly events that are important enough to make an impression, facilitating the recall. In addition, these visits to the ED are generally noted in the child's health record, which is examined by the pediatrician. Due to the open cohort design, the follow-up duration of each child was different, which may introduce some bias. Finally, severe exacerbations leading to ED visits are only some of those experienced by asthmatic children, since most exacerbations are treated in an out-of-hospital setting. Our study also has clinical consequences. ED visitation rates and early hospitalization are markers of asthma severity that need to be taken into account.
In conclusion, in our out-of-hospital cohort of asthmatic children followed up by a specialized pediatrician, half of the children experienced emergency department visits and those with the absence of atopic dermatitis and hospitalization before two years of age are less prone to these visits.