The effect of macrolide therapy on sub-clinical infection and inflammation in human lung transplantation.

对于许多慢性肺部疾病，如年轻人的囊性纤维化，肺移植可能是晚期疾病的唯一治疗方法。这可以延长预期寿命和质量，并允许恢复日常活动，但慢性排斥是主要问题。我们将研究少量的感染，这些感染不会立即引起临床问题，可能会导致随后的慢性排斥反应。这在以前没有被认为是重要的，因此没有被研究过。选择这个研究领域是因为它是英国呼吸医学的强项。弗里曼医院是世界上最大的移植中心之一，因此这项工作是可行的。为什么肺移植会产生慢性排斥反应的问题在国内和国际上都具有重要意义。为了完成我们的工作，我们将使用非常敏感的分子方法来量化低水平的感染，看看是否有证据表明这可能会导致气道炎症和瘢痕形成。我们认为这会导致进行性呼吸短促和慢性移植排斥反应。新的抗生素疗法已经用于慢性排斥反应，这似乎对一些人有帮助，但没有人知道这是如何起作用的。我们将对这种方法进行正式的科学研究，以改进现有证据。我们还将对移植患者的肺样本进行实验，目的是研究潜在的机制，以及为什么有些人做得很好，而另一些人却不行。为了进行这些实验，我们将从小样本中培养移植细胞，以提供所需的大量细胞。我们所有的工作都将使用人类样本，因为这些样本最适合我们的研究。预计我们的结果将表明，即使是低水平的感染对肺移植患者来说也是一个问题，抗生素治疗可以帮助解决这个问题。这将改变慢性排斥反应的治疗方式，我们认为这可能有助于保护移植的肺，延长预期寿命。

For many chronic lung diseases, such as cystic fibrosis in young people, lung transplantation can be the only present treatment for advanced disease. This can extend life expectancy and quality, and allows resumption of day to day activities, but chronic rejection is a major problem. We will carry out research into how small amounts of infection, which do not cause immediate clinical problems, might cause subsequent chronic rejection. This has previously not been considered significant, and therefore has not been studied. This area of research has been chosen because it is a strength of respiratory medicine in the UK. The Freeman Hospital is one of the worlds largest transplant centres, making the work feasible. The question of why lung transplants develop chronic rejection is of national and international importance.To do our work we will be using very sensitive molecular methods to quantify low levels of infection, to see if there is evidence to suggest that this may cause inflammation and scarring of the airways. We believe that this causes progressive shortness of breath and chronic transplant rejection.New antibiotic therapies have been used in chronic rejection and this seems to help some people, but no one knows how this works. We will perform a formal scientific study of this approach to improve the available evidence. We will also perform experiments with lung samples from transplant patients that aim to investigate potential mechanisms, and why some people do well but others do not. To allow these experiments we will grow transplant cells from small samples to give the larger numbers of cells needed. All of our work will be done using human samples because these are the most appropriate for our research.It is expected that our results will show that even low levels of infection are a problem to lung transplant patients and that antibiotic treatment helps this. This would change how chronic rejection is treated and we think this may help to protect transplanted lungs and extend life expectancy.