The Study On Improving Sleep Hypoxemia By Three Drugs Of Different Mechanisms And The Anti-inflammatory Effect Of Tiotropium In Patients With Obstructive Pulmonary Disease

Objective:Different degrees of damage may be caused by sleep hypoxemia in patients with COPD. It was involved in the deterioration of sleep quality, arrhythmia, heart failure and even sudden death during the sleep. Effective drugs were required for the remission of sleep hypoxemia and improvement of life and sleep quality in patients with COPD. M receptor antagonist-tiotropium was proposed to become a research focus in vitro anti-inflammatory mechanism in COPD in recent years. The anti-inflammatory effects of tiotropium was not yet reached the same conclusion in clinical research. For these reasons, we researched respectively in:(1) To investigate the influence of sleep hypoxemia on arterial blood gases analysis, pulmonary function in daytime and sleep architecture, sleep quality, life quality. To predict reference indexes of sleep hypoxemia in COPD. (2) To investigate the effects of three different mechanisms of drugs, that was M receptor blocker, theophylline,β-agonists combined inhaled corticosteroid, which was the best one to improve sleep hypoxemia, sleep and life quality in COPD patients. (3)To investigate the changes of inflammatory cells and inflammatory mediators in induced sputum of patients with COPD and the efects of anti-cholinergic drugs. To explore theoretical basis of the anti-inflammatory mechanism of anti-cholinergic drugs in COPD. Contents:1. The study on sleep hypoxemia in patients with obstructive pulmonary disease 2. The study on improving sleep hypoxemia and sleep quality by three drugs of different mechanisms in patients with COPD.3. The study on the anti-inflammatory effects of tiotropium in patients with stable COPD. Methods:(1)All enrollment COPD patients were performed with arterial blood gases analysis, pulmonary function in daytime, respiratory drive, sleep quality questionnaire score, quality of life questionnaire score, while the overnight polysomnography were also performed. (2)The patients with sleep hypoxemia screened by PSG were given different three drugs. To investigate the efficacy on these performed indicators of different drugs. (3)To compare the difference of inflammatory cells and inflammatory mediators in induced sputum between COPD patients and healthy controls.The COPD patients were given small doses of sustained-release theophylline tablets and inhaled tiotropium therapy respectively. To observe changes of inflammatory cells and mediators before and after treatment in COPD patients. Results:The first part:1.There were significantly differences in daytime SaO2,nocturnal SaO2, lung function, measurements of PSG, sleep quality, life quality between nocturnal oxygen desaturation(NOD) and Non-NOD(P<0.05).2. The measurements of blood gases analysis, lung function in daytime were respectively correlated with sleep hypoxemia. Among these measurements, PaCO2 was the best correlated with T90(r=0.767), MSaO2 (r=-0.758), MiniSaO2(r=-0.689), suggesting that PaCO2 can be as a predictor of sleep hypoxemia. The second part:1.There were some improvement in blood gases analysis, pulmonary function, respiratory drive, sleep hypoxemia, sleep quality, life quality after taken tiotropium, salmeterol and fluticasone, theophylline sustained-release tablets in patients with COPD.2.The efficacy of the tiotropium group was significantly better than theophylline group in FEV1% (F=6.839, P<0.01), NREM sleep latency (F=4.679,P<0.05), MiniSO2 (F=4.160,P<0.05), PSQI total score (F=7.822,P<0.05), general health (F=7.769, P<0.05). The third part:1.The levels of IL-8 and LTB4 in induced sputum can be significantly decreased both in tiotropium group and theophylline group in COPD patients (both P<0.01). but the levels of MPO can be decreased with no significant differences.2.Compared the effects on inflammatory cells and mediators in induced sputum,there was no difference between the two groups. Conclusions:1.The measurements of daytime SaO2,nocturnal SaO2, lung function, sleep architecture, sleep quality, life quality were poorer in NOD than in Non-NOD. PaO2,SaO2, PaCO2 in daytime were significantly correlated with sleep hypoxemia in patients with COPD. 2.There was some improvement in blood gas analysis, pulmonary function, respiratory drive, sleep hypoxemia, sleep quality, life quality after taken tiotropium, salmeterol and fluticasone, theophylline sustained-release tablets in patients with COPD. The efficacy of the tiotropium group was better than other groups in sleep quality and life quality in COPD patients.3.Effect of tiotropium on inflammatory cells and mediators as similar as theophylline in patients with COPD.