| Part 1 Residual sleep apnea in OSA patients on PAP and the predictorsBackground:Positive airway pressure(PAP)is the first line therapy for patients with obstructive sleep apnea(OSA)as maintaining the open of the upper airway.However,OSA is a disease combined with more than one pathologies rather than upper airway collapse,such as high loop gain,low arousal threshold,which can not be released by the PAP.The rate of residual sleep apnea in patients treated with PAP and it’s predictors remained unclear.Methods:The adult patients who were diagnosed as OSA and underwent the split-night polysomnography(PSG)in the sleep medicine center,Beth Israel Deacons Medical Center,Harvard Medical School and followed up by the Encoreanywhere system were prospectively included.All the machine detected respiratory events related parameters and manual scored results in every month were collected.The ratio of patients with residual sleep apnea(defined as apnea hypopnea index(AHI)≥ 15times/hour in manual scored results or AHI ≥ 5 times/hour in machine detected results)in 3rd month and 12 th month were calculated.Linear regression model was done to explore the predictors of residual sleep apnea on PAP.Results:One hundred and ninety five patients were included.In the 3rd month,there were166 patients still on PAP.There were 74(44.58%)of them have residual AHI ≥ 15times/h according to the manual scored results and 46(27.71%)patients have residual AHI ≥ 5 times/h according to the machine detected results.In the 12 th month,there were 93 patients still on PAP.There were 41(44.09%)patients have residual AHI ≥15 according to the manual scored results and 26(27.96%)patients have residual AHI≥ 5 according to the machine detected results.In the short term,treatment CAHI(β=0.511,SE=0.123,p=0.001),age(β= 0.123,SE=0.054,p=0.025),and hypertension(β=3.627,SE=1.536,p=0.019)were the predictors for residual sleep apnea according to the manual scored results.Treatment CAHI(β= 0.192,SE=0.070,p=0.007)and renal failure(β= 5.560,SE=1.461,p<0.001)were the predictors for residual sleep apnea according to machine detected results.In the long term,treatment CAHI(β= 0.598,SE=0.163,p=0.001),gender(β=-5.117,SE=2.005,p=0.013)and baseline mean arousal duration(β=-0.601,SE=0.184,p=0.002)were the predictors for residual sleep apnea according to the manual scored results.Congestive heart failure(β= 0.126,SE=0.062,p=0.044)and treatment CAHI(β=3.286,SE=1.000,p=0.002)were the predictors for machine detected residual sleep apnea.Conclusions:There was a high percentage of patients with OSA who were on PAP have residual sleep apnea.Treatment CAHI was a strong predictor.Part 2 Acute effect of acetazolamide in high loop gain sleep apneaBackground:Obstructive sleep apnea is a disease with different driver phenotypes,including high loop gain(HLG),which means the respiratory drive is over sensitivity to the change of the carbon dioxide in the arterial.Acetazolamide(AZT)reduces HLG through multiple mechanisms.The acute effect of AZT used during titration polysomnography in HLG sleep apnea(HLGSA,predominantly obstructive)is described here.HLGSA is a non rapid eye movement(NREM)-dominant disease.Methods:HLGSA was identified by one or more of the followings: 1)baseline or titration CAHI(central apnea hypopnea index)of 5 or more,baseline or titration periodic breathing,or high residual apnea/periodic breathing on PAP in the absence of large leak.Retrospective analysis of polysomnograms from patients with HLGSA who underwent a PAP titration study and took ATZ(125 or 250 mg)after a baseline component of PAP titration.A responder was defined as a minimum reduction of the AHI3% of 50%.Multivariable logistic regression model estimated responder predictors.Results:Two hundred and thirty-one patients with a median age of 61.00(51.00-68.00)years and 184(79.65%)males,were included.77 patients were given 125 mg ATZ and 154 patients took 250 mg after about 3 hours of initial drug-free titration.Compared to PAP alone,PAP plus ATZ improved the sleep efficiency(71.70[58.80-84.00] vs.66.90[55.40-78.50],p=0.002)and reduced the breathing related arousal index(4.90[2.10-10.20] vs.8.40[3.00-15.60],p<0.001),AHI3%(10.65[4.53-20.62] vs.19.08[7.29-37.41],p<0.001),AHI4% (1.83[0.41-4.68] vs.1.85[0.23-8.65],P=0.008),RDI(13.55[7.34-25.80] vs.23.89[10.49-42.35],p <0.001).ATZ minimally improved the Min Sp O2(91.00[88.00-92.00] vs.90.00[87.00-92.00],p =0.012).98 patients were responders.Multiple logistic regression analysis showed that the NREM AHI3% was the predictor for responder status with ATZ exposure(OR 1.031,95%CI [1.016-1.046],p<0.001).And the effect of ATZ also related with the dose(OR 1.006,95%CI[1.000-1.012],p=0.035).Conclusions:ATZ acutely improves PAP efficacy in HLGSA.The NREM AHI3% is a predictor for the ATZ responders.Part 3 The compliance,effect of acetazolamide and the side effect in the patients with obstructive sleep apnea on positive airway pressure in the real worldBackground:Although acetazolamide(AZT)has been approved to improve the sleep apnea in patients with obstructive sleep apnea(OSA)at high altitude,and some experiments as well as our previous study showed the effectiveness of AZT in improving the high loop gain sleep apnea(HLGSA,predominantly obstructive)on positive airway pressure(PAP),no long term and large sample study has been done to explore the compliance and adverse outcome of AZT in the real world.Moreover,our previous study showed that one dose AZT before sleep was effective,which is different from the way of administration in other disease.Thus,we conducted this study to show the compliance and adverse outcome of AZT in HLGSA who were on PAP in the real world.Methods:All the patients diagnosed as OSA in Beth Israel Deacons Medical Center,Harvard Medical School have been screened.The patients who have HLG sleep apnea as estimated by their sleep doctors and were prescribed AZT were included.The respiratory events related parameters detected by the PAP or manual scored before and after AZT,compliance to AZT and the adverse outcome were collected.Results:A total of 325 patients were included in our study.43 patients stopped AZT in one month.In the 282 patients who used AZT for long term,109 of them have both machine detected respiratory events related parameters.AZT could further reduce the machine detected apnea hypopnea index(AHI)(2.60[1.70-5.35]5.10[2.90-10.25]vs.5.10[2.90-10.25],p<0.001)in patients on PAP.Meantime,the usage of AZT did not influence the mean daily usage of PAP(372.53[295.26-444.22] vs.368.50[273.00-438.87],p=0.275)or the percentage of the day using the machine >4hours(87.50[75.00-100.00] vs.87.50[62.50-100.00],p=0.999).75 patients have manual scored data.AZT could reduce the manual scored AHI(21.11[15.07-28.14] vs.28.55[21.92-35.45],p<0.001)Moreover,AZT could also decrease the Epworth sleepiness scale(5.00[4.00-8.00] vs.6.50[4.00-12.00],p=0.009).Among the 282 patients,there were 60 patients reported side effects.The most common one was paresthesia(7.09%)and polyuria(5.32%).Conclusions:The chronic usage of AZT could further reduce the AHI in HLG sleep apnea(HLGSA,predominantly obstructive)treated by PAP.The compliance of AZT was good.The most common one was paresthesia. |
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