[Efficacy and Safety of Tiotropium Bromide in the Treatment of Chronic Obstructive Pulmonary Disease--a Multi-center Randomized Clinical Trial].

OBJECTIVE: To investigate the efficacy and safety of domestic tiotropium inhalation capsule in patients with chronic obstructive pulmonary disease (COPD) with multi-center randomized clinical trial. METHODS: Patients with stable slight to moderate COPD were randomized into trial group (n=109) with tiotropium 18 pg Qd or control group (n =111) with ipratropium 40 µg Qid for a treatment of four weeks. The spirometry and scoring questionaire were recorded at different visits during the treatment. Rescue medication consumption and adverse events were recorded. Results Forced expiratory volume in 1 s (FEV1) of both groups increased obviously 30 min and 3 h after first dosing. After four weeks treatments, FEV, and forced vital capacity (FVC) in both groups were improved obviously, and the improvement in tiotropium group was significantly higher than that ipratropium group. COPD symptom scores were significantly reduced in both groups, and the improvement in tiotropium group was significantly better than that in ipratropium group. There was no significant difference in rescue medication consumption between the two groups. The ratios of adverse events were 22. 02% and 15. 32% in tiotropium and ipratropium group, respectively (P=0. 23). CONCLUSION: Domestic tiotropium inhalation capsule is efficient and safe in the treatment of COPD.

[The changes of apoptosis and proliferation of pulmonary tissue in chronic obstructive pulmonary disease rats].

OBJECTIVE: To observe the changes of apoptosis and proliferation of pulmonary tissue cells in rats with chronic obstructive pulmonary disease (COPD). METHODS: The rat model of COPD was established by exposure to cigarette smoking. Thirty-three Wistar rats were randomly divided into a normal control (NC) group, a smoking inhalation for 1 month (COPD-1) group and a smoking inhalation for 2 month (COPD-2) group. Pathologic changes of lung tissues and inflammatory cell differentials were studied. Immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) methods were carried out to examine the percentage of positive cells and distribution of apoptotic cells and proliferating cells in the lung tissue. RESULTS: Significant increases in total leukocyte numbers and neutrophils in the bronchoalveolar lavage were found in the COPD groups as compared to NC group. Two months after smoking exposure, enlargement of airspaces distal to the terminal bronchiole, destruction of alveolar walls, and loss of the alveolar unit were observed. The percentage of apoptotic cells of airway epithelium, alveolar wall cell and vascular smooth muscle cells were (36.2 +/- 8.5)%, (32.7 +/- 6.4)%, (16.1 +/- 7.2)% in COPD-1 group; (39.5 +/- 9.3)%, (37.3 +/- 7.6)%, (21.4 +/- 6.5)% in COPD-2 group; the difference being significant (all P < 0.01), as compared with NC group [(5.8 +/- 1.7)%, (6.1 +/- 2.3)%, (4.9 +/- 1.4)%]. The percentage of proliferative cells of airway epithelium, alveolar wall cell and vascular smooth muscle cells were (33.4 +/- 6.3)%, (30.1 +/- 4.6)%, (28.4 +/- 6.3)% in COPD-1 group; (35.5 +/- 9.8)%, (33.2 +/- 7.7)%, (34.5 +/- 6.7)% in COPD-2 group; the difference being significant (all P < 0.01), as compared with NC group [(7.4 +/- 2.3)%, (5.2 +/- 2.1)%, (4.4 +/- 1.8)%]. The numbers of apoptotic and proliferating cells were significantly higher in the COPD-2 group than those in the COPD-1 group (all P < 0.01). The ratio of proliferative index (PI)/apoptotic index (AI) of the pulmonary tissue cells were also different. The ratio of PI/AI of airway epithelium in COPD-1 and COPD-2 group [(0.82 +/- 0.13)%, (0.78 +/- 0.24)%] was much lower than NC group [(1.12 +/- 0.23)%, P < 0.05]; The ratio of PI/AI in small pulmonary vessels in the COPD groups [(1.55 +/- 0.25)%, (1.47 +/- 0.28)%] was significantly higher than NC group [(0.92 +/- 0.05)%, P < 0.05]. CONCLUSION: The changes of apoptosis and proliferation of pulmonary tissue in COPD rats might contribute to the pathogenesis of COPD.