A Prospective, Open-label Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- KU Leuven
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Histology on bronchial and/or transbronchial biopsies
研究概览
简要总结
This study investigates the role of azithromycin treatment for lymphocytic bronchitis/bronchiolitis after lung transplantation.
详细描述
Lymphocytic bronchitis/bronchiolitis is one of the major risk factors for development of chronic rejection/BOS after lung transplantation. There is currently no established treatment available for this condition. There is now mounting evidence that IL-17 producing lymphocytes (TH17) not only participate in chronic allograft rejection/BOS, but are also present within the airway wall during lymphocytic bronchiolitis and that IL-17 mRNA-levels in bronchoalveolar lavage fluid of these patients are upregulated. As such, TH17 may account for the increased BAL neutrophilia seen in these patients, as IL-17 may be responsible for driving IL-8 secretion (a neutrophil-attracting chemokine) from various cell types in the airways. Since azithromycin has previously been shown to reduce both IL-17 induced IL-8 production by human airway smooth muscle cells 'in vitro' and bronchoalveolar IL-8/neutrophil levels in LTx recipients with established BOS, we believe that azithromycin has great potential for treating lymphocytic bronchi(oli)tis by attenuating this TH17/IL-17/IL-8-mediated airway inflammation, possibly even halting the subsequent development of chronic rejection/BOS after lung transplantation. In this study, histologic, spirometric, bronchoalveolar an radiologic features will be investigated in patients treated with confirmed lymphocytic bronchitis/bronchiolitis treated with azithromycin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •Adult (age at least 18 years old at moment of transplantation)
- •Able to take oral medication
- •Histologic diagnosis of lymphocytic bronchiolitis or bronchitis ('grade B') without concurrent acute cellular allograft rejection 'grade A' ≥2
排除标准
- •Severe suture problems (e.g. airway stenosis) requiring lasering or stenting
研究组 & 干预措施
Azithromycin
Add-on of study-drug (azithromycin) to 'standard of care': 250 mg daily for 5 days, followed by 250 mg every other day until the end of the study-period (6 months treatment).
干预措施: Azithromycin Dihydrate (Drug)
结局指标
主要结局
Histology on bronchial and/or transbronchial biopsies
时间窗: after 3 months of treatment
Evolution of lymphocytic airway inflammation after 3 months of treatment
Pulmonary function (FEV1)
时间窗: after 3 months of treatment
Evolution of FEV1 after 3 months of treatment
Bronchoalveolar cellularity and protein levels (IL-8, IL-17)
时间窗: after 3 months of treatment
Evolution of bronchoalveolar cellularity and protein levels (IL-8, IL-17) after 3 months of treatment
Radiologic features
时间窗: after 3 months of treatment
Evolution of radiologic features (e.g. tree-in-bud, consolidation, bronchiectasis, air trapping, etc.) on chest X-ray or HRCT after 3 months of treatment
次要结局
- Pulmonary function (FEV1)(after 6 months of treatment)
研究者
GM. Verleden
Medical Director Leuven Lung Transplant Programme
KU Leuven
