Severe Acute Asthma Exacerbation Research Articles

Characteristics of asthmatic children with <em>Mycoplasma pneumoniae</em> infection in Vietnam

Introduction: Mycoplasma pneumoniae is regarded as an involved factor in refractory asthma exacerbations. The link between Mycoplasma pneumoniae infection and asthma is not fully understood, particularly regarding clinical and paraclinical characteristics.Objectives: To determine the frequency of Mycoplasma pneumoniae infection in asthmatic children, identify clinical and paraclinical characteristics along with clinical management in children aged 6 to 15 years at Can Tho Children's Hospital, Vietnam.Method: From March 2019 to April 2021, 124 patients participated in a cross-sectional study that was done. Mycoplasma pneumoniae was detected using an immunoglobulin N (IgM) serology test.Results: Mycoplasma pneumoniae-IgM serology was positive in 32.3% asthmatic children. IgM-positive individuals had significantly greater percentages of accessory respiratory muscle contraction, coarse crackles, fever, and increased heart rate. Mycoplasma pneumoniae infection occurred in 42.3% of children who were hospitalized for the first time and had asthma diagnosis. Mycoplasma pneumoniae infection and the severity of acute asthma exacerbations had a positive association (p<0.05). A longer hospital stay (6.74±1.91 days) and a higher exacerbation recurrence rate (32.4%) were observed in the IgM-positive group (p<0.05). Conclusions: Mycoplasma pneumoniae infections were highly prevalent in asthmatic children. Severity of acute asthma exacerbations, first-time asthma diagnosis, and recurrence of asthma exacerbation were significantly associated with Mycoplasma pneumoniae infection.

Profile of adult patients hospitalized for asthma exacerbation

A variable proportion of patients presenting to the emergency department (ED) with acute asthma require admission to hospital. Previous studies have identified select factors associated with admission following ED presentation .However, patients hospitalized for AEs are highly heterogeneous and remain largely unexplored.This review discusses current aspects on the pathogenesis and pathophysiology of acute severe asthma exacerbations and provides the current perspectives on the management of acute severe asthma attacks in the emergency department and the intensive care unit.

Core outcomes and factors influencing the experience of care for children with severe acute exacerbations of asthma: a qualitative study

ObjectiveTo identify the outcomes considered important, and factors influencing the patient experience, for parents and caregivers of children presenting to hospital with a severe acute exacerbation of asthma. This work...

The Effectiveness of Combining Ipratropium Bromide and Salbutamol for the Treatment of Acute Severe Exacerbation of Asthma in Children: A Literature Review

The most common symptoms of asthma include episodes of wheezing, shortness of breath, and cough. When a person develops asthma in their childhood, it is usually seen to arise as a consequence of hay fever or allergic rhinitis and eczema, or atopic dermatitis. Maternal factors during the prenatal period have been found to be responsible to some extent in some infants, however, the role of breastfeeding and other nutritional allergies as the causes of asthma stands out to be unclear and controversial. The maintenance therapy of asthma in children comprises the following options, which are recommended to be used symptom-wise and only after keeping all the safety guidelines in mind.  The combination therapy has been found to be very useful in treating asthma and reducing the complications that arise due to it.

Asthma in the intensive care unit: A review of patient characteristics and outcomes.

Most asthma-related deaths occur in low- and middle-income countries, and South Africa (SA) is ranked fifth in global asthma mortality. Little is known about the characteristics and outcome of asthma patients requiring intensive care unit (ICU) admission in SA. To identify and characterise patients with acute severe asthma admitted to the respiratory ICU at Groote Schuur Hospital, Cape Town, SA, in order to evaluate outcomes and identify predictors of poor outcomes in those admitted. We performed a retrospective descriptive study of patients with severe asthma admitted to the respiratory ICU at Groote Schuur Hospital between 1 January 2014 and 31 December 2019. One hundred and three patients (110 admission episodes) were identified with an acute asthma exacerbation requiring ICU admission; all were mechanically ventilated. There was a female preponderance (53.6%; n=59/110), with a median (range) age overall of 33 (13 - 84) years. Of all admissions, 40 (36.4%) were current tobacco smokers and 16 (14.5%) patients with a history of substance abuse. Two thirds (60.0%; n=66/110) of the patients were using an inhaled corticosteroid (ICS). No predictors of mortality were evident in multivariate modelling, although those who died were older, and had higher Acute Physiology and Chronic Health Evaluation (APACHE II) scores and longer duration of admission. Only 59 of the surviving 96 individual patients (61.5%) attended a specialist pulmonology clinic after discharge. Among patients admitted to the respiratory ICU at Groote Schuur Hospital for asthma exacerbations, there was a high prevalence of smokers and poor coverage with inhaled ICSs. Although mortality was low compared with general ICU mortality, more needs to be done to prevent acute severe asthma exacerbations. What the study adds. Intensive care unit (ICU) admission represents the most severe form of exacerbation of asthma. South Africa (SA) has a very high rate of asthma deaths, and this study demonstrates that admission to an ICU with a very severe asthma exacerbation frequently results in a good outcome. However, many of the patients admitted to the ICU were not adequately treated with background asthma medications prior to their admission. Implications of the findings. Death from asthma should be avoidable, and admission to an ICU is not associated with high mortality. Patients are therefore likely to be dying at home or out of hospital. Better education and access to medication and early access to health services rather than improved in-hospital care would potentially alter SA's high asthma mortality.

The association between PM2.5 concentration and the severity of acute asthmatic exacerbation in hospitalized children: A retrospective study in Chongqing, China.

Ambient PM2.5 is associated with asthma exacerbation. The association between the concentration of PM2.5 and the severity of asthma exacerbation has yet to be thoroughly clarified. The study aims to explore the association between the piror 30 days average concentration of PM2.5 and the severity of acute asthma exacerbation in hospitalized children. A total of 269 children with acute exacerbation of asthma were enrolled and divided into three groups according to the PM2.5 exposure concentrations: group 1 (PM2.5: <37.5 μg/m3 ), group 2 (PM2.5: 37.5-75 μg/m3 ), group 3 (PM2.5: ≥75 μg/m3 ), respectively. The ordered logistic regression modeling was conducted to explore the influence of daily PM2.5 concentration on the clinical severity of children's asthma exacerbation. Multiple linear regression was conducted to explore the association between the concentration of PM2.5 and the length of stay in the hospital (LOS). We also conducted a receiver operating characteristic (ROC) curve analysis to explore the cutoff value of PM2.5 to predict the children's asthma exacerbation. There was no statistical difference among the three groups of children in gender, age, body mass index, ethnicity, the first diagnosis of asthma, allergic history, passive smoke exposure, or family history of asthma. There was a statistically significant difference in many hospitalization characteristics (p < 0.05) among the three groups of children. Significant differences were found in terms of accessory muscles of respiration (p = 0.005), respiratory failure (p = 0.012), low respiratory tract infectious (p = 0.020), and the severity of asthma exacerbation (p < 0.001) among the three groups. PM2.5 concentration was primarily positively correlated to neutrophile inflammation. The ordered multivariate logistic regression model showed that higher PM2.5 concentrations were significantly associated with greater odds of more severe asthma exacerbation in one and two-pollutant models. The adjusted odds ratio of severe asthma exacerbation was 1.029 (1.009, 1.049) in the one-pollutant model. The most significant odds ratio of severe asthma exacerbation was 1.050 (1.027, 1.073) when controlling NO2 in the two-pollutant models. Multiple linear regression showed that PM2.5 concentration was significantly associated with longer LOS in both one-pollutant and two-pollutant models. By performing ROC analysis, the average daily concentration of 44.5 µg/m3 of PM2.5 (AUC = 0.622, p = 0.002) provided the best performance to predict severe asthma of children exacerbation with a sensitivity of 59.2% and a specificity of 63.8%. The increased prior 30 days average concentration of PM2.5 was associated with greater asthma exacerbation severity and longer length of stay in the hospital of children with asthma exacerbation.

A Wireless Wearable Patch for Remote Monitoring of Respiratory and Cardiac Rhythm in Children.

Remote patient monitoring (RPM) is an innovative strategy to promote health and improve patient management and care. Recent advances in healthcare technologies have seen the emergence of wearable sensors allowing longitudinal physiological measurements in any environment. This paper introduces a wireless wearable patch 'Leo' for continuous remote monitoring of physiological data at home and healthcare settings. This includes single lead ECG, chest impedance, heart rate (HR), respiration rate (RR) and body posture. To test Leo's ability to capture longitudinal physiological data at home, 15 children experiencing acute severe asthma exacerbations were recruited during their emergency department (ED) visits. Participants wore the Leo device for 7 (+/-2) days post-hospital discharge. Nocturnal RR and HR and variability were higher during the first half of the night on Day1 compared to Day7 (p<0.005). Participants also completed a usability questionnaire and reported the patch wear to be comfortable (average score of 3.3 out of 5) and easy to wear during the night (average score of 3.5 out of 5) with 5/15 (33%) reported very slight barely perceptible skin irritation/redness and 2 (13%) reported well defined skin irritation and redness.Clinical Relevance- These results highlight the potential use of the Leo device in clinical practice for continuous un-obstructive monitoring of diseased populations, such as asthma.

LPS binding protein and activation signatures are upregulated during asthma exacerbations in children

Asthma exacerbations in children are associated with respiratory viral infection and atopy, resulting in systemic immune activation and infiltration of immune cells into the airways. The gene networks driving the immune activation and subsequent migration of immune cells into the airways remains incompletely understood. Cellular and molecular profiling of PBMC was employed on paired samples obtained from atopic asthmatic children (n = 19) during acute virus-associated exacerbations and later during convalescence. Systems level analyses were employed to identify coexpression networks and infer the drivers of these networks, and validation was subsequently obtained via independent samples from asthmatic children. During exacerbations, PBMC exhibited significant changes in immune cell abundance and upregulation of complex interlinked networks of coexpressed genes. These were associated with priming of innate immunity, inflammatory and remodelling functions. We identified activation signatures downstream of bacterial LPS, glucocorticoids and TGFB1. We also confirmed that LPS binding protein was upregulated at the protein-level in plasma. Multiple gene networks known to be involved positively or negatively in asthma pathogenesis, are upregulated in circulating PBMC during acute exacerbations, supporting the hypothesis that systemic pre-programming of potentially pathogenic as well as protective functions of circulating immune cells preceeds migration into the airways. Enhanced sensitivity to LPS is likely to modulate the severity of acute asthma exacerbations through exposure to environmental LPS.

Managing Severe Acute Asthma Exacerbation in Pregnancy during the COVID-19 Pandemic: A Case Report from a Resource-limited Setting

BACKGROUND: One-third of pregnant women will experience worsening asthma requiring emergency hospitalization. However, no report comprehensively discussed the management of asthma attacks in pregnant women in impoverished settings. We attempt to illuminate what general practitioners can do to stabilize and improve the outcome of severe acute asthma exacerbations in primary care with resource limitations. CASE REPORT: A nulliparous 29-year-old woman in her 21st week of pregnancy presented severe acute asthma exacerbation in moderate persistent asthma with uncontrolled asthma status along with gestational hypertension, uncompensated metabolic acidosis with a high anion gap, anemia, respiratory infection, and asymptomatic bacteriuria, all of which influenced her exacerbations. This patient was admitted to our resource-limited subdistrict hospital in Indonesia during the COVID-19 pandemic for optimal stabilization. Crystalloid infusions, oxygen supplementation, nebulized beta-agonist with anticholinergic agents, inhaled corticosteroids, intravenous methylprednisolone, broad-spectrum antibiotics, subcutaneous terbutaline, mucolytics, magnesium sulphate, oral antihypertensives, and continuous positive airway pressure were used to treat her life-threatening asthma. After she was stabilized, we referred the patient to a higher-level hospital with more advanced pulmonary management under the supervision of a multidisciplinary team to anticipate the worst scenario of pregnancy termination. CONCLUSION: Limitations in primary care, including the lack of sophisticated intensive care units and laboratory panels, may complicate challenges in managing severe acute asthma exacerbation during pregnancy. To enhance maternal-fetal outcomes, all multidisciplinary team members should be well-informed about key asthma management strategies during pregnancy using evidence-based guidelines regarding the drug, rationale, and safety profile.

Antibiotic Use in Paediatric Patients Hospitalized with Acute Severe Asthma.

Antibiotic use during asthma exacerbations in paediatric patients is not routinely recommended but common practise in out-patient and in-patient settings. Objective of this study was to analyse frequency of antibiotic use during acute severe asthma exacerbations, antibiotic classes utilized and clinical decision-making. All in-patient admissions over 10 years in a single German Children's University hospital due to acute severe asthma were included in this retrospective analysis. Age, length of stay, oxygen supplementation, treatment, laboratory parameters and chest x-rays of all patients ranging from 1 to 17 years were analysed. 580 hospital admissions were included in this study. Overall antibiotic use was high but decreased with age (1-5 years 69,6%, 6-11 years 57,6% and 12-17 years 39,7%, p<0.001). Analysis of antibiotic treatment without clear indication showed a consistently lower treatment rate of 28.3%, with macrolides being the most common antibiotic class. Younger age significantly decreased, whereas, increase of CrP value, use of oxygen supplementation and concomitant fever all significantly increased the odds ratio (OR 0.967; 4.366, 2.472 and 2.011 respectively) of receiving antibiotic treatment without clear indication. Antibiotic treatment without clear indication during acute severe asthma is common in this German single-centre cohort. Clinical parameters of more severe disease affect clinician's decision to administer antibiotics despite evidence of bacterial infection or improved outcome.

The prevalence of mucus plugging in severe eosinophilic asthma and its relationship to clinical efficacy of anti–IL-5R treatment

Mucus plugging (MP) of the airways is well recognized in the pathogenesis of acute severe and fatal asthma exacerbations.1 Patients with MP are more likely to have severe asthma and require higher inhaled corticosteroid and maintenance oral corticosteroid (mOCS) use.2 Subsegmental MP can be readily detectable by computed tomography (CT) imaging and is associated with airflow obstruction and gas trapping. The plugs themselves are typically eosinophil-rich, and the degree of MP has been shown to relate to the degree of sputum eosinophilia.

Ketamine for Adults with Severe Asthma Exacerbation: A Systematic Review and Meta-analysis

BACKGROUND: Severe asthma mandates careful attention and timely management, and the benefit of ketamine in severe asthma exacerbations in adult patients require further exploration. METHODS: We conducted a systematic review and meta-analysis of the use of ketamine in cases of acute asthma exacerbation in adults. We searched PubMed, Google Scholar, Cochrane databases, and gray literature (ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform); we also searched the reference lists of included articles and any systematic reviews and meta-analyses identified therein. Our search covered the period from 1963 to August 20, 2021. Search terms were “ketamine” AND “asthma”. RESULTS: Of 25 540 articles, two studies were included in the analysis. The total number of patients included in the studies was 136 (68 in the ketamine groups and 68 in the placebo group). The pooled effect size was 0.30 (95% CI: -0.04, 0.63) favouring ketamine over placebo, p=0.08, (I2=0%, p=0.39). A paired t-test revealed that ketamine improved the mean peak expiratory flow rate (PEFR) from 242.4 (SD=146.23) to 286.95 (SD=182.22), p=0.33, representing an 18.38% improvement. CONCLUSION: Ketamine can induce a 30% improvement in PEFR, representing a small positive effect in the treatment of acute severe asthma exacerbation in the emergency department (ED). The improvement was not statistically significant; nonetheless, since the improvement could be as great as 63% versus only a 4% possibility of no benefit/harm, the benefit appears to considerably outweigh any harm.

Prospective Observational Study of Clinical Outcomes After Intravenous Magnesium for Moderate and Severe Acute Asthma Exacerbations in Children

There is limited knowledge regarding whether intravenous magnesium (IV-Mg) improves outcomes in children with acute asthma exacerbations. To examine whether IV-Mg improves outcomes in children with moderate and severe exacerbations. We performed a secondary analysis using data from a prospective observational cohort of children aged 5 to 17 years with moderate and severe exacerbations. Standardized treatment included systemic corticosteroid and inhaled albuterol, with consideration of IV-Mg (75 mg/kg) for patients with insufficient response after 20 minutes. Propensity score (PS) models were used to examine associations of IV-Mg treatment with change in the validated Acute Asthma Intensity Research Score, hospitalization rate, and time to spacing of inhaled albuterol of 4 hours or more among hospitalized participants. Among 301 children, median (interquartile range) age was 8.1 (6.4-10.2) years, 170 were Black (57%), 201 were male (67%), and 84 received IV-Mg (28%). In a PS covariate-adjusted multivariable linear regression model, IV-Mg treatment was associated with a 2-hour increase in the Acute Asthma Intensity Research Score (β-coefficient= 0.98; 95% confidence interval [CI], 0.20-1.77), indicating increased exacerbation severity. Three additional PS-based models yielded similar results. Participants receiving IV-Mg had 5.8-fold (95% CI, 2.8-11.9) and 6.8-fold (95% CI, 3.6-12.9) greater odds of hospitalization in PS-based multivariable regression models. Among hospitalized participants, there was no difference in time to albuterol of every 4 hours or more in a PS covariate-adjusted Cox proportional hazards model (hazard ratio= 1.2; 95% CI, 0.8-1.8). Among children with moderate and severe exacerbations, IV-Mg is associated with increased exacerbation severity, increased risk for hospitalization, and no acceleration in exacerbation resolution among hospitalized participants.

Analysis of eosinophil and lymphocyte concentrations on the incidence of mild and severe acute asthma exacerbations

Introduction: Exacerbation of asthma is an episode characterized by an increase in symptoms of progressive shortness of breath, coughing, wheezing, chest tightness, and a progressive decrease in lung function. Among the cells involved and activated in acute exacerbations in asthma are eosinophils and lymphocytes.

Pediatric respiratory assessment measure in evaluation of the severity of bronchial asthma exacerbation in children

Objective The aim was to study the role of pediatric respiratory assessment measure (PRAM) score in evaluation of acute asthma exacerbation in children. Background Acute severe asthma is one of the most common medical emergency situations in childhood, where accurate assessment and management is of extreme importance and may be lifesaving. PRAM score has been used to classify asthma severity and treatment. Patients and methods A prospective cohort study was adopted by applying the PRAM score on 108 asthmatic children presented to the Emergency Department of Elraml Pediatric Hospital in Alexandria by acute asthma exacerbation in the period of the study. Results The study included 66 (61.1%) boys and 42 (38.9%) girls, aged from 2 to 12 years, with mean age of 5.07 ± 2.68 years. The most common triggering factor according to our study was viral infection or common cold (90.7%). Increasing severity of acute asthma exacerbation was associated with increasing initial PRAM score. There was significantly increased severity of grade of PRAM score after initial bronchodilator therapy in relation to young aged children ( Conclusion PRAM score in this study is useful for predicting fate of patients in emergency room, and after initial bronchodilator therapy, it is an excellent sensitive and specific tool to predict the admitted patients from the discharged patients.

Analysis of eosinophil and lymphocyte concentrations on the incidence of mild and severe acute asthma exacerbations.

Introduction: Exacerbation of asthma is an episode characterized by an increase in symptoms of progressive shortness of breath, coughing, wheezing, chest tightness, and a progressive decrease in lung function. Among the cells involved and activated in acute exacerbations in asthma are eosinophils and lymphocytes.

The Impact of Terbutaline As Adjuvant Therapy In The Treatment Of Severe Acute Asthma Exacerbation In The Pediatric Emergency Department

The Impact of Terbutaline As Adjuvant Therapy In The Treatment Of Severe Acute Asthma Exacerbation In The Pediatric Emergency Department

Hospitalization, Asthma Phenotypes, and Readmission Rates in Pre-school Asthma.

Objective: Children with pre-school asthma suffer disproportionally more often from severe asthma exacerbations with emergency visits and hospital admissions compared to school children. Despite this high disease burden, there are only a few reports looking at this particular severe asthma cohort. Similarly, there is little real-life research on the distribution of asthma phenotypes and personalized treatment at discharge in this age group.Patients and Methods: Retrospective analysis of the electronic charts of all children aged 1–5 years with asthma hospitalizations (ICD J45) at the Frankfurt University between 2008 and 2017. An acute severe asthma exacerbation was defined as dyspnea, oxygen demand, and/or systemic steroid therapy. Age, gender, duration of hospitalization, asthma phenotype, treatment, and readmission rate were analyzed.Results: Of 572 patients, 205 met the definition of acute severe asthma. The phenotypic characterization showed 56.1% had allergic asthma, 15.2% eosinophilic asthma and 28.7% non-allergic asthma. Of these patients, 71.7% were discharged with inhaled corticosteroids (ICS) or ICS + long-acting-beta-agonists (LABA), 15.1% with leukotriene antagonists (LTRA) and 7.3% salbutamol on demand. The rate of emergency presentations (emergency department and readmission) within 12 months after discharge was high (n = 42; 20.5%). No phenotype tailored treatment was detectable. Neither the number of eosinophils (>300/μl) nor the treatment at discharge had an effect on emergency visits and readmission rate.Conclusion: Despite protective therapy with ICS, ICS + LABA, or LTRA, the readmission rate was high. Thus, current care and treatment strategies should be reevaluated continuously, in order to better control asthma in pre-school children and prevent hospitalization.

The Impact of Terbutaline as Adjuvant Therapy in the Treatment of Severe Asthma in the Pediatric Emergency Department.

Patients were identified using a retrospective cohort analysis from a single, tertiary care, urban children's hospital. Patients presenting directly to our emergency department aged 2 to 18 years were included if they had a diagnosis of severe asthma exacerbation, defined by an initial Respiratory Clinical Score (RCS) of 9 or higher. A total of 787 patients were identified during the study timeframe (December 16, 2017, to December 31, 2018), and of those, 651 patients met study criteria and were included in the analysis. The χ2 test was used to establish P values for categorical variables. For normally distributed variables, a t test was used. For nonnormally distributed variables, the Kruskal-Wallis test was used. A P value of 0.05 or less was interpreted as statistically significant. Patients who received terbutaline had an increased risk of admission to the PICU (P < 0.001). This association was lost after controlling for age, sex, continuous albuterol use, and intramuscular epinephrine use (P = 0.362). Patients receiving terbutaline in the emergency department also had a higher risk of admission to the hospital (odds ratio, 1.55; confidence interval, 1.08-2.22; P = 0.020) as compared with their nonterbutaline counterparts. Overall, patients in the terbutaline group had a higher initial RCS at presentation. Upon further analysis, patients with the same RCS at presentation were more likely to be admitted if they received terbutaline than those who did not. There was no statistically significant difference in length of stay (P = 0.298) and BiPAP/CPAP use (P = 0.107). The patients on terbutaline were relatively more likely to require oxygen (P = 0.003) and intramuscular epinephrine (P = 0.010) than the patients not on terbutaline. Terbutaline administration given to pediatric patients experiencing a severe asthma exacerbation was not associated with decreased PICU or general hospital floor admission. The study is limited given that it was a retrospective analysis. Further randomized controlled trials are needed to assess the role of terbutaline in severe acute asthma exacerbations in pediatric patients.

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

Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is characterised by acute or subacute worsening of shortness of breath, cough, wheezing, and chest tightness and may be triggered by viral respiratory infection, poor compliance with usual medication, a change in the weather, or exposure to allergens or irritants. Most children with asthma have mild or moderate exacerbations and respond well to first-line therapy (inhaled short-acting beta-agonists and systemic corticosteroids). However, the best treatment for the small proportion of seriously ill children who do not respond to first-line therapy is not well understood. Currently, a large number of treatment options are available and there is wide variation in management. Main objective - To summarise Cochrane Reviews with or without meta-analyses of randomised controlled trials on the efficacy and safety of second-line treatment for children with acute exacerbations of asthma (i.e. after first-line treatments, titrated oxygen delivery, and administration of intermittent inhaled short-acting beta2-agonists and oral corticosteroids have been tried and have failed) Secondary objectives - To identify gaps in the current evidence base that will inform recommendations for future research and subsequent Cochrane Reviews - To categorise information on reported outcome measures used in trials of escalation of treatment for acute exacerbations of asthma in children, and to make recommendations for development and reporting of standard outcomes in future trials and reviews - To identify relevant randomised controlled trials that have been published since the date of publication of each included review METHODS: We included Cochrane Reviews assessing interventions for children with acute exacerbations of asthma. We searched the Cochrane Database of Systematic Reviews. The search is current to 28 December 2019. We also identified trials that were potentially eligible for, but were not currently included in, published reviews. We assessed the quality of included reviews using the ROBIS criteria (tool used to assess risk of bias in systematic reviews). We presented an evidence synthesis of data from reviews alongside an evidence map of clinical trials. Primary outcomes were length of stay, hospital admission, intensive care unit admission, and adverse effects. We summarised all findings in the text and reported data for each outcome in 'Additional tables'. We identified 17 potentially eligible Cochrane Reviews but extracted data from, and rated the quality of, 13 reviews that reported results for children alone. We excluded four reviews as one did not include any randomised controlled trials (RCTs), one did not provide subgroup data for children, and the last two had been updated and replaced by subsequent reviews. The 13 reviews included 67 trials; the number of trials in each review ranged from a single trial up to 27 trials. The vast majority of comparisons included between one and three trials, involving fewer than 100 participants. The total number of participants included in reviews ranged from 40 to 2630. All studies included children; 16 (24%) included children younger than two years of age. Most of the reviews reported search dates older than four years. We have summarised the published evidence as outlined in Cochrane Reviews. Key findings, in terms of our primary outcomes, are that (1) intravenous magnesium sulfate was the only intervention shown to reduce hospital length of stay (high-certainty evidence); (2) no evidence suggested that any intervention reduced the risk of intensive care admission (low- to very low-certainty evidence); (3) the risk of hospital admission was reduced by the addition of inhaled anticholinergic agents to inhaled beta2-agonists (moderate-certainty evidence), the use of intravenous magnesium sulfate (high-certainty evidence), and the use of inhaled heliox (low-certainty evidence); (4) the addition of inhaled magnesium sulfate to usual bronchodilator therapy appears to reduce serious adverse events during hospital admission (moderate-certainty evidence); (5) aminophylline increased vomiting compared to placebo (moderate-certainty evidence) and increased nausea and nausea/vomiting compared to intravenous beta2-agonists (low-certainty evidence); and (6) the addition of anticholinergic therapy to short-acting beta2-agonists appeared to reduce the risk of nausea (high-certainty evidence) and tremor (moderate-certainty evidence) but not vomiting (low-certainty evidence). We considered 4 of the 13 reviews to be at high risk of bias based on the ROBIS framework. In all cases, this was due to concerns regarding identification and selection of studies. The certainty of evidence varied widely (by review and also by outcome) and ranged from very low to high. This overview provides the most up-to-date evidence on interventions for escalation of therapy for acute exacerbations of asthma in children from Cochrane Reviews of randomised controlled trials. A vast majority of comparisons involved between one and three trials and fewer than 100 participants, making it difficult to assess the balance between benefits and potential harms. Due to the lack of comparative studies between various treatment options, we are unable to make firm practice recommendations. Intravenous magnesium sulfate appears to reduce both hospital length of stay and the risk of hospital admission. Hospital admission is also reduced with the addition of inhaled anticholinergic agents to inhaled beta2-agonists. However, further research is required to determine which patients are most likely to benefit from these therapies. Due to the relatively rare incidence of acute severe paediatric asthma, multi-centre research will be required to generate high-quality evidence. A number of existing Cochrane Reviews should be updated, and we recommend that a new review be conducted on the use of high-flow nasal oxygen therapy. Important priorities include development of an internationally agreed core outcome set for future trials in acute severe asthma exacerbations and determination of clinically important differences in these outcomes, which can then inform adequately powered future trials.