請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66379
標題: | 異位性皮膚炎患童的睡眠與退黑激素的關係 The Relationship of Sleep and Urine Levels of Melatonin in Children with Atopic Dermatitis |
作者: | Kai-Lin Chang 張凱琳 |
指導教授: | 江伯倫(Bor-Luen Chiang) |
關鍵字: | 異位性皮膚炎,退黑激素,SCORAD index,IDQOL,CDLQI,DFI,Actigraphy, atopic dermatitis,melatonin,SCORAD index,IDQOL,CDLQI,DFI,Actigraphy, |
出版年 : | 2012 |
學位: | 碩士 |
摘要: | 研究背景及目的
異位性皮膚炎是孩童時期最常見的慢性搔癢性皮膚病變,病童常因夜間搔抓而造成睡眠品質的下降,對身心健康及生長發育造成許多負面影響,因此改善夜間睡眠品質應為治療異位性皮膚炎患童的目標之一。退黑激素為一種神經性賀爾蒙,可調節人體的生理時鐘、幫助睡眠,同時也具有免疫調節的作用,但異位性皮膚炎病童的退黑激素分泌是否異常而影響睡眠,以及在此疾病的病因中所扮演的角色,目前仍少有人研究。故本研究計畫的目的即評估異位性皮膚炎患童的睡眠狀況與退黑激素分泌是否和正常小孩有差異,並探討睡眠和疾病嚴重度、生活品質、以及退黑激素之間的相關性。此外,由於目前治療異位性皮膚炎病童失眠問題的方法仍有限,故也希望藉由此研究,能評估退黑激素用來改善病童睡眠的可行性,以期讓病人有更佳的生活品質。 研究方法 本研究之對象為1~16歲異位性皮膚炎的病童,另收集年齡相仿的健康孩童做為對照組。異位性皮膚炎的疾病嚴重度以SCORAD index作評分,並請病童或照顧者填寫皮膚炎生活品質(IDQOL、CDLQI)及家庭衝擊(DFI)問卷。所有受試者必須在檢查的當晚於睡覺時配戴Actigraph在非慣用手上,以評估睡眠狀態及夜間手腕的活動情形,並於睡眠檢查的隔天清晨起床時收集尿液10∼15c.c,再以 enzyme immunoassay的方法測量尿液中退黑激素代謝物6-hydroxymelatonin sulfate的濃度,之後比較兩組的睡眠品質、搔抓頻率和退黑激素分泌是否有差異,並分析病童的Actigraphy測量結果、SCORAD、問卷分數、以及退黑激素之間的相關性。 研究結果 我們收集了26位異位性皮膚炎的病童和28位健康的對照組,平均年齡分別為7.1 ± 4.4及8.4 ± 3.9歲。和健康對照組相比,異位性皮膚炎病童的入睡所需時間較長,睡眠效率較差,睡覺時搔抓的動作較頻繁,且疾病嚴重度與睡眠效率呈明顯負相關性、和搔癢活動的頻率則有顯著正相關。病童的生活品質及家庭衝擊問卷評分和Actigraphy的測量結果皆無顯著相關性,不過生活品質問卷的分數與疾病嚴重度有顯著正相關。至於睡眠和搔癢程度的相關性,病童Actigraphy的睡眠及搔抓動作測量結果呈顯著負相關,分析SCORAD的主觀評分項目也發現失眠程度和搔癢嚴重度有明顯的正相關。另外我們也評估以主觀及客觀方法測量的睡眠及搔癢結果是否一致,發現Actigraphy所測得的睡眠效率及搔抓活動分別與SCORAD的失眠及搔癢程度主觀評分有顯著相關。在退黑激素的比較方面,異位性皮膚炎病童的尿中退黑激素濃度和健康孩童並無差異,和Actigraphy的檢查結果以及疾病嚴重度亦無明顯相關性。 結論 我們的研究顯示異位性皮膚炎病童有睡眠品質不佳的問題,且睡眠和生活品質與疾病嚴重度相關。病童的失眠及搔癢程度呈顯著正相關,表示皮膚癢感引起的搔抓動作可能是干擾睡眠的原因之一。我們的研究結果也證明Actigraphy除了可用來測量異位性皮膚炎病童的夜間睡眠及搔抓情形外,也是評估疾病嚴重度的有效工具。而雖然本研究中主觀和客觀的睡眠檢查結果呈顯著相關性,不過利用儀器進行檢測能提供更多更精確的睡眠分析結果,也具有較高的可信度,因此我們認為客觀的測量工具仍是較佳的睡眠檢查方法。另外我們還發現異位性皮膚炎病童於夜間的退黑激素分泌量和健康孩童並無顯著差異,和睡眠品質、疾病嚴重度亦無顯著相關。由於本研究僅收集受試者清晨起床的第一泡尿液,無法得知病童白天的退黑激素分泌量及週期性的分泌型態是否改變,因此對於異位性皮膚炎病童的退黑激素分泌情形,以及退黑激素在異位性皮膚炎治療上的應用是否可行,仍有待更多的研究進一歩去釐清。我們希望未來在治療異位性皮膚炎病童的皮膚症狀之外,也能儘早開發出有效的藥物以改善其失眠問題,讓病童有更好的生活品質。 Background and Objectives Atopic dermatitis (AD) is a chronic allergic skin disease with significant costs and morbidity to patients and their families. The pathogenesis is proposed to be contributed by multi-factors, including inherited genetic susceptibility, environmental triggers and allergens, abnormal immune response, and skin barrier disorder. The incidence of AD is increasing world-wide, with 10-20% among pediatric patients and 2-3% among adults. Sleep disturbance is one of the most common complaints among these patients, which can result in daytime fatigue, mood disorder, reduced behavior and neurocognitive functioning, and compromised quality of life. Recent studies have advanced our understanding that allergic inflammation triggers neuronal dysfunction, thereby modulating inflammatory responses through neuromediators in affected tissues including the skin. Melatonin is a neurohormone produced mainly by the pineal gland and has been shown to influence many biological functions, including hypnotic effect and modulating immune cell production and action. It remains unknown that if melatonin plays a role in skin inflammation and sleep problems in patients with AD. The purpose of our study was to compare the sleep condition, nocturnal wrist movements and urine levels of melatonin between pediatric patients with AD and healthy controls, and to further correlate the sleep condition with urine concentration of melatonin, disease severity and quality of life in AD patients. Materials and Methods Participants and Study design Children who aged between 1 and 16 years and visited the pediatric allergy clinic of National Taiwan University Hospital between May and October 2011 with a diagnosis of atopic dermatitis were recruited in this study. Patients were excluded if they: had co-morbidities of other major systemic diseases; had received therapy for insomnia within 1 month before entering this study; had received systemic steroid or immunosuppressant medication 1 month prior to the study. Age-matched healthy children were enrolled as controls. SCORAD index The eczema of disese of children with AD patients was assessed using the Severity sCORing of Atopic Dermatitis (SCORAD) index system (Fig. 1), which combines extent, intensity and subjective symptoms. The rule of nine is used to estimate the extent of involvement of total body surface area (TBSA) by eczema (Fig. 2). The six intensity items included erythema, edema/population, oozing/crust, excoriation, lichenification and dryness. The subjective components in SCORAD index consist of questions to sleep loss and pruritus, and children with AD or their caretakers were asked to record their responses to each question on a 10-cm horizontal visual analogue scale. Questionnaires Children with AD or their caretakers were instructed to complete the 10-item questionnaires of Infants’(IDQOL, Table 1) or Children’s (CDLQI, Table 2) Dermatology Life Quality Index based on age younger or older than 4 years old. The caretakers of children with AD were asked to complete the 10-item Dermatitis Family Impact questionnaire (DFI) (Table 3) on which they quantified the impact of AD on family. Actigraphy We assess the sleep condition and wrist movements of all participants by Actigraphy, which is a watch-shaped wrist-worn accelerometer and can record the integration of intensity, amount and duration of wrist movements (Fig. 3). Participants wore the Actigraph on their non-dominant wrist through one night. Actigraph data used for this investigation included onset latency (time to sleep onset), sleep efficiency (proportion of time in bed spent asleep), and % mobile (percentage of total mobile time in the total recording time). Melatonin assay After an overnight sleep measure with the Actigraph, 10~15 c.c. first morning urine output was collected on the next day from each volunteer. Urinary levels of melatonin primary metabolite, 6-hydroxymelatonin sulfate, were determined in enzyme immunoassay (ELISA) with commercial ELISA kits. The Actigraph measures and the urine concentrations of melatonin were compared between patients and healthy controls. Correlations among sleep quality, SCORAD, and questionnaires scores were analyzed. Associations between the Actigraph measures and the subjective elements about sleep and itch were determined. The relation of urine levels of melatonin to Actigraph recordings and SCORAD scores were also investigated. Statistical analysis The Actigraphy data and urine levels of melatonin were compared by the Student’s t test between AD group and controls. Correlation among Actigraph measures, urine levels of melatonin, SCORAD and questionnaires scores were made using Spearman nonparametric correlation coefficients. Results were considered significant if the p value was less than 0.05. All of the statistical analyses were performed with SPSS version 13.0 for Windows (SPSS Inc., Chicago, IL, USA). Results The patient group consisted of 12 males and 14 females (mean ± SD age 7.1 ± 4.4 yr). Twenty eight normal children (14 males, 14 females, mean ± SD age 8.4 ± 3.9 yr) served as controls. The median (interquartile range) SCORAD was 29.3 (19.975-40.9). Results of Actigraphy sleep measures A significantly longer sleep latency (50.69 ± 33.99 vs. 22.84 ± 16.90, p = 0.001), lower sleep efficiency (73.42 ± 9.72 vs. 83.09 ± 7.16, p < 0.001) and more frequent wrist movements (% mobile, 11.58 ± 7.25 vs. 6.66 ± 3.02, p = 0.003) in the patient group than that of the control group were found (Table 4). Results of urine melatonin levels urine melatonin levels, there was no significance between the two groups (170.89 ± 120.91 ng/ml, n=20 in the AD group vs. 133.29 ± 94.07 ng/ml, n=28 in the control group, p = 0.232) (Fig. 4). Correlations among Actigraphy recordings, SCORAD and questionnaires scores The result of a negative correlation between sleep latency and the SCORAD score was surprising, but the relation between them was poor (-0.019, p = 0.926) (Table 5). The SCORAD score was significantly negatively correlated with sleep efficiency (-0.438, p = 0.025) and positively correlated with wrist activities (% mobile) (0.551, p = 0.004) (Table 5). In respect of questionnaires, there was little relation between the Dermatology Life Quality Index (DLQI includes IDQOL and CDLQI) and the Actigraph parameters, but the DLQI was significantly correlated with the SCORAD score (0.567, p = 0.003) (Table 6). The Dermatitis Family Impact (DFI) did not associate either with the Actigraph measures or the SCORAD scores (Table 5, 6). Relation between sleep and pruritus measures We investigated the relationship between sleep and pruritus measures in children with AD. The Actigraph sleep efficiency score was significantly inversely related to wrist movement score (-0.605, p = 0.0011) (Fig. 5). The sleep self-rating also correlated well with itch self-rating (0.623, p = 0.0007) (Fig. 6). Relation of objective measures to self-reported sleep and pruritus To determine how objectively measured sleep efficiency and wrist activity compare with self-rated sleep and itch, associations between each measure were examined. The Actigraph sleep efficiency was well-correlated with self-reported sleep loss (-0.662, <0.001) (Fig. 7), and the Actigraph wrist movements (% mobile) was significantly related to self-reported itch (0.515, p = 0.007) (Fig. 8). Correlation of urine melatonin levels with Actigraphy recordings and SCORAD Urine levels of melatonin did not correlate with either the Actigraph measures or the SCORAD scores (Table 7). Conclusion This study demonstrated that sleep is significantly compromised in AD subjects. Children with AD spent more time to fall asleep, slept more poorly, and had more nocturnal scratching than the control subjects. The results of our study also revealed that decreased sleep efficiency and increased scratching were associated with increasing disease severity. The quality of life of AD children was significantly inversely correlated with disease severity. The relation between sleep and pruritus were straightforward, and the patients’perception about sleep and itch correlated well with the objective measures. In the case of nocturnal urine levels of melatonin, there was no significant difference between the AD group and the control group. The relation between melatonin concentrations and sleep quality was imperfect, and the association between melatonin levels and disease activity was also not significant. Our study provides more detailed and accurate information about sleep and builds an evidence base for further studies to investigate the role of melatonin in AD. Additional studies should also be conducted to direct somnolent therapeutic guidelines for children of AD. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66379 |
全文授權: | 有償授權 |
顯示於系所單位: | 臨床醫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-101-1.pdf 目前未授權公開取用 | 469.14 kB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。