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Magnesium sulfate vs aminophylline as a second line of treatment in children with severe acute asthma. Randomized clinical trial.
Kassisse, E, Jiménez, J, Mayo, N, Kassisse, J
Andes pediatrica : revista Chilena de pediatria. 2021;(3):367-374
Abstract
INTRODUCTION Second-line drugs for acute asthma, such as salbutamol, magnesium sulfate, and aminophylline, are generally intravenously administered. OBJECTIVE To compare the efficacy and safety of using mag nesium sulfate or aminophylline in children who did not respond to initial treatment. PATIENTS AND METHOD Randomized clinical trial. Children who did not improve the Modified Pulmonary Index Score (mPSI) receive at random magnesium sulfate (50 mg/kg/single dose) or aminophylline (5 mg/ kg/dose followed by continuous infusion at 1 mg/kg/hour for 3 hours). Primary endpoints were changes in mPSI and oxygen saturation; secondary endpoints: hospitalization rate, need for transfer to the intensive care unit, use of a third intervention, and adverse effects. RESULTS 131 patients were studied (66 patients in the aminophylline group and 65 MgSO4). The mean age was 5 ± 2.3 years, the demographic and clinical parameters did not differ between the groups. In the group that received magnesium sulfate, the mPSI and oxygen saturation changed significantly in favor from 13.1 ± 1.3 to 4.9 ± 2.5 (p < 0.001) and from 3.3 ± 2.5; (p 0.021), respectively, and their risk of hospital admission (RR 0.68 95% CI [0.56, 0.82]) and of secondary failure (0.16 95% CI 95% [0 , 07; 0.38]) decreased. Only one adverse event (tachycardia) was recorded. CONCLUSION The administration of a single dose of magnesium sulfate proved to be more effective and safe than the use of aminophylline as a second- line drug.
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Association Between Intravenous Magnesium Therapy in the Emergency Department and Subsequent Hospitalization Among Pediatric Patients With Refractory Acute Asthma: Secondary Analysis of a Randomized Clinical Trial.
Schuh, S, Freedman, SB, Zemek, R, Plint, AC, Johnson, DW, Ducharme, F, Gravel, J, Thompson, G, Curtis, S, Stephens, D, et al
JAMA network open. 2021;(7):e2117542
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Abstract
IMPORTANCE Despite guidelines recommending administration of intravenous (IV) magnesium sulfate for refractory pediatric asthma, the number of asthma-related hospitalizations has remained stable, and IV magnesium therapy is independently associated with hospitalization. OBJECTIVE To examine the association between IV magnesium therapy administered in the emergency department (ED) and subsequent hospitalization among pediatric patients with refractory acute asthma after adjustment for patient-level variables. DESIGN, SETTING, AND PARTICIPANTS This post hoc secondary analysis of a double-blind randomized clinical trial of children with acute asthma treated from September 26, 2011, to November 19, 2019, at 7 Canadian tertiary care pediatric EDs was conducted between September and November 2020. In the randomized clinical trial, 816 otherwise healthy children aged 2 to 17 years with Pediatric Respiratory Assessment Measure (PRAM) scores of 5 points or higher after initial therapy with systemic corticosteroids and inhaled albuterol with ipratropium bromide were randomly assigned to 3 nebulized treatments of albuterol plus either magnesium sulfate or 5.5% saline placebo. EXPOSURES Intravenous magnesium sulfate therapy (40-75 mg/kg). MAIN OUTCOMES AND MEASURES The association between IV magnesium therapy in the ED and subsequent hospitalization for asthma was assessed using multivariable logistic regression analysis. Analyses were adjusted for year epoch at enrollment, receipt of IV magnesium, PRAM score after initial therapy and at ED disposition, age, sex, duration of respiratory distress, previous intensive care unit admission for asthma, hospitalizations for asthma within the past year, atopy, and receipt of oral corticosteroids within 48 hours before arrival in the ED, nebulized magnesium, and additional albuterol after inhaled magnesium or placebo, with site as a random effect. RESULTS Among the 816 participants, the median age was 5 years (interquartile range, 3-7 years), 517 (63.4%) were boys, and 364 (44.6%) were hospitalized. A total of 215 children (26.3%) received IV magnesium, and 190 (88.4%) of these children were hospitalized compared with 174 of 601 children (29.0%) who did not receive IV magnesium. Multivariable factors associated with hospitalization were IV magnesium receipt from 2011 to 2016 (odds ratio [OR], 22.67; 95% CI, 6.26-82.06; P < .001) and from 2017 to 2019 (OR, 4.19; 95% CI, 1.99-8.86; P < .001), use of additional albuterol (OR, 5.94; 95% CI, 3.52-10.01; P < .001), and increase in PRAM score at disposition (per 1-U increase: OR, 2.24; 95% CI, 1.89-2.65; P < .001). In children with a disposition PRAM score of 3 or lower, receipt of IV magnesium therapy was associated with hospitalization (OR, 8.52; 95% CI, 2.96-24.41; P < .001). CONCLUSIONS AND RELEVANCE After adjustment for patient-level characteristics, receipt of IV magnesium therapy after initial asthma treatment in the ED was associated with subsequent hospitalization. This association also existed among children with mild asthma at ED disposition. Evidence of a benefit of IV magnesium regarding hospitalization may clarify its use in the treatment of refractory pediatric asthma. TRIAL REGISTRATION ClinicalTrials.gov: NCT01429415.
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The Montelukast Therapy in Asthmatic Children with and without Food Allergy: Does It Make Any Difference?
Sahiner, UM, Arik Yilmaz, E, Fontanella, S, Haider, S, Soyer, O, Custovic, A, Kalayci, O, Sackesen, C
International archives of allergy and immunology. 2021;(12):1212-1221
Abstract
INTRODUCTION Children with food allergy are at increased risk for asthma and asthma morbidity. Since leukotrienes are implicated in the pathogenesis of both asthma and probably in food allergies, we hypothesized that asthmatic children with concomitant food allergy may have a favorable response to antileukotriene treatment. METHODS Asthmatic children aged 6-18 years with and without food allergy were treated with montelukast and placebo in a double-blind, placebo-controlled cross-over parallel-group study. The primary outcome of the study was improvement in FEV1%. Asthma control tests, spirometry and methacholine challenges were performed as well as Fractional Exhaled Nitric Oxide (FeNO) levels. PGD2, CystLT, and lipoxin levels were measured in exhaled breath condensate (EBC). RESULTS A total of 113 children were enrolled and 87 completed the study in accordance with the protocol. At baseline, children with food allergy and asthma (FAA) had higher levels of PGD2 and CysLT levels in the EBC than children with asthma alone (AA) (p < 0.001 for each). In the montelukast arm, although FEV1% was significantly higher in the FAA group compared to AA (p = 0.005), this effect was linked to the baseline difference of FEV1% between both arms. Montelukast treatment failed to improve FEV1% in both groups compared to the placebo. No effect of montelukast was observed in the remaining study parameters. CONCLUSION Although children with FAA do not show a more favorable response to montelukast treatment compared to AA, a significant difference between baseline PGD2 and CystLT levels between FAA and AA groups may point to a different endotype of childhood asthma.
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Characterising a Weight Loss Intervention in Obese Asthmatic Children.
Eslick, S, Jensen, ME, Collins, CE, Gibson, PG, Hilton, J, Wood, LG
Nutrients. 2020;(2)
Abstract
The prevalence of obesity in asthmatic children is high and is associated with worse clinical outcomes. We have previously reported that weight loss leads to improvements in lung function and asthma control in obese asthmatic children. The objectives of this secondary analysis were to examine: (1) changes in diet quality and (2) associations between the baseline subject characteristics and the degree of weight loss following the intervention. Twenty-eight obese asthmatic children, aged 8-17 years, completed a 10-week diet-induced weight loss intervention. Dietary intake, nutritional biomarkers, anthropometry, lung function, asthma control, and clinical outcomes were analysed before and after the intervention. Following the intervention, the body mass index (BMI) z-score decreased (Δ = 0.18 ± 0.04; p < 0.001), %energy from protein increased (Δ = 4.3 ± 0.9%; p = 0.002), and sugar intake decreased (Δ = 23.2 ± 9.3 g; p= 0.025). Baseline lung function and physical activity level were inversely associated with Δ% fat mass. The ΔBMI z-score was negatively associated with physical activity duration at baseline. Dietary intervention is effective in achieving acute weight loss in obese asthmatic children, with significant improvements in diet quality and body composition. Lower lung function and physical engagement at baseline were associated with lesser weight loss, highlighting that subjects with these attributes may require greater support to achieve weight loss goals.
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Airway mechanics after withdrawal of a leukotriene receptor antagonist in children with mild persistent asthma: Double-blind, randomized, cross-over study.
Kim, JH, Lee, S, Shin, YH, Ha, EK, Lee, SW, Kim, MA, Yoon, JW, Baek, HS, Choi, SH, Han, MY
Pediatric pulmonology. 2020;(12):3279-3286
Abstract
BACKGROUND To determine the response of airway mechanics and the changes in asthma symptoms to stepping down of leukotriene receptor antagonist (LTRA) therapy. METHODS Thirty children (mean age: 7.1 years) with mild, well-controlled, and persistent asthma who took LTRA as maintenance treatment were randomized into a double-blind, placebo-controlled, cross-over study. Each group received an LTRA (montelukast) or placebo daily for 2 weeks, followed by a 1-week washout period, and then the alternate treatment for 2 weeks. Spirometry and impulse oscillation system (IOS) measurements before and after four puffs of salbutamol inhalation, fractional exhaled nitric oxide (FeNO), and the childhood asthma control test (C-ACT) were evaluated at baseline, the end of placebo treatment, and the end of LTRA treatment. RESULTS Changes of FEV1 /FVC (p = .113) and FEV1 (p = .109) from baseline to posttreatment did not differ significantly between the placebo and montelukast groups. In the placebo group, prebronchodilator (pre-) FEV1 /FVC was decreased (83% vs. 86%) and bronchodilator response (BDR) in FEV1 was diminished (10.7% vs. 6.4%) at posttreatment compared with baseline. However, the montelukast group had no significant changes in pre-FEV1 /FVC (p = .865) and BDR in FEV1 (p = .461). In addition, compared with the montelukast group, the placebo group showed no significant changes in Rrs5 (total airway resistance), Rrs5-20 (peripheral airway resistance), FeNO, and symptoms by the C-ACT. CONCLUSION In children with well-controlled mild persistent asthma, changes in spirometry, IOS, FeNO, and C-ACT results did not differ between the placebo and montelukast groups within 2 weeks.
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Does a tailored intervention to promote adherence in patients with chronic lung disease affect exacerbations? A randomized controlled trial.
Gregoriano, C, Dieterle, T, Breitenstein, AL, Dürr, S, Baum, A, Giezendanner, S, Maier, S, Leuppi-Taegtmeyer, A, Arnet, I, Hersberger, KE, et al
Respiratory research. 2019;(1):273
Abstract
BACKGROUND Poor medication-adherence is common in chronic lung patients, resulting in reduced health-outcomes and increased healthcare-costs. This study aimed to investigate the impact of an acoustic reminder and support calls on adherence to inhaled therapy in asthma and COPD patients and to determine their effect on exacerbations. METHODS This single-blinded randomized controlled trial investigated asthma and COPD patients during 6 months in an ambulatory setting. The intervention consisted of daily alarm clock and support phone calls, whenever use of rescue medication doubled or inhaled medication was not taken as prescribed. Primary outcome was time to next exacerbation. Frequency of exacerbations, adherence to inhaled medication and quality of life scores were secondary outcomes. Cox and Poisson regression were used to determine intervention effect on time to exacerbation and frequency of exacerbations, respectively. RESULTS Seventy-five participants were assigned to the intervention group and 74 to usual follow-up care. During a median follow-up of 6.2 months, 22 and 28% in the intervention and control groups respectively, experienced at least one exacerbation. Intervention had no effect on time to first exacerbation (HR 0.65, 95% CI 0.21 to 2.07, P = .24), but showed a trend toward a 39% decreased frequency of exacerbations (RR = 0.61, 95% CI 0.35 to 1.03, P = .070) for the adjusted models, respectively. The intervention group had significantly more days with 80-100% taking adherence regarding puff inhalers (82 ± 14% vs. 60 ± 30%, P < .001) and dry powder capsules (90 ± .10% vs. 80 ± 21%, P = .01). Timing adherence in participants using puff inhalers was higher in the intervention group (69 ± 25% vs. 51 ± 33%, P < .001). No significant differences in QoL were found between the two groups. CONCLUSION Participants assigned to the intervention group had significantly better taking and timing adherence of inhaled medication resulting in a trend towards a decreased frequency of exacerbations. However, no effect on time to next exacerbation was observed. TRIAL REGISTRATION ClinicalTrials.gov: NCT02386722, Registered 14 February 2014.
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Comparison between montelukast and tiotropium as add-on therapy to inhaled corticosteroids plus a long-acting β2-agonist in for patients with asthma.
Hoshino, M, Akitsu, K, Ohtawa, J
The Journal of asthma : official journal of the Association for the Care of Asthma. 2019;(9):995-1003
Abstract
Objective: Asthma often remains uncontrolled despite treatment with inhaled corticosteroids (ICS) alone or with ICS plus a long-acting β2-agonist (LABA). The recommended alternative is the addition of either montelukast or tiotropium. The aim of this study was to compare the effects of montelukast and tiotropium on airway inflammation and remodeling in persistent asthma. Methods: Eighty-seven patients with asthma were treated with budesonide and formoterol (640/18 μg); then, the patients were randomly allocated to three groups to receive oral montelukast (10 mg/day), inhaled tiotropium (5 μg/day), or no add-on to the maintenance therapy for 48 weeks. Fractional exhaled nitric oxide (FeNO) and pulmonary function were measured, and quantitative computed tomography was performed. Results: Compared to the maintenance therapy, add-on montelukast significantly decreased FeNO (p < 0.05) and improved airflow obstruction (p < 0.05), whereas airway dimensions remained unchanged. Changes in FeNO were significantly correlated with changes in FEV1 (r = -0.71, p < 0.001). In contrast, the addition of tiotropium significantly decreased airway wall area corrected for body surface area (WA/BSA) (p < 0.05), decreased wall thickness (T/√BSA) (p < 0.05) and improved airflow obstruction (p < 0.05) with no change in FeNO. Changes in WA/BSA and T/√BSA were significantly correlated with the change in percentage predicted FEV1 (r = -0.84, p < 0.001 and r = -0.59, p < 0.01, respectively). Conclusions:Adding either montelukast or tiotropium to ICS/LABA may provide additive benefits with respect to the pulmonary function and airway inflammation or remodeling in patients with asthma.
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Exercise training as an adjunctive therapy to montelukast in children with mild asthma: A randomized controlled trial.
Zhang, YF, Yang, LD
Medicine. 2019;(2):e14046
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BACKGROUND This study investigated the effectiveness and safety of exercise training (ET) as an adjunctive therapy to montelukast for children with mild asthma (MA). METHODS A total of 72 children, ages 4 to 12 years with MA were randomly assigned to a treatment group or a control group at a ratio of 1:1. The subjects in the treatment group received ET plus montelukast, while the participants in the control group received montelukast alone. The primary endpoint was lung function, as measured by forced expiratory volume in 1 second (FEV1) and ratio between FEV1 and forced vital capacity (FEV1/FVC). The secondary endpoints included the symptom improvements, as measured by clinical assessment score, and quality of life (QoL), as assessed with Paediatric Allergic Disease Quality of Life Questionnaire (PADQLQ) scores. In addition, adverse events were also assessed during the period of this study. All outcomes were measured at baseline, at the end of 6-week treatment and 2-week follow-up after the treatment. RESULTS After 6-week treatment and 2-week follow-up, although ET plus montelukast did not show better effectiveness in improving lung function, as evaluated by the FEV1 (P > .05) and FEV1/FVC (P > .05) than montelukast alone, significant relief in clinical symptoms (P < .01), and improvement in QoL (P < .01) have achieved. Additionally, both groups had similar safety profile. CONCLUSION The results of this study showed that ET as an adjunctive therapy to montelukast may benefit for children with MA. Further studies are still needed to warrant the results of this study.
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Predictive role of IL-17A/IL-10 ratio in persistent asthmatic patients on vitamin D supplement.
Shabana, MA, Esawy, MM, Ismail, NA, Said, AM
Immunobiology. 2019;(6):721-727
Abstract
Asthma is an airway inflammatory disorder. Vitamin (Vit) D is a potent immuno-modulator. It suppresses Interleukin (IL)-17 and induces IL-10. This study aims to investigate the role of IL-17A and IL-10 in predicting asthma control in case of Vit D supplementation. Seventy-nine patients enrolled in this study (42 patients received Vit D supplement and 37 patients did not receive the supplement). The enrolled patients were assessed at the beginning of this study and after 3 months. At the end of the study, there was a significant improvement in pulmonary function parameters in the Vit D supplemented group when compared to both the baseline values and the non-supplemented group. There was a significant decrease in serum IL-17A levels and a significant increase in serum IL-10 levels in comparison with the baseline values (p < 0.0001). The highest correlation of FEV1% improvement percentage was associated with the baseline IL-17A/IL-10 ratio (r = 0.65; p < 0.0001). The IL-17A/IL-10 ratio at a cutoff ≥ 2.66 had a sensitivity of 72.2% and a specificity of 83.3%. The IL-17A/IL-10 ratio had an adjusted odds ratio = 4.66 (p = 0.04). Vit D supplementation reduces the serum IL-17A levels and elevates the serum IL-10 levels in persistent asthmatic patients. So, Vitamin D can be used as an adjunct therapy side by side with the conventional asthma therapy. The IL-17A/IL-10 ratio seems to be a possible predictive biomarker for asthma improvement in patients depending on Vit D supplementation.
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A randomized, double-blinded, placebo-controlled study of the use of viscous oral cromolyn sodium for the treatment of eosinophilic esophagitis.
Lieberman, JA, Zhang, J, Whitworth, J, Cavender, C
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2018;(5):527-531
Abstract
BACKGROUND There is a need for effective, nonsteroid pharmacologic therapies for eosinophilic esophagitis (EoE). Cromolyn sodium offers an option because mast cells have been implicated in the symptomatology of EoE and cromolyn has been shown to have some anti-eosinophilic properties. OBJECTIVE To evaluate the efficacy of cromolyn in decreasing esophageal eosinophilia in patients with EoE. Secondary outcomes included symptom improvement and adverse effects. METHODS We conducted a randomized, double-blinded, placebo-controlled trial of viscous oral cromolyn for EoE in pediatric patients. Subjects were randomized to 100 mg (2-11 years of age) or 200 mg (12-17 years of age) of cromolyn or placebo 4 times daily. The medications were mixed with powdered sugar at home to make them viscous. RESULTS Sixteen subjects (50% boys, median age 11.4 years) were enrolled. Nine were randomized to cromolyn and 7 were randomized to placebo. Cromolyn decreased the peak eosinophil count from 62.1 to 57.3 eosinophils per high-powered field (P = .78) and placebo decreased the peak eosinophil count from 87.0 to 71.3 eosinophils per high-powered field (P = .62) One subject randomized to cromolyn and none in the placebo arm had complete resolution of eosinophilia. Cromolyn decreased symptoms scores from a mean baseline score of 37.8 to a mean post-therapy score of 17.5, which was a 54% decrease (P = .04). Placebo decreased the symptom scores from a baseline score of 32.2 to a post-therapy score of 23.3, which was a 28% decrease (P = .05). CONCLUSION Cromolyn, when mixed into a viscous preparation, did not significantly decrease esophageal eosinophilia. However, it did decrease symptom scores (although not significantly more than placebo) and led to complete resolution in 1 subject.