Inhaled Combined Budesonide–Formoterol as Needed in Mild Asthma

O'Byrne, Paul M.; FitzGerald, J. Mark; Bateman, Eric D.; Barnes, Peter J.; Zhong, Nanshan; Keen, Christina; Jorup, Carin; Lamarca, Rosa; Ivanov, Stefan; Reddel, Helen K.

doi:10.1056/nejmoa1715274

Cited by 474 publications

(591 citation statements)

References 34 publications

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“…Given the superiority of an on-demand ICS-containing regimen in two separate trials performed in patients with mild asthma in reducing the risk of exacerbation [186,187], later confirmed in a real-life setting [188], the last GINA update promotes this strategy as early as step 1, acknowledging the obvious inflammatory nature of the disease and in particular during episodes of poor control that precedes exacerbation.…”

Section: Current Small Molecule Asthma Therapies Corticosteroidsmentioning

confidence: 99%

ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions

et al. 2019

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Despite the use of effective medications to control asthma, severe exacerbations in asthma are still a major health risk and require urgent action on the part of the patient and physician to prevent serious outcomes such as hospitalisation or death. Moreover, severe exacerbations are associated with substantial healthcare costs and psychological burden, including anxiety and fear for patients and their families. The European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS) set up a task force to search for a clear definition of severe exacerbations, and to also define research questions and priorities. The statement includes comments from patients who were members of the task force.

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Section: Current Small Molecule Asthma Therapies Corticosteroidsmentioning

confidence: 99%

ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions

et al. 2019

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“…The fourth paradox is that ICS/SABA reliever monotherapy is more efficacious than SABA reliever monotherapy at step 1 and has similar efficacy to ICS maintenance and SABA reliever therapy at step 2 [25], and yet is not recommended in international guidelines at either step. More recently, ICS/fast-onset LABA reliever monotherapy has also been shown to be more efficacious than SABA reliever monotherapy at step 1 and has similar efficacy to ICS maintenance and SABA reliever therapy at step 2, in terms of severe exacerbation risk [26,27]. Those patients who are over-reliant on SABA and nonadherent with ICS may gain particular benefit from combination ICS/fast-onset β-agonist reliever monotherapy, as ICS use will be driven by the use of such combination medications as reliever therapy.…”

Section: Fourth Paradoxmentioning

confidence: 99%

The further paradoxes of asthma management: time for a new approach across the spectrum of asthma severity

et al. 2018

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@ERSpublicationsA paradigm shift in asthma management that addresses the paradoxes of SABA reliever therapy is required; consideration needs to be given to replacement of SABA reliever with ICS/fast-onset β-agonist reliever therapy across the range of asthma severity http://ow.ly/ccff30lNLPv Cite this article as: Beasley R, Bird G, Harper J, et al. The further paradoxes of asthma management: time for a new approach across the spectrum of asthma severity. Eur Respir J 2018; 52: 1800694 [https://doi.org/ 10.1183/13993003.00694-2018].Should short-acting β-agonist (SABA) reliever monotherapy be replaced by combination inhaled corticosteroid (ICS)/fast-onset β-agonist as reliever therapy in asthma patients at Global Initiative for Asthma step 1 [1]? This uncertainty is the latest chapter in the controversy relating to the risks and benefits of β-agonist therapy in asthma management [2]. This 70-year controversy began with the introduction of isoprenaline and the concerns that it caused severe refractory asthma and an increased risk of death [3][4][5].The dilemma of evaluating the relative efficacy and risk of β-agonists has persisted since then. Two asthma mortality epidemics in the 1960s and 1970s/1980s were primarily caused by use of high-dose preparations of the potent, yet poorly β 2 -selective agonists, isoprenaline [6] and fenoterol [7], respectively. The epidemics ended abruptly with regulatory restriction and withdrawal of these agents [2,8]. In response to evidence that regular scheduled use of SABAs could increase asthma severity and the risk of exacerbations, the recommendation for their use was changed to "as required for relief of symptoms". This therapeutic approach, together with the increasing use of ICSs, both as separate inhalers and combination ICS/long-acting β-agonist (LABA) inhalers, has been associated with a marked reduction in asthma mortality since the 1990s, although the global rates of asthma mortality have now plateaued [9]. There is clearly a need for alternative treatment strategies to achieve further reductions in global asthma mortality.One strategy is to reduce the potential risks associated with starting SABA reliever monotherapy in intermittent and mild persistent asthma. This strategy was the focus of a recent review in the European Respiratory Journal [1], which identified five paradoxes of this therapeutic approach. The review summarised evidence that SABA reliever monotherapy exposes patients to significant avoidable risk and leads to learned behaviours, which result in difficulties for both patients and doctors (table 1). SABA reliever therapy not only reduces the potential to achieve optimal control at step 1, but also when patients progress to higher treatment steps in the stepwise approach to pharmacological therapy. In this editorial,

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“…The main issues with outcomes such as exacerbation are the rate of the events, which are infrequent in mild to moderate allergic asthma. The absence of daily symptoms and exacerbations define asthma control, but these criteria may respond differently to any specific intervention . Thus, asthma outcomes recommended by health authorities might have different relevance compared to those reported in real life by patients with allergic asthma …”

Section: Introduction Backgroundmentioning

confidence: 99%

EAACI Guidelines on Allergen Immunotherapy: House dust mite‐driven allergic asthma

Agache

Lau

Akdiş

et al. 2019

Allergy

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blind placebo controlled; EAACI, European Academy of Allergy and Clinical Immunology; FEF 25-75, forced expiratory flow at 25-75% of the pulmonary volume; FEV1, forced expiratory volume in 1 second; GINA, Global Initiative for Asthma; GRADE, The Grading of Recommendations Assessment, Development and Evaluation; HCP, healthcare professional; HDM, house dust mites; ICS, inhaled corticosteroids; MEF 25, maximal expiratory flow at 25% of forced vital capacity; MEF 50, maximal expiratory flow at 50% of forced vital capacity; MEF 75, maximal expiratory flow at 75% of forced vital capacity; PD20, provocative dose causing a 20% drop in FEV1; QoL, quality of life; RCTs, randomized control trials; ROB, risk of bias; SCIT, subcutaneous allergen immunotherapy; SLIT, sublingual allergen immunotherapy; SmPC, Summary of product characteristics; WAO, World Allergy Organization; WHO, World Health Organization.Agache and Lau are joint first co-authorship. External peer-reviewers: AbstractAllergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence-based recommendations for the use of house dust mites (HDM) AIT as add-on treatment for HDM-driven allergic asthma. This guideline was developed by a multi-disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AITwith HDM SLIT-tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add-on to regular asthma therapy for adults with controlled or partially controlled HDM-driven allergic asthma (conditional recommendation, moderate-quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM-driven allergic asthma as the add-on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low-quality evidence). K E Y W O R D Sallergen immunotherapy, allergy, asthma, asthma control, asthma exacerbations, GRADE, house dust mites, lung function

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Inhaled Combined Budesonide–Formoterol as Needed in Mild Asthma

Cited by 474 publications

References 34 publications

ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions

ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions

The further paradoxes of asthma management: time for a new approach across the spectrum of asthma severity

EAACI Guidelines on Allergen Immunotherapy: House dust mite‐driven allergic asthma

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