The Effects And Mechanism Of Theophylline On Mild And Modest Obstructive Sleep Apnea Syndrome(OSAS) And Stable Chronic Obstructive Pulmonary Disease(COPD)

Background: Nocturnal hypoxemia occurs commonly in patients with obstructive sleep apnea syndrome(OSAS) and chronic obstructive pulmonary disease(COPD). Severe hypoxemia causes ATP depletion and increased plasm adenosine level. Adenosine is a inhibitory neuromodulator which can induce sleep, inhibit respiratory, make OSAS even worse. Theophylline, an non-special adenosine antagonist, has been proved to play a role in therapy of OSAS and COPD. Can it really be helpful and what may be the mechanism? This trial was designed in order to investigate the effects of theophylline on OSAS and COPD, and to deduce the possible mechanism.Methods and results: Group 1 Twenty-six patients with mild and modest OSAS were enrolled in a randomized self-controlled crossover trial of two different doses of oral sustained-release theophylline, 200mg or 300mg, taken at 9PM(QN), for two weeks, overnight polysomnography(PSG) was performed at the end of each treatment period with spirometry at 6AM. The total number of apneas(A) and hypopneas(H) decreased significantly from 1472 to 947(200mg,QN), 738(300mg,QN) respectively, p<0.05. The apnea and hypopnea index(AHI) was reduced by 46.4% and 50.5%. The mean overnight SaO2(%) was improved slightly (92.48±1.55 vs 93.71±2.12 and 94.42±0.90, p<0.05), and the time of sleep with oxygen saturation below 90% (T90) was reduced (0.57±0.31 vs 0.36±0.19 and 0.36±0.22,p<0.05). However, the mean duration of A or H remains unchanged (p>0.05). A theophylline level, drawn at 6AM, was (6.13±1.27)ug.ml-1 and (8.30±1.62)ug.ml-1 morning P0.1,MIP was better after theophylline administration. No differents have been detected betweenthe two different doses group. Group 2: To investigate the effect of theophylline on sleep and nocturnal hypoxemia of stable COPD, we studied twenty subjects with a age of (57.6 ±9.9) yr and a FEVi of (42.49±12.19)%. Before theophylline given, the baseline measurements on polysomnography and morning respiratory functional parameters(P0.1, FEV,, FEVrFVC ', PEFR, MEP, MEP) were performed, And then, using a randomized self-controlled protocol, Oral sustained-release theophylline was administered on the following two weeks. Sleep study were performed on night 14 with other testings similar as baseline measurements. A theophylline level, drawn at 6AM, was 3.95+1.25P-g-mr',the morning PO. l,FEVj,MIP was better after theophylline administration. The awaken SaO2,mean overnight SaO2 and T90 was improved slightly. Within both of the two group, the total sleep time, the number of arousals and the fraction of time spent in Stages I+II, and IH+IV and REM were unchanged.P>0.05. Group 3: plasm adenosine concentration was measure in 3 groups of objects: twenty-six patients with OSAS, twenty patients with COPD, sixteen control subjects. OSAS has the highest degree, COPD has the lowest.Conclusion: Theophylline therapy can reduce the total number and time of overnight episodes of A and H in mild and modest OSAS and the duration of arterial oxyhemoglobin desaturation during sleep of OSAS and stable COPD. No difference have been detected between the two different dose groups. The mechanism by which theophylline improves OSAS is likely to competition with adenosine receptor, but in COPD, adenosine seems less important.