Azithromycin for Prevention of Exacerbations of COPD

Albert, Richard K.; Connett, John E.; Bailey, William C.; Casaburi, Richard; Cooper, John A.; Criner, Gerard J.; Curtis, Jeffrey L.; Dransfield, Mark T.; Han, Mei Lan K.; Lazarus, Stephen C.; Make, Barry J.; Marchetti, Nathaniel; Martínez, Fernando J.; Madinger, Nancy; McEvoy, Charlene; Niewoehner, Dennis E.; Porsasz, Janos; Price, Connie S.; Reilly, John J.; Scanlon, Paul D.; Sciurba, Frank C.; Scharf, Steven M.; Washko, George R.; Woodruff, Prescott G.; Anthonisen, Nicholas R.

doi:10.1056/nejmoa1104623

Cited by 1,056 publications

(974 citation statements)

References 35 publications

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“…ALBERT et al [80] reported an excess rate of hearing decrements of ,5% attributable to azithromycin use. Ototoxicity following long-term azithromycin therapy has also been reported in patients with disseminated Mycobacterium avium disease [111].…”

Section: Risks Of Long-term Macrolide Treatmentmentioning

confidence: 99%

“…A number of studies have evaluated whether long-term macrolide treatment decreases the risk of AECOPD, with conflicting results [73][74][75][76][77][78][79]. More recently, in a prospective, parallel-group study, 1142 patients with COPD at increased risk of exacerbation were randomly assigned in a 1:1 ratio to receive azithromycin (n5570) at a dose of 250 mg daily or placebo (n5572) for 1 year in addition to their usual care [80]. The median time to the first acute exacerbation of COPD (the primary outcome) was 266 days in the azithromycin group, compared with 174 days in the placebo group (p,0.001).…”

Section: Copdmentioning

confidence: 99%

“…Until clearer evidence of efficacy and safety is available, routine use of azithromycin prophylaxis for preventing acute exacerbations is not recommended due to an unfavourable balance between benefits and side-effects [82]. However, it may be considered for individual severe COPD patients with frequent exacerbations despite best quality, guidelines-based treatment, in those who are not at high risk of cardiovascular complications, with close monitoring of hearing, and after careful review of all medications in order to avoid any potential adverse interactions [80].…”

Section: Copdmentioning

confidence: 99%

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Long-term macrolide treatment for chronic respiratory disease

2012

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Long-term macrolide treatment was first shown to alter the natural history of diffuse panbronchiolitis (DPB) in the late 1980s. Since then, macrolides have been demonstrated to exert antiinflammatory and immunomodulatory activity in addition to being antimicrobial. Indeed, their spectrum of action extends to the regulation of leukocyte function and production of inflammatory mediators, control of mucus hypersecretion, resolution of inflammation and modulation of host defence mechanisms. As such, the potential benefit of macrolide antibiotics has been evaluated in a variety of chronic respiratory diseases. The best studied condition is cystic fibrosis, of which there have been six randomised controlled trials showing evidence of benefit. However, most of the studies were limited by small numbers of patients and short follow-up. More recently, landmark studies have demonstrated the efficacy of azithromycin in reducing the risk of acute exacerbations in patients with chronic obstructive pulmonary disease, but the optimal duration and dosing of macrolide treatment remain uncertain.With the exception of patients with DPB and cystic fibrosis, until clear evidence of efficacy is available, the long-term use of macrolides should be limited to highly selected patients after careful evaluation of benefit and harm, or in the context of randomised controlled clinical trials. @ERSpublications Several studies evaluating macrolide antibiotics for the treatment of chronic respiratory diseases are underway

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Section: Risks Of Long-term Macrolide Treatmentmentioning

confidence: 99%

Section: Copdmentioning

confidence: 99%

Section: Copdmentioning

confidence: 99%

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Long-term macrolide treatment for chronic respiratory disease

2012

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“…The MAPK pathways, in particular p38 MAPK , are also involved in the regulation of the synthesis of inflammatory mediators at the level of transcription and translation, making them potential targets for anti-inflammatory agents [140,141]. These findings suggest a potential effect of azithromycin not only as an immunomodulatory, but also as an anti-angiogenic agent, at least driven by ASM cells [125,142]. Due to their known side effects, long-term treatment with systemic corticosteroids is not advised in patients.…”

Section: Macrolidesmentioning

confidence: 99%

Pulmonary vascular changes in asthma and COPD

Harkness

Kanabar

Sharma

et al. 2014

Pulmonary Pharmacology & Therapeutics

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In chronic lung disorders such as in asthma and chronic obstructive pulmonary disease (COPD) there is increased bronchial angiogenesis and remodelling of pulmonary vessels culminating to altered bronchial and pulmonary circulation. The involvement of residential cells such as endothelial cells, smooth muscle cells and pulmonary fibroblasts, all appear to have a crucial role in the progression of vascular inflammation and remodelling. The regulatory abnormalities, growth factors and mediators implicated in the pulmonary vascular changes of asthma and COPD subjects and potential therapeutic targets have been described in this review.

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“…Under these circumstances, macrolides may reduce the risk for AECOPD although patients should be selected carefully considering the risk of bacterial resistance and side effects. [183][184][185] Whether this benefit is due to the antibacterial effect or more from direct anti-inflammatory effects is uncertain, but biomarkers of bacterial colonization in COPD could be valuable to target azithromycin or other emerging antibacterial approaches. However, we need studies to support or challenge these new pharmacotherapy approaches and to weigh the benefits and risks.…”

Section: Box 2 Preventing Acute Exacerbation In Stable Copdmentioning

confidence: 99%

CTS position statement: Pharmacotherapy in patients with COPD—An update

Bourbeau

Bhutani

Hernández

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

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RATIONALE: Since the last published Canadian Thoracic Society (CTS) COPD guideline in 2007 and the 2008 update -highlights for primary care, many new clinical trials have challenged COPD treatment practices. The current Canadian position statement provides the reader with an update on pharmacotherapy of patients with COPD as reviewed by the CTS. OBJECTIVES: The objectives of this position statement are: 1) to summarize the literature on topics relevant to the pharmacological therapy of patients with stable COPD; and 2) to provide clinical guidance with evidence-based recommendations and expert-informed key messages for the pharmacological therapy for patients with stable COPD. METHODS: The authors 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-informed opinion, were agreed upon by a majority consensus. MAIN RESULTS: There is typically a significant delay in seeking medical care by patients with dyspnea, often waiting until symptoms affect the performance of activities of daily living. The diagnosis of COPD requires spirometry to confirm the presence of airflow obstruction in any patient presenting with symptoms and/or risk factors of COPD. An effective management plan for individuals with COPD should include: smoking cessation, vaccination and education. A number of non-pharmacological treatments are available for COPD patients with symptoms to improve outcomes such as self-management with coaching from a health care professional; pulmonary rehabilitation; supplemental oxygen in selected patients; and surgery.Current pharmacotherapy for COPD has been shown to alleviate symptoms and prevent exacerbations and related complications such as hospital admissions. In symptomatic patients with stable COPD not having or having infrequent exacerbation, treatment should be started with inhaled LAMA or LABA monotherapy, and if experiencing persistent or increased dyspnea, exercise intolerance, and/or reduced health status despite use of monotherapy, patients should be considered for treatment "step up" with an inhaled LAMA plus LABA dual therapy. In this situation, the use of a single inhaler would be preferred to simplify the treatment regimen and minimize the cost. In patients with stable COPD experiencing exacerbations despite the use of LAMA or LABA monotherapy, treatment "step up" with inhaled LAMA plus LABA dual therapy should be considered unless a patient has concomitant asthma (Asthma/COPD overlap (ACO)). There has been recent interest in using biomarkers to identify patients who are more likely to respond to ICS. Most of the studies have demonstrated that high blood eosinophils could be valuable to predict an increase response in terms of reduction of exacerbation rate when treated with combination ICS/LABA; there is still uncertainty about the exact cut-off level of blood eosinophils having potential therapeutic value. If a pa...

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Azithromycin for Prevention of Exacerbations of COPD

Cited by 1,056 publications

References 35 publications

Long-term macrolide treatment for chronic respiratory disease

Long-term macrolide treatment for chronic respiratory disease

Pulmonary vascular changes in asthma and COPD

CTS position statement: Pharmacotherapy in patients with COPD—An update

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