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The Cochrane Database of Systematic... Nov 2014Acute cough due to upper respiratory tract infection (URTI) is a common symptom. Non-prescription, over-the-counter (OTC) medicines are frequently recommended as a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute cough due to upper respiratory tract infection (URTI) is a common symptom. Non-prescription, over-the-counter (OTC) medicines are frequently recommended as a first-line treatment, but there is little evidence as to whether these drugs are effective.
OBJECTIVES
To assess the effects of oral OTC cough preparations for acute cough in children and adults in community settings.
SEARCH METHODS
We searched CENTRAL (2014, Issue 1), MEDLINE (January 1966 to March week 3 2014), EMBASE (January 1974 to March 2014), CINAHL (January 2010 to March 2014), LILACS (January 2010 to March 2014), Web of Science (January 2010 to March 2014) and the UK Department of Health National Research Register (March 2010).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing oral OTC cough preparations with placebo in children and adults suffering from acute cough in community settings. We considered all cough outcomes; secondary outcomes of interest were adverse effects.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened potentially relevant citations, extracted data and assessed study quality. We performed quantitative analysis where appropriate.
MAIN RESULTS
Due to the small numbers of trials in each category, the limited quantitative data available and the marked differences between trials in terms of participants, interventions and outcome measurement, we felt that pooling of the results was inappropriate.We included 29 trials (19 in adults, 10 in children) involving 4835 people (3799 adults and 1036 children). All studies were placebo-controlled RCTs. However, assessment of the risk of bias of the included studies was limited by poor reporting, particularly for the earlier studies.In the adult studies, six trials compared antitussives with placebo and had variable results. Three trials compared the expectorant guaifenesin with placebo; one indicated significant benefit, whereas the other two did not. One trial found that a mucolytic reduced cough frequency and symptom scores. Two studies examined antihistamine-decongestant combinations and found conflicting results. Four studies compared other combinations of drugs with placebo and indicated some benefit in reducing cough symptoms. Three trials found that antihistamines were no more effective than placebo in relieving cough symptoms.In the child studies, antitussives (data from three studies), antihistamines (data from three studies), antihistamine-decongestants (two studies) and antitussive/bronchodilator combinations (one study) were no more effective than placebo. No studies using expectorants met our inclusion criteria. The results of one trial favoured active treatment with mucolytics over placebo. One trial tested two paediatric cough syrups and both preparations showed a 'satisfactory response' in 46% and 56% of children compared to 21% of children in the placebo group. One new trial indicated that three types of honey were more effective than placebo over a three-day period.Twenty-one studies reported adverse effects. There was a wide range across studies, with higher numbers of adverse effects in participants taking preparations containing antihistamines and dextromethorphan.
AUTHORS' CONCLUSIONS
The results of this review have to be interpreted with caution because the number of studies in each category of cough preparations was small. Availability, dosing and duration of use of over-the-counter cough medicines vary significantly in different countries. Many studies were poorly reported making assessment of risk of bias difficult and studies were also very different from each other, making evaluation of overall efficacy difficult. There is no good evidence for or against the effectiveness of OTC medicines in acute cough. This should be taken into account when considering prescribing antihistamines and centrally active antitussive agents in children; drugs that are known to have the potential to cause serious harm.
Topics: Acute Disease; Administration, Oral; Adult; Ambulatory Care; Antitussive Agents; Child; Cough; Drug Therapy, Combination; Expectorants; Histamine H1 Antagonists; Humans; Nonprescription Drugs; Randomized Controlled Trials as Topic
PubMed: 25420096
DOI: 10.1002/14651858.CD001831.pub5 -
The Journal of Allergy and Clinical... Jun 2020Although nebulized corticosteroids (NebCSs) are a key treatment option for young children with asthma or viral-induced wheezing (VIW), there are no uniform... (Review)
Review
Although nebulized corticosteroids (NebCSs) are a key treatment option for young children with asthma or viral-induced wheezing (VIW), there are no uniform recommendations on their best use. This systematic review aimed to clarify the role of NebCSs in children 5 years or younger for the management of acute asthma exacerbations, asthma maintenance therapy, and the treatment of VIW. Electronic databases were used to identify relevant English language articles with no date restrictions. Studies reporting efficacy data in children 5 years or younger, with a double-blind, placebo- or open-controlled, randomized design, and inclusion of 40 or more participants (no lower patient limit for VIW) were included. Ten articles on asthma exacerbation, 9 on asthma maintenance, and 7 on VIW were identified. Results showed NebCSs to be at least as efficacious as oral corticosteroids in the emergency room for the management of mild to moderate asthma exacerbations. In asthma maintenance, nebulized budesonide, the agent of focus in all trials analyzed, significantly reduced the risk of further asthma exacerbations compared with placebo, cromolyn sodium, and montelukast. Intermittent NebCS treatment of VIW was as effective as continuous daily treatment. In summary, NebCSs are effective and well tolerated in patients 5 years or younger for the management of acute and chronic asthma.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Humans; Randomized Controlled Trials as Topic; Respiratory Sounds
PubMed: 32006721
DOI: 10.1016/j.jaip.2020.01.042 -
Respiratory Research Aug 2022Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD exacerbations are associated with a worsening of lung... (Review)
Review
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD exacerbations are associated with a worsening of lung function, increased disease burden, and mortality, and, therefore, preventing their occurrence is an important goal of COPD management. This review was conducted to identify the evidence base regarding risk factors and predictors of moderate-to-severe exacerbations in patients with COPD.
METHODS
A literature review was performed in Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials (CENTRAL). Searches were conducted from January 2015 to July 2019. Eligible publications were peer-reviewed journal articles, published in English, that reported risk factors or predictors for the occurrence of moderate-to-severe exacerbations in adults age ≥ 40 years with a diagnosis of COPD.
RESULTS
The literature review identified 5112 references, of which 113 publications (reporting results for 76 studies) met the eligibility criteria and were included in the review. Among the 76 studies included, 61 were observational and 15 were randomized controlled clinical trials. Exacerbation history was the strongest predictor of future exacerbations, with 34 studies reporting a significant association between history of exacerbations and risk of future moderate or severe exacerbations. Other significant risk factors identified in multiple studies included disease severity or bronchodilator reversibility (39 studies), comorbidities (34 studies), higher symptom burden (17 studies), and higher blood eosinophil count (16 studies).
CONCLUSIONS
This systematic literature review identified several demographic and clinical characteristics that predict the future risk of COPD exacerbations. Prior exacerbation history was confirmed as the most important predictor of future exacerbations. These prognostic factors may help clinicians identify patients at high risk of exacerbations, which are a major driver of the global burden of COPD, including morbidity and mortality.
Topics: Adult; Bronchodilator Agents; Disease Progression; Humans; Prognosis; Pulmonary Disease, Chronic Obstructive; Risk Factors
PubMed: 35999538
DOI: 10.1186/s12931-022-02123-5 -
Anesthesia and Analgesia Apr 2022Despite several clinical index tests that are currently applied for airway assessment, unpredicted difficult laryngoscopy may still represent a serious problem in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite several clinical index tests that are currently applied for airway assessment, unpredicted difficult laryngoscopy may still represent a serious problem in anesthesia practice. The aim of this systematic review and meta-analysis was to evaluate whether preoperative airway ultrasound can predict difficult direct laryngoscopy in adult patients undergoing elective surgery under general anesthesia.
METHODS
We searched the Medline, Scopus, and Web of Science databases from their inception to December 2020. The population of interest included adults who required tracheal intubation for elective surgery under general anesthesia without clear anatomical abnormalities suggesting difficult laryngoscopy. A bivariate model has been used to assess the accuracy of each ultrasound index test to predict difficult direct laryngoscopy.
RESULTS
Fifteen studies have been considered for quantitative analysis of summary receiver operating characteristic (SROC). The sensitivity for distance from skin to epiglottis (DSE), distance from skin to hyoid bone (DSHB), and distance from skin to vocal cords (DSVC) was 0.82 (0.74-0.87), 0.71 (0.58-0.82), and 0.75 (0.62-0.84), respectively. The specificity for DSE, DSHB, and DSVC was 0.79 (0.70-0.87), 0.71 (0.57-0.82), and 0.72 (0.45-0.89), respectively. The area under the curve (AUC) for DSE, DSHB, DSVC, and ratio between the depth of the pre-epiglottic space and the distance from the epiglottis to the vocal cords (Pre-E/E-VC) was 0.87 (0.84-0.90), 0.77 (0.73-0.81), 0.78 (0.74-0.81), and 0.71 (0.67-0.75), respectively. Patients with difficult direct laryngoscopy have higher DSE, DSVC, and DSHB values than patients with easy laryngoscopy, with a mean difference of 0.38 cm (95% confidence interval [CI], 0.17-0.58 cm; P = .0004), 0.18 cm (95% CI, 0.01-0.35 cm; P = .04), and 0.23 cm (95% CI, 0.08-0.39 cm; P = .004), respectively.
CONCLUSIONS
Our study demonstrates that airway ultrasound index tests are significantly different between patients with easy versus difficult direct laryngoscopy, and the DSE is the most studied index test in literature to predict difficult direct laryngoscopy. However, it is not currently possible to reach a definitive conclusion. Further studies are needed with better standardization of ultrasound assessment to limit all possible sources of heterogeneity.
Topics: Adult; Anesthesia, General; Humans; Intubation, Intratracheal; Laryngoscopy; Respiratory System; Ultrasonography
PubMed: 34914641
DOI: 10.1213/ANE.0000000000005839 -
BMC Pulmonary Medicine Oct 2018Pulmonary function tests (PFTs) are routinely performed in the upright position due to measurement devices and patient comfort. This systematic review investigated the...
BACKGROUND
Pulmonary function tests (PFTs) are routinely performed in the upright position due to measurement devices and patient comfort. This systematic review investigated the influence of body position on lung function in healthy persons and specific patient groups.
METHODS
A search to identify English-language papers published from 1/1998-12/2017 was conducted using MEDLINE and Google Scholar with key words: body position, lung function, lung mechanics, lung volume, position change, positioning, posture, pulmonary function testing, sitting, standing, supine, ventilation, and ventilatory change. Studies that were quasi-experimental, pre-post intervention; compared ≥2 positions, including sitting or standing; and assessed lung function in non-mechanically ventilated subjects aged ≥18 years were included. Primary outcome measures were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC, FEV1/FVC), vital capacity (VC), functional residual capacity (FRC), maximal expiratory pressure (PEmax), maximal inspiratory pressure (PImax), peak expiratory flow (PEF), total lung capacity (TLC), residual volume (RV), and diffusing capacity of the lungs for carbon monoxide (DLCO). Standing, sitting, supine, and right- and left-side lying positions were studied.
RESULTS
Forty-three studies met inclusion criteria. The study populations included healthy subjects (29 studies), lung disease (nine), heart disease (four), spinal cord injury (SCI, seven), neuromuscular diseases (three), and obesity (four). In most studies involving healthy subjects or patients with lung, heart, neuromuscular disease, or obesity, FEV1, FVC, FRC, PEmax, PImax, and/or PEF values were higher in more erect positions. For subjects with tetraplegic SCI, FVC and FEV1 were higher in supine vs. sitting. In healthy subjects, DLCO was higher in the supine vs. sitting, and in sitting vs. side-lying positions. In patients with chronic heart failure, the effect of position on DLCO varied.
CONCLUSIONS
Body position influences the results of PFTs, but the optimal position and magnitude of the benefit varies between study populations. PFTs are routinely performed in the sitting position. We recommend the supine position should be considered in addition to sitting for PFTs in patients with SCI and neuromuscular disease. When treating patients with heart, lung, SCI, neuromuscular disease, or obesity, one should take into consideration that pulmonary physiology and function are influenced by body position.
Topics: Humans; Lung; Posture; Respiratory Function Tests
PubMed: 30305051
DOI: 10.1186/s12890-018-0723-4 -
Advances in Therapy Nov 2022Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) dual maintenance therapies for... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) dual maintenance therapies for patients with chronic obstructive pulmonary disease (COPD). This systematic literature review and network meta-analysis (NMA) compared the efficacy of umeclidinium/vilanterol (UMEC/VI) versus other dual and mono-bronchodilator therapies in symptomatic patients with COPD.
METHODS
A systematic literature review (October 2015-November 2020) was performed to identify RCTs ≥ 8 weeks long in adult patients with COPD that compared LAMA/LABA combinations against any long-acting bronchodilator-containing dual therapy or monotherapy. Data extracted on changes from baseline in trough forced expiratory volume in 1 s (FEV), St George's Respiratory Questionnaire (SGRQ) total score, Transitional Dyspnoea Index (TDI) focal score, rescue medication use and moderate/severe exacerbation rate were analysed using an NMA in a frequentist framework. The primary comparison was at 24 weeks. Fixed effects model results are presented.
RESULTS
The NMA included 69 full-length publications (including 10 GSK clinical study reports) reporting 49 studies. At 24 weeks, UMEC/VI provided statistically significant greater improvements in FEV versus all dual therapy and monotherapy comparators. UMEC/VI provided similar improvements in SGRQ total score compared with all other LAMA/LABAs, and significantly greater improvements versus UMEC 125 μg, glycopyrronium 50 μg, glycopyrronium 18 μg, tiotropium 18 μg and salmeterol 50 μg. UMEC/VI also provided significantly better outcomes versus some comparators for TDI focal score, rescue medication use, annualised moderate/severe exacerbation rate, and time to first moderate/severe exacerbation.
CONCLUSION
UMEC/VI provided generally better outcomes compared with LAMA or LABA monotherapies, and consistent improvements in lung function (measured by change from baseline in trough FEV at 24 weeks) versus dual therapies. Treatment with UMEC/VI may improve outcomes for symptomatic patients with COPD compared with alternative maintenance treatments.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Drug Combinations; Dyspnea; Forced Expiratory Volume; Glycopyrrolate; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quinuclidines; Salmeterol Xinafoate; Tiotropium Bromide; Treatment Outcome
PubMed: 35857184
DOI: 10.1007/s12325-022-02234-x -
The Journal of Allergy and Clinical... Feb 2024A maintenance oral corticosteroid (OCS) in addition to high-dose inhaled corticosteroids plus long-acting β-agonists in patients with severe asthma leads to long-term... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A maintenance oral corticosteroid (OCS) in addition to high-dose inhaled corticosteroids plus long-acting β-agonists in patients with severe asthma leads to long-term adverse events. Oral corticosteroid-sparing agents are of high priority.
OBJECTIVE
This network meta-analysis assessed biologics' comparative efficacy and safety in OCS-dependent patients with asthma.
METHODS
We performed a systematic search through PubMed, Scopus, Embase, the Cochrane Center of Controlled Trials, and Google Scholar for randomized controlled trials that addressed the efficacy and safety of biologics compared with placebo in OCS-dependent patients with asthma from inception to July 2023. The primary outcome was an overall reduction in the OCS dose while asthma control was maintained.
RESULTS
We included seven randomized controlled trials involving 1,052 OCS-dependent patients with asthma. Compared with placebo, benralizumab every 8 weeks, benralizumab every 4 weeks, dupilumab, and mepolizumab were efficacious in achieving a reduction in the OCS dose with low to moderate confidence (odds ratio [95% CI]: 4.12 [2.22-7.64]; 4.09 [2.22-7.55]; 3.25 [1.90-5.55]; and 2.39 [1.25-4.57], respectively) whereas tralokinumab, tezepelumab, and subcutaneous reslizumab were ineffective. An indirect comparison found no significant differences among benralizumab, dupilumab, and mepolizumab. Efficacy in reducing exacerbations was consistent with the primary analysis. High baseline blood eosinophil counts benefit from anti-IL-5 therapies, whereas high FeNO levels favor dupilumab regardless of blood eosinophil counts. Adverse events between biologics and placebo were comparable, except for eosinophilia with dupilumab.
CONCLUSIONS
In OCS-dependent patients with asthma, benralizumab, dupilumab, and mepolizumab were superior to placebo in reducing the OCS dose. Evaluating baseline biomarkers helps in choosing the proper biologics to maximize treatment effects.
Topics: Humans; Anti-Asthmatic Agents; Biological Products; Network Meta-Analysis; Asthma; Adrenal Cortex Hormones; Eosinophilia
PubMed: 37972921
DOI: 10.1016/j.jaip.2023.11.007 -
Journal of Medical Economics 2022To compare the efficacy of tezepelumab with other approved biologics indirect treatment comparisons (ITCs) in patients aged ≥ 12 years with severe uncontrolled asthma. (Meta-Analysis)
Meta-Analysis
AIMS
To compare the efficacy of tezepelumab with other approved biologics indirect treatment comparisons (ITCs) in patients aged ≥ 12 years with severe uncontrolled asthma.
MATERIALS AND METHODS
Data from randomized controlled trials (RCTs) identified from a systematic literature review were synthesized using two different ITC approaches: network meta-analysis (NMA) and simulated treatment comparison (STC). Outcomes of interest were annualized asthma exacerbation rate (AAER) and AAER for exacerbations leading to hospitalization. To address potential heterogeneity between study populations, various subgroup analyses were performed for the NMA (based on blood eosinophil count, fractional exhaled nitric oxide level, and presence of allergic asthma), and for the STC, models were adjusted for potential treatment effect modifiers. Sensitivity analyses were performed to assess the impact of study design (exclusion of non-placebo-controlled studies and non-phase 3 or 4 studies). Results were reported as rate ratios (RRs) with 95% credible/confidence intervals and ranking statistics were computed for the NMAs.
RESULTS
Sixteen RCTs were included in at least one of the ITCs. All biologics (tezepelumab, dupilumab, benralizumab, mepolizumab, reslizumab, and omalizumab) had similar efficacy, with no statistically significant RRs for either exacerbation outcome; however, tezepelumab was favorably associated with numerically lower AAERs and was ranked first in the network for both types of exacerbation outcome. This trend was consistent in the subgroup and sensitivity analyses. As with the primary NMA, the STC results did not demonstrate any significant differences between biologics, but point estimates were favorable towards tezepelumab.
LIMITATIONS
Heterogeneity between trials was observed among eligibility criteria and clinically important patient characteristics; however, the impact on findings is expected to be low, based on consistency across analyses.
CONCLUSIONS
Findings from both ITCs (NMA and STC) support the use of tezepelumab in a broad patient population of severe uncontrolled asthma of any phenotype.
Topics: Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Biological Products; Eosinophils; Humans; Omalizumab
PubMed: 35570578
DOI: 10.1080/13696998.2022.2074195 -
The Cochrane Database of Systematic... Jun 2019Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. Although treatment with ICS is generally considered to be safe in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. Although treatment with ICS is generally considered to be safe in children, the potential adverse effects of these drugs on growth remains a matter of concern for parents and physicians.
OBJECTIVES
To assess the impact of different inhaled corticosteroid drugs and delivery devices on the linear growth of children with persistent asthma.
SEARCH METHODS
We searched the Cochrane Airways Trials Register, which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, Embase, CINAHL, AMED and PsycINFO. We handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases, or contacted the manufacturer, to search for potential relevant unpublished studies. The literature search was initially conducted in September 2014, and updated in November 2015, September 2018, and April 2019.
SELECTION CRITERIA
We selected parallel-group randomized controlled trials of at least three months' duration. To be included, trials had to compare linear growth between different inhaled corticosteroid molecules at equivalent doses, delivered by the same type of device, or between different devices used to deliver the same inhaled corticosteroid molecule at the same dose, in children up to 18 years of age with persistent asthma.
DATA COLLECTION AND ANALYSIS
At least two review authors independently selected studies and assessed risk of bias in included studies. The data were extracted by one author and checked by another. The primary outcome was linear growth velocity. We conducted meta-analyses using Review Manager 5.3 software. We used mean differences (MDs) and 95% confidence intervals (CIs ) as the metrics for treatment effects, and the random-effects model for meta-analyses. We did not perform planned subgroup analyses due to there being too few included trials.
MAIN RESULTS
We included six randomized trials involving 1199 children aged from 4 to 12 years (per-protocol population: 1008), with mild-to-moderate persistent asthma. Two trials were from single hospitals, and the remaining four trials were multicentre studies. The duration of trials varied from six to 20 months.One trial with 23 participants compared fluticasone with beclomethasone, and showed that fluticasone given at an equivalent dose was associated with a significant greater linear growth velocity (MD 0.81 cm/year, 95% CI 0.46 to 1.16, low certainty evidence). Three trials compared fluticasone with budesonide. Fluticasone given at an equivalent dose had a less suppressive effect than budesonide on growth, as measured by change in height over a period from 20 weeks to 12 months (MD 0.97 cm, 95% CI 0.62 to 1.32; 2 trials, 359 participants; moderate certainty evidence). However, we observed no significant difference in linear growth velocity between fluticasone and budesonide at equivalent doses (MD 0.39 cm/year, 95% CI -0.94 to 1.73; 2 trials, 236 participants; very low certainty evidence).Two trials compared inhalation devices. One trial with 212 participants revealed a comparable linear growth velocity between beclomethasone administered via hydrofluoroalkane-metered dose inhaler (HFA-MDI) and beclomethasone administered via chlorofluorocarbon-metered dose inhaler (CFC-MDI) at an equivalent dose (MD -0.44 cm/year, 95% CI -1.00 to 0.12; low certainty evidence). Another trial with 229 participants showed a small but statistically significant greater increase in height over a period of six months in favour of budesonide via Easyhaler, compared to budesonide given at the same dose via Turbuhaler (MD 0.37 cm, 95% CI 0.12 to 0.62; low certainty evidence).
AUTHORS' CONCLUSIONS
This review suggests that the drug molecule and delivery device may impact the effect size of ICS on growth in children with persistent asthma. Fluticasone at an equivalent dose seems to inhibit growth less than beclomethasone and budesonide. Easyhaler is likely to have less adverse effect on growth than Turbuhaler when used for delivery of budesonide. However, the evidence from this systematic review of head-to-head trials is not certain enough to inform the selection of inhaled corticosteroid or inhalation device for the treatment of children with persistent asthma. Further studies are needed, and pragmatic trials and real-life observational studies seem more attractive and feasible.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child, Preschool; Fluticasone; Growth; Humans; Metered Dose Inhalers; Randomized Controlled Trials as Topic; Time Factors
PubMed: 31194879
DOI: 10.1002/14651858.CD010126.pub2 -
The Cochrane Database of Systematic... Aug 2020Asthma 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...
BACKGROUND
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.
OBJECTIVES
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 beta-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'.
MAIN RESULTS
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 beta-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 beta-agonists (low-certainty evidence); and (6) the addition of anticholinergic therapy to short-acting beta-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.
AUTHORS' CONCLUSIONS
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 beta-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.
Topics: Acute Disease; Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aminophylline; Anti-Asthmatic Agents; Anti-Bacterial Agents; Asthma; Bias; Bronchodilator Agents; Child; Child, Preschool; Cholinergic Antagonists; Disease Progression; Helium; Humans; Infant; Length of Stay; Leukotriene Antagonists; Magnesium Sulfate; Nausea; Oxygen; Positive-Pressure Respiration; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Vomiting; Work of Breathing
PubMed: 32767571
DOI: 10.1002/14651858.CD012977.pub2