Interventions for escalation of therapy for acute exacerbations of asthma in children: an overview of Cochrane Reviews

Craig, Simon; Dalziel, Stuart R; Powell, Colin; Graudins, Andis; Babl, Franz E; Lunny, Carole

doi:10.1002/14651858.cd012977.pub2

Cited by 26 publications

(35 citation statements)

References 80 publications

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“…However, in 85% of children receiving escalated therapy with intravenous bronchodilator treatment, this was confined to just three different regimens; intravenous magnesium alone or in combination with either aminophylline or salbutamol. Once again, the lack of high-quality evidence,15 as well as inconsistent local guidelines, may contribute to this variation. While magnesium and salbutamol are listed as second-line and third-line bronchodilators for management of acute severe paediatric asthma in Australian national guidelines,27 some state-based guidelines prefer magnesium and aminophylline 28.…”

Section: Discussionmentioning

confidence: 99%

“…Cochrane reviews of advanced pharmacologic treatment of children with acute exacerbations of asthma highlight a number of knowledge gaps 15. The evidence supporting intravenous magnesium is extremely limited (including only 5 studies and 182 children),31 while only one study (showing no significant benefit) was identified regarding intravenous ketamine 32.…”

Section: Discussionmentioning

confidence: 99%

“…Other management strategies similarly lack high-quality evidence, or even any evidence of effect on the key outcomes of LOS and admission into hospital. High-quality multicentre research to address these important evidence gaps is a research priority for major paediatric emergency research networks 14 15…”

Section: Introductionmentioning

confidence: 99%

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Treatment patterns and frequency of key outcomes in acute severe asthma in children: a Paediatric Research in Emergency Departments International Collaborative (PREDICT) multicentre cohort study

et al. 2022

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RationaleSevere acute paediatric asthma may require treatment escalation beyond systemic corticosteroids, inhaled bronchodilators and low-flow oxygen. Current large asthma datasets report parenteral therapy only.ObjectivesTo identify the use and type of escalation of treatment in children presenting to hospital with acute severe asthma.MethodsRetrospective cohort study of children with an emergency department diagnosis of asthma or wheeze at 18 Australian and New Zealand hospitals. The main outcomes were use and type of escalation treatment (defined as any of intensive care unit admission, nebulised magnesium, respiratory support or parenteral bronchodilator treatment) and hospital length of stay (LOS).Measurements and main resultsOf 14 029 children (median age 3 (IQR 1–3) years; 62.9% male), 1020 (7.3%, 95% CI 6.9% to 7.7%) had treatment escalation. Children with treatment escalation had a longer LOS (44.2 hours, IQR 27.3–63.2 hours) than children without escalation 6.7 hours, IQR 3.5–16.3 hours; p<0.001). The most common treatment escalations were respiratory support alone (400; 2.9%, 95% CI 2.6% to 3.1%), parenteral bronchodilator treatment alone (380; 2.7%, 95% CI 2.5% to 3.0%) and both respiratory support and parenteral bronchodilator treatment (209; 1.5%, 95% CI 1.3% to 1.7%). Respiratory support was predominantly nasal high-flow therapy (99.0%). The most common intravenous medication regimens were: magnesium alone (50.4%), magnesium and aminophylline (24.6%) and magnesium and salbutamol (10.0%).ConclusionsOverall, 7.3% children with acute severe asthma received some form of escalated treatment, with 4.2% receiving parenteral bronchodilators and 4.3% respiratory support. There is wide variation treatment escalation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Treatment patterns and frequency of key outcomes in acute severe asthma in children: a Paediatric Research in Emergency Departments International Collaborative (PREDICT) multicentre cohort study

et al. 2022

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“…Ultimately, AAEs in children remain a significant burden on children’s health and substantial work is required to improve the care of children with AAEs. Identified directions for continued growth include 6 , 7 , 11 , 61 , 97 higher quality studies on ideal dosing, duration, and efficacy of existing pharmacotherapies and mechanical ventilation (particularly with critical AAEs) targeting outcomes such as hospitalization rates and including data from diverse populations; increased understanding of adverse drug events and developmental impacts of AAE; novel pharmacotherapies; strategies to deliver equitable care for children from identified racial minority and disadvantaged socioeconomic backgrounds; improved knowledge translation and implementation of AAE pathways; and improved integration of AAEs and long-term asthma care approaches.…”

Section: Discussionmentioning

confidence: 99%

Paediatrics: how to manage acute asthma exacerbations

Leung¹

2021

DIC

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Background Asthma is the most common chronic disease of childhood and a major source of childhood health burden worldwide. These burdens are particularly marked when children experience characteristic ‘symptom flare-ups’ or acute asthma exacerbations (AAEs). AAE are associated with significant health and economic impacts, including acute Emergency Department visits, occasional hospitalizations, and rarely, death. To treat children with AAE, several medications have been studied and used. Methods We conducted a narrative review of the literature with the primary objective of understanding the evidence of their efficacy. We present this efficacy evidence in the context of a general stepwise management pathway for paediatric AAEs. This framework is developed from the combined recommendations of eight established (inter)national paediatric guidelines. Discussion Management of paediatric AAE centres around four major care goals: (1) immediate and objective assessment of AAE severity; (2) prompt and effective medical interventions to decrease respiratory distress and improve oxygenation; (3) appropriate disposition of patient; and (4) safe discharge plans. Several medications are currently recommended with varying efficacies, including heliox, systemic corticosteroids, first-line bronchodilators (salbutamol/albuterol), adjunctive bronchodilators (ipratropium bromide, magnesium sulfate) and second-line bronchodilators (aminophylline, i.v. salbutamol, i.v. terbutaline, epinephrine, ketamine). Care of children with AAE is further enhanced using clinical severity scoring, pathway-driven care and after-event discharge planning. Conclusions AAEs in children are primarily managed by medications supported by a growing body of literature. Continued efforts to study the efficacy of second-line bronchodilators, integrate AAE management with long-term asthma control and provide fair/equitable care are required.

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“…If more than four domains were regarded as unclear or no, the study was deemed as having a high risk of bias. The study was regarded as having a moderate risk of bias if two or three domains were considered no or unclear [18]. Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) was used to carry out the quality assessment and investigation of publication bias.…”

Section: Data Extraction and Qualitymentioning

confidence: 99%

Analysis of the Efficacy and Mechanism of Action of Xuebijing Injection on ARDS Using Meta-Analysis and Network Pharmacology

Zhang

Wang

Liu

et al. 2021

BioMed Research International

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Objective. Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process known as cytokine storm. Xuebijing injection (hereinafter referred to as Xuebijing) is a patent drug that was used to treat ARDS or severe pneumonia (SP) in China. However, its efficacy and mechanism of actions remain unclear. In this study, we used meta-analysis and network pharmacology to assess these traits of Xuebijing. Methods. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases for randomized controlled trials (RCTs) that evaluated Xuebijing therapy for ARDS or SP. The outcomes were total mortality, intensive care unit (ICU) stay time, and TNF-α and IL-6 levels. We performed a meta-analysis using RevMan 5.3 software. The putative targets, top 10 proteins, and possible pathway of Xuebinjing on ARDS were analyzed by network pharmacology. TNF-α and IL-6 were further docked with the six main active components of Xuebinjing using AutoDock 4.2.6 and PyMol 1.5.0.3 software. Results. Fifteen RCTs involving 2778 patients (13 ARDS and 2 SP) were included. Compared with the control, Xuebijing treatment significantly reduced the mortality rate (risk ratio, 0.64 (95% credible interval (CrI), 0.54–0.77)), reduced the ICU stay time (mean difference (MD), -4.51 (95% CrI, -4.97–-4.06)), reduced the TNF-α ((MD), -1.23 (95% CrI, -1.38–-1.08)) and IL-6 ((MD), -1.15 (95% CrI, -1.52–-0.78)) levels. The 56 putative targets, top 10 proteins (MAPK1 (mitogen-activated protein kinase 1), MAPK8 (mitogen-activated protein kinase 8), RELA (transcription factor p65), NFKB1 (nuclear factor NF-kappa-B p105 subunit), JUN (transcription factor AP-1), SRC (proto-oncogene tyrosine-protein kinase), TNF (tumor necrosis factor), HRAS (GTPase HRas), IL6 (interleukin-6), and APP (amyloid-beta A4 protein)), and possible pathways (Ret tyrosine kinase, IL2-mediated signaling events, CD4+/CD8+ T cell-related TCR signaling, p75(NTR)-mediated signaling, CXCR4-mediated signaling events, LPA receptor-mediated events, IL12-mediated signaling events, FAS (CD95) signaling pathway, and immune system) of Xuebinjing’s action on ARDS were obtained. The molecular docking results showed that all the six components of Xuebinjing docked with TNF-α, and two components docked with IL-6 got the binding energies lower than -5. Conclusion. Our results recommended Xuebijing treatment for patients with ARDS. Xuebijing has therapeutic effects on ARDS patients partly by regulating the immune cell/cytokine pathways and thus inhibiting the cytokine storm. TNF-α is the cytokine both directly and indirectly inhibited by Xuebijing, and IL-6 is the cytokine mainly indirectly inhibited by Xuebijing.

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Interventions for escalation of therapy for acute exacerbations of asthma in children: an overview of Cochrane Reviews

Abstract: Interventions for escalation of therapy for acute exacerbations of asthma in children: an overview of Cochrane Reviews.

Cited by 26 publications

References 80 publications

Treatment patterns and frequency of key outcomes in acute severe asthma in children: a Paediatric Research in Emergency Departments International Collaborative (PREDICT) multicentre cohort study

Treatment patterns and frequency of key outcomes in acute severe asthma in children: a Paediatric Research in Emergency Departments International Collaborative (PREDICT) multicentre cohort study

Paediatrics: how to manage acute asthma exacerbations

Analysis of the Efficacy and Mechanism of Action of Xuebijing Injection on ARDS Using Meta-Analysis and Network Pharmacology

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