A NON-INVASIVE METHOD FOR EVALUATING PULMONARY ENDOTHELIAL CELL APOPTOSIS AND ITS APPLICATION TO THERAPY IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

肺内血管生成的生长因子失衡是指在同一间隔内，如肺泡间隔和气道壁，一种生长因子的表达或活性高于另一种生长因子，通常具有相反的效果。因此，生长因子(如血管内皮生长因子、碱性成纤维细胞生长因子和肝细胞生长因子)和对抗性因子(如内皮抑素)应在肺的不同间隔内进行测量。在COPD的实质和呼吸道组织中，确定生长因子的动态平衡对于血管生成非常重要。这些发现可能有力地支持血管参与COPD过程的新理论。我们将连续检测诱导痰、支气管肺泡灌洗和呼气冷凝液中各种血管生成生长因子、氧化剂和抗氧化剂的浓度。吸烟对生长因子水平的影响也将被评估。如果肺气肿患者需要血管生成因子来维持肺泡室，人们可能会认为血管生成因子会减少，因为需要血管生成因子相关信号来维持的远端肺泡间隔较少。然而，在慢性支气管炎中，发生活跃的异常气道重塑，人们可能会预期过度的生长因子水平。目前，没有证据表明已知的药物治疗可以改变COPD患者肺功能的逐年下降。然而，我们的发现可能会导致一种新的干预COPD过程的策略，而针对肺泡间隔和气道壁血管生成的量身定制治疗将用于治疗个别COPD患者。

The imbalance of growth factors for angiogenesis in the lung represents a situation in which the expression or activity of one growth factor predominates over another, usually of opposing effect, within the same compartment such as alveolar septa and airway walls. Therefore, growth factors (e.g., VEGF, bFGF and HGF) and opposing factors (e.g., endostatin) should be measured within the various compartments of the lung. It is very important to characterize homeostasis of growth factors for angiogenesis in parenchymal and airway tissues of COPD. These findings may strongly support the new theory of vascular involvement in the processes of COPD. We will serially measure the concentrations of various growth factors for angiogenesis, oxidants and anti-oxidants in induced sputum, bronchoalveolar lavage and exhaled breath condensate. The effects of cigarette smoking on growth factor levels will be also evaluated. If angiogenic factors are required for maintenance of the alveolar compartment in patients with emphysema, one might expect angiogenic factors to be reduced, since there are fewer distal alveolar septa to require angiogenic factor-related signaling for maintenance. However, in chronic bronchitis, in which active abnormal airway remodeling is occurring, one would expect excessive growth factor levels. Currently, there is no evidence that known pharmacologic therapies change annual decline of lung function in COPD patients. However, our findings may lead to a new strategy for intervention in the processes of COPD, and tailor-made therapy for targeting of angiogenesis in alveolar septa and airway walls will for the treatment of individual COPD patients.