Chronic Azithromycin Decreases The Frequency Of Chronic Obstructive Pulmonary Disease Exacerbations

Albert, Richard K.; Bailey, William C.; Casaburi, Richard; Connett, John; Cooper, Allen D.; Criner, Gerard J.; Curtis, Jeff L.; Han, MeiLan K.; Lazarus, Stephen C.; Make, Barry J.; Marchetti, Nathaniel; Martínez, Fernando J.; Mattinger, Nancy; McEvoy, Charlene; Niewoehner, Dennis E.; Pórszász, János; Price, Connie S.; Riley, John; Scanlon, Paul D.; Sciurba, Frank C.; Scharf, Steven M.; Washko, George R.; Woodruff, Prescott G.; Anthonisen, N. R.

doi:10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a6416

Cited by 4 publications

(5 citation statements)

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“…Preliminary data from the prospective, placebo-controlled MACRO study in 1142 COPD patients randomized to receive azithromycin 250 mg or placebo daily for 1 year have been promising. 15 Inclusion criteria were use of supplemental oxygen or treatment with systemic steroids for an AECOPD within the previous year. The frequency of AECOPD for those receiving azithromycin was lower at 1.4 versus 1.8 patients/year ( P = 0.004).…”

Section: Discussionmentioning

confidence: 99%

“…It remains to be established whether the therapeutic effect of erythromycin reflects antimicrobial activity, an immunomodulatory effect, or both. Preliminary data have recently been reported for the MACRO study, a randomized controlled trial evaluating the utility of long-term azithromycin therapy to reduce AECOPD, with promising results 15. Compared with erythromycin, the prototypical 15 member-ring macrolide, azithromycin, appears to have a better safety profile in long-term use, as well as improved bacteriological activity 16…”

Section: Introductionmentioning

confidence: 99%

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Long-term azithromycin therapy in patients with severe COPD and repeated exacerbations

Pomares¹,

Montón²,

Espasa³

et al. 2011

COPD

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BackgroundThe aim of this study was to determine whether long-term intermittent azithromycin therapy reduces the frequency of exacerbation in severe chronic obstructive pulmonary disease (COPD).MethodsWe retrospectively investigated the clinical benefits of long-term azithromycin (500 mg orally three times per week) over 12 months in patients with severe COPD and a minimum of four acute exacerbations (AECOPD) per year or chronic bronchial colonization by Pseudomonas aeruginosa, comparing the number of AECOPD, hospitalizations due to respiratory disease, days of hospital stay, and bacterial infections during azithromycin treatment and in the year prior to this therapy.ResultsTwenty patients who completed the 12-month treatment period were analyzed. No clinically significant adverse events were observed during azithromycin treatment. Compared with baseline data, azithromycin therapy significantly reduced the number of AECOPD (2.8 ± 2.5 versus 6.8 ± 2.8, P < 0.001), hospitalizations (1.4 ± 1.5 versus 3.6 ± 1.4, P < 0.001), and cumulative annual days of hospital stay (25 ± 32.2 versus 43.7 ± 21.4, P = 0.01). The improvement was particularly significant in patients with exacerbations caused by common potentially pathogenic microorganisms, who had 70% fewer AECOPD and hospitalizations. Patients colonized by P. aeruginosa had reductions of 43% in AECOPD and 47% in hospitalizations.ConclusionLong-term azithromycin is well tolerated and associated with significant reductions in AECOPD, hospitalizations, and length of hospital stay in patients with severe COPD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long-term azithromycin therapy in patients with severe COPD and repeated exacerbations

Pomares¹,

Montón²,

Espasa³

et al. 2011

COPD

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“…102 A recent study, in COPD patients, suggest that the chronic administration (one year) of azithromycin is associated with significant reduction in COPD exacerbation. 103 However, the chronic use of these agents in smokers with asthma needs further studies.…”

Section: Hdac2 Enhancersmentioning

confidence: 99%

The effects of cigarette smoke on airway inflammation in asthma and COPD: Therapeutic implications

Tamimi

Serdarevic

Hanania

2012

Respiratory Medicine

158

117

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Asthma and COPD are two chronic inflammatory disorders of the airway characterized by airflow limitation. While many similarities exist between these two diseases, they are pathologically distinct due to the involvement of different inflammatory cells; predominantly neutrophils, CD8 lymphocytes in COPD and eosinophils and CD4 lymphocytes in asthma. Cigarette smoking is associated with accelerated decline of lung function, increased mortality, and worsening of symptoms in both asthma and COPD. Furthermore, exposure to cigarette smoke can alter the inflammatory mechanisms in asthma to become similar to that seen in COPD with increasing CD8 cells and neutrophils and may therefore alter the response to therapy. Cigarette smoke exposure has been associated with a poor response to inhaled corticosteroids which are recommended as first line anti-inflammatory medications in asthma and as an add-on therapy in patients with severe COPD with history of exacerbations. While the main proposed mechanism for this altered response is the reduction of the histone deacetylase 2 (HDAC2) enzyme system, other possible mechanisms include the overexpression of GR-β, activation of p38 MAPK pathway and increased production of inflammatory cytokines such as IL-2, 4, 8, TNF-α and NF-Kß. Few clinical trials suggest that leukotriene modifiers may be an alternative to corticosteroids in smokers with asthma but there are currently no drugs which effectively reduce the progression of inflammation in smokers with COPD. However, several HDAC2 enhancers including low dose theophylline and other potential anti-inflammatory therapies including PDE4 inhibitors and p38 MAPK inhibitors are being evaluated.

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“…Recently, results of a large 1-yr study with azithromycin (250 mg per day) were reported: this macrolide reduced exacerbation frequency by 28% and improved quality of life [68]. Such results are undoubtedly encouraging, although azithromycin treatment was also more frequently associated with hearing impairment.…”

Section: Copd and Inflammation: New Data For New Treatmentsmentioning

confidence: 99%

Beyond corticosteroids: future prospects in the management of inflammation in COPD

Roche¹,

Marthan²,

Berger³

et al. 2011

Eur Respir Rev

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Inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways and stimulates innate and adaptive immune mechanisms. Airway inflammation is involved in increased bronchial wall thickness, increased bronchial smooth muscle tone, mucus hypersecretion and loss of parenchymal elastic structures. Oxidative stress impairs tissue integrity, accelerates lung ageing and reduces the efficacy of corticosteroids by decreasing levels of histone deacetylase-2. Protease-antiprotease imbalance impairs tissues and is involved in inflammatory processes. Inflammation is also present in the pulmonary artery wall and at the systemic level in COPD patients, and may be involved in COPD-associated comorbidities.Proximal airways inflammation contributes to symptoms of chronic bronchitis while distal and parenchymal inflammation relates to airflow obstruction, emphysema and hyperinflation. Basal levels of airways and systemic inflammation are increased in frequent exacerbators.Inhaled corticosteroids are much less effective in COPD than in asthma, which relates to the intrinsically poor reversibility of COPD-related airflow obstruction and to molecular mechanisms of resistance relating to oxidative stress. Ongoing research aims at developing new drugs targeting more intimately COPD-specific mechanisms of inflammation, hypersecretion and tissue destruction and repair. Among new anti-inflammatory agents, phosphodiesterase-4 inhibitors have been the first to emerge.

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Chronic Azithromycin Decreases The Frequency Of Chronic Obstructive Pulmonary Disease Exacerbations

Cited by 4 publications

References 0 publications

Long-term azithromycin therapy in patients with severe COPD and repeated exacerbations

Long-term azithromycin therapy in patients with severe COPD and repeated exacerbations

The effects of cigarette smoke on airway inflammation in asthma and COPD: Therapeutic implications

Beyond corticosteroids: future prospects in the management of inflammation in COPD

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