Reliever Therapy Research Articles

Overuse of reliever inhalers and associated healthcare utilization of asthma patients

Global Initiative for Asthma 2019 guidelines recommend to avoid strengthening patients’ reliance on relievers since they increase exacerbation risk. Our aim was to examine the association between reliever inhalers overuse and all-cause healthcare utilization (HCU). A retrospective study among Clalit Health Services (CHS) adult enrollees (n = 977) for 2012–2017. Reliever inhalers overuse was defined as consistent prescription refills of ≥ 3 canisters annually. Adherence to controllers was calculated using the proportion of days covered. HCU included: hospitalizations, diagnostic and surgical procedures, medications, emergency room (ER) visits, and clinic visits. 27% of the study population (n = 264) consistently refilled ≥ 3 relievers prescriptions annually, and had higher adherence to controllers (0.38 vs. 0.24, p < 0.001). Their total 6-year HCU costs were not higher than that of others ($5,550 vs. $5,562, p = 0.107). Most HCU components [including hospitalization (p = 0.405) and ER visits (p = 0.884)] were comparable; however, medication costs were higher ($1734 vs. $1504, p < 0.001). A multivariable ordered-logit model revealed that frequent and regular use of relievers was not associated with higher HCU costs (OR = 0.82, 95% CI 0.62–1.09, p = 0.175). Higher adherence to maintenance and reliever therapy (OR = 2.18, 95% CI 1.44–3.28, p < 0.001), other controllers (OR = 3.30, 95% CI 2.11–5.16, p < 0.001), and nebulized SABAs and SAMAs (OR = 1.08, 95% CI 1.02–1.14, p = 0.007) was associated with higher costs. Overuse of reliever inhalers was prevalent and associated with higher adherence to controllers, yet not associated with higher all-cause HCU. This highlights the need to examine the sources of elevated usage in order to develop intervention strategies to optimize pharmaceutical therapy of asthma patients.

Asthma in the anti-inflammatory reliever therapy era

Asthma in the anti-inflammatory reliever therapy era

What matters most to patients when choosing treatment for mild–moderate asthma? Results from a discrete choice experiment

BackgroundAn as-needed combination preventer and reliever regimen was recently introduced as an alternative to conventional daily preventer treatment for mild asthma. In a subgroup analysis of the PRACTICAL study, a...

Detecting asthma exacerbations using daily home monitoring and machine learning

Objective Acute exacerbations contribute significantly to the morbidity of asthma. Recent studies have shown that early detection and treatment of asthma exacerbations leads to improved outcomes. We aimed to develop a machine learning algorithm to detect severe asthma exacerbations using easily available daily monitoring data. Methods We analyzed daily peak expiratory flow and symptom scores recorded by participants in the SAKURA study (NCT00839800), an international multicentre randomized controlled trial comparing budesonide/formoterol as maintenance and reliever therapy versus budesonide/formoterol maintenance plus terbutaline as reliever, in adults with persistent asthma. The dataset consisted of 728,535 records of daily monitoring data in 2010 patients, with 576 severe exacerbation events. Data post-processing techniques included normalization, standardization, calculation of differences or slopes over time and the use of smoothing filters. Principal components analysis was used to reduce the large number of derived variables to a smaller number of linearly independent components. Logistic regression, decision tree, naïve Bayes, and perceptron algorithms were evaluated. Model accuracy was assessed using stratified cross-validation. The primary outcome was the detection of exacerbations on the same day or up to three days in the future. Results The best model used logistic regression with input variables derived from post-processed data using principal components analysis. This had an area under the receiver operating characteristic curve of 0.85, with a sensitivity of 90% and specificity of 83% for severe asthma exacerbations. Conclusion Asthma exacerbations may be detected using machine learning algorithms applied to daily self-monitoring of peak expiratory flow and asthma symptoms.

Today's improvement in asthma treatment: role of MART and Easyhaler.

Asthma affects more than 330 million people worldwide, but many analyses have shown that there are still a lot of unmet needs for both patients and physicians in the treatment of asthma: poor adherence to treatment is one of the main causes of sub-optimal clinical results. Maintenance and Reliever Therapy (MART) with the combination of formoterol and inhaled corticosteroids (ICS) has an established scientific rationale and demonstrated to reduce asthma exacerbations. The aim of this review is to highlight how in asthmatic patients MART can be able to express its maximum therapeutic potential when administered through an ‘ideal inhaler’. Since the treatment may be necessary several times a day, the use of a single combination inhaler simplifies the management, potentially improving adherence; moreover, easiness of use and comfort in administration of asthma treatment devices are not secondary aspects. Asthmatic patients are often young, with a normal relational and working life and they could request for a comfortable and not too noticeable device. Finally to the “ideal inhaler” is requested to guarantee accuracy, dose consistency, and resistance to stress conditions. Easyhaler® more closely demonstrates many expected characteristics: effective, consistent performance regardless of inspiration rate, stability, versatility, with several patient acceptability advantages. Asthma control is enhanced by a strong adherence obtained through the combination in a single inhaler of both maintenance and reliever therapy and the availability of a device as close as possible to the characteristics of the ideal inhaler.

Inhaled therapy for asthma

Andrew Booth explains why this is the preferred − and more successful − method when managing asthmaInhaled therapy is key to the successful treatment of asthma. National guidelines provide us with the aim of asthma management, which is to maintain control of the disease. The correct combination of drug and device can be individually tailored to the patient. Drugs consist of bronchodilators and anti-inflammatories. Devices consist of aerosol inhalers, also known as pressurised metered dose inhalers, and dry powder inhalers. Both the drug and the device need to be prescribed if the treatment is to be clinically effective. A combination of inhaled steroid with long-acting B2 agonist is one of the most clinically effective ways of delivering asthma treatment. This can be prescribed either as a fixed daily dose with a concomitant short-acting B2 agonist as a reliever, or as maintenance and reliever therapy, which has been shown to improve asthma control and reduce exacerbations.

Inhaled therapy for asthma

Inhaled therapy is key to the successful treatment of asthma. National guidelines provide us with the aim of asthma management, which is to maintain control of the disease. The correct combination of drug and device can be individually tailored to the patient. Drugs consist of bronchodilators and anti-inflammatories. Devices consist of aerosol inhalers, also known as pressurised metered dose inhalers, and dry powder inhalers. Both the drug and the device need to be prescribed if the treatment is to be clinically effective. A combination of inhaled steroid with long-acting B2 agonist is one of the most clinically effective ways of delivering asthma treatment. This can be prescribed either as a fixed daily dose with a concomitant short-acting B2 agonist as a reliever, or as maintenance and reliever therapy, which has been shown to improve asthma control and reduce exacerbations.

Sustainability in Inhaled Drug Delivery.

Asthma and chronic obstructive pulmonary disease (COPD) are amongst the most common chronic diseases worldwide, and are largely preventable by improving the quality of the air we breathe. The most commonly deployed treatment, the metered dose inhaler (MDI), uses hydrofluorocarbon propellants, which are powerful greenhouse gases that contribute disproportionately to the climate crisis. Alternative treatment strategies are required if we are to avoid contributing to the worst effects of climate change. These strategies include promoting non-pharmacological therapies like smoking cessation and pulmonary rehabilitation; empowering patients to gain better disease control through written management plans and encouraging preventer, rather than reliever therapies. Pharmacological strategies include: improving inhaler technique and spacer use; minimising propellant release by using smaller volume MDIs and simpler dosing regimes; dose counters to prevent waste; switching to low global warming potential inhalers; and inhaler recycling. There are also opportunities to improve disease control alongside reduced greenhouse gas emissions, including better matching of patients' devices to inhaler technique rather than defaulting to MDIs, stopping unnecessary inhaled steroids in COPD and maintenance and reliever therapy in asthma. New, lower global warming potential propellants are on the horizon, and their introduction could offer a golden opportunity to enhance MDIs usability and sustainability by making them refillable, integrating whistles to optimise inhalation technique, adding integrated caps, optimising materials for recycling and adding dose counters to all MDIs.

SMART and as-needed therapies in mild-to-severe asthma: a network meta-analysis.

To date, there are no network meta-analyses comparing the impact of as-needed treatments in asthma, including the single maintenance and reliever therapy (known as "SMART" or "MART"; for simplicity, SMART will be used hereafter) and the use of inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) combination exclusively on an as-needed basis. Therefore, we performed a systematic review and network meta-analysis concerning the efficacy and safety of SMART and as-needed therapies in asthma. Data from 32 096 asthmatic patients were extracted from 21 studies, lasting from 6 to 12 months. In adult mild-to-moderate asthmatic patients low-dose SMART and as-needed low-dose ICS/LABA combination were significantly (relative effect <0.78; p<0.05) more effective than the other as-needed therapies in reducing the risk of exacerbation, and both were ranked as the first treatment option reaching the first quartile of the surface under the cumulative ranking curve analysis (SUCRA). In adult moderate-to-severe asthmatic patients, low-dose to medium-dose SMART and high-dose ICS/LABA+as-needed short-acting β2-agonist were equally effective in reducing the risk of severe asthma exacerbation (p>0.05), although only low- to medium-dose SMART was ranked as the first treatment option (first SUCRA quartile). Overall, these treatments were well tolerated, and effective also on lung function and disease control. This study supports SMART and as-needed therapies as a suitable therapeutic option for asthma, by providing the most effective positioning of each specific treatment according to the disease severity.

Bronchial thermoplasty versus mepolizumab: Comparison of outcomes in a severe asthma clinic.

BT and interleukin-blocking monoclonal antibodies are both effective therapies for severe asthma, but there have been no direct comparisons between the two treatments. The aim of this study was to compare the efficacy and safety of BT and mepolizumab, in a real-world setting. Patients with severe asthma despite optimized inhaler therapy were drawn from a severe asthma clinic in a tertiary hospital. Every patient commencing therapy with BT or mepolizumab was prospectively included in a national registry. At predetermined assessment points over a 12-month period, assessments were made of ACQ, spirometry, oral corticosteroid requiring exacerbations, reliever medication and maintenance oral corticosteroid use. A total of 91 patients with severe asthma participated: mean ACQ score 3.5 ± 1.0, FEV1 51.4 ± 17.7%, maintenance oral steroids 48.3% and 11.5 ± 10.0 inhalations/day reliever therapy. Forty-seven patients received mepolizumab and 44 received BT. Baseline characteristics were similar except significantly higher blood eosinophil count in the mepolizumab group. At 12 months, there were no differences between treatment outcomes for ACQ (1.9 ± 1.3 mepolizumab vs 1.7 ± 1.3 BT), exacerbation rate (0.9 ± 1.1 vs 0.9 ± 1.5), reduction in reliever use (-6.3 ± 10.5 vs -5.0 ± 8.8 puffs/day) or reduction in oral corticosteroids (-3.3 ± 7.5 vs - 5.8 ± 6.7 mg/day). The FEV1 improved equally (160 ± 290 vs 150 ± 460 mL). Readmission or prolonged admission was observed in 18.2% of BT patients, whilst 25.5% of mepolizumab patients had discontinued treatment at 12 months, 14.9% due to an adverse event or non-compliance. The results suggest that BT is as efficacious as mepolizumab for the treatment of severe asthma.

Prescribing inhaled therapy in asthma: health professionals' habits and beliefs

National and international asthma guidelines provide the evidence base for prescribing growing array of different inhaled therapies. However, the advice given is generic. The influence of nurses in prescribing inhaled therapy continues to grow, yet there is little published to help understand how and why nurses prescribe or advise on the prescribing of inhaled therapy in asthma. The aim of the study was to gain a better understanding of how health professionals make prescribing decisions in inhaled therapy, which was done by taking a survey. The survey gathered data of the habits and beliefs on prescribing inhaled corticosteroid/inhaled long-acting B2 agonist therapy in asthma, from 100 primary healthcare professionals. As a result of the study, patient preference, dose counter and maintenance and reliever therapy were reported to be considered the most important elements by health professionals. The device was considered more important than the drug, and there is an ongoing need for further education of health professionals in this area. Comparing responses from this study with similar responses from people with asthma may bring together the thinking of patients and professionals.

What have we learnt about asthma control from trials of budesonide/formoterol as maintenance and reliever?

Despite improvements in medications, devices and understanding of the disease, about half of all asthma patients worldwide remain inadequately controlled, suggesting the need for a new approach to asthma management. Poor adherence to prescribed maintenance therapy and over-reliance on SABA reliever medication is a common cause of inadequate control. This article reviews published data from 6- to 12-month, double-blind, RCT and open-label real-world studies involving budesonide/formoterol maintenance and reliever therapy (MART) and relevant comparator approaches to asthma management, and considers how these compare in achieving the treatment goals described in guidelines. The data confirm that patients with asthma treated with budesonide/formoterol MART achieved the same or better asthma symptom control compared with ICS/LABA plus SABA regimens at similar or higher ICS doses, with consistently lower rates of exacerbations and considerably lower annual requirement for oral corticosteroids. These findings have been confirmed across a range of severities of persistent asthma. With the MART approach, maintenance dosing ensures coverage for day-to-day control, and the use of a reliever with anti-inflammatory properties (budesonide/formoterol) provides extra doses of ICS as soon as symptoms prompt the use of reliever, resulting in a 40-50% reduction of exacerbations compared with an ICS-based treatment approach plus as-needed SABA as reliever. As-needed, budesonide/formoterol has also recently been shown to be more effective as a reliever in mild asthma than SABA alone, reducing exacerbations by up to 64% in the SYGMA studies.

How to design an education programme for patients with chronic obstructive disease?

Introduction: COPD is a debilitating disease and a major death cause by 2020. Our current knowledge of the opportunities of patient education in the community pharmacy is growing, though yet limited.&#x0D; Objectives: (1) To assess the potential of a patient education programme in a Hungarian pharmacy, (2) to understand patient attitudes and gather insight for the development of an education project, (3) to create a sustainable local good practice.&#x0D; Methods: We invited patients with a confirmed COPD diagnosis to take part in an in-depth interview, and to assess their symptoms. Later on, we offered them tailor-made education to learn about their attitudes to create the guidelines for optimal content. &#x0D; Results: Key elements of the education content should focus on the desire of active life, improve poor adherence, teach about reliever and maintenance therapy and emphasise the chronic component of the disease. Smoking cessation should be fostered, whilst patients would benefit from proper breathing techniques and posture. &#x0D; Conclusion: Hungarian patients may prefer to get fast and basic education in the community pharmacies. The ideal education content should include pathophysiology, signs and symptoms, treatment options, explanation of medication, inhaler use, smoking cessation and breathing techniques.

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.

ICS-formoterol reliever therapy stepwise treatment algorithm for adult asthma

A practical “anti-inflammatory reliever therapy”-based algorithm based on the GINA 2019 update is presented, together with a prototype action plan to facilitate its implementation.http://bit.ly/33C2s5u

Twenty-five years of Respirology: Advances in asthma.

Twenty-five years of Respirology: Advances in asthma.

Dose-response relationship of ICS/fast-onset LABA as reliever therapy in asthma

Background and objectiveThe dose-response relationship of inhaled corticosteroid (ICS)/fast-onset long acting beta agonist (LABA) reliever therapy has not been formally addressed. The objective of this retrospective analysis is to ascertain from the available evidence whether ICS/fast-onset LABA administered as reliever therapy has a different dose-response relationship than maintenance fixed dose ICS/fast-onset LABA therapy in reducing risk of severe exacerbations.MethodsA systematic literature review was undertaken to identify randomised controlled trials (RCTs) in which randomised treatments included either i) budesonide/formoterol reliever monotherapy versus budesonide/formoterol fixed dose maintenance with short acting beta agonist (SABA) reliever therapy, or ii) budesonide/formoterol reliever therapy in addition to budesonide/formoterol maintenance versus higher fixed dose maintenance budesonide/formoterol with SABA as reliever therapy. Eligible studies were reviewed to allow determination of the relative potency and efficacy of the comparator regimens to reduce the risk of a severe exacerbation.ResultsThe one RCT of budesonide/formoterol reliever monotherapy showed a 4.6-fold (95% CI 2.9 to 7.3) greater potency than budesonide/formoterol fixed dose maintenance plus SABA reliever therapy in reducing the risk of severe exacerbations. In the one RCT that compared budesonide/formoterol maintenance and reliever therapy with higher fixed dose maintenance budesonide/formoterol plus SABA reliever therapy, there was an additional 26% (95% CI 4 to 42%) reduction in severe exacerbation risk with the addition of budesonide/formoterol reliever therapy to maintenance budesonide/formoterol, despite a 25% lower total budesonide/formoterol dose.ConclusionThe limited available evidence suggests that budesonide/formoterol reliever therapy has greater potency and efficacy than budesonide/formoterol fixed dose maintenance plus SABA reliever therapy in reducing the risk of a severe exacerbation. This is an important concept which has the potential to guide clinical practice in asthma, although the small number of studies available highlights the need for further research to better define these pharmacological properties.

PRS4 SABA OVERUSE AND HEALTH CARE RESOURCE UTILIZATION IN A NATIONWIDE SWEDISH ASTHMA COHORT (HERA)

Short-acting beta2-agonists (SABA) are used as reliever therapy in asthma, and over-reliance on SABA is a marker of uncontrolled asthma. This study assessed the association between SABA use and health care resource use in a general asthma population in Sweden. We identified 365,324 patients with asthma aged 12–45 years from national registers. Asthma status was defined as collection of ≥2 drugs for obstructive lung disease in any 12-month period during 2006-2014 (date of inclusion was 2nd collection date). SABA over-reliance was defined as >2 SABA canisters in a 12-month baseline period following inclusion. Patients that were over-reliant on SABA were further grouped as 3-5, 6-10, or ≥11 canisters/year. Health care resource use was defined as rates of total and asthma-related hospitalization and outpatient visits. Mean age of patients was 27.6 years; 55% were women. Thirty percent of patients were over-reliant on SABA: 21% collected 3-5; 7% 6-10; and 2% ≥11 canisters/year. Patients over-reliant on SABA and those who were not over-reliant were similar in relation to age, gender, and co-morbidities. Patients over-reliant on SABA had more exacerbations (29.8 per/1000 patient-years (PY) vs 17.6), total hospitalizations (62.4 per/1000 PY vs 48.3), asthma-related hospitalizations (4.6 per/1000 PY vs 1.0), total outpatient visits (587.5 per/1000 PY vs 507.1), and asthma-related outpatient visits (209.4 per/1000 PY vs 132.1) than patents who were not over-reliant on SABA. Higher numbers of SABA canisters collected was associated with higher rates of hospitalizations and outpatient visits. In this nationwide asthma population, up to 30% of patients were over-reliant on SABA. These patients were at greater risk for hospitalization and outpatient visits than those who were not over-reliant on SABA. Improved outpatient follow-up of patients over-reliant on SABA may help to reduce the rates of hospitalizations for asthma.

PRS46 TREATMENT OF SEVERE ASTHMA IN PORTUGAL: INSIGHTS FROM A PHYSICIANS' SURVEY

Severe Asthma (SA) is characterized by difficulty of controlling exacerbations and asthma symptoms despite optimized therapy. The aim of this study was to identify physicians’ prescribing behavior when treating patients with SA, focusing on their willingness to prescribe biologics. A physician’s primary market research study was conducted through computer assisted web interviewing. Among a sample of 62 physicians, a total of 50 physicians who prescribed a biologic completed the survey (30 pneumologists and 20 allergists). It is estimated that approximately 3.6% of asthma patients aged above 12 years old (19,733 patients) were treated for SA by pneumologists and allergists in 2018. Concerning their corticosteroid therapy, 52% of treated patients received an inhaled corticosteroids (ICS) plus long-acting reliever therapy; 41% received ICS plus oral corticosteroids (OCS) and long-acting reliever; 5% received a biologic plus ICS or OCS and long-acting reliever; and 2% were treated with other combinations. Among treated patients, approximately 46% were uncontrolled with current therapy, and 73% of these (6,673 patients) could benefit from a biologic to control exacerbations and symptomatology (regardless of patient adherence). Focusing on patients already under biologic therapy, 17% remained uncontrolled by current biologic. Concerning key treatment attributes influencing SA patient therapeutic strategy, 94% of physicians ranked efficacy in symptom control as one of the three most important attributes, followed by efficacy in exacerbations prevention and control (84%), and lung function improvement (80%). The study allowed a broad understanding of SA treatment prescribing behavior and the effectiveness of therapies in SA control. Almost half of SA patients were uncontrolled with current treatment and a substantial proportion could benefit from biologics, demonstrating the high unmet need and the need for new innovative solutions for patients uncontrolled with biologics.

Anti-inflammatory reliever therapy for asthma

Anti-inflammatory reliever therapy for asthma