-
1.
Comparative effectiveness of budesonide inhalation suspension and montelukast in children with mild asthma in Korea.
Shin, J, Oh, SJ, Petigara, T, Tunceli, K, Urdaneta, E, Navaratnam, P, Friedman, HS, Park, SW, Hong, SH
The Journal of asthma : official journal of the Association for the Care of Asthma. 2020;(12):1354-1364
Abstract
Objective: The comparative effectiveness of low-dose budesonide inhalation suspension (BIS) versus oral montelukast (MON) in managing asthma control among children with mild asthma was assessed in Korea.Methods: Claims from Korea's national health insurance database for children (2-17 years) with mild asthma (GINA 1 or 2) who initiated BIS or MON during 2015 were retrospectively analyzed. Pre- and post-index windows were 1 year each. Adherence, persistency, asthma control, asthma-related health-care resource utilization, and costs were evaluated using unadjusted descriptive statistics and propensity score-matched regression analyses.Results: The number of children identified was 26,052 for unmatched (n = 1,221 BIS; n = 24,831 MON) and 2,290 for matched populations (n = 1,145 per cohort). Medication adherence, measured by proportion of days covered, was low for both cohorts but significantly higher for MON versus BIS (13.8% vs. 4.5%; p < .001). Time to loss of persistency was longer for MON versus BIS (82.3 vs. 78.4 days, respectively; p < .001). Mean number of post-index asthma-related office visits was 6.6 for BIS versus 8.3 for MON (p < .001). However, a greater proportion of patients in the BIS cohort had an asthma exacerbation-related office visit than the MON cohort (78.3% vs. 56.1%; p < .001). Asthma-related total health-care costs were higher with MON versus BIS (₩ 190,185 vs. ₩ 167,432, respectively; p < .001), likely driven by higher pharmaceutical costs associated with MON (₩ 69,113 vs. ₩ 49,225; p < .001).Conclusions: Montelukast patients had better adherence, a longer time to loss of persistency, and were less likely to experience an exacerbation-related office visit in the post-index period than BIS patients.
-
2.
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.
-
3.
Anti-IL-5 monoclonal antibodies for the treatment of asthma: an update.
Walsh, GM
Expert opinion on biological therapy. 2020;(10):1237-1244
Abstract
INTRODUCTION Asthma exhibits marked heterogeneity in symptoms with severe or refractory asthma representing a clear area of unmet medical need. These patients require more specifically targeted treatments with monoclonal antibody-based biologics targeted at inhibition of the type 2 cytokines IL-4, IL-5 and IL-13 having considerable potential as effective treatments for severe asthma. For the most part, anti-cytokine-based biologic therapies are more likely to give significant clinical benefit in carefully selected patient populations that take asthma phenotypes and endotypes into account. AREAS COVERED This review is based on recent English-language original articles in Pub Med or MedLine that reported significant clinical findings on the current status, therapeutic potential and safety of the anti-IL-5 biologics mepolizumab, reslizumab and benralizumab in the treatment of severe refractory asthma. EXPERT OPINION Anti-IL-5 treatment appears effective in patients with eosinophilic asthma through exacerbation prevention with accumulating evidence of glucocorticoid-sparing effects with an acceptable safety profile for these biologics.
-
4.
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.
-
5.
Impact of Omalizumab on Food Allergy in Patients Treated for Asthma: A Real-Life Study.
Fiocchi, A, Artesani, MC, Riccardi, C, Mennini, M, Pecora, V, Fierro, V, Calandrelli, V, Dahdah, L, Valluzzi, RL
The journal of allergy and clinical immunology. In practice. 2019;(6):1901-1909.e5
Abstract
BACKGROUND The effects of omalizumab on food allergy thresholds have been little studied. OBJECTIVE To assess the real-life effects of omalizumab on food threshold tolerability in children treated for severe asthma. METHODS In this observational, real-life, efficacy study, we reviewed the food allergen thresholds of patients with severe asthma, as well as their immediate reactions to 2+ foods before and after a 4-month treatment with omalizumab. We also evaluated their control of asthma and their quality of life, as measured by Pediatric Quality of Life Inventory (PedsQL). RESULTS Fifteen children, allergic to 37 foods, were evaluated. Omalizumab induced an increase in the allergen threshold for milk, egg, wheat, and hazelnut from a mean 1012.6 ± 1464.5 mg protein to 8727 ± 6463.3 eliciting dose (P < .001). A total of 70.4% of subjects tolerated the complete challenge dose after 4 months of treatment with omalizumab. These foods were reintroduced in the patients' diet without the need for any oral immunotherapy procedures. The remaining foods were partially tolerated. The number of reactions to the unintended ingestion of allergenic foods over 4 months dropped from 47 to 2. The PedsQL increased from 61 ± 5.32 to 87 ± 7.33 (parental judgment; P < .001) and from 65 ± 7.39 to 90 ± 4.54 (patients' judgment; P < .001). The mean cost of omalizumab was €1311.63 per month. CONCLUSIONS During treatment with omalizumab for severe uncontrolled asthma, the food allergen threshold increases to 8.6 times its original value. The quality of life of patients also increased, due to a better asthma control and a reduction in dietary restrictions. The cost/benefit ratio of such treatment for selected cases of food allergy remains to be evaluated.
-
6.
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.
-
7.
Anti-IgE Significantly Changes Circulating Interleukin-25, Vitamin-D and Interleukin-33 Levels in Patients with Allergic Asthma.
Yalcin, AD, Uzun, R
Current pharmaceutical design. 2019;(35):3784-3795
Abstract
BACKGROUND Multi-center, randomized-controlled trials and observational studies have demonstrated that, in severe asthmatic patients receiving omalizumab treatment, the frequency of exacerbations, the number of urgent adverse events, and the need for oral steroids tend to decrease. MATERIALS AND METHODS This study included a total of 32 patients. The patients were divided into two groups as Group IA (pre-omalizumab) and Group IB (post-omalizumab). Serum IL-25 and IL-33 levels were measured and the number of emergency admissions, length of hospitalization (day), Asthma Control Test (ACT) scores, eosinophil cationic protein (ECP), and fractional exhaled nitric oxide (FeNO) value were analyzed. RESULTS ACT and FeNO values increased after omalizumab treatment, while IL-33, IL-25 levels decreased after the completion of omalizumab treatment. Furthermore, there was a weak, positive, and significant relationship between the changes in the ECP levels and IL-33 levels (r=0.38, p=0.03). CONCLUSION To the best of our knowledge, this is the first study to compare circulating IL-25 and IL-33 levels with specific IgE synthesis in the literature. Multivariate correlation analysis showed that the changes in serum IL-33 levels were significantly correlated with the changes in the mite sIgE levels and length of hospital stay (Fmodel=11.2, p=0.01, r2=0.45). On the other hand, there was no significant relationship between the other variables and changes in the IL-25 levels.
-
8.
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.
-
9.
Limitations of the results from randomized clinical trials involving intravenous and nebulised magnesium sulphate in adults with severe acute asthma.
Javor, E, Grle, SP
Pulmonary pharmacology & therapeutics. 2019;:31-37
Abstract
The role of intravenous (IV) or nebulised magnesium sulphate (MgSO4) in the treatment of severe acute asthma in adults is unclear. A controversy exists regarding its efficacy. In children MgSO4 has a more evident clinical effect, but the child population has not been considered in this work. The applicability of the results from randomized clinical trials (RCTs) involving MgSO4 in adult population is questioned in the optimal treatment of asthma exacerbations. According to the newest guidelines from the Global Initiative for Asthma (GINA), optimal treatment in the emergency department (ED) is based on short-acting beta2-agonists (SABA), oral or IV corticosteroids (CS), short acting muscarinic antagonists (SAMA) and the controlled oxygen therapy. Further improvements with IV or nebulised MgSO4 were assessed in a recent large multicentre, double-blind, placebo-controlled randomized 3 Mg trial, which failed to demonstrate clinical benefit. Several other RCTs found some benefit with MgSO4, although the majority lacked some treatment options that are used in the optimal treatment of asthma exacerbations. Therefore, we reviewed the limitations of RCTs of IV or nebulised MgSO4 in adults with acute asthma, with the aim to answer in which subpopulation MgSO4 could be beneficial.
-
10.
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.