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

肺中血管生成的生长因子的不平衡代表这样一种情况，即在同一隔室（例如肺泡间隔和气道壁）内，一种生长因子的表达或活性优于另一种生长因子，通常具有相反的作用。因此，应在肺的各个区室中测量生长因子（例如 VEGF、bFGF 和 HGF）和相反因子（例如内皮抑素）。表征 COPD 实质和气道组织中血管生成的生长因子的稳态非常重要。这些发现可能有力地支持了 COPD 过程中血管参与的新理论。我们将连续测量诱导痰、支气管肺泡灌洗液和呼出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。还将评估吸烟对生长因子水平的影响。如果肺气肿患者需要血管生成因子来维持肺泡室，人们可能会期望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，正在发生活跃的异常气道重塑，人们预计生长因子水平会过高。目前，没有证据表明已知的药物疗法可以改变慢性阻塞性肺病患者肺功能的逐年下降。然而，我们的研究结果可能会带来一种干预 COPD 过程的新策略，并且针对肺泡间隔和气道壁血管生成的定制疗法将用于治疗个体 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.