Dynamics of nasal transcriptomics during step-up treatment in children with uncontrolled asthma.

Uncontrolled asthma can occur in children receiving low dose inhaled corticosteroids, but evidence to guide step-up treatment is currently lacking. In this study, 182 children (6–17 years of age) with...

To identify the best step-up pharmacologic treatment in patients with uncontrolled asthma despite inhaled corticosteroid (ICS) use.The study included 8,168 patients (5,381 individual participant data and 2,787 aggregate data) whose data were provided from randomized clinical trials that included participants age < 18 years with poorly controlled asthma on ICS alone.The study is a systematic review and meta-analysis using individual participant data and additional aggregate data from randomized clinical trials that compared at least 2 asthma interventions of interest between the period of July 1, 2014 and May 5, 2023. Meta-analyses and meta-regression analysis were used to determine potential effect modifiers. The primary outcomes were defined as exacerbation and asthma control. Secondary outcomes included forced expiratory volume, quality of life, mortality, adverse events, and hospital admissions. Potential treatment effect modifiers were evaluated, including age, sex, ethnicity, eczema, eosinophilia, and baseline asthma severity. Specific treatment options analyzed included ICS (low, medium, or high dose), ICS + LABA (long-acting β2-agonists), ICS + LTRA (leukotriene receptor antagonists), LTRA alone, theophylline, and placebo.For a child with poorly controlled asthma despite treatment with ICS, the odds of an asthma exacerbation were reduced by stepping up to a medium dose ICS + LABA as compared with a low dose ICS. Lung function tests indicate that medium-dose ICS plus LABA is superior compared with any dose of ICS without LABA and low-dose ICS with LABA. Finally, low or high-dose ICS + LABA were associated with increased odds of asthma control versus LTRA monotherapy.Medium-dose ICS + LABA is recommended as step-up therapy in patients with uncontrolled asthma on low-dose ICS therapy.Many factors contribute to poor asthma control, and it behooves the clinician to troubleshoot why recommended therapies are unsuccessful before changing the treatment plan. In many cases, however, despite the optimization of inhaled therapies, patients with asthma will require, at least transiently, a “step-up” in therapy. As national guidelines differ, this article provides helpful insight into best practices for step-up therapy in children and adolescents.

Eczema and race as combined determinants for differential response to step-up asthma therapy

CS Murray. M Thomas. K Richardson. DB Price. SW Turner. J Allergy Clin Immunol Pract. 2017;5(4):1082–1090.e7 Current guidelines offer a number of different choices for step-up treatment of uncontrolled asthma in children on low-dose inhaled corticosteroids (ICSs). In this study, the authors compared the relative effectiveness of step-up treatment to fixed-dose combination (FDC) ICSs and long-acting β2-agonists as opposed to an increased dose of inhaled corticosteroids (i-ICSs) or adding a leukotriene receptor antagonist (LTRA). This matched cohort study included children with uncontrolled persistent asthma aged 5 to 12 years from 2 UK primary-care databases who were receiving …

There is no clear preferential option for initial step-up of treatment for children with uncontrolled asthma on inhaled corticosteroid. Evaluate the clinical effectiveness of pharmacological treatments to use in children with uncontrolled asthma on inhaled corticosteroid; identify and evaluate the potential for treatment effect modification to optimise treatment delivery; assess the cost-effectiveness of treatments. Systematic review and individual participant data network meta-analysis. Studies were eligible if they were parallel or crossover randomised controlled trials comparing at least one of the pharmacological treatments of interest in participants aged < 18 years with uncontrolled asthma on any dose inhaled corticosteroid alone. We searched MEDLINE®, Cochrane Library, Cochrane Central Register of Controlled Trials, EMBASE, National Institute for Health and Care Excellence Technology Appraisals, and the National Institute for Health and Care Research Health Technology Assessment series. Primary outcomes: exacerbation and asthma control. Secondary outcomes: health-related quality of life, mortality, forced expiratory volume in 1 second, adverse events, hospital admissions, symptoms (not analysed). We assessed the Risk Of Bias using the Cochrane Risk Of Bias tool and carried out Bayesian meta-analyses, network meta-analysis and network meta-regression, including treatment by covariate (age, sex, ethnicity, eczema, eosinophilia, asthma severity) interactions. A Markov decision-analytic model with a 12-month time horizon, which adopted the perspective of the National Health Service and Personal Social Services in the United Kingdom, was developed to compare alternative treatments. Cost-effectiveness was based on incremental costs per quality-adjusted life-years gained, with uncertainty considered in one-way, structural and probabilistic sensitivity analyses. We identified and screened 4708 publications from the search and confirmed 144 randomised controlled trials as eligible. We obtained individual participant data from 29 trials (5381 participants) and extracted limited aggregate data from a further 19 trials. The majority of trials had low risk of bias. The network meta-analysis suggests that medium-dose inhaled corticosteroid + long-acting β2-agonist is the preferred treatment for reducing odds of exacerbation [odds ratio 95% credibility interval: 0.43 (0.20 to 0.92) vs. low-dose inhaled corticosteroid; 40 studies, 8168 patients] and increasing forced expiratory volume in 1 second [mean difference 95% credibility interval: 0.71 (0.35 to 1.06) vs. low-dose inhaled corticosteroid; 23 studies, 2518 patients] while leukotriene receptor antagonist alone is the least preferred. No clear differences were found for asthma control (16 studies, 3027 patients). Limited pairwise analyses suggest some improvement in health-related quality of life for medium-dose inhaled corticosteroid versus inhaled corticosteroid + long-acting β2-agonist [two studies, paediatric asthma quality of life questionnaire, mean difference 95% credibility interval: 0.91 (0.29 to 1.53)]. The rate of hospitalisation due to an asthma attack ranged from 0.5% to 2.7% of patients across five trials. Slightly fewer patients reported neurological disorders (mild/moderate) on inhaled corticosteroid + long-acting β2-agonist versus inhaled corticosteroid + leukotriene receptor antagonist [odds ratio 95% confidence interval: 0.09 (0.01 to 0.82), one study]. There were no deaths recorded. We did not find convincing, consistent evidence to suggest that age, sex, ethnicity, eczema, eosinophilia, asthma severity would be regarded as an effect modifier. The economic analysis indicated that low-dose inhaled corticosteroid was the most cost-effective treatment option while medium-dose inhaled corticosteroid (alone and + long-acting β2-agonist) was associated with the highest number of quality-adjusted life-years, but their incremental cost-effectiveness exceeded the National Institute for Health and Care Excellence threshold. Medium-dose inhaled corticosteroid + long-acting β2-agonist is recommended for children with asthma that is uncontrolled on inhaled corticosteroid alone; leukotriene receptor antagonist alone should be avoided. We could not include data from 67% of the eligible trials, conclusions should therefore be viewed with some caution. This study is registered as PROSPERO CRD42019127599. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/110/16) and is published in full in Health Technology Assessment; Vol. 29, No. 15. See the NIHR Funding and Awards website for further award information.

Objective The aim of the present study was to determine the cost-utility of single inhaler combination inhaled corticosteroid and a long-acting β2-agonist (ICS/LABAs) as both maintenance and reliever (SMART) compared with a step-up maintenance treatment with a fixed medium to high dose of ICS combined with LABA and a short-acting β2-agonist (SABA) as reliever (ICS-LABA maintenance plus SABA) among patients aged 12 years or more with poorly controlled asthma in Colombia. Methods A Markov-type model was developed to estimate the costs and health outcomes of a simulated cohort of patients aged 12 years or more with uncontrolled asthma treated for 12 months. The main effectiveness data were obtained from a recent meta-analysis. The main outcome was the variable ‘‘quality-adjusted life-years’’ (QALYs). Results The base-case analysis showed that the budesonide/formoterol (BUD/FORM) SMART strategy was associated with lower overall treatment costs (US $3,062.37 vs. $4,462.02 average cost per patient over 12 months) and the greatest gain in QALYs (0.8511 vs. 0.8258 QALYs on average per patient over 12 months) compared with ICS-LABA maintenance plus SABA at step 4, thus leading to dominance. Conclusions In patients aged 12 years or more with uncontrolled asthma at GINA step 3 or 4, the BUD/FORM SMART strategy at either step 3 or 4 is cost-effective compared with the ICS-LABA maintenance plus SABA at step 4 strategy, because it shows a greater gain in QALYs at lower total treatment costs.

IntroductionAsthma affects millions of children worldwide—1.1 million children in the UK. Asthma symptoms cannot be cured but can be controlled with low-dose inhaled corticosteroids (ICSs) in the majority of individuals....

ObjectivesAround 10–15% of children do not achieve adequate asthma control when using low-dose inhaled corticosteroids (ICS). When asthma exacerbations occur, treatment involves add-on preventer therapies, although there is uncertainty concerning...

<b>Aim:</b> Delivering optimal asthma care is a challenge in primary care setting. This study aimed to examine current asthma care provided to patients attending six public primary care clinics in the Klang District, Malaysia. <b>Methods:</b> All children (5-17years old), and adults (≥18years old) with physician-diagnosed asthma or who had been given asthma treatment in the previous year were recruited between June2019-January2020. <b>Results:</b> 1, 280 patients were recruited (15% children). The majority (76%) fell into the low household income group (&lt;USD1196). Only 7% of adults and 4% of children had spirometry done at diagnosis. Based on GINA 2017 criteria, 34% adults had good asthma control, 37% and 29% had partly and uncontrolled asthma. In children, 54% had good control, 32% partly controlled and 14% had uncontrolled asthma. 81% of adults and 67% of children reported using inhaled controller in the last 12-months. Only a third of adults (71%) and children (70%) had scheduled follow-up visits. More than 90% (adults and children) had received some form of asthma education, however asthma diary and provision of an asthma action plan (AAP) were least emphasised. Only 14% of adults reported being given AAP and 39% had an asthma diary; in children these proportions were 28% and 50% respectively. <b>Conclusion:</b> Although many patients having used controller medication in 12-months’, most do not have good control suggesting failure to step-up treatment and/or poor adherence. Supported self-management for asthma remains under-utilised. Interventions need to target practices, healthcare professionals and patients to improve asthma management.

<b>Background:</b> In patients with uncontrolled, moderate to severe asthma despite treatment with medium-dose ICS/LABA, GINA recommends to increase the dose of ICS to high-dose (HD) ICS/LABA or to add a LAMA on top of medium-dose (MD) ICS/LABA. <b>Methods:</b> We conducted a retrospective cohort study using healthcare data from 3 GP databases: IPCI (NL), HSD (IT) and CPRD GOLD (UK) and one prescription database: Aarhus (DK). We identified adult asthma patients from Jan 2010 to April 2020, treated with&nbsp;MD ICS/LABA for at least 3 months and receiving treatment step-up. <b>We investigated determinants of choice</b> of&nbsp;MD ICS/LABA+LAMA versus&nbsp;HD ICS/LABA. <b>Results:</b> 6,126 patients were stepped up to&nbsp;MD ICS/LABA+LAMA and 18,947 patients to&nbsp;HD ICS/LABA.&nbsp;MD ICS/LABA+LAMA was more often prescribed to older patients, concomitant COPD, gastro-esophageal reflux disease (GERD), exacerbations in previous year and current or past smoking, and less to patients with atopic disorders (table 1, meta-analysis of database results). <b>Conclusion:</b> In patients with uncontrolled asthma on&nbsp;medium dose ICS/LABA, step-up with add-on LAMA was more likely than step-up to HD ICS/LABA in case of older age, current smoking, a history of asthma exacerbations and a concomitant diagnosis of COPD.

AimsGuidelines recommend that asthma patients with elevated biomarkers of T2 inflammation, and who have repeated exacerbations, be considered for add-on biologic treatment. In previous clinical trials, we have shown that...

Tweetable abstractUsing medium-dose inhaled corticosteroids (ICS) with long-actingβ2-agonists reduces the odds of exacerbation and increasesFEV1 in patients age 6–17 years whose asthma is uncontrolledon a low dose of ICS alone.https://bit.ly/47buW6o

Objective: The burden of uncontrolled asthma on patients in Jordan is largely unknown. This study assessed different aspects of asthma clinical features: the level of asthma control, its correlation with quality of life, and possible predictors of asthma control. Methods: Face-to-face interviews with asthmatic patients (≥16 years old) in north Jordan from 2013 to 2014 were conducted. Outcomes measures were assessed using the asthma control test (ACT), the mini asthma quality of life questionnaire (mini-AQLQ), and the Generic health-related quality of life (EQ-5D). The relationship between asthma control and quality of life was examined using Spearman’s correlation coefficient. Predictors of asthma control were determined using multivariable logistic regression adjusted for confounders. Results: A total of 255 patients were recruited (mean age 45.16 years, 74.5% female). Approximately one-third of subjects (30.6%; n = 78) had controlled asthma (ACT ≥ 20). A strong correlation between asthma control and both mini-AQLQ and EQ-5D scores was identified (p < 0.001). Subjects who required to step-up treatment (OR = 0.12, 95% CI: 0.02–0.63, p = 0.01) and with acute asthma exacerbation (OR = 0.32, 95% CI: 0.18–0.58, p < 0.001) were independently associated with poor asthma control. Conclusions: Most of the recruited patients have not achieved optimal asthma control and was associated with low quality of life. The study highlights that even in low-income countries, a simple assessment tool such as the ACT can be utilized to screen and categorize asthma control. This approach would facilitate a better treatment plan and eventually improve asthma control and quality of life in asthma patients.

Comparative Effectiveness of Step-up Therapies in Children with Asthma Prescribed Inhaled Corticosteroids: A Historical Cohort Study