臺灣博碩士論文加值系統

背景介紹
許多過去的研究都顯示肥胖與孩童氣喘關係密切，也有幾個可能的致病機轉被提出來解釋其中的關聯，然而從來沒有縱貫性的世代研究探討並比較這些與肥胖和氣喘相關的致病機轉在其中的致病效應。

研究目標
我們以腹部肥胖導致孩童氣喘間的致病機轉為研究目標，希望找出其中最顯著的致病路徑。

研究方法
「台灣孩童健康研究」收錄了2777名孩童的健康資料，是一個全國性、以學校孩童為基礎的世代研究。孩童家長需填寫問卷，以評估孩童的過敏體質與氣喘狀況。從2010年到2012年這三年期間，每年收集家長版問卷、孩童肥胖測量、與孩童肺功能等資料，並於2012年採集呼氣一氧化氮濃度的資料。統計方法採用廣義估計方程式與廣義線性模型探討腹部肥胖與孩童氣喘的關係中可能的中介致病因子，並以結構方程模式探索腹部肥胖與孩童氣喘間的致病機轉。

研究結果
腹部肥胖（腰臀比）最能預測孩童氣喘的發生。過敏體質、呼吸道發炎、與肺功能低下都是腹部肥胖導致孩童氣喘的顯著致病機轉。無論在「最近一年內發生氣喘」或「曾經發生喘鳴聲」的模型中，肺功能低下的中介致病效應都比過敏體質與呼吸道發炎為大。

研究結論
肺功能低下是腹部肥胖導致孩童氣喘最重要的致病路徑。肥胖孩童應加強肺功能方面的訓練，以預防氣喘的發生。

Background
There was abundant evidence supporting a strong correlation between obesity and childhood asthma. Several possible mediators had been proposed to explain the association. However, these mediators were never discussed and compared in a longitudinal cohort.

Objectives
We aimed to investigate the mediating mechanisms and search for the most prominent pathological pathway from central obesity to childhood asthma.

Methods
The TCHS was a longitudinal study of a nationwide, schoolchildren-based cohort. A questionnaire was distributed to parents of the participants to assess children atopic conditions and asthma. Data regarding parents’ questionnaire, obesity measures, and pulmonary function tests were collected annually for three years from 2010 to 2012. Fractional exhaled nitric oxide was recorded in the 2012 survey. Generalized estimating equations (GEE) and general linear models (GLM) were used to examine the associations amongst central obesity, possible mediators, and the respiratory outcomes (active asthma and lifetime wheeze). Structural equation models (SEM) were applied to explore the mechanisms, which mediate the link between central obesity and the respiratory outcomes.


Measurements and Main Results
Central obesity (waist-to-hip ratio) predicted active asthma most accurately. Atopy, airway inflammation, and reduction in pulmonary function were all significant mediators in the pathways from central obesity to active asthma and lifetime wheeze. The percentage of mediation of pulmonary function was greater than that of atopy and airway inflammation in both models for active asthma and lifetime wheeze.

Conclusions
Decrease in pulmonary function was the most important pathological pathway in childhood asthma caused by central obesity. Future studies should aim to elucidate the pathogenesis in other phenotypes of childhood asthma.

Contents
ABSTRACT IN CHINESE（中文摘要）.........................1
ABSTRACT ...............................................2
1. Introduction ........................................4
1.1 Introduction to asthma .............................4
1.1.1 Clinical symptoms of asthma ......................4
1.1.2 Prevalence of asthma .............................4
1.1.3 Diagnosis of asthma ..............................4
1.2 Obesity and asthma .................................5
1.3 Mechanisms from central obesity to asthma and current study gap ..............................................6
1.4 Taiwan Children Health Study .......................6

2. Materials and methods ...............................8
2.1 Data collection and measurements ...................8
2.1.1 Data collection ..................................8
2.2 Measurements .......................................8
2.2.1 Outcome definition ...............................8
2.2.2 Obesity measures .................................9
2.2.3 Atopic conditions ...............................10
2.2.4 Airway inflammation .............................11
2.2.5 Pulmonary function tests ........................11
2.3 Statistical analysis ..............................12
2.3.1 Generalized estimating equations for the association between obesity measures and the respiratory outcomes .12
2.3.2 Structural equation modeling for mediation analysis
.......................................................13
2.3.3 Generalized estimating equations for the association between central obesity and the mediators .............14
2.3.4 Generalized estimating equations for the association between the mediators and respiratory outcomes ........15

3.Results .............................................17
3.1 Characteristics of study participants .............17
3.2 Associations between obesity measures and respiratory outcomes by generalized estimating equations...........17
3.3 Mediation analysis by structural equation modeling 18
3.4 Associations among central obesity, the mediators,
and respiratory outcomes by generalized estimating equations .............................................19

4.Discussion ..........................................21
4.1 Uniqueness of the findings ........................21
4.2 Mediators in the pathway between central obesity and respiratory outcomes ..................................21
4.2.1 Atopy ...........................................21
4.2.2 Airway inflammation .............................22
4.2.3 Pulmonary function ..............................23
4.3 Strengths and limitations of the study ............23
4.4 Conclusions .......................................25

5. Tables .............................................26
5.1 Table 1. Characteristics of All Participants of Fourth-, Fifth-, and Sixth- Grade in Taiwan Children Health
Study .................................................26
5.2 Table 2. Associations between Obesity Measures and Respiratory Outcomes Using Generalized Estimating Equation Model .................................................27
5.3 Table 3. Standardized Path Coefficients for Pathways from Central Obesity to Respiratory Outcomes by Mediators in Structural Equation Model ..........................28
5.4 Table 4. Standardized Effects for Pathways from Central Obesity to Respiratory Outcomes by Mediators in Structural Equation Model.........................................29
5.5 Table 5. Associations between Central Obesity and Airway Inflammation, Atopy, Pulmonary Function Using Generalized Estimating Equation Model .................30
5.6 Table 6. Associations between Airway Inflammation, Atopy, Pulmonary Function, and Respiratory Outcomes Using Generalized Estimating Equation Model .................31

6. Figures ............................................32
6.1 Figure 1. Structural equation model with pathways from central obesity to respiratory outcomes by different mediators .............................................32

7. Reference ..........................................33

8. Appendix ...........................................41
8.1 Geographical distribution of Taiwan Children Health Study cohort ..........................................41
8.2 Mplus codes .......................................42
8.2.1 Mplus codes for the model of active asthma ......42
8.2.2 Mplus codes for the model of lifetime wheeze ....43

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