Immunomodulatory Effects of Macrolide Antibiotics – Part 2: Advantages and Disadvantages of Long-Term, Low-Dose Macrolide Therapy

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.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Macrolide Therapy Decreases Chronic Obstructive Pulmonary Disease Exacerbation: A Meta-Analysis

Yao

Zhang

et al. 2013

“…Macrolide antibiotics appear to possess anti-inflammatory properties independent of their antibiotic effect and have been shown to be beneficial in a number of pulmonary disorders, mainly in diffuse panbronchiolitis, and in other chronic pulmonary inflammatory disorders, including cystic fibrosis , non-cystic fibrosis bronchiectases, chronic obstructive pulmonary diseases, and asthma [9]. Although the exact mechanism for the beneficial effect of macrolides has not been completely clarified, it is clearly not related to their antibiotic properties.…”

Section: Discussionmentioning

confidence: 99%

Clarithromycin Stops Lung Function Decline in Airway-Centered Interstitial Fibrosis

Jouneau

Kerjouan²,

Caulet‐Maugendre³

et al. 2012

Airway-centered interstitial fibrosis (ACIF) is a distinct type of lung interstitial fibrosis characterized by lesions centered on the airways. Several cases reported in the literature showed little to no effect of corticosteroids and a high mortality rate in the absence of lung transplantation. No other efficient approach is described for the treatment of this type of fibrosis. We report for the first time the case of a 44-year-old patient diagnosed with ACIF on surgical lung biopsy and stabilized with clarithromycin after failure of systemic corticosteroids. We need to confirm this benefit in other patients to ascertain the anti-inflammatory effect of macrolides, which are far less harmful compared to corticosteroids or immunosuppressant drugs.

“…Pathologically, interstitial foamy macrophages around respiratory bronchioles is the most distinctive feature. Treatment with low-dose macrolides has been shown to significantly improve survival [2,3]. …”

Section: Discussionmentioning

confidence: 99%

A Case of Diffuse Panbronchiolitis Complicated by Peripheral T Cell Lymphoma Not Otherwise Specified

Feng

Yu²,

Liu³

et al. 2011

We report a case of diffuse panbronchiolitis (DPB) complicated by peripheral T cell lymphoma not otherwise specified. A 40-year-old Chinese man presented with intermittent fever, cough and significant white sputum production for more than 9 years, in addition to dyspnea and chest congestion that worsened after exercise. A chest CT scan indicated diffuse centrilobular fine nodular opacities with a ‘tree-in-bud’ appearance in both lungs. An open-lung biopsy was performed, and DPB was diagnosed by histopathological analysis. Three months later, the patient’s pulmonary symptoms worsened. A chest CT of both lungs revealed multiple patchy opacities as well as enlargement of the hilar, mediastinal and multiple superficial lymph nodes. A whole-body bone scan revealed multiple osteolytic lesions located in the thoracic, lumbar and sacral spine. A biopsy of the right supraclavicular lymph node was performed, and peripheral T cell lymphoma not otherwise specified was diagnosed histopathologically. Cases of DPB complicated by non-Hodgkin’s lymphoma are a rare occurrence. To our knowledge, there is only one earlier report of such a case in the literature (in Japanese). However, the prevalence of DPB complicated by T cell tumors is relatively high, indicating a possible association in pathogenesis of T cell disorders and DPB.