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研究生:陳嬿今
研究生(外文):Yen-ChinChen
論文名稱:愛滋感染者的阻塞型睡眠呼吸中止症
論文名稱(外文):Obstructive Sleep Apnea of persons with HIV Infection
指導教授:柯乃熒柯乃熒引用關係
指導教授(外文):Nai-Ying Ko
學位類別:博士
校院名稱:國立成功大學
系所名稱:護理學系
學門:醫藥衛生學門
學類:護理學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:英文
論文頁數:88
中文關鍵詞:睡眠困擾阻塞性睡眠呼吸中止症愛滋病毒感染者睡眠障礙
外文關鍵詞:sleep disturbanceobstructive sleep apnea (OSA)HIV-infected personssleep disorders
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背景:阻塞型睡眠呼吸中止症(Obstructive sleep apnea, OSA)在愛滋病(human immunodeficiency virus, HIV)感染者是一種常見的疾病,同時也會提高全病因致死率,但目前仍鮮少有研究關注在OSA,此可治療以及可管理的疾病上。另外我們也發現,研究很少在探討合併有睡眠困擾的HIV感染者,其睡眠相關症狀、睡眠階層以及不同類型的睡眠障礙與一般組群的不同。
目的:本研究包含兩個部分-第一部分為探討抗病毒藥物治療(highly active antiretroviral therapy, HAART)對於阻塞性睡眠呼吸中止症的成效;第二部分為比較HIV感染者以及對照組在睡眠相關症狀、睡眠階層以及不同類型的睡眠障礙的異同。
研究方法:第一階段採全人口世代研究設計,於2000-2010年全民健保資料庫中定義出19,962位HIV感染者以及738,482位一般族群(已排除曾被診斷過罹患HIV)。透過年齡以及性別標準化發生率比(standardized incidence ratio, SIR),來估算HIV感染者以及一般族群罹患OSA相關危險性,並透過Cox比例風險模式(Cox proportional hazards models)估算HIV感染者其使用HAART與發生OSA之相關。第二階段招募共170位男性其匹茲堡睡眠品質量表大於5分者,其中包括44位為HIV感染者以及126位對照組(非HIV感染者),對照組的選樣係以感染者之性別、年齡(-/+ 3.0 years)以及身體質量指數(-/+ 3.0 kg/m2)作頻率取樣。全部170位樣本均接受過夜型睡眠檢查,使用學生t檢定或卡方檢定,比較兩組在睡眠相關症狀、睡眠階層以及不同睡眠障礙的異同。
結果:在全人口研究中發現,HIV感染者相較一般組群約有1.4倍的風險罹患OSA,尤其是女性HIV感染者以及年齡介於中壯年(15-39歲)的族群。在HIV染者,HAART 對於OSA有保護效果(aHR, 0.18; 95% CI, 0.11-0.30),特別是那些服藥遵從度大於95%者。相較於使用非核甘反轉錄酶抑制劑者,使用蛋白酶抑制劑者似乎會提高OSA的發生率。在第二部分研究,結果顯示合併有睡眠困擾的HIV感染者,相較於對照組其精神困擾(72.7% vs.40.5%,p〈0.001)以及快速動眼睡眠行為障礙rapid eye movement (REM) behavior disorder (RBD) (25.0% vs.4.8%,p〈0.01)有顯著比率提升。
結論:HIV感染者相對於一般族群有較高罹患OSA風險,早期偵測以及持續規律服藥大於95%可能可降低OSA風險。另外,HIV感染者合併有睡眠障礙的主訴,有極高比率是精神困擾以及呼吸道相關障礙引起,在研究中也發現HIV感染者其RBD為顯著高於對照組。持續使用HAART超過六個月以及服藥遵從性大於95%,對降低OSA的發生有潛在助益,進一步的研究需要再進一步驗證合併有睡眠困擾的HIV感染者其RBD的相關因素。
Background: Obstructive sleep apnea (OSA) is a common disease in HIV patients and as an independent risk factor for all-cause mortality. A few studies have focused on OSA, a treatable and manageable disease. In the other hand, Recognition of comorbid sleep disorders in patients with HIV is hampered by limited knowledge on the differences of sleep-related symptoms, sleep architecture, and types of sleep disorders to controls.
Purposes: This study includes two parts: In part one: to toward determining the impact of highly active antiretroviral therapy (HAART) on the incidence of OSA; in part two: we aimed to compare the difference of sleep related symptoms, sleep architecture, and sleep disorders between HIV-infected persons and controls in HIV clinics.
Methods: In part one, a population-based cohort design was conducted using the National Health Insurance Research Database (NHIRD) from 2000 to 2010 containing 13,962 HIV-positive and 738,482 HIV-negative individuals from the general population. The age- and sex-standardized incidence ratio (SIR) will be calculated to estimate the relative risk of OSA, and Cox proportional hazards models are used to evaluate the correlation between HAART and OSA among HIV-infected persons. In part two, the study included 170 men with a Pittsburgh sleep quality index (PSQI) greater than 5, composed of 44 HIV-infected men and 126 male controls who were frequency-matched by sex, age (-/+ 3.0 years) and BMI (-/+ 3.0 kg/m2). For all participants an overnight sleep study using a Somte V1 monitor was conducted. Differences in sleep-related symptoms and sleep disorders between HIV-infected patients and controls were examined using t-tests or Chi-square tests.
Results: In our population-based study, we found that the HIV-infected persons had a 1.4-fold OSA risk compared to that of the general population. The most increased risk for OSA was observed in HIV-infected women and aged between 15-39 years. HAART is a protection factor for OSA (aHR, 0.18; 95% CI, 0.11-0.30) in HIV-infected persons, particularly in those with greater than or equal to 95% adherence to HAART. An increased risk of OSA could be more frequent in those regimens with protease inhibitors (PIs), compared with those containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) regimens. In part 2 study, the data showed that HIV-infected persons with sleep disturbances more often had psychological disturbances (72.7% vs. 40.5%, p〈0.001) and rapid eye movement (REM) behavior disorder (RBD) (25.0% vs. 4.8%, p〈0.01) than that of controls. The sleep-disordered breathing (SDB) in HIV-infected persons was less common than that in controls (56.8% vs. 87.3%, p〈0.001). The mean percentage of REM sleep among HIV-infected patients was higher than that among the controls (20.6% vs. 16.6%, p〈0.001). Enuresis was more common in HIV-infected persons than controls (40.9% vs. 22.2%, p=0.02).
Conclusions: HIV-infected persons have an elevated risk for OSA compared to the general population. Early detection and continuing HAART over 95% adherence may reduce the risk of OSA. Additionally, psychological disturbances and SDB can be the possible explanations of sleep disturbances in HIV-infected persons, in which RBD is notable. Suggested a potential benefit of continued HAART use for at least six months and achieved 95% adherence to reduce the incidence of OSA for persons with an HIV infection. Further studies are warranted to examine underlying factors of RBD among HIV-infected persons with sleep disturbances.
中文摘要 I
Abstract III
誌謝 VI
Chapter One: Introduction 1
1.1 Background 1
1.2 Significance of this study 3
1.3 Study Purposes 7
Chapter Two: Literature Review 8
2.1 Sleep disturbances and HIV infection 8
2.1.1 The prevalence of sleep disturbances in HIV 8
2.1.2 The negative consequences of sleep disturbances in HIV 11
2.1.3 The etiology of sleep disturbances in HIV 12
2.2 OSA and HIV infection 12
2.2.1 The prevalence of OSA in HIV 12
2.2.2 Associated OSA factors in HIV 15
Chapter Three: Methodology 22
3.1 Part one: A population-based cohort study 22
3.1.1 Study design and data sources 22
3.1.2 Study subjects 23
3.1.3 Outcome variable 24
3.1.4 Confounders 24
3.1.5 Data analysis 26
3.2 Part two: A comparative study design 27
3.2.1 Study design 27
3.2.2 Study participants 27
3.2.2.1 HIV-infected men with sleep disturbances 27
3.2.2.2 Controls with sleep disturbances 27
3.2.3 Primary outcomes 28
3.2.3.1 Sleep Disordered Breathing (SDB) 28
3.2.3.2 Periodic limb movement (PLM) 29
3.2.3.3 REM behavior disorder (RBD) 29
3.2.3.4 Psychological disturbances 29
3.2.4 Measures 30
3.2.4.1 Polysomnography study 30
3.2.4.2 Questionnaire measurements 30
3.2.4.3 Clinical data collection 30
3.2.5 The data collection procedure for evaluating sleep disorders 32
3.2.6 Data Analysis 33
Chapter Four: Results 34
4.1 Part one: A population-based cohort study 34
4.1.1 Demographic Characteristics 34
4.1.2 SIR of OSA in HIV-infected persons 34
4.1.3 Factors associated with OSA among HIV-infected persons 35
4.1.4 The role of HAART on incidence of OSA among HIV-infected persons 35
4.2 Part two: A comparative study 36
4.2.1 Demographics 36
4.2.2 The difference of sleep architecture 36
4.2.3 Different types of sleep disorders present 37
4.2.4 Difference in sleep-related complaints 37
Chapter Five: Discussions 38
Chapter Six: Conclusions 45
References 47
Tables
Table 1. The prevalence of sleep disturbances in HIV-infected persons 8
Table 2. Studies exploring the prevalence of OSA among HIV-infected persons 13
Table 3. Studies exploring risk factors for OSA in HIV-infected persons 20
Table 4. Summary of the two questionnaires for clinical measurement tools for sleep related symptoms 32
Table 5. Comparison of demographic characteristics between HIV-infected persons and the general population. 71
Table 6. Incidences and SIR of OSA between HIV-infected persons and the general population during 2000-2010 73
Table 7. Hazard ratios of obstructive sleep apnea of different parameters in HIV-infected persons. 74
Table 8. HAART effects on incidences of obstructive sleep apnea among HIV-infected persons who are being treated more than a half-year (n = 6,507) 77
Table 9. Demographic of participants (N = 170) 78
Table 10. Difference in sleep architecture between HIV patients and controls 80
Table 11. Sleep disorders present in HIV and controls 82
Figure
Figure 1. Frequency of sleep-related chief complaints among HIV-infected persons compared with controls. 83
Appendix
Appendix 1 The willing form of receving home-based PSG 69
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