"探討肥胖,體適能及靜態活動與兒童氣喘之間的相關性:統合分析及臺灣孩童健康長期追蹤研究"

Abstract

本論文包含一篇孩童肥胖造成新發生氣喘的統合分析以及一個關於探討肥胖, 體適能/靜態活動時間與兒童氣喘之間的相關性的臺灣孩童健康長期追蹤研究。統合分析旨在定量孩童肥胖對於氣喘發生的危險性，因著發現孩童肥胖對新發生氣喘的影響達到兩倍以上，接著，我們執行以下兩個研究分別用以比較多種肥胖測量對孩童氣喘的相關性，找出最合適預測孩童氣喘的肥胖指標;結果我們發現，是腹部肥胖與孩童氣喘最有相關性，所以我們透過結構方程式統計模型更進一步探討腹部肥胖，體適能/靜態活動，與氣喘的相關致病機轉，此外，透過結構方程式統計模型驗證肺功能的降低是否為腹部肥胖導致氣喘的機轉。最後再收集第一年無腹部肥胖或氣喘者，計算追蹤兩年的肥胖或氣喘發生率。以驗證結構方程式所發現的肥胖，氣喘，體適能及靜坐時間這因果三角關係。孩童肥胖與氣喘的罹患率在過去二十年來不斷上升，而很多長期追蹤研究均指出肥胖發生在氣喘之前，但少有研究將學童體適能/靜態活動考慮進去，過去關於孩童肥胖對氣喘發生的影響在性別上的差異也有許多報告，但缺少一致性的結論。 研究一: 探討孩童肥胖對於新發生氣喘的危險性:統合分析 我們的研究先藉由統合分析整理現有文獻，目的是要(1)定量孩童肥胖對於氣喘發生的危險性; (2)探討肥胖對氣喘發生的影響在性別上的差異。納入文獻的條件是長期追蹤之孩童世代研究，並有使用年齡性別分類的BMI作為孩童肥胖的定義。追蹤的結果要看新發生的氣喘。經過大型資料庫的系統性文獻回顧，總共有1027個研究被選出，經過細部查閱，發現僅有六篇符合納入條件。經過統合分析，發現體重過重造成新發生的氣喘，相較於不重的孩童，達到1.19倍(95%信賴區間, 1.03-1.37)。若是肥胖孩童比上非肥胖孩童則達到2.02倍(95%信賴區間, 1.16-3.50)。BMI上升對於新發生氣喘達到劑量效應(p for trend, 0.004)。肥胖男孩比肥胖女孩的危險高，達到男孩2.47倍，女孩1.25倍，且男孩的危險性有顯著的劑量效應。性別差異的機轉可能透過肥胖所引起的肺功能降低，肥胖造成的呼吸睡眠障礙，肥胖所引起的賀爾蒙Leptin改變。因此，進一步有關機轉的探討需被用以釐清肥胖造成氣喘的性別差異。 研究二: 比較多種肥胖測量對孩童氣喘的相關性，及體適能/靜態活動在肥胖及氣喘間所扮演的角色 接續統合分析的發現，我們接著比較多種肥胖測量對孩童氣喘的相關性。先前有關孩童肥胖與氣喘之研究多僅使用BMI當作肥胖指標。有用其他肥胖測量的研究如: 腰高比，瘦體組織…等，較為缺乏。我們研究的目的在於(1)比較多種肥胖測量對孩童氣喘的相關性，找出最合適預測孩童氣喘的肥胖指標; (2) 藉由重複測量分析探討體適能/靜態活動在肥胖及氣喘間所扮演的角色 我們自2010年進行的一個具有台灣代表性的世代追蹤研究”台灣孩童健康研究”，在台灣北中南東14個社區收案2,758位10歲學童。自2010到2012年每年透過孩童及其家長追蹤問卷，關心孩童呼吸過敏疾病之健康相關，並且每年到校測量BMI，腰臀圍，皮下脂肪厚度，身體組成分析，體適能及靜態活動(2010,2012年)，肺功能。肥胖相關測量均標準化，靜態活動採中文版的國際體能活動量表，體適能由教育部體育司統一以標準程序每年於學校執行，其中因”八百公尺短跑”與肥胖及氣喘最相關，故被我們當做體適能的指標。主要的依變項為自家長問卷獲得的，醫師診斷之氣喘及近一年發作的現行氣喘。統計上我們對於連續重複測量使用Generalized Estimating Equation (GEE)，以探討各種肥胖測量對的相關性。並進一步使用GEE探討腹部肥胖，體適能/靜態活動，與氣喘的相關性。結果發現，腹部肥胖與醫師診斷之氣喘及現行氣喘的相關性最大，且能反映出劑量效應。低體適能/高靜態活動與腹部肥胖有關，但與氣喘沒有直接相關。 研究三:透過結構方程模式探討腹部肥胖，體適能/靜態活動，與氣喘的相關機轉，並透過存活分析驗證前後因果關係。透過結構方程模式進一步驗證肺功能的降低是否為腹部肥胖導致氣喘的機轉。 透過結構方程式統計模型，可以用以探索並建立疾病機轉的路徑分析。為了驗證結構方程式所發現的肥胖，氣喘，體適能及靜坐時間這因果三角關係，我們收集第一年無腹部肥胖或氣喘者，計算追蹤兩年的肥胖或氣喘發生率，此存活分析使用SAS PROC LIFEREG進行。 不論用GEE，結構方程式或計算發生率，我們皆一致發現，體適能/靜態活動並不是腹部肥胖到氣喘的中介因子。而是低體適能及高靜坐時間先導致腹部肥胖，進而導致氣喘。體適能及靜坐時間乃是腹部肥胖致氣喘的前導因子。低體適能及高靜坐時間乃是間接地導致氣喘。此外，腹部肥胖乃透過肺功能的降低導致氣喘。 腹部肥胖的相關測量應納入未來預測孩童氣喘的相關危險因子。孩童應被鼓勵增強體適能及減少靜坐時間，以避免腹部肥胖引起的氣喘。

The dissertation includes a meta-analysis of childhood obesity in prediction of incident asthma and a cohort study exploring interrelationships between obesity, physical fitness, sedentary time, and childhood asthma. Aim of meta-analysis were to quantify the risk of childhood obesity on incident asthma. The following two studies were to compare various anthropometric measures of obesity in relation to childhood asthma, and to further characterising the interrelations amongst central obesity, physical fitness level, sedentary time, and asthma. Study I: Childhood Overweight and Obesity Predict the Risk of Incident Asthma: Meta-analysis Aims of our meta-analysis were: (1) to quantify the predictability of childhood overweight and obesity on the risk of incident asthma; (2) to evaluate the gender difference on this relationship. The selection criteria were including prospective cohort pediatric studies which use age and sex-specific BMI as a measure of childhood overweight and the primary outcome of incident asthma. A total of 1027 studies were initially identified through online database searches, and finally 6 studies met the inclusion criteria. The combined result of reported relative risk from the 6 included studies revealed that overweight children conferred increased risks of incident asthma as compared with non-overweight children (relative risk, 1.19; 95% CI, 1.03-1.37). The relationship was further elevated for obesity versus non-obesity (relative risk, 2.02; 95% CI, 1.16-3.50). A dose-responsive of elevated BMI on asthma incidence was observed (p for trend, 0.004). Obese boys had a significantly larger effect than obese girls (relative risk, boys: 2.47; 95% CI, 1.57-3.87; girls: 1.25; 95% CI, 0.51-3.03), with significant dose-dependent effect. Proposed mechanisms of gender difference could be through pulmonary mechanics, sleep disordered breathing, and leptin. Further research might be needed to better understand the exact mechanism of gender difference on the obesity-asthma relationship. Study II: Comparing various different anthropometric measures in relations to asthma and the role of physical fitness/sedentary time in the link between obesity and asthma UAvailable prospective study on obesity and asthma used only body mass index as an indicator of adiposity. Studies using more detailed obesity measurements such as waist to height ratio, or lean body mass are lacking. In 2010, we conducted a nationwide “Taiwan Children Health Study (TCHS) ”, of 2,758 ten-years-old school children in 14 Taiwanese communities. They were followed up annually from 2010-2012. Our annual follow-up items were parent’s and children’s health questionnaires, BMI, abdominal/hip circumference, skin fold thickness, body composition, physical fitness and sedentary time (2010 and 2012), and pulmonary function tests. All anthropometric measurements were standardized. Sedentary time was assessed by Chinese version of the international Physical Activity Questionnaire (IPAQ-C). Physical fitness tests were performed through standardized protocol by our Education bureau in each school during our follow ups survey. Amongst these tests, an 800-metre sprint was used to determine the cardiorespiratory endurance of each child, which was most likely relevant to both obesity and asthma. Childhood asth ma was defined according to active asthma and physician-diagnosed asthma in the parent’s questionnaire. The generalized estimating equation (GEE) was used for three years of repeated measurements to analyse the interrelation amongst obesity, sedentary time, physical fitness level, and asthma. Central obesity is the best predictor for active asthma and physician-diagnosed asthma, with significant dose responsiveness. Low physical fitness levels and high screen time were associated with increased risk of central obesity, but was not significantly related to childhood asthma. Study III: Exploring the interrelationships between central obesity, physical fitness/sedentary time, and asthma in Structual Equation Model (SEM). A structural equation model (SEM) was used to explore the pathogenesis amongst central obesity, physical fitness/sedentary time, and asthma. Asthma incidence was analysed during a 2-year follow-up amongst centrally obese and non-obese groups in baseline non-asthmatic children. Moreover, according to previous literature, one possible biological mechanism from central obesity to asthma could be mediated by poor pulmonary function. Therefore, we also aim to examine the role of pulmonary function between central obesity and childhood asthma. Through three different kinds of statistical analysis, we found that physical fitness/sedentary time were not intermediate factor between central obesity and asthma. In the pathway from central obesity to childhood asthma, physical fitness and sedentary time are leading factors. Physical fitness levels and sedentary time indirectly influence asthma risk. Obesity-related reduction in pulmonary function is a possible mechanism in the pathway from central obesity to asthma. Conclusively, we discovered that incident asthma risk was increased by 20 % in overweight children. Boys, rather than girls suffered from significantly higher risk in the obesity-asthma relationship. Central obesity measures most accurately predict asthma and should be incorporated in childhood asthma risk predictions. Children are encouraged to increase their physical fitness levels and reduce their sedentary time to prevent central-obesity-related asthma.