Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial

Gibson, Peter G.; Yang, Ian A.; Upham, John W.; Reynolds, Paul N.; Hodge, Sandra; James, Alan; Jenkins, Christine; Peters, Matthew J.; Marks, Guy B.; Baraket, Melissa; Powell, Heather; Taylor, Steven; Leong, Lex E. X.; Rogers, Geraint B.; Simpson, Jodie L.

doi:10.1016/s0140-6736(17)31281-3

Cited by 538 publications

(513 citation statements)

References 30 publications

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“…In contrast, a recent trial 36 of azithromycin showed a significant decrease in the risk of severe asthma exacerbations in individuals, independent of their level of sputum eosinophil counts. b) Fractional exhaled nitric oxide (FeNO) Nitric oxide is generated by the airway epithelium due to upregulation of inducible nitric oxide synthase which is induced by IL-13.…”

Section: Biomarkers Associated With Th2 Inflammationmentioning

confidence: 63%

“…One trial concluded that subjects with blood eosinophil counts 200/mL receiving azithromycin experienced fewer severe exacerbations than subjects with blood eosinophil count >200 /mL, 36 while another trial observed a similar number of exacerbations in azithromycin-treated subjects independently of their levels of blood eosinophil counts. 42 Two post hoc analyses performed in two adult clinical trials found that high blood eosinophils (260 to 300/mL) identified subjects with a greater response to omalizumab compared with subjects with low blood eosinophil counts.…”

Section: Biomarkers Associated With Th2 Inflammationmentioning

confidence: 99%

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Recognition and management of severe asthma: A Canadian Thoracic Society position statement

FitzGerald

Lemière

Lougheed

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

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RATIONALE: While severe asthma affects approximately 5% of all individuals with asthma, this small minority of individuals accounts for a large proportion of the asthma-related costs. Greater understanding of the pathophysiology of asthma combined with the emergence of novel biologic therapies for severe asthma supported the need for a thorough review of the diagnosis, investigation, phenotyping, and management of severe asthma. OBJECTIVES: We aimed to propose a practical approach to distinguish uncontrolled asthma due to inadequate asthma management from severe asthma despite optimal asthma management. Moreover, based on emerging scientific evidence, we sought to provide guidance for characterizing individuals with severe asthma and considering a phenotype-specific management. We also aimed to review other novel new potential therapeutic approaches. METHODS: We systematically reviewed the relevant literature focusing on randomized controlled trials and when available, systematic reviews of randomized controlled trials. The proposed key messages, based on scientific evidence and expert opinion, were agreed upon by unanimous consensus. MAIN RESULTS: We defined severe asthma and outlined its significant impact from the societal and patient perspectives. We outlined a practical approach to distinguish severe from uncontrolled but not severe asthma, based on stepwise investigation and management of potential reasons for uncontrolled asthma. After reviewing the current evidence we concluded that: 1) Several biomarkers (e.g. sputum or blood eosinophil count, total IgE, or FeNO) can help identify potential responders to new therapeutic options; 2) Tiotropium may be considered as an add-on therapy for individuals 12 years of age and over with severe asthma uncontrolled despite combination ICS/LABA therapy; 3) The chronic use of macrolides may decrease asthma exacerbations in individuals 18 years of age and over with severe asthma independent of their inflammatory profile; 4) Children aged 6 years and older and adults who are sensitized to at least one relevant perennial allergen and who remain poorly controlled asthmatics despite high dose ICS and a second controller can benefit from the addition of anti-IgE therapy to reduce asthma exacerbations; due to the known risk of side effects associated with high-dose ICS in children, omalizumab should also be considered in children and adolescents who repeatedly exacerbate or have poor control when therapy is stepped down from high-dose to moderate-dose ICS and at least one other controller; 5) Anti-IL5 therapies may be considered for adults 18 years of age and over with severe eosinophilic asthma who experience recurrent asthma exacerbations in spite of high doses of ICS in addition to at least one other controller; and 6) Although bronchial thermoplasty has shown a decrease in asthma exacerbations in one study, its role in the treatment of severe asthma remains uncertain. CONCLUSIONS: After reviewing existing and emerging therapies for severe asthma, we developed ke...

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Section: Biomarkers Associated With Th2 Inflammationmentioning

confidence: 63%

Section: Biomarkers Associated With Th2 Inflammationmentioning

confidence: 99%

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

FitzGerald

Lemière

Lougheed

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

View full text Add to dashboard Cite

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“…Recent results from the AMAZES study suggest, that low-dose long-term macrolide treatment may improve asthma control in eosinophilic asthma, as well as non-eosinophilic asthma (see below) [125]…”

Section: Management Of Severe Asthmamentioning

confidence: 99%

“…Treatment with a low dose azithromycin: 250 mg 3 days per week have been shown to reduce the risk of exacerbations in patients with non-eosinophilic asthma (B-Eos≤ 0.2 x 10 9 /L) [126]. In the recently published AMAZES study, low-dose Azithromycin (500 mg 3 days/week for 48 weeks), in addition to usual treatment, reduced exacerbations in uncontrolled eosinophilic as well as non-eosinophilic asthma, as well as asthma-related quality of life [125]. Macrolides reduce neutrophilic airway inflammation [127], but further mechanistic studies are required to understand the mechanisms of action in eosinophilic asthma.…”

Section: Management Of Severe Asthmamentioning

confidence: 99%

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

Porsbjerg

Ulrik

Skjold

et al. 2018

European Clinical Respiratory Journal

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Although a minority of asthma patients suffer from severe asthma, they represent a major clinical challenge in terms of poor symptom control despite high-dose treatment, risk of exacerbations, and side effects. Novel biological treatments may benefit patients with severe asthma, but are expensive, and are only effective in appropriately targeted patients. In some patients, symptoms are driven by other factors than asthma, and all patients with suspected severe asthma (‘difficult asthma’) should undergo systematic assessment, in order to differentiate between true severe asthma, and ‘difficult-to-treat’ patients, in whom poor control is related to factors such as poor adherence or co-morbidities. The Nordic Consensus Statement on severe asthma was developed by the Nordic Severe Asthma Network, consisting of members from Norway, Sweden, Finland, Denmark, Iceland and Estonia, including representatives from the respective national respiratory scientific societies with the aim to provide an overview and recommendations regarding the diagnosis, systematic assessment and management of severe asthma. Furthermore, the Consensus Statement proposes recommendations for the organization of severe asthma management in primary, secondary, and tertiary care.

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“…Therefore, the best biomarker to use biologics in severe T2 asthma is rather simple (blood cell count) and somewhat contrasts with the great deal of sophisticated research that has been needed to establish the role of IgE and interleukin-5 in severe asthma and to characterise T2 asthma. Outside T2 asthma, high sputum neutrophil count in severe asthmatics has been suggested to predict good biologic response to macrolides in a small pilot study [5]; however, a recent large prospective trial primarily looking at exacerbations and quality of life did not find significant differences in the efficacy of azithromycin on exacerbations between patients with versus without higher sputum eosinophils [21]. One interesting finding from the U-BIOPRED study is the identification by transcriptomics of a cluster with heavy airway neutrophilic inflammation, proteasome activation and tumour necrosis factor (TNF)-α expression, a cluster named TAC2 (transcriptome-associated cluster 2).…”

Section: Asthma As An Illustration Of Progress Towards Personalised Mmentioning

confidence: 99%

Personalised medicine: are we ready?

Louis

Roche

2017

Eur Respir Rev

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Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial

Cited by 538 publications

References 30 publications

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

Personalised medicine: are we ready?

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