慢性阻塞性肺疾病（COPD）是一种从支气管炎到肺部肺气肿的多种疾病。然而，这种渴望通过简单参数（例如肺功能和单一可溶性炎症标记）来定义COPD中的疾病状态。这导致了关于嵌入疾病严重程度的某种共识GOLD initiative.

Unfortunately, COPD cannot be accurately described by general one-dimensional characteristics as the disease is heterogeneous in the lung and is clearly associated by systemic manifestations such as muscle dysfunction, systemic inflammation and metabolic dysfunction.

If we persist in approaching this disease as if it is caused by a single general pathogenetic mechanism these therapeutic strategies are bound to fail.

此外，该疾病的特征是急性恶化时期通常称为恶化。该疾病的这些阶段会对肺组织造成不可逆转的损害，并且是预防策略的主要重点。

众多临床和基础研究都没有导致成功治疗COPD的治疗策略。实际上，为这种毁灭性疾病开发新药物有巨大的未满足医疗需求，在未来几年中将增加third cause of death worldwide. However, if we persist in approaching this disease as if it is caused by a single general pathogenetic mechanism these therapeutic strategies are bound to fail.

Defining systematic inflammation

当前文献中重要的未解决的问题之一是系统性炎症在COPD发病机理中的重要性。这主要是由于缺乏明确的全身性炎症定义引起的。这导致了大量研究，这些研究无法彼此进行比较，因为每项研究都使用了自己的流行介体和/或疾病机制。

全身性炎症可以定义为将局部炎症性疾病过程传播到远处组织功能障碍的机制。这个相当神秘的定义意味着COPD中肺中产生的介质会影响远方的组织，例如肌肉。

It will be immediately clear that systemic inflammation in COPD is not a single mechanism as signs of dysfunction of distant tissues are very different between COPD patients ranging from pink puffers (‘more wasting phenotype/emphesema’) to blue bloaters (‘more obese/metabolic phenotype/bronchitis’). Recently, even a new phenotype of COPD emerged that is characterized by eosinophilic inflammation. This form of COPD is referred to as asthma COPD overlap syndrome or ACOS.

Also in this field there was the fixed idea to translate systemic inflammation into the occurrence of single mediators such C-reactive protein (CRP) or single cytokines such as interleukin-6 (IL-6) and tumor necrosis factor (TNF). It will be clear from the above that that approach was also doomed to fail.

我们各自通过另一种方法解决该问题ch and hypothesized that all pro- and anti-inflammatory systemic signals will change the cells expressing the receptors for these mediators.

There are many reasons why single mediators cannot fulfill the desired read-out for systemic inflammation. Important reasons are discussed by us in our recent文章inRespiratory Research和include lack of knowledge regardingallmediators found in COPD, cross-talk between the function of mediators, the change in disease mechanisms between stable and instable disease, and the presence or absence of infection. Therefore, only measuring soluble mediators will not likely lead to solving the riddle of the mechanisms underlying systemic inflammation.

我们各自通过另一种方法解决该问题ch and hypothesized that all pro- and anti-inflammatory systemic signals will change the cells expressing the receptors for these mediators. So these cells integrate all information and will change their phenotype accordingly.

In our study cellular diagnostics by proteomics and flow cytometry was combined with luminex technology that allows multiplex analysis of multiple cytokines in peripheral blood. Our study provides proof-of-principle that cellular diagnostics in stable COPD is able to identify at least two systemic inflammatory processes. These differences were not associated with GOLD stages again pointing at the fact that sterile inflammation is not reflected in the GOLD stages found in the COPD patients.

The study was performed in a small population of stable COPD patients not stratified for clinical or immunological characteristics. Even more types of systemic inflammation will be found when multiple forms of COPD will be compared with each other. Consequently it is not to be expected that the complex mechanism of underlying systemic inflammation in COPD will be identified when we persist in performing studies designed under the assumption that COPD is caused by a single dominant disease mechanism that is caught by simple disease markers.