Inhaled Corticosteroid Monotherapy Research Articles

Once-daily fluticasone furoate/vilanterol vs once-daily fluticasone furoate in patients with asthma aged 5 to 17 years

BackgroundLimited data exist comparing inhaled corticosteroid (ICS) plus adjunctive therapy vs ICS alone in pediatric asthma patients. ObjectiveTo evaluate the efficacy and safety of fluticasone furoate/vilanterol (FF/VI) vs FF in children and adolescents with asthma. MethodsThis phase 3, randomized, double-blind, multicenter study (NCT03248128) included participants aged 5 to 17 years with six months or more asthma history uncontrolled on ICS monotherapy. Participants received 4-week open-label fluticasone propionate (100 µg) twice daily before 1:1 randomization to 24-week double-blind FF (50 µg:100 µg) or FF/VI (50/25 µg:100/25 µg) once daily. Two populations with different primary endpoints were analyzed to meet United States (week 12 weighted mean forced expiratory volume in 1 second [FEV1; 0-4 hours]; participants aged 5–17 years) and European (change from baseline predose morning peak expiratory flow [ΔAM PEF] averaged over weeks 1-12; participants aged 5-11 years) regulatory requirements. ResultsOverall, 902 participants, including 673 children aged 5 to 11 years, were randomized and treated. In participants aged 5 to 17, week 12 weighted mean FEV1 (0-4 hours) was greater with FF/VI vs FF (difference: 0.083 L; P < .001). In participants aged 5 to 11, ΔAM PEF over weeks 1 to 12 showed numerical improvement with FF/VI vs FF but was not statistically significant (difference: 3.2 L/min; P = .228). No drug-related serious adverse events or deaths were reported. ConclusionFF/VI significantly improved weighted mean FEV1 (0-4 hours; participants aged 5-17 years), but not ΔAM PEF (participants aged 5-11 years) vs FF. No new safety concerns were apparent. Trial RegistrationClinicalTrials.gov Identifier: NCT03248128.

Understanding the Clinical Implications of Individual Patient Characteristics and Treatment Choice on the Risk of Exacerbation in Asthma Patients with Moderate-Severe Symptoms.

The assessment of future risk has become an important feature in the management of patients with asthma. However, the contribution of patient-specific characteristics and treatment choices to the risk of exacerbation is poorly understood. Here we evaluated the effect of interindividual baseline differences on the risk of exacerbation and treatment performance in patients receiving regular maintenance doses of inhaled corticosteroids (ICS) or ICS/long-acting beta-agonists (LABA) combination therapy. Exacerbations and changes to asthma symptoms 5-item Asthma Control Questionnaire (ACQ-5) were simulated over a 12-month period using a time-to-event and a longitudinal model developed from phaseIII/IV studies in patients with moderate-severe asthma (N = 16,282). Simulations were implemented to explore treatment performance across different scenarios, including randomised designs and real-world settings. Treatment options included regular dosing with ICS monotherapy [fluticasone propionate (FP)] and combination therapy [fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR)]. Exacerbation rate was analysed using the log-rank test. The cumulative incidence of events was summarised stratified by treatment. Being a woman, smoker, having higher baseline ACQ-5 and body mass index (BMI) and lower forced expiratory volume in the first second (FEV1) are associated with increased exacerbation risk (p < 0.01). This risk is bigger in winter because of the seasonal variation effect. Across the different scenarios, the use of FP/SAL resulted in a 10% lower annual incidence of exacerbations relative to FP or regular dosing BUD/FOR, independently of baseline characteristics. Similar differences in the annual incidence of exacerbations were also observed between treatments in obese patients (BMI ≥ 25-35kg/m2) (p < 0.01) and in patients who do not achieve symptom control on FP monotherapy. Individual baseline characteristics and treatment choices affect future risk. Achieving comparable levels of symptom control whilst on treatment does not imply comparable risk reduction, as shown by the lower exacerbation rates in FP/SAL vs. BUD/FOR-treated patients. These factors should be considered as a basis for personalised clinical management of patients with moderate-severe asthma.

Managing moderate-to-severe paediatric asthma: a scoping review of the efficacy and safety of fluticasone propionate/salmeterol

BackgroundFluticasone propionate/salmeterol xinafoate (FP/SAL) is an inhaled corticosteroid (ICS) and long-acting β2-agonist (LABA) combination, indicated for the regular treatment of children (aged >4 years) with asthma that is inadequately controlled...

EE540 Budget Impact of Anti-Inflammatory Reliever Therapy with Budesonide-Formoterol Combination in the Treatment of Mild Asthma in Costa Rica

Asthma is a heterogeneous disease characterized by airway inflammation. Daily inhaled corticosteroid (ICS) plus short-acting beta-agonist (SABA) as a reliever is the standard of care (SoC) in Costa Rica for mild asthma. Anti-inflammatory reliever (AIR) therapy with budesonide–formoterol (Bud-Form) as needed is as effective as ICS monotherapy plus SABA as a reliever in reducing oral corticosteroid use, emergency room (ER) visits and hospitalizations; however, in Costa Rica, the information on the budget impact of the efficacy of AIR in patients with mild asthma is unknown.

EE73 Budget Impact of Anti-Inflammatory Reliever Therapy with Budesonide-Formoterol Combination in the Treatment of Mild Asthma in Honduras

Asthma is a heterogeneous disease characterized by airway inflammation. Daily inhaled corticosteroid (ICS) plus short-acting beta-agonist (SABA) as a reliever is the standard of care (SoC) in Honduras for mild asthma. Anti-inflammatory reliever (AIR) therapy with budesonide–formoterol (Bud-Form) as needed is at least as effective as ICS monotherapy plus SABA as a reliever in reducing oral corticosteroid use, emergency room (ER) visits and hospitalizations; however, in Honduras, the information on the budget impact of the efficacy of AIR in patients with mild asthma is unknown.

EE185 Budget Impact of Anti-Inflammatory Reliever Therapy with Budesonide-Formoterol Combination in the Treatment of Mild Asthma in Panama

Asthma is a heterogeneous disease characterized by airway inflammation. Daily inhaled corticosteroid (ICS) plus short-acting beta-agonist (SABA) as a reliever is the standard of care (SoC) in Panama for mild asthma. Anti-inflammatory reliever (AIR) therapy with budesonide–formoterol (Bud-Form) as needed is at least as effective as ICS monotherapy plus SABA as a reliever in reducing oral corticosteroid use, emergency room (ER) visits and hospitalizations; however, in Panama, the information on the budget impact of the efficacy of AIR in patients with mild asthma is unknown.

The association between inhaled corticosteroid and the risks of SARS-COV-2 infection: A systematic review and meta-analysis

BackgroundThe effect of inhaled corticosteroid (ICS) on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection is unclear. MethodsWe performed a systematic review and meta-analysis of clinical studies that assessed the association between the use of ICS and the risk of SARS-COV-2 infection. PubMed, Web of Science, Scopus, Cochrane Library and Google Scholar were searched to January 1st, 2023. ROBINS-I was used to assess risk of bias of included studies. The outcome of interest was the risk of SARS-COV-2 infection in patients and odds ratio (OR) with 95% confidence interval (95% CI) were calculated using Comprehensive Meta-analysis software version 3. ResultsTwelve studies involving seven observational cohort studies, three case-control studies, and two cross-sectional studies were included in this meta-analysis. Overall, compared to non-ICS use, the pooled odds ratio (OR) of the risk of SARS-COV-2 infection was 0.997 (95% confidence interval [CI] 0.664–1.499; p = 0.987) for patients with ICS use. Subgroup analyses demonstrated no statistical significance in the increased risk of SARS-COV-2 infection in patients with ICS monotherapy or in combination with bronchodilators (pooled OR=1.408; 95% CI=0.693–2.858; p = 0.344 in ICS monotherapy, and pooled OR=1.225; 95% CI=0.533–2.815; p = 0.633 in ICS combination, respectively). In addition, no significant association was observed between ICS use and the risk of SARS-COV-2 infection for patients with COPD (pooled OR=0.715; 95% CI=0.415–1.230; p = 0.225) and asthma (pooled OR=1.081; 95% CI=0.970–1.206; p = 0.160). ConclusionsThe use of ICS, either monotherapy or in combination with bronchodilators, does not have impact on the risk of SARS-COV-2 infection.

Real-world evaluation of asthma reliever therapy among continuous users of asthma maintenance medication in Japan: A retrospective cohort study using a claims database

BackgroundThe decrease in mortality rate owing to asthma has slowed in recent years. A large proportion of patients with asthma remain uncontrolled in Japan. This study aimed to determine the prevalence of short-acting beta 2 agonists (SABA) overuse and its associated factors. MethodsThis large-scale retrospective cohort study analyzed continuously treated patients with asthma aged 15–74 years between January 2017 and December 2017 using a Japanese insurance claims database. Characteristics, disease information, and prescribed drugs were extracted from the database, and treatment steps were defined according to drug combinations based on the criteria of the Japanese asthma guidelines. SABA overuse was defined as ≥3 canisters per year. Factors associated with SABA overuse were estimated using multivariable logistic regression. ResultsAmong 7,483 patients with mild-to-moderate asthma, 7,001 (93.6%) and 482 (6.4%) had low and high SABA use, respectively. Inhaled corticosteroids (ICS)/long-acting β-agonists (LABA) were the main asthma control treatments. The proportions of patients who overused SABA were 347 (9.9%) and 1,201 (5.6%) in the ICS and ICS/LABA groups, respectively. The factors associated with SABA overuse were male sex, ICS monotherapy, higher treatment steps, no history of allergic rhinitis, no history of chronic sinusitis, and no asthma management. ConclusionsThere is a relatively low prevalence of SABA overuse among asthmatic patients in Japan. ICS/LABA therapy, treatment steps, allergic rhinitis, chronic sinusitis, and asthma management are associated with a decreased risk of SABA overuse. Further studies are needed to investigate the association between SABA overuse and asthma exacerbation and mortality.

Safety of SABA Monotherapy in Asthma Management: a Systematic Review and Meta-analysis.

Short-acting β2-agonist (SABA) reliever overuse is common in asthma, despite availability of inhaled corticosteroid (ICS)-based maintenance therapies, and may be associated with increased risk of adverse events (AEs). This systematic literature review (SLR) and meta-analysis aimed to investigate the safety and tolerability of SABA reliever monotherapy for adults and adolescents with asthma, through analysis of randomized controlled trials (RCTs) and real-world evidence. An SLR of English-language publications between January 1996 and December 2021 included RCTs and observational studies of patients aged ≥ 12years treated with inhaled SABA reliever monotherapy (fixed dose or as needed) for ≥ 4weeks. Studies of terbutaline and fenoterol were excluded. Meta-analysis feasibility was dependent on cross-trial data comparability. A random-effects model estimated rates of mortality, serious AEs (SAEs), and discontinuation due to AEs (DAEs) for as-needed and fixed-dose SABA treatment groups. ICS monotherapy and SABA therapy were compared using a fixed-effects model. Forty-two studies were identified by the SLR for assessment of feasibility. Final meta-analysis included 24 RCTs. Too few observational studies (n = 2) were available for inclusion in the meta-analysis. One death unrelated to treatment was reported in each of the ICS, ICS + LABA, and fixed-dose SABA groups. No other treatment-related deaths were reported. SAE and DAE rates were < 4%. DAEs were reported more frequently in the SABA treatment groups than with ICS, potentially owing to worsening asthma symptoms being classified as an AE. SAE risk was comparable between SABA and ICS treatments. Meta-analysis of data from RCTs showed that deaths were rare with SABA reliever monotherapy, and rates of SAEs and DAEs were comparable between SABA reliever and ICS treatment groups. When used appropriately within prescribed limits as reliever therapy, SABA does not contribute to excess rates of mortality, SAEs, or DAEs.

COPD Population in US Primary Care: Data From the Optimum Patient Care DARTNet Research Database and the Advancing the Patient Experience in COPD Registry.

To describe demographic and clinical characteristics of chronic obstructive pulmonary disease patients managed in US primary care. This was an observational registry study using data from the Chronic Obstructive Pulmonary Disease (COPD) Optimum Patient Care DARTNet Research Database from which the Advancing the Patient Experience COPD registry is derived. Registry patients were aged ≥35 years at diagnosis. Electronic health record data were collected from both registries, supplemented with patient-reported information/outcomes from the Advancing the Patient Experience registry from 5 primary care groups in Texas, Ohio, Colorado, New York, and North Carolina (June 2019 through November 2020). Of 17,192 patients included, 1,354 were also in the Advancing the Patient Experience registry. Patients were predominantly female (56%; 9,689/17,192), White (64%; 9,732/15,225), current/ex-smokers (80%; 13,784/17,192), and overweight/obese (69%; 11,628/16,849). The most commonly prescribed maintenance treatments were inhaled corticosteroid with a long-acting β2-agonist (30%) and inhaled corticosteroid with a long-acting muscarinic antagonist (27%). Although 3% (565/17,192) of patitents were untreated, 9% (1,587/17,192) were on short-acting bronchodilator monotherapy, and 4% (756/17,192) were on inhaled corticosteroid monotherapy. Despite treatment, 38% (6,579/17,192) of patients experienced 1 or more exacerbations in the last 12 months. These findings were mirrored in the Advancing Patient Experience registry with many patients reporting high or very high impact of disease on their health (43%; 580/1,322), a breathlessness score 2 or more (45%; 588/1,315), and 1 or more exacerbation in the last 12 months (50%; 646/1,294). Our findings highlight the high exacerbation, symptom, and treatment burdens experienced by COPD patients managed in US primary care, and the need for more real-life effectiveness trials to support decision making at the primary care level.

Diagnosis and management of cough-variant asthma

Abstract Cough is a natural defence mechanism of the lungs to prevent aspiration and to keep the airway clean. Cough, wheezing and shortness of breath are common symptoms of asthma. Cough-variant asthma is one of the phenotypes of asthma with the main symptom of cough without shortness of breath and wheezing. Cough-variant asthma is largely observed in patients with bronchial hyperresponsiveness who experience cough due to innocuous stimuli, and it is associated with a family history and seasonal allergy. In the present study, in patients with cough-variant asthma, no abnormalities were found during the lung function test, particularly forced expiratory flow in the first second (FEV1) or peak expiratory flow (PEF), although these values were lower than those in normal individuals. A bronchial provocation test using methacholine is needed to assess airway hyperresponsiveness, and depending on the outcome of the test, an assessment can be made as to the probability of the patient requiring a diagnosis of cough-variant asthma. Administration of inhalation therapy with bronchodilators and corticosteroids is the mainstay of management in patients with cough-variant asthma presenting with the symptom of persistent cough. Until now, there have been no specific guidelines for drug selection, dose and duration of inhaled corticosteroid use in cough-variant asthma. If symptoms do not resolve with inhaled corticosteroid monotherapy, consideration may be given to increase the inhalation dose or to add other drugs such as long-acting B2 agonists, slow-release theophylline or leukotriene receptor antagonist (LTRA).

ADRB2 haplotypes and asthma exacerbations in children and young adults: An individual participant data meta-analysis.

The polymorphism Arg16 in β2 -adrenergic receptor (ADRB2) gene has been associated with an increased risk of exacerbations in asthmatic children treated with long-acting β2 -agonists (LABA). However, it remains unclear whether this increased risk is mainly attributed to this single variant or the combined effect of the haplotypes of polymorphisms at codons 16 and 27. We assessed whether the haplotype analysis could explain the association between the polymorphisms at codons 16 (Arg16Gly) and 27 (Gln27Glu) in ADRB2 and risk of asthma exacerbations in patients treated with inhaled corticosteroids (ICS) plus LABA. The study was undertaken using data from 10 independent studies (n=5903) participating in the multi-ethnic Pharmacogenomics in Childhood Asthma (PiCA) consortium. Asthma exacerbations were defined as asthma-related use of oral corticosteroids or hospitalizations/emergency department visits in the past 6 or 12months prior to the study visit/enrolment. The association between the haplotypes and the risk of asthma exacerbations was performed per study using haplo.stats package adjusted for age and sex. Results were meta-analysed using the inverse variance weighting method assuming random-effects. In subjects treated with ICS and LABA (n=832, age: 3-21years), Arg16/Gln27 versus Gly16/Glu27 (OR: 1.40, 95% CI: 1.05-1.87, I2 =0.0%) and Arg16/Gln27 versus Gly16/Gln27 (OR: 1.43, 95% CI: 1.05-1.94, I2 =0.0%), but not Gly16/Gln27 versus Gly16/Glu27 (OR: 0.99, 95% CI: 0.71-1.39, I2 =0.0%), were significantly associated with an increased risk of asthma exacerbations. The sensitivity analyses indicated no significant association between the ADRB2haplotypes and asthma exacerbations in the other treatment categories, namely as-required short-acting β2 -agonists (n=973), ICS monotherapy (n=2623), ICS plus leukotriene receptor antagonists (LTRA; n=338), or ICS plus LABA plus LTRA (n=686). The ADRB2 Arg16haplotype, presumably mainly driven by the Arg16, increased the risk of asthma exacerbations in patients treated with ICS plus LABA. This finding could be beneficial in ADRB2genotype-guided treatment which might improve clinical outcomes in asthmatic patients.

Once-daily mometasone plus indacaterol versus mometasone or twice-daily fluticasone plus salmeterol in patients with inadequately controlled asthma (PALLADIUM): a randomised, double-blind, triple-dummy, controlled phase 3 study

Fixed-dose combinations (FDCs) of inhaled corticosteroids (ICS) and long-acting β2-adrenoceptor agonists (LABA) are considered safe and efficacious in asthma management. Most available FDCs require twice-daily dosing to achieve optimum therapeutic effect. The objective of the PALLADIUM study was to assess the efficacy and safety of once-daily FDC of mometasone furoate plus indacaterol acetate (MF-IND) versus mometasone furoate (MF) monotherapy in patients with inadequately controlled asthma. This 52-week, double-blind, triple-dummy, parallel-group, phase 3 study recruited patients from 316 centres across 24 countries. Patients aged 12 to 75 years with a documented diagnosis of asthma for at least 1 year, percentage of predicted FEV1 of 50-85%, and an Asthma Control Questionnaire 7 score of at least 1·5 despite treatment with medium-dose or high-dose ICS or low-dose ICS plus LABA were included. A history of asthma exacerbations was not a study requirement. Participants were randomily assigned (1:1:1:1:1) via interactive response technology to receive one of the following treatments for 52 weeks: high-dose MF-IND (320 μg, 150 μg) or medium-dose MF-IND (160 μg, 150 μg) once daily via Breezhaler; high-dose MF (800 μg [400 μg twice daily]) or medium-dose MF (400 μg once daily) via Twisthaler; or high-dose fluticasone propionate-salmeterol xinafoate (FLU-SAL; 500 μg, 50 μg) twice daily via Diskus. Participants received placebo via inhalation through the Breezhaler, Twisthaler, or Diskus devices in the mornings and evenings, as appropriate. The primary endpoint was improvement in trough FEV1 with high-dose and medium-dose MF-IND versus respective MF doses from baseline at 26 weeks, analysed in the full analysis set by means of a mixed model for repeated measures. High-dose MF-IND once daily was compared with high-dose FLU-SAL twice daily for non-inferiority on improving trough FEV1 at week 26 with a margin of -90 mL using mixed model for repeated measures as one of the secondary endpoints. Safety was assessed in all patients who had received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT02554786, and is completed. Between Dec 29, 2015, and May 4, 2018, 2216 patients were randomly assigned (high-dose MF-IND, n=445; medium-dose MF-IND, n=439; high-dose MF, n=442; medium-dose MF, n=444; high-dose FLU-SAL, n=446), of which 1973 (89·0%) completed the study treatment and 234 (10·6%) prematurely discontinued study treatment. High-dose MF-IND (treatment difference [Δ] 132 mL [95% CI 88 to 176]; p<0·001) and medium-dose MF-IND (Δ 211 mL [167 to 255]; p<0·001) showed superiority in improving trough FEV1 over corresponding MF doses from baseline at week 26. High-dose MF-IND was non-inferior to high-dose FLU-SAL in improving trough FEV1 from baseline at week 26 (Δ 36 mL [-7 to 80]; p=0·101). Overall, the incidence of adverse events was similar across the treatment groups. Once-daily FDC of ICS and LABA (MF-IND) significantly improved lung function over ICS monotherapy (MF) at week 26; high-dose MF-IND was non-inferior to twice-daily combination of ICS and LABA (high-dose FLU-SAL) for improvement in trough FEV1. The combination of MF-IND provides a novel once-daily dry powder option for asthma control. Novartis Pharmaceuticals.

Considerations for the Correct Diagnosis of COPD and Its Management With Bronchodilators

COPD is often misdiagnosed and inappropriately treated in many patients. COPD is a distinct disease from adult-onset asthma; however, some patients with COPD may present with several forms of airway disease described as asthma-COPD overlap (ACO). Bronchodilators and inhaled corticosteroids (ICS) both have a place in standard maintenance treatment of COPD and asthma; however, recommendations for use differ widely. In patients with COPD, long-acting bronchodilators are effective initial monotherapy treatment, whereas ICS monotherapy is recommended as initial treatment in patients with asthma. Clinicians need to be confident in their diagnosis to ensure that correct treatment is given because misguided treatment decisions can result in significantly increased safety risks for patients. This review highlights the differences in diagnosis and treatment between COPD, asthma, and ACO and discusses the data supporting guideline recommendations for use of bronchodilators in COPD treatment in contrast to asthma or ACO.

Patterns of use of long-acting bronchodilators in patients with COPD: A nationwide follow-up study of new users in New Zealand.

While several studies have found that prescribing practices do not conform to chronic obstructive pulmonary disease (COPD) treatment guidelines, none have examined longitudinal patterns of use of long-acting beta2 -agonist (LABA) and long-acting muscarinic antagonist (LAMA) therapy across an entire country. We undertook a nationwide follow-up study to describe treatment patterns in new users of long-acting bronchodilators. National health and pharmaceutical dispensing data were used to identify patients aged ≥45 years who initiated LABA and/or LAMA therapy for COPD between 1 February 2006 and 31 December 2013. Dispensings of LABAs, LAMAs and inhaled corticosteroids (ICSs) were aggregated into episodes of use of therapeutic regimens. Kaplan-Meier curves, sunburst plots and sequence index plots were generated to summarize, respectively, the duration of the first regimen, the sequences in which unique regimens were used and the patterns of use and non-use during follow-up. The study cohort included 83 435 patients with 290 400 person-years of follow-up. The most commonly initiated regimen was a LABA with an ICS. ICS use was inconsistent with international guidelines: over- and under-treatment occurred in patients with infrequent and frequent exacerbations, respectively, and ICS monotherapy was common. The median duration of the first regimen was 46 days. Many patients used multiple regimens over time and periods of non-use were common. In this nationwide study, patterns of use of LABAs, LAMAs and ICSs were complex and often did not comply with treatment guidelines. Further work is required to address the discrepancy between guidelines and prescribing practices.

Extrafine Versus Fine Inhaled Corticosteroids in Relation to Asthma Control: A Systematic Review and Meta-Analysis of Observational Real-Life Studies

The particle size of inhaled corticosteroids (ICSs) may affect airway drug deposition and effectiveness. To compare the effectiveness of extrafine ICSs (mass median aerodynamic diameter, <2 μm) versus fine-particle ICSs administered as ICS monotherapy or ICS-long-acting β-agonist combination therapy by conducting a meta-analysis of observational real-life asthma studies to estimate the treatment effect of extrafine ICSs. MEDLINE and EMBASE databases were reviewed for asthma observational comparative effectiveness studies from January 2004 to June 2016. Studies were included if they reported odds and relative risk ratios and metall inclusion criteria (Respiratory Effectiveness Group/European Academy of Allergy and Clinical Immunology quality standards, comparison of extrafine ICSs with same or different ICS molecule, ≥12-month follow-up). End-point data (asthma control, exacerbations, prescribed ICS dose) were pooled. Random-effects meta-analysis modeling was used. The study protocol is published in the PROSPERO register CRD42016039137. Seven studies with 33,453 subjects aged 5 to 80 years met eligibility criteria for inclusion. Six studies used extrafine beclometasone propionate and 1 study used both extrafine beclometasone propionate and extrafine ciclesonide as comparators with fine-particle ICSs. The overall odds of achieving asthma control were significantly higher for extrafine ICSs compared with fine-particle ICSs (odds ratio, 1.34; 95% CI, 1.22-1.46). Overall exacerbation rate ratios (0.84; 95% CI, 0.73-0.97) and ICS dose (weighted mean difference,-170 μg; 95% CI,-222 to-118 μg) were significantly lower for extrafine ICSs compared with fine-particle ICSs. This meta-analysis demonstrates that extrafine ICSs have significantly higher odds of achieving asthma control with lower exacerbation rates at significantly lower prescribed doses than fine-particle ICSs.

Fluticasone/salmeterol reduces remodelling and neutrophilic inflammation in severe equine asthma

Asthmatic airways are inflamed and undergo remodelling. Inhaled corticosteroids and long-acting β2-agonist combinations are more effective than inhaled corticosteroid monotherapy in controlling disease exacerbations, but their effect on airway remodelling and inflammation remains ill-defined. This study evaluates the contribution of inhaled fluticasone and salmeterol, alone or combined, to the reversal of bronchial remodelling and inflammation. Severely asthmatic horses (6 horses/group) were treated with fluticasone, salmeterol, fluticasone/salmeterol, or with antigen avoidance for 12 weeks. Lung function, central and peripheral airway remodelling, and bronchoalveolar inflammation were assessed. Fluticasone/salmeterol and fluticasone monotherapy decreased peripheral airway smooth muscle remodelling after 12 weeks (p = 0.007 and p = 0.02, respectively). On average, a 30% decrease was observed with both treatments. In central airways, fluticasone/salmeterol reversed extracellular matrix remodelling after 12 weeks, both within the lamina propria (decreased thickness, p = 0.005) and within the smooth muscle layer (p = 0.004). Only fluticasone/salmeterol decreased bronchoalveolar neutrophilia (p = 0.03) to the same extent as antigen avoidance already after 8 weeks. In conclusion, this study shows that fluticasone/salmeterol combination decreases extracellular matrix remodelling in central airways and intraluminal neutrophilia. Fluticasone/salmeterol and fluticasone monotherapy equally reverse peripheral airway smooth muscle remodelling.

Neuropsychiatric adverse drug reactions in children initiated on montelukast in real-life practice.

Although montelukast is generally well tolerated, postmarketing studies have reported serious neuropsychiatric adverse drug reactions (ADRs) leading to a United States Food and Drug Administration black box warning. The objective of this study was to determine the incidence of neuropsychiatric ADRs leading to discontinuation of montelukast in asthmatic children.We conducted a retrospective cohort study in children aged 1-17 years initiated on montelukast. In a nested cohort study, children initiated on montelukast as monotherapy or adjunct therapy to inhaled corticosteroids (ICS) were matched to those initiated on ICS monotherapy. A non-leading parental interview served to ascertain the occurrence of any ADRs with any asthma medication, and circumstances related to, and evolution of, the event.Out of the 106 participants who initiated montelukast, most were male (58%), Caucasian (62%) with a median (interquartile range) age of 5 (3-8) years. The incidence (95% CI) of drug cessation due to neuropsychiatric ADRs was 16 (10-26)%, mostly occurring within 2 weeks. Most frequent ADRs were irritability, aggressiveness and sleep disturbances. The relative risk of neuropsychiatric ADRs associated with montelukast versus ICS was 12 (2-90).In the real-life setting, asthmatic children initiated on montelukast experienced a notable risk ofneuropsychiatric ADRs leading to drug cessation, that is significantly higher than that associated withICS.

Didelių dozių beklometazono dipropionato ir formoterolio fumarato itin smulkių dalelių fiksuotos dozės derinys astmai gydyti

Lietuvos mokslo institucijų, sveikatos priežiūros specialistų, vaistų kūrėjų bendradarbiavimas su ligoniais tampa vis glaudesnis, todėl ir gaminami vaistai tampa vis veiksmingesni bei saugesni. Itin smulkių dalelių beklometazono dipropionato ir formoterolio fumarato (BDP/Form) 200/6 μg sudėtis sukurta, siekiant sustiprinti gydymą įkvepiamaisiais gliukokortikoidais, nedidinant bronchodilatatoriaus dozės pacientams, kuriems astma netinkamai kontroliuojama vartojant ankstesnį gydymą. Atliktas tyrimas padėjo įvertinti poveikį astmos kontrolei kaip statistiškai reikšmingą (Foster 200/6 palyginus su monoterapija BDP). Apibendrinus duomenis, galima teigti, kad BDP/Form 200/6 μg pagerina plaučių funkciją ir teigiamai veikia simptomus, padeda kontroliuoti astmą. Todėl BDP/Form 200/6 μg gali būti laikomas veiksmingu ir saugiu vaistu tiems astma sergantiems pacientams, kuriems astma netinkamai kontroliuojama skiriant didelę dozę įkvepiamųjų gliukokortikoidų arba vidutinę dozę įkvepiamojo gliukokortikoido su ilgo veikimo β2-agonistu.

Changes in Asthma Maintenance Therapy Prescribing Patterns Following the 2006 Long-acting β-Agonist FDA Drug Warning

PurposeThe US Food and Drug Administration issued a boxed warning on all products containing a long-acting β-agonist (LABA) in March 2006, after the findings from a trial suggested an increased risk for death in patients treated with salmeterol monotherapy. Almost nothing is known about the impact of this warning on LABA prescribing patterns or on clinicians’ approaches to asthma maintenance therapy. MethodsA cohort of asthmatic adults on LABA therapy was retrospectively identified from a Baltimore-area Medicaid data warehouse. Pharmacy claims were used for determining the utilization rates of all asthma maintenance medications. Rates from the 6-month period before the warning (September 1, 2005, to February 28, 2006) were compared with rates from a similar 6-month period 1 year afterward (September 1, 2006, to February 28, 2007). The demographic characteristics of patients who continued LABA use were compared with those of discontinuers. In LABA discontinuers, utilization of alternative maintenance drugs was assessed. FindingsIn this cohort of 455 asthmatic patients, LABAs were prescribed only in combination with inhaled corticosteroids. Following the warning, 53% of patients discontinued LABA use, and the mean number of LABA prescription fills per patient decreased from 2.6 to 1.8 (P < 0.0001). Concurrently, the use of inhaled corticosteroids increased from 0.3 to 0.8 fills per patient (P < 0.0001). LABA continuers were younger (P = 0.0005), more likely to be black (P = 0.0079), and more consistent with LABA fills prewarning (P < 0.0001). Of the 243 LABA discontinuers, 155 were placed on no alternative maintenance therapy. ImplicationsThe management of asthma changed significantly after the LABA warning. The use of LABAs combined with inhaled corticosteroids plummeted, while the use of inhaled corticosteroid monotherapy increased. More than half of patients who discontinued LABAs were not placed on alternative maintenance therapy.