Combination Of Inhaled Corticosteroids Research Articles

Clinical response to withdrawal of Inhaled Corticosteroids in stable mild to moderate chronic obstructive pulmonary disease in a tertiary hospital of central Nepal

Introduction: The mainstay treatment according to the Global Initiative for Chronic Obstructive Lung Disease 2023 guidelines for Chronic Obstructive Pulmonary Disease is combination of long acting bronchodilators with addition of inhaled corticosteroids only in patients with increased exacerbations and an eosinophil count of ≥ 300 cells/μL. Despite the recommendations, inhaled corticosteroids are most commonly overprescribed. So, this study aims to follow patients with mild to moderate cases of this disease who are currently on inhaled corticosteroids combination therapy for clinical efficacy after its withdrawal. Methods: The study was a prospective interventional study conducted at Dhulikhel Hospital that followed individuals with mild to moderate COPD for eight weeks after a sudden ICS withdrawal. Forced Expiratory Volume in first second, modified Medical Research Council grading, COPD Assessment Tool score and number of exacerbations were assessed with follow-up either by telephone or face to face. Results: Total of 33 patients were enrolled in the study with mean age 68.9 years and standard deviation 9.3 years. Paired t-test analysis showed no significant mean difference in Forced Expiratory Volume in first second and COPD Assessment Tool values before and eight weeks after the withdrawal of Inhaled Corticosteroids. Conclusions: Our study supported the conclusion of previous larger studies that withdrawing ICS in stable mild to moderate COPD patients makes no difference in clinical symptoms and spirometry.

Medications for chronic obstructive pulmonary disease: a historical non-interventional cohort study with validation against RCT results.

Chronic obstructive pulmonary disease treatment is informed by randomised controlled trial results, but it is unclear if these findings apply to people excluded from these trials. We used data from the TORCH (TOwards a Revolution in COPD Health) randomised controlled trial to validate non-interventional methods for assessing the clinical effectiveness of chronic obstructive pulmonary disease treatment in the UK Clinical Practice Research Datalink, before applying these methods to the analysis of people who would have been excluded from TORCH. To validate the use of non-interventional Clinical Practice Research Datalink data and methods for estimating chronic obstructive pulmonary disease treatment effects against trial results, and, using validated methods, to determine treatment effects in people who would have been excluded from the TORCH trial. A historical non-interventional cohort design, including validation against randomised controlled trial results. The UK Clinical Practice Research Datalink. People aged ≥ 18 years with chronic obstructive pulmonary disease registered in Clinical Practice Research Datalink GOLD between January 2000 and January 2017. For objective 1, we prepared a cohort that was analogous to the TORCH trial cohort by applying TORCH trial inclusion/exclusion criteria followed by individual matching to TORCH trial participants. For objectives 2 and 3, we prepared cohorts that were analogous to the TORCH trial that, nevertheless, would not have been eligible for the TORCH trial because of age, asthma, comorbidity or mild disease. The long-acting beta-2 agonist and inhaled corticosteroid combination product Seretide (GlaxoSmithKline plc) [i.e. fluticasone propionate plus salmeterol (FP-SAL)] compared with (1) no FP-SAL exposure or (2) exposure to salmeterol (i.e. the long-acting beta-2 agonist) only. Exacerbations, mortality, pneumonia and time to treatment change. For objective 1, the exacerbation rate ratio was comparable to that in the TORCH trial for FP-SAL compared with salmeterol (0.85, 95% confidence interval 0.74 to 0.97, vs. TORCH trial 0.88, 95% confidence interval 0.81 to 0.95), but not for FP-SAL compared with no FP-SAL (1.30, 95% confidence interval 1.19 to 1.42, vs. TORCH trial 0.75, 95% confidence interval 0.69 to 0.81). Active comparator results were also consistent with the TORCH trial for mortality (hazard ratio 0.93, 95% confidence interval 0.65 to 1.32, vs. TORCH trial hazard ratio 0.93, 95% confidence interval 0.77 to 1.13) and pneumonia (risk ratio 1.39, 95% confidence interval 1.04 to 1.87, vs. TORCH trial risk ratio 1.47, 95% confidence interval 1.25 to 1.73). For objectives 2 and 3, active comparator results were consistent with the TORCH trial for exacerbations, with the exception of people with milder chronic obstructive pulmonary disease, in whom we observed a stronger protective association (risk ratio 0.56, 95% confidence interval 0.46 to 0.70, vs. TORCH trial risk ratio 0.85, 95% confidence interval 0.74 to 0.97). For the analysis of mortality, we saw a lack of association with being prescribed FP-SAL (vs. being prescribed salmeterol), with the exception of those with prior asthma, for whom we observed an increase in mortality (hazard ratio 1.49, 95% confidence interval 1.21 to 1.85, vs. TORCH trial-analogous HR 0.93, 95% confidence interval 0.64 to 1.32). Routinely collected electronic health record data can be used to successfully measure chronic obstructive pulmonary disease treatment effects when comparing two treatments, but not for comparisons between active treatment and no treatment. Analyses involving patients who would have been excluded from trials mostly suggests that treatment effects for FP-SAL are similar to trial effects, although further work is needed to characterise a small increased risk of death in those with concomitant asthma. Some of our analyses had small numbers. The differences in treatment effects that we found should be investigated further in other data sets. Currently recommended chronic obstructive pulmonary disease inhaled combination therapy (other than FP-SAL) should also be investigated using these methods. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 51. See the NIHR Journals Library website for further project information.

The TRIFLOW study: a randomised, cross-over study evaluating the effects of extrafine beclometasone/formoterol/glycopyrronium on gas trapping in COPD

BackgroundThe effects of triple therapy on gas trapping in COPD are not fully understood. We evaluated the effects of the long acting bronchodilator components of the extrafine single inhaler triple therapy beclometasone dipropionate/formoterol/glycopyrronium (BDP/F/G) pMDI on gas trapping.MethodsThis open-label, randomised, single centre, 2-way cross-over study recruited 23 COPD patients taking inhaled corticosteroid combination treatments and with residual volume (RV) > 120% predicted at screening. Inhaled BDP was taken during run-in and washout periods. Baseline lung function (spirometry, lung volumes, oscillometry) was measured over 12 h prior to randomisation to BDP/F/G or BDP/F for 5 days followed by washout and crossover. Lung function was measured prior to dosing on day 1 and for 12 h post-dose on day 5.ResultsCo-primary endpoint analysis: BDP/F/G had a greater effect than BDP/F on FEV1 area under the curve over 12 h (AUC0–12) (mean difference 104 mls, p = 0.0071) and RV AUC0–12 (mean difference − 163 mls, p = 0.0028). Oscillometry measurements showed a greater effect of BDP/F/G on the difference between resistance at 5 and 20 Hz (R5–R20) AUC0–12, which measures small airway resistance (mean difference − 0.045 kPa/L/s, p = 0.0002). Comparison of BDP/F with the baseline measurements (BDP alone) showed that F increased FEV1 AUC0–12 (mean difference 227 mls) and improved RV AUC0–12 (mean difference − 558 mls) and R5–R20 AUC0–12 (mean difference − 0.117 kPa/L/s), all p < 0.0001.ConclusionsIn COPD patients with hyperinflation, the G and F components of extrafine BDP/F/G improved FEV1, RV and small airway function. These long acting bronchodilators target small airway function, thereby improving gas trapping and airflow.Trial registration The study was retrospectively registered at ClinicalTrials.gov on 15th February 2019 (No.: NCT03842904, https://clinicaltrials.gov/ct2/show/NCT03842904).

Update on the NAEPPCC Asthma Guidelines: The wait is over, or is it?

As an asthma specialist, one is often asked to discuss the asthma guidelines. The challenge that one faces is deciding which guidelines to use as a resource for discussion or presentation. It often comes down to the following questions: What is the question? What message does one want to deliver? Where is the most current information? and Who is the target audience? This commentary will help answer those questions as it guides the reader through the new update of the National Heart, Lung and Blood Institute/National Asthma Education and Prevention Program guidelines and then outlines differences between 2 widely used strategies for the management of asthma: the Global Initiative for Asthma and the National Heart, Lung and Blood Institute/National Asthma Education and Prevention Program Guidelines for the Diagnosis and Management of Asthma.

Bringing Stability to the Chronic Obstructive Pulmonary Disease Patient: Clinical and Pharmacological Considerations for Frequent Exacerbators.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are critical events associated with an accelerated loss of lung function, increased morbidity, and excess mortality. AECOPD are heterogeneous in nature and this may directly impact clinical decision making, specifically in patients with frequent exacerbations. A 'frequent exacerbator' is a sub-phenotype of chronic obstructive pulmonary disease (COPD) and is defined as an individual who experiences two or more moderate-to-severe exacerbations per year. This distinct subgroup has higher mortality and accounts for more than half of COPD-related hospitalizations annually. Thus, it is imperative to identify individuals at risk for frequent exacerbations and choose optimal strategies to minimize risk for these events. New paradigms for using combination inhalers and the introduction of novel oral compounds provide expanded treatment options to reduce the risk and frequency of exacerbations. The goals of managing frequent exacerbators or patients at risk for AECOPD are: (1) maximizing bronchodilation; (2) reducing inflammation; and (3) targeting specific molecular pathways implicated in COPD and AECOPD pathogenesis. Novel inhaler therapies including combination long-acting muscarinic agents plus long-acting beta agonists show promising results compared with monotherapy or a long-acting beta agonist inhaled corticosteroid combination in reducing exacerbation risk among individuals at risk for exacerbations and among frequent exacerbators. Likewise, oral medications including macrolides and phosphodiesterase-4 inhibitors reduce the risk for AECOPD in select groups of individuals at high risk for exacerbation. Future direction in COPD management is based on the identification of various subtypes or 'endotypes' and targeting therapies based on their pathophysiology. This review describes the impact of AECOPD and the challenges posed by frequent exacerbators, and explores the rationale for different pharmacologic approaches to preventing AECOPD in these individuals.

Benefits and Risks of Long-Term Asthma Management in Children: Where Are We Heading?

International guidelines provide recommendations for a stepwise approach to the management of asthma in children 0-4 years old, 5-11 years old, and adolescents who are treated as adults. Therapy is aimed at two domains of control: current impairment and future risk. The long-term controller medications, inhaled corticosteroids (ICSs), ICSs in combination with long-acting β2 agonists, leukotriene receptor antagonists, and immunomodulators, exhibit different efficacies for these domains. The risk:benefit ratios of the available medications need to be carefully assessed. This review briefly presents the benefits and the potential risks of available asthma medications in children to assist the practitioner in the optimal use of asthma medications. Specifically, the systemic activity of the ICSs and how to minimize their effects on growth and adrenal activity are reviewed as well as other potential adverse effects. Dosing strategies such as intermittent therapy are also assessed.

Using Big Data to Assess Prescribing Patterns in Greece: The Case of Chronic Obstructive Pulmonary Disease.

IntroductionChronic Obstructive Pulmonary Disease (COPD) is one of the top leading causes of death and disability, and its management is focused on reducing risk factors, relieving symptoms, and preventing exacerbations. The study aim was to describe COPD prescribing patterns in Greece by using existing health administrative data for outpatients.MethodsThis is a retrospective cross-sectional study based on prescriptions collected by the largest social insurance fund, during the first and last trimester of 2012. Selection criteria were the prescription of specific active substances and a COPD diagnosis. Extracted information included active substance, strength, pharmaceutical form and number of packages prescribed, diagnosis, time of dispensing, as well as insurees’ age, gender, percentage of co-payment and social security unique number. Statistical analysis included descriptive statistics and logistic regression.Results174,357 patients received medicines for COPD during the study period. Patients were almost equally distributed between male and female, and age above 55 years was strongly correlated with COPD. Most patients received a long-acting beta agonist plus inhaled corticosteroid combination (LABA +ICS), followed by long-acting muscarinic agonist (LAMA). 63% patients belonging in the 35–54 age received LABA+ICS. LAMA was prescribed more frequently among males and was strongly correlated with COPD.ConclusionThe study provides big data analysis of Greek COPD prescribing patterns. It highlights the need for appropriate COPD classification in primary care illustrating the role of electronic prescribing in ensuring appropriate prescribing. Moreover, it indicates possible gender differences in treatment response or disease severity, and the impact of statutory co-payments on prescribing.

Physicians′ prescribing pattern, perceived safety of asthma medications and management of asthma during pregnancy in Nigeria

Background: Under-treatment of asthma in pregnancy can result in adverse fetal and maternal outcomes. The potential risk of teratogenicity may limit prompt and adequate management of medical disorders in pregnancy. Objectives: The objective of this study was to investigate the physicians' prescribing pattern, their perceived safety of asthma medications and management of asthma during pregnancy in obstetric care units of a developing country. Materials and Methods: A self-administered questionnaire containing case vignettes and multiple choice questions were used to evaluate the physicians prescribing practices, their perceived safety of medications and approach to asthma management in pregnancy. Result: Of the 144 doctors that participated in the study; 76 (52.8%) would prefer inhaled long-acting β2 agonist and inhaled corticosteroids combination (LABA/ICSs) while 10 (6.9%) would prefer leukotriene antagonists (LTA) as a controller medication in the first trimester of pregnancy. Short-acting β2 agonists, LABA, and theophylline were perceived to be safest throughout pregnancy, corticosteroids and cromoglycates were considered unsafe in first trimester while LTA were considered unsafe in all the trimesters by a majority of respondents. To gain asthma control in a patient already on low dose LABA/ICS, 94 (65.3%) of the doctors would refer their to a respiratory specialist instead of increasing the dose of LABA/ICS. Less than half (42.3%) were willing to address medication compliance in nonconforming patients. The majority (72.2%) of the doctors' self-reported nonadherence to the asthma treatment guideline. Conclusion: Even though, most of the physicians caring for pregnant women seem to prefer LABA/ICS combination for asthma control, there exist a knowledge gap in the stepwise management of asthma, perceived safety of most asthma medications and tackling poor medication adherence.

Combination long-acting β-agonists and inhaled corticosteroids compared with long-acting β-agonists alone in older adults with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), a manageable respiratory condition, is the third leading cause of death worldwide. Knowing which prescription medications are the most effective in improving health outcomes for people with COPD is essential to maximizing health outcomes. To estimate the long-term benefits of combination long-acting β-agonists (LABAs) and inhaled corticosteroids compared with LABAs alone in a real-world setting. Population-based, longitudinal cohort study conducted in Ontario, Canada, from 2003 to 2011. All individuals aged 66 years or older who met a validated case definition of COPD on the basis of health administrative data were included. After propensity score matching, there were 8712 new users of LABA-inhaled corticosteroid combination therapy and 3160 new users of LABAs alone who were followed up for median times of 2.7 years and 2.5 years, respectively. Newly prescribed combination LABAs and inhaled corticosteroids or LABAs alone. Composite outcome of death and COPD hospitalization. The main outcome was observed among 5594 new users of LABAs and inhaled corticosteroids (3174 deaths [36.4%]; 2420 COPD hospitalizations [27.8%]) and 2129 new users of LABAs alone (1179 deaths [37.3%]; 950 COPD hospitalizations [30.1%]). New use of LABAs and inhaled corticosteroids was associated with a modestly reduced risk of death or COPD hospitalization compared with new use of LABAs alone (difference in composite outcome at 5 years, -3.7%; 95% CI, -5.7% to -1.7%; hazard ratio [HR], 0.92; 95% CI, 0.88-0.96). The greatest difference was among COPD patients with a codiagnosis of asthma (difference in composite at 5 years, -6.5%; 95% CI, -10.3% to -2.7%; HR, 0.84; 95% CI, 0.77-0.91) and those who were not receiving inhaled long-acting anticholinergic medication (difference in composite at 5 years, -8.4%; 95% CI, -11.9% to -4.9%; HR, 0.79; 95% CI, 0.73-0.86). Among older adults with COPD, particularly those with asthma and those not receiving a long-acting anticholinergic medication, newly prescribed LABA and inhaled corticosteroid combination therapy, compared with newly prescribed LABAs alone, was associated with a significantly lower risk of the composite outcome of death or COPD hospitalization.

Risk of congenital malformations for asthmatic pregnant women using a long-acting β2-agonist and inhaled corticosteroid combination versus higher-dose inhaled corticosteroid monotherapy

Current recommendations for managing persistent asthma during pregnancy when low-dose inhaled corticosteroids (ICSs) are insufficient include adding a long-acting β₂-agonist (LABA) or increasing the ICS dose. However, there are no data to help clinicians evaluate the safest regimen during pregnancy. We sought to compare the risk of major congenital malformations in asthmatic women exposed to a LABA plus ICS combination and those exposed to ICS monotherapy at higher doses during the first trimester. A cohort of asthmatic pregnant women exposed to ICSs during the first trimester who delivered between January 1990 and March 2009 was established. The primary outcome was major malformation recorded at birth or during the first year of life. Two subcohorts were established as follows: (1) users of a LABA plus low-dose ICS combination or users of a medium-dose ICS and (2) users of a LABA plus medium-dose ICS combination or users of a high-dose ICS. Generalized estimating equations were used to compare the risk of major malformations between the groups. In one subcohort there were 643 women who used a LABA plus low-dose ICS and 305 who used a medium-dose ICS; the other subcohort included 198 users of a LABA plus medium-dose ICS and 156 users of a high-dose ICS. The prevalence of major malformations was 6.9% and 7.2%, respectively. The adjusted odds ratio for major malformations was 1.1 (95% CI, 0.6-1.9) when a LABA plus low-dose ICS was used compared with a medium-dose ICS and 1.2 (95% CI, 0.5-2.7) when a LABA plus medium-dose ICS was used compared with a high-dose ICS. The risk of major malformations was similar with a LABA plus ICS combination and ICS monotherapy at higher doses, suggesting that both therapeutic options can be considered during pregnancy.

Combination inhaled corticosteroids and long-acting beta2-agonists for children and adults with bronchiectasis.

Bronchiectasis is a major contributor to chronic respiratory morbidity and mortality worldwide. Wheeze and other asthma-like symptoms and bronchial hyperreactivity may occur in people with bronchiectasis. Physicians often use asthma treatments in patients with bronchiectasis. To assess the effects of inhaled long-acting beta2-agonists (LABA) combined with inhaled corticosteroids (ICS) in children and adults with bronchiectasis during (1) acute exacerbations and (2) stable state. The Cochrane Airways Group searched the the Cochrane Airways Group Specialised Register of Trials, which includes records identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other databases. The Cochrane Airways Group performed the latest searches in October 2013. All randomised controlled trials (RCTs) of combined ICS and LABA compared with a control (placebo, no treatment, ICS as monotherapy) in children and adults with bronchiectasis not related to cystic fibrosis (CF). Two review authors extracted data independently using standard methodological procedures as expected by The Cochrane Collaboration. We found no RCTs comparing ICS and LABA combination with either placebo or usual care. We included one RCT that compared combined ICS and LABA with high-dose ICS in 40 adults with non-CF bronchiectasis without co-existent asthma. All participants received three months of high-dose budesonide dipropionate treatment (1600 micrograms). After three months, participants were randomly assigned to receive either high-dose budesonide dipropionate (1600 micrograms per day) or a combination of budesonide with formoterol (640 micrograms of budesonide and 18 micrograms of formoterol) for three months. The study was not blinded. We assessed it to be an RCT with overall high risk of bias. Data analysed in this review showed that those who received combined ICS-LABA (in stable state) had a significantly better transition dyspnoea index (mean difference (MD) 1.29, 95% confidence interval (CI) 0.40 to 2.18) and cough-free days (MD 12.30, 95% CI 2.38 to 22.2) compared with those receiving ICS after three months of treatment. No significant difference was noted between groups in quality of life (MD -4.57, 95% CI -12.38 to 3.24), number of hospitalisations (odds ratio (OR) 0.26, 95% CI 0.02 to 2.79) or lung function (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)). Investigators reported 37 adverse events in the ICS group versus 12 events in the ICS-LABA group but did not mention the number of individuals experiencing adverse events. Hence differences between groups were not included in the analyses. We assessed the overall evidence to be low quality. In adults with bronchiectasis without co-existent asthma, during stable state, a small single trial with a high risk of bias suggests that combined ICS-LABA may improve dyspnoea and increase cough-free days in comparison with high-dose ICS. No data are provided for or against, the use of combined ICS-LABA in adults with bronchiectasis during an acute exacerbation, or in children with bronchiectasis in a stable or acute state. The absence of high quality evidence means that decisions to use or discontinue combined ICS-LABA in people with bronchiectasis may need to take account of the presence or absence of co-existing airway hyper-responsiveness and consideration of adverse events associated with combined ICS-LABA.

Management of Asthma and Chronic Obstructive Pulmonary Disease with Combination Inhaled Corticosteroids and Long-Acting β-Agonists: A Review of Comparative Effectiveness Research

The value of combination therapy with inhaled corticosteroids and long-acting β-agonists (ICS/LABA) is well recognized in the management of asthma and chronic obstructive pulmonary disease (COPD). Despite differences in the pharmacological properties between two well-established ICS/LABA products (budesonide/formoterol and fluticasone/salmeterol), data from randomized clinical trials (RCTs) and meta-analyses suggest that these two products perform similarly under RCT conditions. In contrast, a few recently reported real-world comparative effectiveness studies have suggested that there are substantial differences between ICS/LABA combination treatments in terms of clinical and healthcare outcomes in patients with asthma or COPD. The purpose of this article is to provide a brief review of the benefits, as well as the limitations, of comparative effectiveness research (CER) in the therapeutic area of asthma and COPD. We conducted a structured literature review of the current CER studies on ICS/LABA combinations in asthma and COPD. These articles were then used to illustrate the unique challenges of CER studies, providing a summary of study results and limitations. We focus particularly on difficult biases and confounding factors that may be introduced before, during, and after the initiation of therapy. Beyond being a review of these two ICS/LABA combination treatments, this article is intended to help those who wish to assess the quality of CER published projects in asthma and COPD, or guide investigators who wish to design new CER studies for chronic respiratory disease treatments.

Cardiovascular Safety of Long Acting Beta Agonist-Inhaled Corticosteroid Combination Products in Adult Patients with Asthma: A Systematic Review

Long-acting beta agonists and inhaled corticosteroids combination products (LABA-ICS) are widely used in the treatment of asthma. However, there appears to be little data on their cardiovascular safety. The purpose of this study was to conduct a systematic review of the available studies and trials on the cardiovascular safety of LABA-ICS in adults with asthma. Two independent reviewers screened citations from PubMed and National Clinical Trials registry to identify studies and trials on the cardiovascular effects of LABA-ICS in patients with asthma. A total of 15 studies (with 17 cohorts on LABA-ICS to compare with a comparator or placebo) with 5,440 total study participants met the inclusion criteria. Two studies on budesonide-formoterol and one on fluticasone-salmeterol reported treatment emergent cardiovascular adverse events, all of which were dysrhythmias. For comparison, the pooled estimate of the Peto odds ratio (0.72; 95% confidence interval [CI] 0.17-3; p=0.65) and the summary risk ratio (0.77; 95% CI 0.26-2.3; p=0.64) indicated a nonsignificant difference between LABA-ICS and comparator/placebo groups. Our systematic review found that few studies and trials reported treatment emergent cardiovascular adverse events with LABA-ICS. However, the Peto odds ratio and risk ratio for these outcomes was statistically nonsignificant. This suggests that LABA-ICS products may have a safe cardiovascular profile in asthma patients.

Long-Acting β2-Agonist Step-off in Patients With Controlled Asthma

Because of concerns about the safety of long-acting β(2)-agonist (LABA) use in patients with asthma, withdrawal of the LABA is recommended by the US Food and Drug Administration once asthma is controlled by combination therapy with a LABA and inhaled corticosteroid (ICS). To perform a systematic review and meta-analysis assessing evidence supporting the discontinuation of LABA therapy once asthma control has been achieved with a combination of ICS and LABA. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched (through August 2010), references of identified studies and selected narrative review articles were evaluated, registries of clinical trials were reviewed, and manufacturers of LABAs were contacted. Randomized controlled trials of discontinuation of LABA therapy in patients with asthma controlled with a combination of ICS and LABA. Two reviewers independently screened each title and abstract in the initial searches and then the full text of each nominated article to extract data for analyses. Of 1492 screened articles, only 5 trials involving patients aged 15 years or older fulfilled a priori–specified inclusion criteria. Results did not favor the LABA step-off approach compared with no change in treatment. The LABA step-off regimen increased asthma impairment, with worse Asthma Quality of Life Questionnaire score (mean difference [95% CI], 0.32 [0.14-0.51] points lower); worse Asthma Control Questionnaire score (0.24 [0.13-0.35] points higher); fewer symptom-free days (9.15% [1.62%-16.69%] less); and greater risk of withdrawal from study resulting from lack of efficacy or loss of asthma control (risk ratio, 3.27 [2.16-4.96]). Risk of exacerbations and deaths after LABA step-off were not evaluable because of the small number of events and short duration of follow-up. Evidence suggests that discontinuing LABA therapy in adults and older children with asthma controlled with a combination of ICSs and LABAs results in increased asthma-associated impairment. Additional trials measuring all long-term patient-important outcomes are needed.

G894T Polymorphism of eNOS Gene is a Predictor of Response to Combination of Inhaled Corticosteroids with Long-Lasting β 2 -Agonists in Asthmatic Children

Nitric oxide synthase enzymes have an important role in airway inflammation in asthmatic children. In the present study, the association between eNOS gene polymorphisms and response to inhaled corticosteroids (ICS) and long-lasting β(2)-agonists (LABAs) was investigated. A total of 81 asthmatic children treated with ICS plus LABAs and 96 healthy controls were genotyped for eNOS G894T and -786T/C polymorphisms and their haplotypes using the PCR-RFLP method. G894T and -786T/C polymorphisms were not associated with asthma susceptibility. Among asthmatic children, 894TT carriers had higher change in forced expiratory volume in 1 s (FEV(1)) in response to ICS plus LABAs compared with 894GG carriers (21.9 ± 3.8 vs 1.6 ± 1.9%; p < 0.001). In responders (FEV(1) change ≥7.5%), frequency of 894TT genotype was significantly higher than in nonresponders (26.2 vs 2.6%, p < 0.001). Results for the -786T/C polymorphism alone were less clear and in most cases nonsignificant. The G894T polymorphism was associated with response to ICS and may serve as a useful pharmacogenetic marker of response to ICS plus LABAs in asthmatic children.

Anti-inflammatory Treatment after Discharge Home from the Emergency Department in Adults with Acute Asthma

Airway inflammation from respiratory infections or exposure to allergens, irritants, or both leads to increased airflow obstruction and respiratory symptoms in patients with acute asthma. Antiinflammatory therapy with systemic corticosteroids (CSs) is therefore a cornerstone of the management of patients with acute asthma, particularly those presenting to the emergency department (ED) (1, 2). After initial management in the ED, most patients improve sufficiently to be discharged home with instructions to complete a short course of daily oral corticosteroids (OCSs) and short-acting inhaled bronchodilators as needed for symptom relief. Unfortunately, up to one third of patients who initially respond to therapy relapse within the first 3 to 4 weeks after ED discharge (e.g., require treatment escalation, urgent care or ED visits, or hospitalizations for asthma) (3, 4). The propensity of many patients to relapse after ED discharge has led to a number of randomized clinical trials evaluating alternative outpatient antiinflammatory treatment strategies in this population, including the use of inhaled corticosteroids (ICSs), intramuscular corticosteroids (IMCSs), and noncorticosteroid anti-inflammatory regimens. The objective of this systematic review is to synthesize the results of randomized clinical trials in adults with acute asthma, comparing alternative outpatient anti-inflammatory treatment strategies to reduce the risk of relapse after discharge home from the ED. More specifically, this systematic review examined the following anti-inflammatory treatment options in adults after ED discharge: (1) IMCSs versus OCSs, (2) ICSs versus OCSs, (3) combination of ICSs plus OCSs versus OCSs alone, and (4) noncorticosteroid anti-inflammatory agents (macrolide antibiotics and leukotriene modifiers) in addition to systemic corticosteroids. This report updates previously published systematic reviews in acute asthma (5–7) with subsequently published studies and provides a single document summarizing this body of literature for easy use by clinicians.

Anti-Inflammatory Treatment After Discharge Home from the Emergency Department in Adults with Acute Asthma

Airway inflammation from respiratory infections or exposure to allergens, irritants, or both leads to increased airflow obstruction and respiratory symptoms in patients with acute asthma. Antiinflammatory therapy with systemic corticosteroids (CSs) is therefore a cornerstone of the management of patients with acute asthma, particularly those presenting to the emergency department (ED) (1, 2). After initial management in the ED, most patients improve sufficiently to be discharged home with instructions to complete a short course of daily oral corticosteroids (OCSs) and short-acting inhaled bronchodilators as needed for symptom relief. Unfortunately, up to one third of patients who initially respond to therapy relapse within the first 3 to 4 weeks after ED discharge (e.g., require treatment escalation, urgent care or ED visits, or hospitalizations for asthma) (3, 4). The propensity of many patients to relapse after ED discharge has led to a number of randomized clinical trials evaluating alternative outpatient antiinflammatory treatment strategies in this population, including the use of inhaled corticosteroids (ICSs), intramuscular corticosteroids (IMCSs), and noncorticosteroid anti-inflammatory regimens. The objective of this systematic review is to synthesize the results of randomized clinical trials in adults with acute asthma, comparing alternative outpatient anti-inflammatory treatment strategies to reduce the risk of relapse after discharge home from the ED. More specifically, this systematic review examined the following anti-inflammatory treatment options in adults after ED discharge: (1) IMCSs versus OCSs, (2) ICSs versus OCSs, (3) combination of ICSs plus OCSs versus OCSs alone, and (4) noncorticosteroid anti-inflammatory agents (macrolide antibiotics and leukotriene modifiers) in addition to systemic corticosteroids. This report updates previously published systematic reviews in acute asthma (5–7) with subsequently published studies and provides a single document summarizing this body of literature for easy use by clinicians.

Anti-inflammatory treatment after discharge home from the emergency department in adults with acute asthma

Airway inflammation from respiratory infections or exposure to allergens, irritants, or both leads to increased airflow obstruction and respiratory symptoms in patients with acute asthma. Antiinflammatory therapy with systemic corticosteroids (CSs) is therefore a cornerstone of the management of patients with acute asthma, particularly those presenting to the emergency department (ED) (1, 2). After initial management in the ED, most patients improve sufficiently to be discharged home with instructions to complete a short course of daily oral corticosteroids (OCSs) and short-acting inhaled bronchodilators as needed for symptom relief. Unfortunately, up to one third of patients who initially respond to therapy relapse within the first 3 to 4 weeks after ED discharge (e.g., require treatment escalation, urgent care or ED visits, or hospitalizations for asthma) (3, 4). The propensity of many patients to relapse after ED discharge has led to a number of randomized clinical trials evaluating alternative outpatient antiinflammatory treatment strategies in this population, including the use of inhaled corticosteroids (ICSs), intramuscular corticosteroids (IMCSs), and noncorticosteroid anti-inflammatory regimens. The objective of this systematic review is to synthesize the results of randomized clinical trials in adults with acute asthma, comparing alternative outpatient anti-inflammatory treatment strategies to reduce the risk of relapse after discharge home from the ED. More specifically, this systematic review examined the following anti-inflammatory treatment options in adults after ED discharge: (1) IMCSs versus OCSs, (2) ICSs versus OCSs, (3) combination of ICSs plus OCSs versus OCSs alone, and (4) noncorticosteroid anti-inflammatory agents (macrolide antibiotics and leukotriene modifiers) in addition to systemic corticosteroids. This report updates previously published systematic reviews in acute asthma (5–7) with subsequently published studies and provides a single document summarizing this body of literature for easy use by clinicians.

Complementary therapy in asthma: inhaled corticosteroids and what?

For optimal asthma control, complementary strategies are advocated to cover several aspects of the disease. This mini-review highlights different complementary strategies with special focus on the combined use of inhaled corticosteroids (ICSs) and long-acting beta2 agonists and as an alternative, the combination of ICSs and antileukotrienes. New data show that combinations of ICSs/long-acting beta2 agonists or ICSs with antileukotrienes improve disease stability with concomitant control of the underlying airway inflammation. Moreover, there is some evidence that combination therapy may prevent some aspects of airway remodelling. The use of a fixed combination of both a reliever and a controller medication may have certain advantages compared with a fixed dose regime with as-needed separate reliever therapy. Alternatively, in some asthma phenotypes, such as combined allergic rhinitis and asthma syndrome, the combination of ICSs with antileukotrienes offers a complementary anti-inflammatory treatment in combination with controller effects on both airway compartments. This review compares different strategies of complementary therapy in asthma with special focus on how to achieve the best clinical control also aimed at controlling the underlying airway inflammation. We have chosen to focus on two major topics: the use of ICSs and long-acting beta2 agonists in two different strategies, that is, a symptom-driven versus a fixed symptom-preventive approach; and the use of ICSs with a long-acting beta2 agonist versus ICSs and a leukotriene receptor antagonist. What regime should be chosen is highly dependent on the individual phenotype and defined treatment goal.

Dose counting and the use of pressurized metered-dose inhalers: running on empty

Pressurized metered-dose inhalers (pMDIs) are the cornerstone of asthma treatment. The pMDI is an economic and portable medication delivery system, but the device does not indicate how much medicine remains in the canister once a patient starts using it. To determine how patients evaluate the contents of their pMDI and whether they are either discarding inhalers when medication remains or using inhalers beyond the indicated number of doses. This study was conducted in April 2003 via a 6.5-minute telephone interview with a random sample of 500 families with asthma from across the United States. Of the 500 respondents participating in the telephone interview, nearly one third (31.6%) named an inhaled corticosteroid or bronchodilator and inhaled corticosteroid combination as the inhaler used when wheezing, coughing, or short of breath. Respondents using a bronchodilator (n = 342) varied in the frequency with which they use their pMDIs: 31.9% daily, 18.7% weekly, 23.4% monthly, and 23.1% less than once per month. More than half (53.8%) of bronchodilator users refill their prescriptions more frequently than recommended by national guidelines. Only 36% of bronchodilator users reported ever having been told to keep track of pMDI doses used. Of those, 79% had been advised to do so by a physician, 6% by a pharmacist, and 3% by a nurse. Eighty-seven (25%) of the 342 respondents who named a bronchodilator reported having found their pMDI empty during an asthma exacerbation. Seven of those patients had to call 911. Of these 87 patients, 71 (82%) considered their pMDI empty when absolutely nothing came out. Patients do not have a reliable means of monitoring the contents of their metered-dose inhalers, which is causing serious problems that need to be addressed. Given the necessity of a reliable dose counting method, it is clear that manufacturers should include dose counters as a standard feature of every metered-dose inhaler.