Predictors of clinical effectiveness and patient’s self-estimation after mandibular advancement device treatment in Obstructive Sleep Apnea Syndrome cases

目的：眠呼吸中止症(Obstructive sleep apnea syndrome)是一種常見的睡眠障礙病症，其會對身體造成嚴重的影響甚而致命而不容忽視。由於此病症之患者有許多相關的臨床症狀，包括嚴重的打鼾，睡眠中數度呼吸停止以及白天嗜睡等等。此外，研究中已證實打鼾可能為高血壓、缺血性心臟疾病及休克的危險因子，因此其對國民身體健康之影響不容忽視。在其多樣性的治療選擇中，目前以止鼾器治療較不具侵犯性、病患適應性良好而為一有效、經濟且接受度高之治療方式。於造成睡眠呼吸中止的致病因子有許多因素，每位患者的致病機轉也不盡相同，所以止鼾器的治療也並非對每位病患皆有明顯效果。回顧目前相關文獻，隨不同實驗樣本與設計，而有不一致的結果。 此，本研究的目的是分析在台大門診中睡眠呼吸中止症病患於接受止鼾器治療後，其治療效果與患者之基礎生理指數、顱顏構造、睡眠評估指數及病患自覺症狀之相關性研究，並試圖找出臨床上簡單易用的止鼾器效果評估方法，以期精準的預估治療效果之成功率。驗材料與方法：實驗採用橫向截面(cross section)的實驗設計。實驗對象為39位由國立台大醫院睡眠中心特別門診就診病患中，具有OSA臨床症狀及經PSG測定之後，判定為中至重度之OSA患者(AHI>15)，並至台大醫院牙科部止鼾器特別門診接受可調整式下顎前移止鼾器之治療。上述患者於治療前紀錄其年齡，量取基礎生理指數包括身高、體重，計算身體質量指數；此外並拍攝側顱X光片進行測顱分析，並發予睡眠日誌評估其合作程度，並於止鼾器治療後三個月至睡眠中心回診，再度接受PSG之測定。此外，治療前與治療後三個月回診時均請患者填寫自覺症狀評量問卷。治療成功率之分類，是以AHI reduction的比例>50%為responder，若<50%則為non-responder。計方法包括以成對樣本T檢定測試治療前後的改變，並使用單變項分析與多變項迴歸分析，以找出與止鼾器治療效果相關之預測因子。果： 本實驗的responder一共為26位，成功率約佔全體實驗對象的66.67%，其中又以男性的responder較多。受試患者的身體質量指數與體重之平均值，於治療後皆有顯著下降的情形，而PSG的各項測定值也均有改善。 本實驗也成功的找出影響止鼾器效果之預測因子，並獲得具臨床參考價值之迴歸模式。其中發現，Responder的患者，具有以下的顱顏結構特徵：low mandibular plane angle、nasopharynx較大、oropharnx較大、下段上呼吸道較寬。Non-responder的患者，則具有以下的顱顏結構特徵：下顎骨較為後縮、舌骨位置較下方及前方，軟腭長度較長，顱底彎曲度較大，此外其治療前血氧飽和度小於90%的比例較高。 在自覺症狀評估方面，Responder於治療前及治療後之生理健康、心理健康與總體自覺症狀指標值皆較non-responder為高，但僅治療前的心理健康指數與總體指數具顯著統計差異。本實驗也發現性別的不同與一些特定的顱顏構造，與患者自覺症狀的改善程度有關。論： 臨床上使用止鼾器對睡眠呼吸中止症的患者治療，其成功率與許多因素相關，包括性別、年齡、體重、顱顏構造等，且治療前的多功能睡眠評估指數也可以作為參考。因此未來在治療時，可以參考本實驗所得到的預估因子，較準確的篩選患者，並告知可能之成功率高低，使患者與醫師對治療的配合度及共識能夠更加提高。Objectives:Obstructive sleep apnea (OSA) syndrome is a common sleep disordered problem. The diagnosis depends on patient’s clinical symptoms features and polysomnographic examination. Symptoms and signs include repetitive upper airwar obstruction, distruptive snoring and daytime sleepiness. Besides, researchers have published that OSA may be the risk factors of hypertension, ischemic heart diseases and shock, meaning that OSA is a life-concerning generalized medical problem.There are several treatment modalities of OSA and oral appliance is a simple, effective and popular treatment option among them. The etiologic factors and pathogenesis of each patient are different, so the treatment effect of oral appliance varies from each other. However, some specific craniofacial features in successful responders of oral appliances have been reported, but the features varied depending on the samples and study design.he purpose of this study was to evaluate the treatment effect of oral appliance in OSA patients in relation to their basic medical condition, craniofacial features, polysomnographic data and the improvement of self-estimated symptoms. We hope to illustrate an effective and specific method for predicting treatment response of oral appliance. aterials and methods: his was a prospective cross-section study. A total of 83 patients from Sleep Center in National Taiwan University had related clinical symtoms and signs, and were diagnosed as moderate ro severe OSA by polysomnography. Then patients were arranged for adjustable mandibular advancement oral appliance therapy in Special Clinic of Oral Appliance in Dental Department of NTU. Pre-treatment age, height and weight were recored, so the BMI were derived. Besides, baseline cephalometry was performed on each patient. Three months after treatment, patients came back to Sleep Center for follow-ups and received post-treatment polysomnography. In the meanwhile, patients were asked to answer the questionnaire of SF-36 before treatment and 3 months after treatment to assess the self-estimated responses of the treatment. Forty-four patients quit this study due to various reasons, and a total of 39 patients were recruited. The subjects were divided into two groups on the basis of the degree of changes in AHI: responders (>50% AHI reduction) and non-responders (<50% AHI reduction).aired t test was performed to examine the changes after treatment. Univariate and multivariate regression analyses were used for searching possible variables to predict the response of treatment.esults: The number of responders in this study was 26 and the males were predominant. The success rate of oral appliance therapy in this study was 66.67%. Average weights and BMI of all the samples significantly decreased after treatment. Improvement in polysomnographic findings were noted as well. Predictors of oral appliance treatment outcome were successfully derived in clinically valid regression models. The characteristics of responders were with low mandibular plane angle, larger nasopharnyx and oropharynx and wider inferior upper airway space. However, non-responders usually had retrognathic mandible, inferiorly and anteriorly positioned hyoid bone, longer soft palate, larger basicranial flexure. Besides, the pre-treatment rate of oxygen saturation <90% was higher in non-responders. From the analysis of questionnaire, both physical and mental conditions were better in responders than in non-responders either before or after oral appliance treatment, though only pretreatment mental and total health scores reached statisical difference. Gender difference and some specific craniofacial features seem to be related to the change of self-estimated responses. onclusion: The treatment effects of oral appliance in patients with OSA were related to multiple factors, including gender, age, weight, craniofacial structures and pre-treatment polysomnography. Therefore, clinicians can predict better treatment outcome if proper indication was established for different treatment modalities.圖目錄 iii目錄 iv謝 v文摘要 vibstract viii一章 背景 10二章 文獻回顧 11一節 睡眠呼吸中止症之盛行率與臨床特徵 11二節 睡眠呼吸中止症之診斷 12三節 睡眠呼吸中止症之致病機轉與潛在因素 13四節 睡眠呼吸中止症之止鼾器治療 14五節 止鼾器之治療效果與臨床預估 16六節 研究目的 18三章 實驗材料與方法 20一節 實驗對象 20二節 實驗儀器設備與實驗方法 20、 基礎生理指數(身高、體重、身體質量指數) 21、 測顱分析 21、 多型態睡眠評估 (Polysomnography) 24、 自覺症狀評量表 24、 統計方法 24四章 實驗結果 25一節 實驗對象特性分析結果 25二節 不同性別實驗對象於各變項之差異 26三節 影響止鼾器治療效果之因素分析 27四節 止鼾器治療效果與自覺評量指數之相關性 30五章 討論 32一節 實驗對象之治療效果與屬性分析 32二節 側顱分析量測值之誤差 34三節 性別差異對實驗結果之影響 35.1 本實驗男性及女性病患之樣本差異處理 35.2 不同性別於本實驗治療效果與顱顏結構之差異 35四節 止鼾器治療效果之因素分析 37五節 止鼾器治療效果與自覺症狀之關係 43六章 結論 46七章 未來展望 47考文獻 80錄 一 84錄 二 8