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了一种情况，其中一种生长因子的表达或活性在相同的隔室如肺泡隔和气道壁内超过另一种生长因子，通常具有相反的作用。因此，生长因子（例如，VEGF、bFGF和HGF）和相反因子（例如，内皮抑制素）应该在肺的各个隔室中测量。研究COPD患者肺实质和气道组织中生长因子的动态平衡对血管生成具有重要意义。这些发现可能有力地支持了血管参与COPD过程的新理论。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。如果肺气肿患者的肺泡隔需要血管生成因子来维持，则可能预期血管生成因子会减少，因为需要血管生成因子相关信号传导来维持的远端肺泡隔较少。然而，在慢性支气管炎中，其中发生主动异常气道重塑，人们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改变COPD患者肺功能的年下降。然而，我们的研究结果可能会导致一种新的策略，在COPD的过程中进行干预，并针对肺泡隔和气道壁中的血管生成进行量身定制的治疗将用于治疗个体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.