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Montelukast and Nasal Corticosteroids to Treat Pediatric Obstructive Sleep Apnea: A Systematic Review and Meta-analysis.
Liming, BJ, Ryan, M, Mack, D, Ahmad, I, Camacho, M
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2019;(4):594-602
Abstract
OBJECTIVE To systematically review the literature on anti-inflammatory medications for treating pediatric obstructive sleep apnea and perform meta-analysis of the available data. DATA SOURCES PubMed/MEDLINE and 4 additional databases. REVIEW METHODS Three authors independently and systematically searched through June 28, 2018, for studies that assessed anti-inflammatory therapy for treatment of pediatric obstructive sleep apnea (OSA). Data were compiled and analyzed using Review Manager 5.3 (Nordic Cochrane Centre). RESULTS After screening 135 studies, 32 were selected for review with 6 meeting inclusion criteria. In total, 668 patients aged 2 to 5 years met inclusion criteria for meta-analysis. Of these, 5 studies (166 children) that evaluated montelukast alone as treatment for pediatric OSA found a 55% improvement in the apnea-hypopnea index (AHI) (mean [SD] 6.2 [3.1] events/h pretreatment and 2.8 [2.7] events/h posttreatment; mean difference [MD] of -2.7 events/h; 95% confidence interval [CI], -5.6 to 0.3) with improvement in lowest oxygen saturation (LSAT) from 89.5 (6.9) to 92.1 (3.6) (MD, 2.2; 95% CI, 0.5-4.0). Two studies (502 children) observing the effects of montelukast with intranasal corticosteroids on pediatric OSA found a 70% improvement in AHI (4.7 [2.1] events/h pretreatment and 1.4 [1.0] events/h posttreatment; MD of -4.2 events/h; 95% CI, -6.3 to -2.0), with an improvement in LSAT from 87.8 (3.1) to 92.6 (2.2) (MD, 4.8; 95% CI, 4.5-5.1). CONCLUSIONS Treatment with montelukast and intranasal steroids or montelukast alone is potentially beneficial for short-term management of mild pediatric OSA.
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Inhaled short-acting bronchodilators for managing emergency childhood asthma: an overview of reviews.
Pollock, M, Sinha, IP, Hartling, L, Rowe, BH, Schreiber, S, Fernandes, RM
Allergy. 2017;(2):183-200
Abstract
International guidelines provide conflicting recommendations on how to use bronchodilators to manage childhood acute wheezing conditions in the emergency department (ED), and there is variation within and among countries in how these conditions are managed. This may be reflective of uncertainty about the evidence. This overview of systematic reviews (SRs) aimed to synthesize, appraise, and present all SR evidence on the efficacy and safety of inhaled short-acting bronchodilators to treat asthma and wheeze exacerbations in children 0-18 years presenting to the ED. Searching, review selection, data extraction and analysis, and quality assessments were conducted using methods recommended by The Cochrane Collaboration. Thirteen SRs containing 56 relevant trials and 5526 patients were included. Results demonstrate the efficacy of short-acting beta-agonist (SABA) delivered by metered-dose inhaler as first-line therapy for younger and older children (hospital admission decreased by 44% in younger children, and ED length of stay decreased by 33 min in older children). Short-acting anticholinergic (SAAC) should be added to SABA for older children in severe cases (hospital admission decreased by 27% and 74% when compared to SABA and SAAC alone, respectively). Continuous nebulization, addition of magnesium sulfate to SABA, and levosalbutamol compared to salbutamol cannot be recommended in routine practice.
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Intravenous magnesium sulfate for treating children with acute asthma in the emergency department.
Griffiths, B, Kew, KM
The Cochrane database of systematic reviews. 2016;(4):CD011050
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BACKGROUND Acute asthma in children can be life-threatening and must be treated promptly in the emergency setting. Intravenous magnesium sulfate is recommended by various guidelines for cases of acute asthma that have not responded to first-line treatment with bronchodilators and steroids. The treatment has recently been shown to reduce the need for hospital admission for adults compared with placebo, but it is unclear whether it is equally effective for children. OBJECTIVES To assess the safety and efficacy of intravenous magnesium sulfate (IV MgSO4) in children treated for acute asthma in the emergency department (ED). SEARCH METHODS We identified studies by searching the Cochrane Airways Review Group Specialised Register up to 23 February 2016. We also searched ClinicalTrials.gov and reference lists of other reviews, and we contacted study authors to ask for additional information. SELECTION CRITERIA We included randomised controlled trials of children treated in the ED for exacerbations of asthma if they compared any dose of IV MgSO4 with placebo. DATA COLLECTION AND ANALYSIS Two review authors screened the results of the search and independently extracted data from studies meeting the inclusion criteria. We resolved disagreements through discussion and contacted study authors in cases of missing data and other uncertainties relating to the studies.We analysed dichotomous data as odds ratios and continuous data as mean differences, both using fixed-effect models. We assessed each study for risk of bias and rated the quality of evidence for each outcome with GRADE and presented the results in a 'Summary of findings' table. There was insufficient evidence to conduct the planned subgroup analyses. MAIN RESULTS Five studies (182 children) met the inclusion criteria, and four contributed data to at least one meta-analysis. The included studies were overall at low risk of bias, but our confidence in the evidence was generally low, mainly due to the small sample sizes. Treatment with IV MgSO4 reduced the odds of admission to hospital by 68% (odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14 to 0.74; children = 115; studies = 3; I(2) = 63%). This result was based on data from just three studies including 115 children. Meta-analysis for the secondary outcomes was extremely limited by paucity of data. We performed meta-analysis for the outcome 'return to the emergency department within 48 hours', which showed a very imprecise effect estimate that was not statistically significant (OR 0.40, 95% CI 0.02 to 10.30; children = 85; studies = 2; I(2) = 0%). Side effects and adverse events were not consistently reported and meta-analysis was not possible, however few side effects or adverse events were reported. AUTHORS' CONCLUSIONS IV MgSO4 may reduce the need for hospital admission in children presenting to the ED with moderate to severe exacerbations of asthma, but the evidence is extremely limited by the number and size of studies. Few side effects of the treatment were reported, but the data were extremely limited.
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Can Vitamin D Supplementation in Addition to Asthma Controllers Improve Clinical Outcomes in Patients With Asthma?: A Meta-Analysis.
Luo, J, Liu, D, Liu, CT
Medicine. 2015;(50):e2185
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Effects of vitamin D on acute exacerbation, lung function, and fraction of exhaled nitric oxide (FeNO) in patients with asthma are controversial. We aim to further evaluate the roles of vitamin D supplementation in addition to asthma controllers in asthmatics. From 1946 to July 2015, we searched the PubMed, Embase, Medline, Cochrane Central Register of Controlled Trials, and ISI Web of Science using "Vitamin D," "Vit D," or "VitD" and "asthma," and manually reviewed the references listed in the identified articles. Randomized controlled trials which reported rate of asthma exacerbations and adverse events, forced expiratory volume in 1 s (FEV1, % of predicted value), FeNO, asthma control test (ACT), and serum 25-hydroxyvitamin D levels were eligible. We conducted the heterogeneities test and sensitivity analysis of the enrolled studies, and random-effects or fixed-effects model was applied to calculate risk ratio (RR) and mean difference for dichotomous and continuous data, respectively. Cochrane systematic review software Review Manager (RevMan) was used to test the hypothesis by Mann-Whitney U test, which were displayed in Forest plots. Seven trials with a total of 903 patients with asthma were pooled in our final studies. Except for asthma exacerbations (I2 = 81%, χ2 = 10.28, P = 0.006), we did not find statistical heterogeneity in outcome measures. The pooled RR of asthma exacerbation was 0.66 (95% confidence interval: 0.32-1.37), but without significant difference (z = 1.12, P = 0.26), neither was in FEV1 (z = 0.30, P = 0.77), FeNO (z = 0.28, P = 0.78), or ACT (z = 0.92, P = 0.36), although serum 25-hydroxyvitamin D was significantly increased (z = 6.16, P < 0.001). Vitamin D supplementation in addition to asthma controllers cannot decrease asthma exacerbation and FeNO, nor improve lung function and asthma symptoms, although it can be safely applied to increase serum 25-hydroxyvitamin D levels.
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Inhaled magnesium sulfate in the treatment of acute asthma.
Powell, C, Dwan, K, Milan, SJ, Beasley, R, Hughes, R, Knopp-Sihota, JA, Rowe, BH
The Cochrane database of systematic reviews. 2012;:CD003898
Abstract
BACKGROUND Asthma exacerbations can be frequent and range in severity from relatively mild to status asthmaticus. The use of magnesium sulfate (MgSO(4)) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO(4) has been demonstrated, little is known of the role of inhaled MgSO(4). OBJECTIVES To determine the efficacy of inhaled MgSO(4) administered in acute asthma on pulmonary functions and admission rates. SPECIFIC AIMS To quantify the effects of inhaled MgSO(4) i) in addition to inhaled β(2)-agonist, ii) in comparison to inhaled β(2)-agonist alone or iii) in addition to combination treatment with inhaled β(2) -agonist and ipratropium bromide. SEARCH METHODS Randomised controlled trials were identified from the Cochrane Airways Group register of trials in September 2012. These trials were supplemented with trials found in the reference list of published studies, studies found using extensive electronic search techniques, as well as a review of the grey literature and conference proceedings. SELECTION CRITERIA Randomised (or pseudo-randomised) controlled trials including adults or children with acute asthma were eligible for inclusion in the review. Studies were included if patients were treated with nebulised MgSO(4) alone or in combination with β(2)-agonist and/or ipratropium bromide and were compared with β(2)-agonist alone or inactive control. DATA COLLECTION AND ANALYSIS Trial selection, data extraction and risk of bias were assessed independently by two review authors. Efforts were made to collect missing data from authors. Results are presented as standardised mean differences (SMD) for pulmonary function and risk ratios (RR) for hospital admission; both are displayed with their 95% confidence intervals (CI). MAIN RESULTS Sixteen trials (21 references) of unclear and high risk of bias were eligible and included 896 patients who were randomised (838 patients completed). Seven of the 16 included studies involved adults exclusively, three included adults and paediatric patients, four studies enrolled paediatric patients and in the remaining two studies the age of participants was not stated.The design, definitions, intervention and outcomes were different in all 16 studies; this heterogeneity made direct comparisons difficult (see additional tables 1-3).The overall risk of bias among the included studies was variable and this is reflected in the 'Summary of findings' table with most outcomes being judged as only moderate or less.Inhaled magnesium sulfate in addition to inhaled β(2)-agonistThere was no statistically significant improvement in pulmonary function when inhaled MgSO(4) and β(2)-agonist was compared with β(2)-agonist alone (SMD 0.23; 95% CI -0.27 to 0.74; three studies, n = 188); however, there was considerable between study heterogeneity. There was no clear advantage in terms of hospital admissions (RR 0.76 95% CI 0.49, 1.16; four studies, n = 249), and there were no serious adverse events reported.Inhaled magnesium sulfate versus inhaled β(2)-agonistThe results of pulmonary function in three studies that compared inhaled MgSO(4) versus β(2)-agonist were too heterogeneous to combine; however, two of the studies found poorer lung function on MgSO(4). There was no significant difference in terms of hospital admissions in a single small study when MgSO(4) was compared to β(2)-agonist (RR 0.53 95% CI 0.05, 5.31; one study, n = 33), and there were no serious adverse events reported.Inhaled magnesium sulfate in addition to inhaled β(2)-agonist and ipratropiumA further comparison has been included in the 2012 update of this review of MgSO(4) given in addition to inhaled ipratropium and β(2)-agonist therapy (as recommended by the GINA guidelines). However, there is not yet enough data for this outcome to come to any definite conclusions, but both small studies in adults with severe asthma exacerbation found improvements in pulmonary function with additional inhaled MgSO(4). AUTHORS' CONCLUSIONS There is currently no good evidence that inhaled MgSO(4) can be used as a substitute for inhaled β(2)-agonists. When used in addition to inhaled β(2)-agonists (with or without inhaled ipratropium), there is currently no overall clear evidence of improved pulmonary function or reduced hospital admissions. However, individual study results from three trials suggest possible improved pulmonary function in those with severe asthma exacerbations (FEV1 less than 50% predicted). Heterogeneity among trials included in this review precludes a more definitive conclusion. Further studies should focus on inhaled MgSO(4) in addition to the current guideline treatment for acute asthma (inhaled β(2) -agonist and ipratropium bromide). As the evidence suggests that the most effective role of nebulised MgSO(4) may be in those with severe acute features and this is where future research should be focused. A set of core outcomes needs to be agreed upon both in adult and paediatric studies to allow improved study comparison in future.
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Airway obstruction lability helps distinguish levels of disease activity in asthma.
Greenberg, S, Liu, N, Kaur, A, Lakshminarayanan, M, Zhou, Y, Nelsen, LM, Smugar, SS, Noonan, G, Reiss, TF, Knorr, BA
Respiratory medicine. 2012;(4):500-7
Abstract
Classifying disease activity in asthma relies on clinical and physiological variables, but these variables do not capture all aspects of asthma that distinguish levels of disease activity. We used data from two pivotal trials of montelukast in asthma to classify disease activity as "high" or "low". We performed a principal component analysis (PCA) of disease activity using 21 efficacy outcome variables, including several novel derived outcome variables reflecting clinical and airway obstruction lability. Then we performed discriminant analysis (DA) based on disease activity classification. PCA revealed 6 factors (daytime asthma control, nighttime-predominant asthma control, airway obstruction, exacerbations, clinical lability, airway obstruction lability) that explained 76% of the variance between outcome variables. Although airway obstruction lability (comprising both diurnal variability in peak expiratory flow and diurnal variability in β-agonist use) accounted for only 6% of the explained variance in PCA, in DA it was more accurate (canonical coefficient 0.75) than traditional measures of asthma severity such as obstruction (-0.54) and daytime control (-0.56) in distinguishing between high and low disease activity. We conclude that airway obstruction lability, a parameter not typically captured in clinical trials, may contribute to more complete assessment of asthma disease activity and may define an emerging clinical target of future therapy.
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[What helps for persistent symptoms of asthma during inhalative steroid therapy?].
Kroegel, C
Deutsche medizinische Wochenschrift (1946). 2011;(42):2130
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Inter-country variations in anti-asthmatic drug prescriptions for children. Systematic review of studies published during the 2000-2009 period.
Bianchi, M, Clavenna, A, Bonati, M
European journal of clinical pharmacology. 2010;(9):929-36
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OBJECTIVE The objective of this study was to analyse inter-and intra-country quantitative and qualitative differences in anti-asthmatic prescriptions to children and adolescents. METHODS A literature search was performed in EMBASE and MEDLINE to identify pharmaco-epidemiological studies published from January 1, 2000 to December 31, 2008 in which anti-asthmatic prescription prevalence in out-hospital children was measured. A meta-analytic weighted average and 95% confidence intervals of prescription prevalences were calculated using a random-effect(s) model. Inter- and intra-country quantitative and, where possible, qualitative prescribing patterns were compared and assessed. RESULTS Twelve studies were identified (ten from Europe, one from Canada and one from the USA), but epidemiological indicators varied widely, and only eight were suitable for meta-analysis. The data from these studies revealed inter-country quantitative differences in prescription prevalences in the overall population CONCLUSIONS This first overall analysis of anti-asthmatic utilization studies in out-of-hospital children indicates a wide variability in anti-asthmatic prescription prevalence. It also reveals that epidemiological evaluations should be improved by using homogeneous indicators and, in order to validate the use of anti-asthmatic prescription as a proxy of disease, the diagnosis of asthma should accompany the data of prescriptions within the same population.
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Inhaled sodium cromoglycate for asthma in children.
van der Wouden, JC, Uijen, JH, Bernsen, RM, Tasche, MJ, de Jongste, JC, Ducharme, F
The Cochrane database of systematic reviews. 2008;(4):CD002173
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BACKGROUND Sodium cromoglycate has been recommended as maintenance treatment for childhood asthma for many years. Its use has decreased since 1990, when inhaled corticosteroids became popular, but it is still used in many countries. OBJECTIVES To determine the efficacy of sodium cromoglycate compared to placebo in the prophylactic treatment of children with asthma. SEARCH STRATEGY We searched the Cochrane Airways Group Trials Register (October 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007), MEDLINE (January 1966 to November 2007), EMBASE (January 1985 to November 2007) and reference lists of articles. We also contacted the pharmaceutical company manufacturing sodium cromoglycate. In 2007 we updated the review. SELECTION CRITERIA All double-blind, placebo-controlled randomised trials, which addressed the effectiveness of inhaled sodium cromoglycate as maintenance therapy, studying children aged 0 up to 18 years with asthma. DATA COLLECTION AND ANALYSIS Two authors independently assessed trial quality and extracted data. We pooled study results. MAIN RESULTS Of 3500 titles retrieved from the literature, 24 papers reporting on 23 studies could be included in the review. The studies were published between 1970 and 1997 and together included 1026 participants. Most were cross-over studies. Few studies provided sufficient information to judge the concealment of allocation. Four studies provided results for the percentage of symptom-free days. Pooling the results did not reveal a statistically significant difference between sodium cromoglycate and placebo. For the other pooled outcomes, most of the symptom-related outcomes and bronchodilator use showed statistically significant results, but treatment effects were small. Considering the confidence intervals of the outcome measures, a clinically relevant effect of sodium cromoglycate cannot be excluded. The funnel plot showed an under-representation of small studies with negative results, suggesting publication bias. AUTHORS' CONCLUSIONS There is insufficient evidence to be sure about the efficacy of sodium cromoglycate over placebo. Publication bias is likely to have overestimated the beneficial effects of sodium cromoglycate as maintenance therapy in childhood asthma.
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Inhaled corticosteroids versus sodium cromoglycate in children and adults with asthma.
Guevara, JP, Ducharme, FM, Keren, R, Nihtianova, S, Zorc, J
The Cochrane database of systematic reviews. 2006;(2):CD003558
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BACKGROUND Inhaled corticosteroids (ICS) and sodium cromoglycate (SCG) have become established as effective controller medications for children and adults with asthma, but their relative efficacy is not clear. OBJECTIVES To compare the relative effectiveness and adverse effects of ICS and SCG among children and adults with chronic asthma. SEARCH STRATEGY Systematic search of the Cochrane Airways Group's special register of controlled trials (to Feb. 2004), hand searches of the reference lists of included trials and relevant review papers, and written requests for identification of additional trials from pharmaceutical manufacturers. SELECTION CRITERIA Randomized controlled trials comparing the effect of ICS with SCG in children and adults with chronic asthma. DATA COLLECTION AND ANALYSIS All studies were assessed independently for eligibility by three review authors. Disagreements were settled by consensus. Trial authors were contacted to supply missing data or to verify methods. Eligible studies were abstracted and fixed- and random-effects models were implemented to pool studies. Separate analyses were conducted for paediatric and adult studies. Subgroup analyses and meta-regression models were fit to explore heterogeneity of lung function outcomes by type of RCT, category of ICS or SCG dosage, asthma severity of participants, and study quality on outcomes. MAIN RESULTS Of 67 identified studies, 17 trials involving 1279 children and eight trials involving 321 adults with asthma were eligible. Thirteen (76%) of the paediatric studies and six (75%) of the adult studies were judged to be high quality. Among children, ICS were associated with a higher final mean forced expiratory volume in 1 second [FEV1] (weighted mean difference [WMD] 0.07 litres, 95% confidence interval [CI] 0.02 to 0.11) and higher mean final peak expiratory flow rate [PEF] (WMD 17.3 litres/minute, 95% CI 11.3 to 23.3) than SCG. In addition, ICS were associated with fewer exacerbations (WMD -1.18 exacerbations per year, 95% CI -2.15 to - 0.21), lower asthma symptom scores, and less rescue bronchodilator use than SCG. There were no group differences in the proportion of children with adverse effects. Among adults, ICS were similarly associated with a higher mean final FEV1 (WMD 0.21 litres, 95% CI 0.13 to 0.28) and a higher final endpoint PEF (WMD 28.2 litres/minute, 95% CI 18.7 to 37.6) than SCG. ICS were also associated with fewer exacerbations (WMD -3.30 exacerbations per year, 95% CI -5.62 to -0.98), lower asthma symptom scores among cross-over trials but not parallel trials, and less rescue bronchodilator use than SCG. There were no differences in the proportion of adults with adverse effects. In subgroup analyses involving lung function measures, paediatric and adult studies judged to be of high quality had results consistent with the overall results. Lung function measures in children were higher in studies with medium BDP-equivalent steroid dosages than low BDP-equivalent dosages, while adult studies could not be compared by steroid dosage since they all incorporated similar dosages. There were no significant differences in lung function by the asthma severity of participants for adult or child studies. AUTHORS' CONCLUSIONS ICS were superior to SCG on measures of lung function and asthma control for both adults and children with chronic asthma. There were few studies reporting on quality of life and health care utilization, which limited our ability to adequately evaluate the relative effects of these medications on a broader range of outcomes. Although there were no differences in adverse effects between ICS and SCG, most trials were short and may not have been of sufficient duration to identify long-term effects. Our results support recent consensus statements in the U.S. and elsewhere that favour the use of ICS over SCG for control of persistent asthma.