Background: Macrolide antibiotics have anti-inflammatory effects, and long-term administration may reduce chronic obstructive pulmonary disease (COPD) exacerbations. Objective: To investigate the effects of long-term treatment of macrolide therapy for COPD. Methods: We searched the PubMed and Embase databases to identify randomized controlled trials that evaluated the effect of macrolide therapy (of at least 2 weeks) for COPD. The primary outcome assessed was the frequency of acute exacerbations during follow-up. Results: Six trials involving 1,485 COPD patients were included in the analysis. Analysis of the pooled data of all 6 trials showed that macrolide administration reduced the frequency of acute exacerbations of COPD [risk ratio (RR) = 0.62; 95% CI 0.43-0.89, p = 0.01]. Subgroup analysis showed that only erythromycin might be associated with decreased COPD exacerbations (erythromycin: p = 0.04, azithromycin: p = 0.22, clarithromycin: p = 0.18). Moreover, macrolide therapy for 3 months did not significantly reduce the number of exacerbations (p = 0.18), whereas a beneficial effect was conclusive in the 6-month (p = 0.009) and 12-month (p = 0.03) treatment subgroups. In addition, nonfatal adverse events were more frequent in the macrolide treatment groups than in the controls (RR = 1.32; 95% CI 1.06-1.64, p = 0.01). However, related clinical factors had no influence on the overall result (p = 0.19). There was no publication bias among the included trials. Conclusions: Macrolide therapy was effective and safe in decreasing the frequency of exacerbations in patients with COPD. Treatment might provide a significant benefit but only when therapy lasts more than 6 months.
"Nonetheless, further studies are still needed to explore the true effects of erythromycin on the number of patients with exacerbations in bronchiectasis. Interestingly, the results indicated that significant benefits in reducing the number of patients with exacerbations took 6 months or more to occur in adults with bronchiectasis, which was consistent with the findings in COPD . Currently, guidelines for treatment of diffuse panbronchiolitis  recommended a maintenance macrolide therapy for 6 months or more, and in serious conditions, a prolonged treatment. "
[Show abstract][Hide abstract] ABSTRACT: A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of macrolide therapy in adults and children with bronchiectasis.
We searched the PUBMED, EMBASE, CENTRAL databases to identify relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcome was the number of bronchiectasis exacerbations. Secondary outcomes included exacerbation-related admissions, quality of life (QoL), spirometry, 6-minute walk test (6MWT) and adverse events.
Nine eligible trials with 559 participants were included. Six were conducted on adults, and the remaining on children. Macrolide therapy significantly reduced the number of patients experiencing one or more exacerbation in adults [risk ratio (RR) = 0.59; 95% CI, 0.40 to 0.86; P = 0.006; I2 = 65%] and children [RR = 0.86; 95% CI, 0.75-0.99; P = 0.04; I2 = 0%], but not the number of patients with admissions for exacerbation. Macrolide therapy was also associated with reduced frequency of exacerbations in adults (RR = 0.42; 95% CI, 0.29 to 0.61; P<0.001; I2 = 64%) and children (RR = 0.50; 95% CI, 0.35 to 0.71; P<0.001). Pooled analyses suggested that spirometry, including FEV1 and FVC, were significantly improved in adults but not in children. Macrolide therapy improved the QoL (WMD, -6.56; 95% CI, -11.99 to -1.12; P = 0.02; I2 = 86%) but no significant difference in 6MWT (WMD, 4.15; 95% CI, -11.83 to 20.13; P = 0.61; I2 = 31%) and the overall adverse events (RR, 0.96; 95% CI, 0.82 to 1.13; P = 0.66; I2 = 0%) in adults. However, reports of diarrhea and abdominal discomforts were higher with macrolide therapy.
Macrolide maintenance therapy, both in adults and children, was effective and safe in reducing bronchiectasis exacerbations, but not the admissions for exacerbations. In addition, macrolide administration in adults was associated with improvement in QoL and spirometry, but not 6WMT. Future studies are warranted to verify the optimal populations and clarify its potential effects on antimicrobial resistance.
PLoS ONE 03/2014; 9(3):e90047. DOI:10.1371/journal.pone.0090047 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic obstructive pulmonary disease (COPD) is characterized by a decreased airflow due to airway narrowing that, once it occurs, is not fully reversible. The disease usually is progressive and associated with an enhanced inflammatory response in the lungs after exposure to noxious particles or gases. After removal of the noxious particles, the inflammation can continue in a self-sustaining manner. It has been established that improper activation of neutrophils lies at the core of the pathology. This paper provides an overview of the mechanisms by which neutrophils can induce the pulmonary damage of COPD. As the pathogenesis of COPD is slowly being unraveled, new points of intervention are discovered, some of which with promising results.
[Show abstract][Hide abstract] ABSTRACT: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. Disease severity evaluation was based on airflow limitation for many years. However, it is now obvious that no single parameter can describe the complexity of COPD and a more holistic approach should be utilized. For this reason, newer classifications of the disease are based on multiple clinical characteristics or biomarkers that can predict different clinically meaningful outcomes, such as symptoms, frequency of exacerbations, progression of disease, response to different medications and mortality. Ongoing research highlights such biomarkers, while guidelines have already incorporated them, as the basis of clinical phenotypes. GOLD highlights the need for more intensive treatment of frequent exacerbators and COPD patients whose disease significantly burdens their quality of life. Moreover, a COPD-asthma overlap syndrome with a different prognosis and potentially different therapeutic approach is also recognized. Spanish guidelines also group frequent exacerbators to predominantly emphysematic versus predominantly bronchitic. Another approach aims to create scoring systems, or multidimensional indices, based on multiple biomarkers which evaluate different aspects of the disease. The recognition of all these prognostic and therapeutic patient subgroups lead to a more personalized approach to each patient and also provides data to the –omics to uncover the pathogenetic background of this diversity and develop new targeted treatments.
Current Respiratory Medicine Reviews 07/2014; 9(6):372-378. DOI:10.2174/1573398X10666140527000115
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