No abstract

In this study, we investigated the occurrence of viral infections in acute exacerbations of chronic obstructive pulmonary disease (COPD) during four seasons. Viral infections were detected by the use of real-time reverse transcriptase polymerase chain reaction on pharyngeal swabs. During a 12-month period pharyngeal swabs were obtained in 136 exacerbations of 63 patients. In 35 exacerbations (25.7%) a viral infection was detected. Most viral infections occurred in the winter (n = 14, 40.0%), followed by summer (n = 9, 25.7%), autumn (n = 6, 17.1%), and spring (n = 6, 17.1%). Rhinovirus was the most frequently isolated virus (n = 19, 51.4%), followed by respiratory syncytial virus (n = 6, 16.2%), human metapneumovirus (n = 5, 13.5%), influenza A (n = 4, 10.8%), parainfluenza 4 (n = 2, 5.4%), and parainfluenza 3 (n = 1, 2.7%). This study showed that virus-induced COPD exacerbations occur in all four seasons with a peak in the winter months. However, the distribution of rhinovirus infections showed a different pattern, with most infections occurring in July.

Objectives: Maintenance treatment with macrolide antibiotics has shown to be effective in reducing exacerbations in COPD patients. A major concern with prolonged treatment with antibiotics is the development of bacterial resistance. In this study we determined the effect of azithromycin on the development and acquisition of resistance to macrolides in the nasopharyngeal flora in COPD patients. Methods: This study was part of the COLUMBUS trial, a randomised, double-blind, placebo-controlled trial to measure the effect of maintenance treatment with azithromycin in 92 COPD patients on the exacerbation rates during a 12-month period. In order to determine resistance to macrolides, we used a targeted metagenomic approach to measure the presence and relative abundance of specific macrolide resistance genes ermB, ermF and mefA in throat samples collected at different time-points during this 12-month period. Results: There was no increased risk for acquisition of macrolide resistance genes in the azithromycin group compared to the placebo group in COPD patients. However, loss of the macrolide resistance gene ermB was increased overtime in the placebo treated group compared to the azithromycin group (n = 5 for the placebo group versus n = 0 for the azithromycin group at 12 months; p = 0.012). The change in relative abundance of the three macrolide-resistance genes showed that all but one (ermF) increased during treatment with azithromycin. Conclusions: The acquisition rate of macrolide resistance genes in COPD patients treated with azithromycin maintenance therapy was limited, but the relative abundance of macrolide resistance genes increased significantly over time compared to placebo. This study was part of the COLUMBUS trial (Clinicaltrials.gov, NCT00985244).

Introduction: Maintenance treatment with macrolides are useful in preventing COPD exacerbations. We investigated which characteristics of COPD patients with frequent exacerbations predicted the best response to maintenance treatment with azithromycin. Methods: This study was part of the COLUMBUS trial, a prospective randomized, double-blind, placebo-controlled study in 92 COPD patients with frequent exacerbations. During the 1-year treatment period, follow-up data were collected for spirometry, mMRC scores, sputum cultures and blood inflammatory markers. Results: In the azithromycin group a significant lower number of exacerbations per patient was observed in patients with the following characteristics: baseline blood eosinophil count ≥2.0% (x̄= 1.26), compared to an eosinophil count < 2.0% (x̄= 2.50; p = 0.02), GOLD stage 1-2 (x̄= 1.06), versus GOLD stage 4 (x̄= 2.62; p = 0.02) and GOLD group C (x̄= 0.45) compared to group D (x̄= 2.18; p < 0.01). Moreover, the number of hospitalizations was significantly lower in patients, with a blood eosinophil count ≥2.0% (x̄= 0.26) compared to an eosinophil count < 2.0% (x̄= 0.90; p = 0.01) and in GOLD stages 1-2 (x̄= 1.06) compared to stage 4 (x̄= 2.62; p = 0.04). Conclusion:In conclusion, azithromycin maintenance treatment appears to be effective in COPD patients with frequent exacerbations, who are either classified in GOLD stage 1-2 or GOLD C and those with a blood eosinophil count of ≥2.0%.

BackgroundChronic obstructive pulmonary disease (COPD) is characterised by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response. Besides smoking, one of the hypotheses for the persistent airway inflammation is the presence of recurrent infections. Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases. There is consistent evidence that macrolide therapy reduces infectious exacerbations, decreases the requirement for additional antibiotics and improves nutritional measures. Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent exacerbations. The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown. Until now, studies investigating macrolide therapy in COPD are limited. The objective of this study is to assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment.Methods/designThe study is set up as a prospective randomised double-blind placebo-controlled single-centre trial. A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included. Subjects will be randomised to receive either azithromycin 500 mg three times a week or placebo. Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment.DiscussionWe investigate whether long-term therapy with macrolide antibiotics can prevent exacerbations in patients with COPD. Additionally, our study aims to assess the effect of long-term use of macrolide on the development of antimicrobial resistance and on inflammatory parameters related to COPD. We believe this study will provide more data on the effects of macrolide treatment in patients in COPD and will add more knowledge on its working mechanisms.Trial registrationhttp://www.clinicaltrials.gov NCT00985244

Chronic obstructive pulmonary disease (COPD) is one of the major health problems in the world. Long-term treatment with macrolide antibiotics is a recent development that has been reported to have beneficial effects on exacerbation frequency. These effects are not only attributed to the antimicrobial effect but also to the immune modulatory effect. Six randomized trials and 1 retrospective study have been performed to investigate the efficacy of macrolides in the prevention of acute exacerbations of COPD. Besides the beneficial effects on the occurrence of exacerbations of COPD, this treatment also seems to improve quality of life and is well tolerated. Antimicrobial resistance is one of the future issues to consider before implementing this therapy.(Clin Pulm Med 2014;21:61-67) C hronic obstructive pulmonary disease (COPD) is one of the major health problems in the world; it was the third leading cause of death in 2010. 1 The natural history of COPD is characterized by progressive airflow obstruction and the occurrence of exacerbations. Frequent acute exacerbations of COPD (AECOPD) can lead to a decreased health-related quality of life, 2 a decline in lung function, 3 an increased risk of hospitalization, 4 and an increase in mortality. 5 Furthermore, the occurrence of an exacerbation is a risk factor for developing recurrent exacerbations. 6 Prevention of AECOPD with long-term macrolide antibiotic treatment is a recent development as this therapy does not only have an antimicrobial effect but also seems to have an immune modulatory effect. 7 Several studies investigated the efficacy of macrolides in the prevention of AECOPD. [8][9][10][11][12][13][14] In this paper these studies and the role of macrolides in the treatment of COPD are reviewed.

Macrolides are effective in reducing the number of exacerbations in COPD patients with the frequent exacerbator phenotype. Our study did not show a persistent effect of azithromycin on exacerbation frequencies after more than one year of usage.

No abstract