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研究生:池岸軒
研究生(外文):An-Hsuan Chih
論文名稱:兒童中央型肥胖導致氣喘的中介致病機轉
論文名稱(外文):Mediating mechanisms from central obesity to childhood asthma
指導教授:李永凌李永凌引用關係
指導教授(外文):Yungling Leo Lee
口試委員:杜裕康黃國晉邱泰源
口試委員(外文):Yu-Kang TuKuo-Chin HuangTai-Yuan Chiu
口試日期:2014-07-03
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:流行病學與預防醫學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:英文
論文頁數:43
中文關鍵詞:中央型肥胖氣喘過敏呼吸道發炎肺功能
外文關鍵詞:Central obesityasthmaatopyairway inflammationpulmonary function
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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

1. Global strategy for asthma management and prevention, Global Initiative for Asthma (GINA) 2012 update.
2. Masoli M, Fabian D, Holt S, Beasley R; Global Initiative for Asthma (GINA) Program. Global Initiative for Asthma (GINA) program: the global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 2004; 59, 469-478.
3. Summary Health Statistics for U.S. Children: National Health Interview Survey, 2011. Centers for Disease Control and Prevention. http://www.cdc.gov/nchs/fastats/asthma.htm.
4. Heieh KH, Shen JJ. Prebalence of childhood asthma in Taipei, Taiwan, and other asian pacific countries. J Asthma 1988; 25: 73-82.
5. Wei-Fong Wu, Kong-Sang Wan, Shiuan-Jenn Wang, Winnie Yang, Wen-Liang Liu. Prevalence, severity, and time trends of allergic conditions in 6-7-year-old schoolchildren in Taipei. Journal of Investigational Allergology and Clinical Immunology Vol. 21(7): 556-562, 2011.
6. National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma - Summary Report 2007. J Allergy Clin Immunol. 2007;120 (5 suppl):S94-S138.
7. Sears MR, Greene JM, Willan AR, Taylor DR, Flannery EM, Cowan JO, Herbison GP, Poulton R. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet. 2002 Sep 21;360(9337):901-7.
8. Sears MR, Greene JM, Willan AR, Wiecek EM, Taylor DR, Flannery EM, Cowan JO, Herbison GP, Silva PA, Poulton R. A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N Engl J Med. 2003 Oct 9;349(15):1414-22.
9. Kozyrskyj AL, Ernst P, Becker AB. Increased risk of childhood asthma from antibiotic use in early life. Chest. 2007 Jun;131(6):1753-9.
10. Wahn U, Lau S, Bergmann R, Kulig M, Forster J, Bergmann K, Bauer CP, Guggenmoos-Holzmann I. Indoor allergen exposure is a risk factor for sensitization during the first three years of life. J Allergy Clin Immunol. 1997 Jun;99(6 Pt 1):763-9.
11. Stein RT, Holberg CJ, Sherrill D, Wright AL, Morgan WJ, Taussig L, Martinez FD. Influence of parental smoking on respiratory symptoms during the first decade of life: the Tucson Children''s Respiratory Study. Am J Epidemiol. 1999 Jun 1;149(11):1030-7.
12. Meurer JR, George V, Subichin S, Yauck J, Layde P. Asthma severity among children hospitalized in 1990 and 1995. Arch Pediatr Adolesc Med. 2000 Feb;154(2):143-9.
13. Gilliland FD, Berhane K, Islam T, McConnell R, Gauderman WJ, Gilliland SS, Avol E, Peters JM. Obesity and the risk of newly diagnosed asthma in school-age children. Am J Epidemiol. 2003 Sep 1;158(5):406-15.
14. Egan KB, Ettinger AS, Bracken MB. Childhood body mass index and subsequent physician-diagnosed asthma: a systematic review and meta-analysis of prospective cohort studies. BMC Pediatr. 2013 Aug 13;13(1):121.
15. Chen YC, Dong GH, Lin KC, Lee YL. Gender difference of childhood overweight and obesity in predicting the risk of incident asthma: a systematic review and meta-analysis. Obes Rev. 2013 Mar;14(3):222-31.
16. Quinto KB, Zuraw BL, Poon KY, Chen W, Schatz M, Christiansen SC. The association of obesity and asthma severity and control in children. J Allergy Clin Immunol. 2011 Nov;128(5):964-9.
17. Forno E, Lescher R, Strunk R, Weiss S, Fuhlbrigge A, Celed&;oacute;n JC; Childhood Asthma Management Program Research Group. Decreased response to inhaled steroids in overweight and obese asthmatic children. J Allergy Clin Immunol. 2011 Mar;127(3):741-9.
18. Forno E, Acosta-P&;eacute;rez E, Brehm JM, Han YY, Alvarez M, Col&;oacute;n-Semidey A, Canino G, Celed&;oacute;n JC. Obesity and adiposity indicators, asthma, and atopy in Puerto Rican children. J Allergy Clin Immunol. 2014 May;133(5):1308-14, 1314.e1-5.
19. Musaad SM, Patterson T, Ericksen M, Lindsey M, Dietrich K, Succop P, Khurana Hershey GK. Comparison of anthropometric measures of obesity in childhood allergic asthma: central obesity is most relevant. J Allergy Clin Immunol. 2009 Jun;123(6):1321-7.e12.
20. Chen YC, Tu YK, Huang KC, Chen PC, Chu DC, Lee YL. Pathway from central obesity to childhood asthma. Physical fitness and sedentary time are leading factors. Am J Respir Crit Care Med. 2014 May 15;189(10):1194-203.
21. Canoy D, Luben R, Welch A, Bingham S, Wareham N, Day N, Khaw KT. Abdominal obesity and respiratory function in men and women in the EPIC-Norfolk Study, United Kingdom. Am J Epidemiol. 2004 Jun 15;159(12):1140-9.
22. Sutherland ER, Goleva E, King TS, Lehman E, Stevens AD, Jackson LP, Stream AR, Fahy JV, Leung DY; Asthma Clinical Research Network. Cluster analysis of obesity and asthma phenotypes. PLoS One. 2012;7(5):e36631.
23. Jensen ME, Collins CE, Gibson PG, Wood LG. The obesity phenotype in children with asthma. Paediatr Respir Rev. 2011 Sep;12(3):152-9.
24. Shore SA. Obesity and asthma: possible mechanisms. J Allergy Clin Immunol. 2008 May;121(5):1087-93.
25. Rasmussen F, Hancox RJ. Mechanisms of obesity in asthma. Curr Opin Allergy Clin Immunol. 2014 Feb;14(1):35-43.
26. Desai D1, Newby C, Symon FA, Haldar P, Shah S, Gupta S, Bafadhel M, Singapuri A, Siddiqui S, Woods J, Herath A, Anderson IK, Bradding P, Green R, Kulkarni N, Pavord I, Marshall RP, Sousa AR, May RD, Wardlaw AJ, Brightling CE. Elevated sputum interleukin-5 and submucosal eosinophilia in obese individuals with severe asthma. Am J Respir Crit Care Med. 2013 Sep 15;188(6):657-63.
27. World medical association declaration of helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997;277:925-926.
28. Slaughter MH, Lohman TG, Boileau RA, Horswill CA, Stillman RJ, Van Loan MD, Bemben DA. Skinfold equations for estimation of body fatness in children and youth. Hum Biol 1988;60:709-723.
29. American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005 Apr 15;171(8):912-30.
30. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38.
31. Huberman M, Langholz B. Application of the missing-indicator method in matched case-control studies with incomplete data. Am J Epidemiol 1999;150: 1340-1345.
32. Craig K. Enders. A primer on maximum likelihood algorithms available for use with missing data. Structural Equation Modeling 2001; 8(1): 128–141.
33. Guerra S1, Wright AL, Morgan WJ, Sherrill DL, Holberg CJ, Martinez FD. Persistence of asthma symptoms during adolescence: role of obesity and age at the onset of puberty. Am J Respir Crit Care Med. 2004 Jul 1;170(1):78-85.
34. Appleton SL, Adams RJ, Wilson DH, Taylor AW, Ruffin RE; North West Adelaide Health Study Team. Central obesity is associated with nonatopic but not atopic asthma in a representative population sample. J Allergy Clin Immunol. 2006 Dec;118(6):1284-91. Epub 2006 Nov 7.
35. Fenger RV, Gonzalez-Quintela A, Vidal C, Gude F, Husemoen LL, Aadahl M, Berg ND, Linneberg A. Exploring the obesity-asthma link: do all types of adiposity increase the risk of asthma? Clin Exp Allergy. 2012 Aug;42(8):1237-45.
36. Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, Wardlaw AJ, Green RH. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008 Aug 1;178(3):218-24.
37. Visness CM, London SJ, Daniels JL, Kaufman JS, Yeatts KB, Siega-Riz AM, Calatroni A, Zeldin DC. Association of childhood obesity with atopic and nonatopic asthma: results from the National Health and Nutrition Examination Survey 1999-2006. J Asthma. 2010 Sep;47(7):822-9.
38. Santamaria F, Montella S, De Stefano S, Sperl&;igrave; F, Barbarano F, Spadaro R, Franzese A. Asthma, atopy, and airway inflammation in obese children. J Allergy Clin Immunol. 2007 Oct;120(4):965-7.
39. Silverberg JI, Kleiman E, Lev-Tov H, Silverberg NB, Durkin HG, Joks R, Smith-Norowitz TA. Association between obesity and atopic dermatitis in childhood: a case-control study. J Allergy Clin Immunol. 2011 May;127(5):1180-6.
40. Taylor DR, Pijnenburg MW, Smith AD, De Jongste JC. Exhaled nitric oxide measurements: clinical application and interpretation. Thorax. 2006 Sep;61(9):817-27.
41. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, Olin AC, Plummer AL, Taylor DR; American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011 Sep 1;184(5):602-15.
42. Roberts G, Hurley C, Bush A, Lack G. Longitudinal study of grass pollen exposure, symptoms, and exhaled nitric oxide in childhood seasonal allergic asthma. Thorax. 2004 Sep;59(9):752-6.
43. Pijnenburg MW1, Hofhuis W, Hop WC, De Jongste JC. Exhaled nitric oxide predicts asthma relapse in children with clinical asthma remission. Thorax. 2005 Mar;60(3):215-8.
44. de Jongste JC, Carraro S, Hop WC; CHARISM Study Group, Baraldi E. Daily telemonitoring of exhaled nitric oxide and symptoms in the treatment of childhood asthma. Am J Respir Crit Care Med. 2009 Jan 15;179(2):93-7.
45. De Winter-de Groot KM, Van der Ent CK, Prins I, Tersmette JM, Uiterwaal CS. Exhaled nitric oxide: the missing link between asthma and obesity? J Allergy Clin Immunol. 2005 Feb;115(2):419-20.
46. Barros R, Moreira A, Fonseca J, Moreira P, Fernandes L, de Oliveira JF, Delgado L, Castel-Branco MG. Obesity and airway inflammation in asthma. J Allergy Clin Immunol. 2006 Jun;117(6):1501-2.
47. Berg CM, Thelle DS, Rosengren A, Lissner L, Tor&;eacute;n K, Olin AC. Decreased fraction of exhaled nitric oxide in obese subjects with asthma symptoms: data from the population study INTERGENE/ADONIX. Chest. 2011 May;139(5):1109-16.
48. Desai D, Newby C, Symon FA, Haldar P, Shah S, Gupta S, Bafadhel M, Singapuri A, Siddiqui S, Woods J, Herath A, Anderson IK, Bradding P, Green R, Kulkarni N, Pavord I, Marshall RP, Sousa AR, May RD, Wardlaw AJ, Brightling CE. Elevated sputum interleukin-5 and submucosal eosinophilia in obese individuals with severe asthma. Am J Respir Crit Care Med. 2013 Sep 15;188(6):657-63.
49. Han YY, Forno E, Celed&;oacute;n JC. Adiposity, FeNO, and Asthma in U.S. Children. Am J Respir Crit Care Med. 2014 Jun 12.
50. Sideleva O, Suratt BT, Black KE, Tharp WG, Pratley RE, Forgione P, Dienz O, Irvin CG, Dixon AE. Obesity and asthma: an inflammatory disease of adipose tissue not the airway. Am J Respir Crit Care Med. 2012 Oct 1;186(7):598-605.
51. Jensen ME, Gibson PG, Collins CE, Wood LG. Airway and systemic inflammation in obese children with asthma. Eur Respir J. 2013 Oct;42(4):1012-9.
52. Gabriele C, Nieuwhof EM, Van Der Wiel EC, Hofhuis W, Moll HA, Merkus PJ, De Jongste JC. Exhaled nitric oxide differentiates airway diseases in the first two years of life. Pediatr Res. 2006 Oct;60(4):461-5.
53. Yao TC, Ou LS, Lee WI, Yeh KW, Chen LC, Huang JL; PATCH study group. Exhaled nitric oxide discriminates children with and without allergic sensitization in a population-based study. Clin Exp Allergy. 2011 Apr;41(4):556-64.
54. Chen Y, Rennie D, Cormier Y, Dosman JA. Waist circumference associated with pulmonary function in children. Pediatr Pulmonol. 2009 Mar;44(3):216-21.
55. Shore SA, Fredberg JJ. Obesity, smooth muscle, and airway hyperresponsiveness. J Allergy Clin Immunol. 2005 May;115(5):925-7.
56. Al-Alwan A, Bates JH, Chapman DG, Kaminsky DA, DeSarno MJ, Irvin CG, Dixon AE. The nonallergic asthma of obesity. A matter of distal lung compliance. Am J Respir Crit Care Med. 2014 Jun 15;189(12):1494-502.
57. Sutherland TJ, Cowan JO, Taylor DR. Dynamic hyperinflation with bronchoconstriction: differences between obese and nonobese women with asthma. Am J Respir Crit Care Med. 2008 May 1;177(9):970-5.
58. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995 Jan 19;332(3):133-8.
59. Bisgaard H, Jensen SM, B&;oslash;nnelykke K. Interaction between asthma and lung function growth in early life. Am J Respir Crit Care Med. 2012 Jun 1;185(11):1183-9.

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