The Effects of Comprehensive Pulmonary Rehabilitation on Anti-Inflammation, Angiogenesis, and Clinical Outcomes of Chronic Obstructive Pulmonary Disease Patients

Patients with chronic obstructive pulmonary disease (COPD) are limited by dyspnea and have impaired exercise capacity and psychological problems, and poor health-related quality of life (HRQoL). The benefit of pulmonary rehabilitation (PR) in patients with COPD in improving exercise capacity and life quality, and in reducing breathlessness and health care utilization has been widely established. In addition, PR training could reduce the chronic inflammation status in COPD patients. Vascular endothelial growth factor (VEGF), Angiopoietin (Ang)-1, and Ang-2 are integrated in endothelial injury and altered permeability in COPD patients. The specific aims for this study project are to clarify the effects of a comprehensive PR program on inflammation, angiogenesis, and clinical outcomes of patients with COPD. In addition, the study will determine the in vitro effects of Ang-1 administration and blockade of Ang-2 on prevention of COPD patients’ serum induced disruption of endothelial cell structure, increased permeability, and expression of adhesion molecules. Our preliminary data has shown that PR training could increase Ang-1 levels and decreased Ang-2 in patients with COPD. In addition, PR training may also have anti-inflammatory effects on COPD patients. The study will recruit COPD patients of moderate to severe severity. All the recruited patients first receive a 12-week pulmonary rehabilitation program. After successful completion of the program, patients are randomized into 3 groups: the outpatient group, at-home group, and control group. During the further 12-month study period, patients’ serum and sputum will be collected at a 3-month interval. Patients will receive 6-min walk test, BODE index measurement, limb muscle power measurement, questionnaire for HRQoL, anxiety, and depression. The serum and sputum concentrations of albumin, CRP, IL-6, IL-8, TNF-α, VEGF, Tie-2, thrombomodulin, angiopoietin-1, angiopoietin-2, vW factor, and TGF-β will be determined. The serial change of these soluble factors and airway vascular permeability (AVP) between the 3 groups will be compared. The correlation between major adverse cardiovascular events (MACEs) development and the soluble factors and AVP will be analyzed. Furthermore, clinical outcomes among these groups will be compared. By means of the in vitro study, our project will further confirm the role of altered angiopoietins levels in mediating increased vascular permeability and inflammation in COPD patients with MACEs. In summary, our study project will provide the evidence for the tailored PR program through an algorithm with stepwise approach may provide clinical benefits in exercise performance, life quality, and long-term clinical outcome. These effects may be mediated through modulation of inflammation and angiogenesis in COPD patients receiving the comprehensive PR training.

Project ID:PC10601-0870
External Project ID:MOST105-2314-B182-043-MY2