Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations

McKeever, Tricia M.; Mortimer, Kevin; Wilson, Andrew; Walker, Samantha; Brightling, Christopher E.; Skeggs, Andrew; Pavord, Ian; Price, David; Duley, Lelia; Thomas, Michael; Bradshaw, Lucy; Higgins, Bernard; Haydock, Rebecca; Mitchell, Eleanor; Devereux, Graham; Harrison, Timothy

doi:10.1056/nejmoa1714257

Cited by 124 publications

(104 citation statements)

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“…5,6 A previous Cochrane review also did not support increases in the dose of ICS to treat exacerbations in adults and children with asthma. In recent months, two large randomized control trials (RCTs) 8,9 were published. In recent months, two large randomized control trials (RCTs) 8,9 were published.…”

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confidence: 99%

“…7 However, this review was limited by the small sample size and imprecisions. One of them 9 was a landmark study discussing this topic, with a population size of 1922 patients dwarfing all the previous RCTs (a combined total of 1669). One of them 9 was a landmark study discussing this topic, with a population size of 1922 patients dwarfing all the previous RCTs (a combined total of 1669).…”

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confidence: 99%

“…In recent months, two large randomized control trials (RCTs) 8,9 were published. However, the two trials 8,9 yielded different results. However, the two trials 8,9 yielded different results.…”

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confidence: 99%

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Increased versus stable dose of inhaled corticosteroids for asthma exacerbations: A systematic review and meta‐analysis

Zhang

Yuan

et al. 2019

Clin Experimental Allergy

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Asthma is one of the most common chronic diseases, with an estimated 300 million people affected worldwide. 1 Asthma exacerbations are frightening for patients, associated with considerable morbidity and mortality, and pose a considerable economic burden on the healthcare system. [2][3][4] The daily use of inhaled corticosteroids (ICS) effectively controls the day-to-day asthma symptoms but have only partial efficacy in aborting exacerbations. Asthma guidelines recommend Abstract Background: Increasing the dose of inhaled corticosteroids (ICS) is commonly used at early signs of loss of asthma control. However, the potential benefits and harms of this strategy remain unclear. We performed a systematic review and meta-analysis to compare increased dose with stable dose of ICS among adults and children with asthma. Methods: We searched MEDLINE, EMBASE and Cochrane Central Register ofControlled Trials from inception to August 02, 2018. Randomized clinical trials comparing increased doses vs stable doses of ICS for home management of asthma exacerbations in adults or children were included. Results:The analyses included 8 trials totalling 3866 patients. Four trials were judged as low risk of bias, three were unclear risk, and one was ranked as high risk. Increased dose of ICS was associated with a significantly reduced risk of treatment failure compared with stable dose (OR 0.82, 95% CI 0.70-0.97, I 2 = 6%; 314 (281 to 351) vs 358 events per 1000 patients; moderate-quality evidence). There was no significant difference in unscheduled physician visits or hospital admission between increased or stable dose of ICS. However, increased dose of ICS increased the risk of non-serious adverse events (OR 3.50, 95% CI 1.93-6.35, I 2 = 0%) but not serious adverse events.Conclusions: Current evidence of moderate quality supports increasing the dose of ICS as part of a self-initiated action plan to reduce risk of requiring a course of systemic corticosteroids in people with an asthma exacerbation. However, we did not find evidence for an impact on hospital admissions or unscheduled physician visits, and increased ICS dose increased risk of non-serious adverse events. K E Y W O R D Sasthma, clinical immunology, pharmacology and pharmacogenomics

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Increased versus stable dose of inhaled corticosteroids for asthma exacerbations: A systematic review and meta‐analysis

Zhang

Yuan

et al. 2019

Clin Experimental Allergy

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“…Although the report concluded that current evidence does not support increasing the dose of ICSs to manage asthma exacerbations, the wide CIs suggest that potential benefit cannot be completely disregarded. Two recent publications again addressed the issue 13,14 The first study evaluated quadrupling the dose of ICSs at the time of asthma deterioration in a pragmatic, unblinded, randomized trial in adolescents and adults with asthma. 13 Participants had to have at least 1 exacerbation in the previous year and were on ICSs with or without add-on therapy.…”

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confidence: 99%

“…Two recent publications again addressed the issue 13,14 The first study evaluated quadrupling the dose of ICSs at the time of asthma deterioration in a pragmatic, unblinded, randomized trial in adolescents and adults with asthma. 13 Participants had to have at least 1 exacerbation in the previous year and were on ICSs with or without add-on therapy. Participants were randomly assigned to the quadrupling or nonquadrupling groups at the time of asthma deterioration.…”

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confidence: 99%

Temporary Increased Dose of Inhaled Corticosteroids in Yellow Zone, Does It Work?

RaissyHengameh

BlakeKathryn

2018

Pediatric Allergy, Immunology, and Pulmonology

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There are limited data as how to manage the ''yellow zone'' in children with asthma. Although increasing the dose of inhaled corticosteroids (ICSs) has been practiced by some providers, the efficacy and safety of this strategy remain unclear. This review presents the existing data for use of adjustable dose of ICSs for prevention of asthma exacerbation in children in yellow zone. The current evidence does not support increasing the dose at early signs of loss of asthma control to prevent asthma exacerbation in children. Well-designed clinical trials are needed to identify potential benefits of this strategy.

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New Therapeutic Strategies for Asthma

Zoratti

O’Connor

2020

JAMA

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For more than 25 years, national and international guidelines have recommended standardized approaches to control the symptoms of asthma and reduce the risk of exacerbation using strategies that are relevant to the majority of patients with asthma. 1,2 As new evidence emerges from randomized clinical trials, clinicians must modify treatment strategies to be consistent with new evidence. In this issue of JAMA, 2 JAMA Insights articles 3,4 highlight new evidence that clinicians should consider when treating patients with asthma.In one article, Tripple and colleagues 3 review new strategies in chronic asthma management that differ from the 2007 National Institutes of Health (NIH) guidelines, the Expert Panel Report-3: Guidelines for the Diagnosis and Management of Asthma, 1 and are incorporated in the 2019 Global Initiative for Asthma Global Strategy for Asthma Management and Prevention. 2 The first of these new strategies involves treatment of adolescent and adult patients with mild and intermittent asthma with a daily inhaled corticosteroid (ICS). Previously, NIH guidelines stated that as-needed inhalation of short-acting β 2 -agonists alone was sufficient treatment for these patients. 1 The rationale for the use of ICS in this setting is in part based on findings from a post hoc analysis of data from a large, multicenter clinical trial. 5 Results of the post hoc analysis showed that even patients with mild intermittent asthma were at risk of severe asthma-related adverse events (a composite outcome of hospitalization, emergency care, or death) and lung function impairment, and that the regular daily use of low-dose ICS reduced these adverse outcomes regardless of how infrequent asthma symptoms were reported to be at baseline. 5 Two additional new strategies for adolescents and adults, symptom-driven ICS use and single maintenance and reliever therapy (SMART), allow a patient's symptoms to determine the dosage of ICS. These approaches link increased symptoms to a concomitant increase of underlying airway inflammation that can be countered by ICS. SMART involves the use of an inhaler that combines a long-acting β 2 -agonist (LABA) with rapid onset of action (formoterol) with corticosteroid for both daily maintenance and additional as-needed use, whereas symptom-driven ICS use may be implemented with either an ICS inhaler or a combination ICS-LABA inhaler. Both of these strategies link the use of ICS, which improves asthma control and prevents exacerbations, to as-needed β 2agonist treatment, which provides rapid symptom relief.Tripple et al 3 discuss results of the SYGMA 1 and 2 trials, 6,7 which demonstrated that symptom-driven (ie, as-needed) combination budesonide-formoterol improved asthma control and reduced exacerbation risk in individuals with mild persistent asthma compared with symptom-driven short-acting β 2agonists (SABAs) alone. Additionally, although regularly scheduled twice-daily low-dose budesonide provided better symptom control than symptom-driven use of the same medication, the approach of using ...

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Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations

Cited by 124 publications

References 12 publications

Increased versus stable dose of inhaled corticosteroids for asthma exacerbations: A systematic review and meta‐analysis

Increased versus stable dose of inhaled corticosteroids for asthma exacerbations: A systematic review and meta‐analysis

Temporary Increased Dose of Inhaled Corticosteroids in Yellow Zone, Does It Work?

New Therapeutic Strategies for Asthma

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