Adverse Drug Events Related to Common Asthma Medications in US Hospitalized Children, 2000–2016

Abstract

Background The reduction in adverse drug events is a priority in healthcare. Medications are frequently prescribed for asthmatic children, but epidemiological trends of adverse drug events related to anti-asthmatic medications have not been described in hospitalized children. Objective The objective of this study was to report incidence trends, risk factors, and healthcare utilization of adverse drug events related to anti-asthmatic medications by major drug classes in hospitalized children in the USA from 2000 to 2016. Methods A population-based temporal analysis included those aged 0–20 years who were hospitalized with asthma from the 2000 to 2016 Kids Inpatient Database. Age-stratified weighted temporal trends of the inpatient incidence of adverse drug events related to anti-asthmatic medications (i.e., corticosteroids and bronchodilators) were estimated. Stepwise multivariate logistic regression models generated risk factors for adverse drug events. Results From 2000 to 2016, 12,640 out of 698,501 pediatric asthma discharges (1.7%) were associated with adverse drug events from anti-asthmatic medications. 0.83% were adverse drug events from corticosteroids, resulting in a 1.14-fold increase in the length of stay (days) and a 1.42-fold increase in hospitalization charges (dollars). The overall incidence (per 1000 discharges) of anti-asthmatic medication adverse drug events increased from 5.3 (95% confidence interval [CI] 4.6–6.1) in 2000 to 21.6 (95% CI 18.7–24.6) in 2016 ( p -trend = 0.024). Children aged 0–4 years had the most dramatic increase in the incidence of bronchodilator adverse drug events from 0.2 (95% CI 0.1–0.4) to 19.3 (95% CI 15.2–23.4) [ p -trend ≤ 0.001]. In general, discharges among asthmatic children with some comorbidities were associated with an approximately two to five times higher odds of adverse drug events. Conclusions The incidence of adverse drug events from common anti-asthmatic medications quadrupled over the past decade, particularly among preschool-age children who used bronchodilators, resulting in substantial increased healthcare costs. Those asthmatic children with complex medical conditions may benefit the most from adverse drug event monitoring. Supplementary Information The online version contains supplementary material available at 10.1007/s40801-022-00304-8.

Current and Optimal Practices in Childhood Asthma Monitoring Among Multiple International Stakeholders

“…Although extensive community studies do not support concerns about the potential long-term effect of inhaled corticosteroids on children’s development, 32 inhaled corticosteroids, especially when used at excessive doses, as well as systemic corticosteroids and other asthma treatments, may have burdensome adverse events that require close monitoring. 33 , 34 The structure of our survey, which only inquired about specific long-term safety parameters, possibly did not fully capture monitoring for adverse drug reactions.…”

“…Most physicians follow a typical monitoring schedule (Figure 1; eFigure 6 in Supplement 1), which includes regular visits every 2 to 6 months (median [IQR], 5.0 [2.5-8.0] months) for mild to moderate asthma and 1 to 3 months (median [IQR], 2.5 [1.0-2.5] months) for severe asthma, with each visit lasting 10 to 40 minutes (median [IQR], 25 [15][16][17][18][19][20][21][22][23][24][25] minutes for mild-moderate asthma and 25 [25][26][27][28][29][30][31][32][33][34][35] minutes for severe asthma) (Figure 1C and 1D). These parameters were very close to the perceived optimal (mild to moderate asthma: median [IQR] frequency, 5.0 [2.5-5.0] months; median [IQR] duration, 25 [15][16][17][18][19][20][21][22][23][24][25]…”

Drug Development from Natural Products Based on the Pathogenic Mechanism of Asthma

“…In particular, in patients aged 0-4 years, the incidence rate of asthma drugs' adverse effects significantly increased from 0.2% to 19.3%. In the early stages of bronchodilator use, excessive doses of compounds such as isoprenaline cause toxicity in users [72]. The side effects of anticholinergics include a dry mouth, constipation, cough, headaches, and nausea; those of β 2 -adrenergic receptor agonists include trembling, nervous tension, headaches, muscle cramps, and heart attack; theophylline, a methylxanthine, causes nausea/vomiting, diarrhea, palpitation, tachycardia, arrhythmia, headaches, and insomnia [73].…”