過敏性疾病(如：氣喘、異位性皮膚炎、過敏性鼻炎)最早可於一歲之前發生，但台灣現階段研究大都以學童為主，因此難以釐清早期環境因子暴露對於過敏性疾病發生之影響。此外，有鑒於橫斷式研究與病例對照研究常無法有效的了解其因果關係。故希望藉由出生世代研究，以探討出生前後環境因子與基因多型性對於過敏性疾病之影響。研究中，將先了解基因多型性對於臍帶血IgE (cbIgE)的影響；而後探討影響異位性皮膚炎之危險因子，並建立預測模式(predictive model)以預測孩童異位性皮膚炎發生之危險性。
本研究共納入2個出生世代研究，分別為本實驗之出生世代(BCL)及台灣出生世代研究(TBCS)。BCL研究對象來自於8間具婦產專科的醫療院所，而於懷孕進入第三孕程的婦女及出生的新生兒始納入研究。自2001年7月至2005年7月，總計共有1,264對母親及其新生兒。除進行問卷訪視外，並收集母親血液、尿液、胎盤及臍帶血。問卷分別於產前、寶寶出生時進行訪視，並進行六次電話訪問直到寶寶兩歲時。且利用ELISA來分析母親與寶寶血清中IgE濃度，以及藉由PCR-RFLP來判斷寶寶基因多型性。TBCS研究對象乃自2005年台灣出生登記檔藉由多階段、系統性分層抽樣方式選取具代表性之母親與新生兒對，總計選取24,200對。分別於寶寶6個月、18個月、3歲時進行居家訪視，以獲得寶寶健康情形、過敏性家族病史以及環境暴露等資訊。
在cbIgE的研究發現，白介素[interleukin (IL)]-4 -590C/T的基因多型性與cbIgE的濃度增加有關，其中以具有IL-4 CC/CT基因型的幼兒cbIgE濃度高於0.35 (kU/l)的危險性較具有IL-4 TT基因型的幼兒為高[勝算比 (95%信賴區間) = 3.06 (1.66-5.75)]。而與IgE具有高親和力的接受器[the  subunit of the high-affinity receptor for IgE (FcRI)]- E237G, 淋巴毒素[lymphotoxin (LT)]-α NcoI基因型,腫瘤壞死因子[tumor necrosis factor (TNF)]-α -308G/A等基因多型性則與cbIgE無統計上顯著之關聯。
在探討影響孩童異位性皮膚炎的因子中，我們發現父母親具有氣喘、過敏性鼻炎或異位性皮膚炎，以及母親的教育程度乃與6個月寶寶異位性皮膚炎的發生有關。此外，家中牆上有黴菌斑以及母親懷孕時家中有重新粉刷或裝潢也會增加寶寶罹患異位性皮膚炎的危險。藉由所發現的這些因子，我們嘗試建立一個預測模式(predictive model)以預測6個月寶寶發生異位性皮膚炎的危險性。結果顯示，我們能預測寶寶6個月時異位性皮膚炎發生之危險性於男寶寶最高可達70% (當：父母親皆曾罹患異位性皮膚炎、母親教育程度高中職以上、家中有黴菌斑以及母親懷孕時家中有重新粉刷及裝潢)，而最低則為女寶寶的3.1% (當：父母親皆無過敏性疾病且無其他上述因子)。
因前述只針對問卷詢問結果來探討影響孩童異位性皮膚炎的因子為何?因此，我們進一步分析寶寶cbIgE濃度、基因多型性以及母親懷孕時的心理狀況與孩童異位性皮膚炎的關聯性，以及了解是否加入這些因子可以增加我們預測孩童發生異位性皮膚炎的危險性。結果顯示，cbIgE濃度高於0.5 (KU/l)、孩童具有LT- NcoI 12/22, 與FcRI- EG/GG基因型，以及母親懷孕時較有壓力乃會增加2歲孩童罹患異位性皮膚炎的危險性。而在預測模式中加入這些因子後，與只納入孩童性別、父母親過敏性疾病史與母親教育程度的模式相比，則能增加預測孩童罹患異位性皮膚炎能力[ROC曲線下的面積分別為0.63 (95%信賴區間 = 0.60-0.67)與0.73 (95%信賴區間 = 0.70-0.76)，且達統計上顯著的差異p值為 0.027]。
本研究結果顯示，易感基因的多型性乃與臍帶血IgE濃度有關，而產前環境因子的暴露、基因多型性、臍帶血IgE濃度以及母親的心理狀態皆與早期異位性皮膚炎的發生有關。過敏性病最早可於一歲之前發生，而異位性皮膚炎也是過敏性疾病進展(atopic march)的第一步，藉由本研究了解了影響異位性皮膚炎的早期危險因子，此將可對於疾病的預防以及早期偵測有所幫助。

Atopic diseases may onset early before 1 year old. In Taiwan, most studies focused on the schoolchildren, however, it’s difficult to evaluate the association between early environmental factors and atopic diseases. Cross-section studies or case-control studies were also difficult to eliminate the causal relationship between exposure and outcome. Thus, we conduct a birth-cohort study to assess the effect of perinatal environments and genetic polymorphisms on development of atopic diseases. At first, we will investigate the association between genotypes and cord blood IgE (cbIgE) concentration. We then evaluate the risk factors of atopic dermatitis (AD) and try to establish predictive model to predict the risk of AD on children.
We combined two birth cohorts, including birth cohort in our laboratory (BCL) and Taiwan birth cohort study (TBCS). The mother-infant pairs of BCL are recruited from 8 maternity hospitals. A total of 1,264 pairs participated in our study from July 2001 to July 2005. Questionnaires will be completed by mother prior to and immediately following birth, and 6 times till 2 years old. Maternal serum and cord blood will be obtained and assayed for IgE levels. PCR and enzyme digestion were used to assess the genetic polymorphisms. In 2005, a representative sample of mother–newborn pairs on TBCS was obtained by multistage, stratified systematic sampling from the Taiwan national birth registration. A total of 24,200 pairs was sampled. Information on hereditary and environmental risk factors was collected by home interview when babies were 6 months, 18 months, and 2 years old.
We found an association between interleukin (IL)-4 -590C/T genotype and cbIgE concentration. Infant with IL-4 CC/CT genotype had higher risk of elevated cbIgE ( 0.35 kU/l) (odds ratio [OR], 95% confident interval (CI) = 3.06, 1.66-5.75). However, the genotypes of the  subunit of the high-affinity receptor for IgE (FcRI)- E237G, lymphotoxin (LT)-α NcoI allele, and tumor necrosis factor (TNF)-α -308G/A were not significantly associated with elevated cbIgE.
For atopic dermatitis on children, the results showed that parental asthma, atopic dermatitis, and allergic rhinitis, and maternal education levels were risk factors for AD in 6-month-old infants. Among environmental factors, fungi on walls of the house, and renovation/painting in the house during pregnancy were significantly associated with early infantile AD. Using these factors, the probability of having infantile AD can be estimated in a predictive model. The highest predicted probability of AD was 70.1%, among boys with maternal education levels > 12 degrees, both parents with AD, renovation and painting of the house during pregnancy, and fungus on wall at home. The lowest probability was 3.1%, among girls with none of above factors.
However, the above mentioned model used questionnaire data only, but no biological markers. We further investigate the effect of biological markers (cbIgE and susceptible genetic polymorphisms) and maternal mentality during pregnancy on the development of childhood AD and to examine whether AD in children could be better predicted by these factors after taking into account gender, socio-demographic factors, and parental atopy. Elevated cbIgE levels ( 0.5 kU/l), LT- NcoI alleles, FcRI- E237G genotype, and maternal psychological stress during pregnancy were significantly associated with AD on 2-year-old children. Comparison with the area under ROC curve (AUC) of the classic model (including gender, maternal education, and parental atopy), the model adding cbIgE levels, genotypes in cytokine genes, and maternal stress (model 2) showed higher ability to discriminate between children with and without AD (AUC statistics: 0.63 [95%CI = 0.60-0.67] vs. 0.73 [95%CI = 0.70-0.76], respectively; model comparison, p = 0.027).
We suggest that genotypes of candidate genes are associated with cbIgE concentration. Prenatal environmental exposure, genetic polymorphisms of cytokine genes, cbIgE, and maternal stress during pregnancy were associated with ever having physician-diagnosed AD in children. Symptoms of atopic diseases can start early in human life. Moreover, AD is often the first step in the atopic march. We found early risk factors for AD on children is helpful for disease prevention and early prediction.

Agabiti N, Mallone S, Forastiere F, Corbo GM, Ferro S, et al. (1999). The Impact of Parental Smoking on Asthma and Wheezing. Sidria Collaborative Group. Studi Italiani Sui Disturbi Respiratori Nell'infanzia E L'ambiente. Epidemiology 10(6): 692-8.
Albuquerque RV, Hayden CM, Palmer LJ, Laing IA, Rye PJ, et al. (1998). Association of Polymorphisms within the Tumour Necrosis Factor (Tnf) Genes and Childhood Asthma. Clin Exp Allergy 28(5): 578-84.
Allam JP, Zivanovic O, Berg C, Gembruch U, Bieber T, et al. (2005). In Search for Predictive Factors for Atopy in Human Cord Blood. Allergy 60(6): 743-50.
Anderson HR, Poloniecki JD, Strachan DP, Beasley R, Bjorksten B, et al. (2001). Immunization and Symptoms of Atopic Disease in Children: Results from the International Study of Asthma and Allergies in Childhood. Am J Public Health 91(7): 1126-9.
Arck PC, Slominski A, Theoharides TC, Peters EM and Paus R (2006). Neuroimmunology of Stress: Skin Takes Center Stage. J Invest Dermatol 126(8): 1697-704.
Arruda LK, Sole D, Baena-Cagnani CE and Naspitz CK (2005). Risk Factors for Asthma and Atopy. Curr Opin Allergy Clin Immunol 5(2): 153-9.
Atici A, Altintas D, Yuksel B, Evliyaoglu N, Evruke C, et al. (1995). Do Parental Smoking and History of Allergy Influence Cord-Serum Ige? Pediatr Allergy Immunol 6(4): 213-5.
Beck HI and Korsgaard J (1989). Atopic Dermatitis and House Dust Mites. Br J Dermatol 120(2): 245-51.
Bener A, Janahi IA and Sabbah A (2005). Genetics and Environmental Risk Factors Associated with Asthma in Schoolchildren. Allerg Immunol (Paris) 37(5): 163-8.
Bergmann RL, Schulz J, Gunther S, Dudenhausen JW, Bergmann KE, et al. (1995). Determinants of Cord-Blood Ige Concentrations in 6401 German Neonates. Allergy 50(1): 65-71.
Bernard SM, Samet JM, Grambsch A, Ebi KL and Romieu I (2001). The Potential Impacts of Climate Variability and Change on Air Pollution-Related Health Effects in the United States. Environ Health Perspect 109 Suppl 2: 199-209.
Bernstein JA, Alexis N, Barnes C, Bernstein IL, Nel A, et al. (2004). Health Effects of Air Pollution. J Allergy Clin Immunol 114(5): 1116-23.
Bieber T (2008). Atopic Dermatitis. N Engl J Med 358(14): 1483-94.
Boguniewicz M (2005). Atopic Dermatitis: Beyond the Itch That Rashes. Immunol Allergy Clin North Am 25(2): 333-51, vii.
Bornehag CG, Sundell J, Bonini S, Custovic A, Malmberg P, et al. (2004a). Dampness in Buildings as a Risk Factor for Health Effects, Euroexpo: A Multidisciplinary Review of the Literature (1998-2000) on Dampness and Mite Exposure in Buildings and Health Effects. Indoor Air 14(4): 243-57.
Bornehag CG, Sundell J, Weschler CJ, Sigsgaard T, Lundgren B, et al. (2004b). The Association between Asthma and Allergic Symptoms in Children and Phthalates in House Dust: A Nested Case-Control Study. Environ Health Perspect 112(14): 1393-7.
Bottini N, Borgiani P, Otsu A, Saccucci P, Stefanini L, et al. (2002). Il-4 Receptor Alpha Chain Genetic Polymorphism and Total Ige Levels in the English Population: Two-Locus Haplotypes Are More Informative Than Individual Snps. Clin Genet 61(4): 288-92.
Burrows B, Halonen M, Barbee RA and Lebowitz MD (1981). The Relationship of Serum Immunoglobulin E to Cigarette Smoking. Am Rev Respir Dis 124(5): 523-5.
Buske-Kirschbaum A, Gierens A, Hollig H and Hellhammer DH (2002). Stress-Induced Immunomodulation Is Altered in Patients with Atopic Dermatitis. J Neuroimmunol 129(1-2): 161-7.
Carroll WD, Lenney W, Child F, Strange RC, Jones PW, et al. (2005a). Maternal Glutathione S-Transferase GSTP1 Genotype Is a Specific Predictor of Phenotype in Children with Asthma. Pediatr Allergy Immunol 16(1): 32-9.
Carroll WD, Lenney W, Jones PW, Strange RC, Child F, et al. (2005b). Effects of Glutathione S-Transferase M1, T1 and P1 on Lung Function in Asthmatic Families. Clin Exp Allergy 35(9): 1155-61.
Cederqvist LL, Eddey G, Abdel-Latif N and Litwin SD (1984). The Effect of Smoking During Pregnancy on Cord Blood and Maternal Serum Immunoglobulin Levels. Am J Obstet Gynecol 148(8): 1123-6.
Chagani T, Pare PD, Zhu S, Weir TD, Bai TR, et al. (1999). Prevalence of Tumor Necrosis Factor-α and Angiotensin Converting Enzyme Polymorphisms in Mild/Moderate and Fatal/near-Fatal Asthma. Am J Respir Crit Care Med 160(1): 278-82.
Chang WT, Sun HL, Lue KH and Chou MC (2005). Predictability of Early Onset Atopic Dermatitis by Cord Blood Ige and Parental History. Acta Paediatr Taiwan 46(5): 272-7.
Chen BY, Chao HJ, Chan CC, Lee CT, Wu HP, et al. (2011). Effects of Ambient Particulate Matter and Fungal Spores on Lung Function in Schoolchildren. Pediatrics 127(3): e690-8.
Chen JY, Chao TH, Guo YL, Hsu CH, Huang YY, et al. (2006). A Simplified Clinical Model to Predict Pulmonary Embolism in Patients with Acute Dyspnea. Int Heart J 47(2): 259-71.
Chuang CH, Chang PJ, Hsieh WS, Guo YL, Lin SH, et al. (2007). The Combined Effect of Employment Status and Transcultural Marriage on Breast Feeding: A Population-Based Survey in Taiwan. Paediatr Perinat Epidemiol 21(4): 319-29.
Cookson WO and Moffatt MF (2002). The Genetics of Atopic Dermatitis. Curr Opin Allergy Clin Immunol 2(5): 383-7.
Croner S and Kjellman NIM (1990). Development of Atopic Disease in Relation to Family History and Cord Blood Ige Levels. Eleven Year Follow up in 1654 Children. Pediatr Allergy Immunol 1(1): 14-20.
Diaz-Sanchez D, Dotson AR, Takenaka H and Saxon A (1994). Diesel Exhaust Particles Induce Local Ige Production in Vivo and Alter the Pattern of Ige Messenger Rna Isoforms. J Clin Invest 94(4): 1417-25.
Dizier MH, Sandford A, Walley A, Philippi A, Cookson W, et al. (1999). Indication of Linkage of Serum Ige Levels to the Interleukin-4 Gene and Exclusion of the Contribution of the (-590 C to T) Interleukin-4 Promoter Polymorphism to Ige Variation. Genet Epidemiol 16(1): 84-94.
Dotterud LK, Odland JO and Falk ES (2001). Atopic Diseases among Schoolchildren in Nikel, Russia, an Arctic Area with Heavy Air Pollution. Acta Derm Venereol 81(3): 198-201.
Doull IJ and Holgate ST (1997). Asthma: Early Predisposing Factors. Br Med Bull 53(1): 71-80.
Doull IJ, Lawrence S, Watson M, Begishvili T, Beasley RW, et al. (1996). Allelic Association of Gene Markers on Chromosomes 5q and 11q with Atopy and Bronchial Hyperresponsiveness. Am J Respir Crit Care Med 153(4 Pt 1): 1280-4.
Edenharter G, Bergmann RL, Bergmann KE, Wahn V, Forster J, et al. (1998). Cord Blood-IgE as Risk Factor and Predictor for Atopic Diseases. Clin Exp Allergy 28(6): 671-8.
Eichenfield LF, Hanifin JM, Beck LA, Lemanske RF, Jr., Sampson HA, et al. (2003). Atopic Dermatitis and Asthma: Parallels in the Evolution of Treatment. Pediatrics 111(3): 608-16.
Elenkov IJ (2004). Glucocorticoids and the Th1/Th2 Balance. Ann N Y Acad Sci 1024: 138-46.
Elliott K, Fitzpatrick E, Hill D, Brown J, Adams S, et al. (2001). The -590c/T and -34c/T Interleukin-4 Promoter Polymorphisms Are Not Associated with Atopic Eczema in Childhood. J Allergy Clin Immunol 108(2): 285-7.
Fryer AA, Bianco A, Hepple M, Jones PW, Strange RC, et al. (2000). Polymorphism at the Glutathione S-Transferase GSTP1 Locus. A New Marker for Bronchial Hyperresponsiveness and Asthma. Am J Respir Crit Care Med 161(5): 1437-42.
Garrett MH, Rayment PR, Hooper MA, Abramson MJ and Hooper BM (1998). Indoor Airborne Fungal Spores, House Dampness and Associations with Environmental Factors and Respiratory Health in Children. Clin Exp Allergy 28(4): 459-67.
Geha RS (1992). Regulation of Ige Synthesis in Humans. J Allergy Clin Immunol 90(2): 143-50.
Gilliland FD, Berhane K, McConnell R, Gauderman WJ, Vora H, et al. (2000). Maternal Smoking During Pregnancy, Environmental Tobacco Smoke Exposure and Childhood Lung Function. Thorax 55(4): 271-6.
Gilliland FD, Li YF, Dubeau L, Berhane K, Avol E, et al. (2002). Effects of Glutathione S-Transferase M1, Maternal Smoking During Pregnancy, and Environmental Tobacco Smoke on Asthma and Wheezing in Children. Am J Respir Crit Care Med 166(4): 457-63.
Guo YL, Lin YC, Sung FC, Huang SL, Ko YC, et al. (1999). Climate, Traffic-Related Air Pollutants, and Asthma Prevalence in Middle-School Children in Taiwan. Environ Health Perspect 107(12): 1001-6.
Hagendorens MM, Ebo DG, Bridts CH, Van de Water L, De Clerck LS, et al. (2004). Prenatal Exposure to House Dust Mite Allergen (Der P 1), Cord Blood T Cell Phenotype and Cytokine Production and Atopic Dermatitis During the First Year of Life. Pediatr Allergy Immunol 15(4): 308-15.
Hahn EL and Bacharier LB (2005). The Atopic March: The Pattern of Allergic Disease Development in Childhood. Immunol Allergy Clin North Am 25(2): 231-46, v.
Halken S (2004). Prevention of Allergic Disease in Childhood: Clinical and Epidemiological Aspects of Primary and Secondary Allergy Prevention. Pediatr Allergy Immunol 15 Suppl 16: 9-32.
Han YY, Lee YL and Guo YL (2009). Indoor Environmental Risk Factors and Seasonal Variation of Childhood Asthma. Pediatr Allergy Immunol 20(8): 748-56.
Henry C, Kabbaj M, Simon H, Le Moal M and Maccari S (1994). Prenatal Stress Increases the Hypothalamo-Pituitary-Adrenal Axis Response in Young and Adult Rats. J Neuroendocrinol 6(3): 341-5.
Herbarth O, Fritz GJ, Rehwagen M, Richter M, Roder S, et al. (2006). Association between Indoor Renovation Activities and Eczema in Early Childhood. Int J Hyg Environ Health 209(3): 241-7.
Higgins S (2002). Smoking in Pregnancy. Curr Opin Obstet Gynecol 14(2): 145-51.
Hill MR and Cookson WO (1996). A New Variant of the  Subunit of the High-Affinity Receptor for Immunoglobulin E (FcRI- E237G): Associations with Measures of Atopy and Bronchial Hyper-Responsiveness. Hum Mol Genet 5(7): 959-62.
Hill MR, James AL, Faux JA, Ryan G, Hopkin JM, et al. (1995). FcRI- Polymorphism and Risk of Atopy in a General Population Sample. Bmj 311(7008): 776-9.
Hizawa N, Yamaguchi E, Jinushi E, Konno S, Kawakami Y, et al. (2001). Increased Total Serum IgE Levels in Patients with Asthma and Promoter Polymorphisms at Ctla4 and Fcer1b. J Allergy Clin Immunol 108(1): 74-9.
Holla LI, Stejskalova A and Vasku A (2006). Polymorphisms of the GSTM1 and GSTT1 Genes in Patients with Allergic Diseases in the Czech Population. Allergy 61(2): 265-7.
Holloway JW, Yang IA and Holgate ST (2010). Genetics of Allergic Disease. J Allergy Clin Immunol 125(2 Suppl 2): S81-94.
Holt PG (1998). Programming for Responsiveness to Environmental Antigens That Trigger Allergic Respiratory Disease in Adulthood Is Initiated During the Perinatal Period. Environ Health Perspect 106 Suppl 3: 795-800.
Howard TD, Meyers DA and Bleecker ER (2000). Mapping Susceptibility Genes for Asthma and Allergy. J Allergy Clin Immunol 105(2 Pt 2): S477-81.
Hsieh KH and Shen JJ (1988). Prevalence of Childhood Asthma in Taipei, Taiwan, and Other Asian Pacific Countries. J Asthma 25(2): 73-82.
Hsieh YY, Chang CC, Tsai FJ, Hsu Y, Tsai HD, et al. (2002). Polymorphisms for Interleukin-4 (Il-4) -590 Promoter, Il-4 Intron3, and Tumor Necrosis Factor α -308 Promoter: Non-Association with Endometriosis. J Clin Lab Anal 16(3): 121-6.
Huang JL, Chen CC, Kuo ML and Hsieh KH (2001). Exposure to a High Concentration of Mite Allergen in Early Infancy Is a Risk Factor for Developing Atopic Dermatitis: A 3-Year Follow-up Study. Pediatr Allergy Immunol 12(1): 11-6.
Huss-Marp J, Eberlein-Konig B, Breuer K, Mair S, Ansel A, et al. (2006). Influence of Short-Term Exposure to Airborne Der P 1 and Volatile Organic Compounds on Skin Barrier Function and Dermal Blood Flow in Patients with Atopic Eczema and Healthy Individuals. Clin Exp Allergy 36(3): 338-45.
ISAAC (1998). Worldwide Variation in Prevalence of Symptoms of Asthma, Allergic Rhinoconjunctivitis, and Atopic Eczema: Isaac. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Lancet 351(9111): 1225-32.
Izakovicova Holla L, Vasku A, Izakovic V and Znojil V (2001). The Interaction of the Polymorphisms in Transporter of Antigen Peptides (Tap) and Lymphotoxin α (LT-α) Genes and Atopic Diseases in the Czech Population. Clin Exp Allergy 31(9): 1418-23.
Jaakkola JJ, Nafstad P and Magnus P (2001). Environmental Tobacco Smoke, Parental Atopy, and Childhood Asthma. Environ Health Perspect 109(6): 579-82.
Johnke H, Norberg LA, Vach W, Host A and Andersen KE (2006). Patterns of Sensitization in Infants and Its Relation to Atopic Dermatitis. Pediatr Allergy Immunol 17(8): 591-600.
Johnson CC, Ownby DR and Peterson EL (1996). Parental History of Atopic Disease and Concentration of Cord Blood Ige. Clin Exp Allergy 26(6): 624-9.
Jones SM (2002). Triggers of Atopic Dermatitis. Immunol Allergy Clin North Am 22(1): 55-72.
Jurado D, Munoz C, Luna Jde D and Munoz-Hoyos A (2005). Is Maternal Smoking More Determinant Than Paternal Smoking on the Respiratory Symptoms of Young Children? Respir Med 99(9): 1138-44.
Liao MF, Liao MN, Lin SN, Chen JY and Huang JL. Prevalence of Allergic Diseases of Schoolchildren in Central Taiwan. From Isaac Surveys 5 Years Apart. J Asthma 46(6): 541-5 (2009a).
Liao PF, Sun HL, Lu KH and Lue KH. Prevalence of Childhood Allergic Diseases in Central Taiwan over the Past 15 Years. Pediatr Neonatol 50(1): 18-25 (2009b).
Kaan A, Dimich-Ward H, Manfreda J, Becker A, Watson W, et al. (2000). Cord Blood IgE: Its Determinants and Prediction of Development of Asthma and Other Allergic Disorders at 12 Months. Ann Allergy Asthma Immunol 84(1): 37-42.
Kabesch M (2006). Gene by Environment Interactions and the Development of Asthma and Allergy. Toxicol Lett 162(1): 43-8.
Kay AB (2000). Overview of 'Allergy and Allergic Diseases: With a View to the Future'. Br Med Bull 56(4): 843-64.
Kay AB (2001). Allergy and Allergic Diseases. First of Two Parts. N Engl J Med 344(1): 30-7.
Kay J, Gawkrodger DJ, Mortimer MJ and Jaron AG (1994). The Prevalence of Childhood Atopic Eczema in a General Population. J Am Acad Dermatol 30(1): 35-9.
Kilpelainen M, Terho EO, Helenius H and Koskenvuo M (2001). Home Dampness, Current Allergic Diseases, and Respiratory Infections among Young Adults. Thorax 56(6): 462-7.
Kim YK, Park HW, Yang JS, Oh SY, Chang YS, et al. (2007). Association and Functional Relevance of E237g, a Polymorphism of the High-Affinity Immunoglobulin E-Receptor  Chain Gene, to Airway Hyper-Responsiveness. Clin Exp Allergy 37(4): 592-8.
Kimata H (2003). Enhancement of Allergic Skin Wheal Responses and in Vitro Allergen-Specific IgE Production by Computer-Induced Stress in Patients with Atopic Dermatitis. Brain Behav Immun 17(2): 134-8.
Kjellman NI (1981). Effect of Parental Smoking on Ige Levels in Children. Lancet 1(8227): 993-4.
Knackstedt MK, Hamelmann E and Arck PC (2005). Mothers in Stress: Consequences for the Offspring. Am J Reprod Immunol 54(2): 63-9.
Koskinen OM, Husman TM, Meklin TM and Nevalainen AI (1999). Adverse Health Effects in Children Associate with Moistire and Mold Observations in House. Int J Environ Health Res 9(2): 143-56.
Kosonen J, Luhtala M, Viander M, Kalimo K, Terho EO, et al. (2005). Candida Albicans-Specific Lymphoproliferative and Cytokine (IL-4 and INF-γ) Responses in Atopic Eczema Dermatitis Syndrome. Evidence of Cd4/Cd8 and Cd3/Cd16+Cd56 Ratio Elevations in Vitro. Exp Dermatol 14(7): 551-8.
Kramer U, Lemmen CH, Behrendt H, Link E, Schafer T, et al. (2004). The Effect of Environmental Tobacco Smoke on Eczema and Allergic Sensitization in Children. Br J Dermatol 150(1): 111-8.
Kurz T and Ober C (2004). The Role of Environmental Tobacco Smoke in Genetic Susceptibility to Asthma. Curr Opin Allergy Clin Immunol 4(5): 335-9.
Langley SJ, Goldthorpe S, Craven M, Morris J, Woodcock A, et al. (2003). Exposure and Sensitization to Indoor Allergens: Association with Lung Function, Bronchial Reactivity, and Exhaled Nitric Oxide Measures in Asthma. J Allergy Clin Immunol 112(2): 362-8.
Laughter D, Istvan JA, Tofte SJ and Hanifin JM (2000). The Prevalence of Atopic Dermatitis in Oregon Schoolchildren. J Am Acad Dermatol 43(4): 649-55.
Lee YL, Li CW, Sung FC, Yu HS, Sheu HM, et al. (2007). Environmental Factors, Parental Atopy and Atopic Eczema in Primary-School Children: A Cross-Sectional Study in Taiwan. Br J Dermatol 157(6): 1217-24.
Lee YL, Lin YC, Hsiue TR, Hwang BF and Guo YL (2003a). Indoor and Outdoor Environmental Exposures, Parental Atopy, and Physician-Diagnosed Asthma in Taiwanese Schoolchildren. Pediatrics 112(5): e389.
Lee YL, Lin YC, Hwang BF and Guo YL (2005). Changing Prevalence of Asthma in Taiwanese Adolescents: Two Surveys 6 Years Apart. Pediatr Allergy Immunol 16(2): 157-64.
Lee YL, Lin YC, Lee YC, Wang JY, Hsiue TR, et al. (2004). Glutathione S-Transferase P1 Gene Polymorphism and Air Pollution as Interactive Risk Factors for Childhood Asthma. Clin Exp Allergy 34(11): 1707-13.
Lee YL, Shaw CK, Su HJ, Lai JS, Ko YC, et al. (2003b). Climate, Traffic-Related Air Pollutants and Allergic Rhinitis Prevalence in Middle-School Children in Taiwan. Eur Respir J 21(6): 964-70.
Lee YL, Su HJ, Sheu HM, Yu HS and Guo YL (2008). Traffic-Related Air Pollution, Climate, and Prevalence of Eczema in Taiwanese School Children. J Invest Dermatol.
Lehmann I, Thoelke A, Rehwagen M, Rolle-Kampczyk U, Schlink U, et al. (2002). The Influence of Maternal Exposure to Volatile Organic Compounds on the Cytokine Secretion Profile of Neonatal T Cells. Environ Toxicol 17(3): 203-10.
Leung R, Ho P, Lam CW and Lai CK (1997). Sensitization to Inhaled Allergens as a Risk Factor for Asthma and Allergic Diseases in Chinese Population. J Allergy Clin Immunol 99(5): 594-9.
Lewis S, Richards D, Bynner J, Butler N and Britton J (1995). Prospective Study of Risk Factors for Early and Persistent Wheezing in Childhood. Eur Respir J 8(3): 349-56.
Li Kam Wa TC, Mansur AH, Britton J, Williams G, Pavord I, et al. (1999). Association between - 308 Tumour Necrosis Factor Promoter Polymorphism and Bronchial Hyperreactivity in Asthma. Clin Exp Allergy 29(9): 1204-8.
Lin S, Cicala C, Scharenberg AM and Kinet JP (1996). The FcRI Subunit Functions as an Amplifier of Fc FcRIγ-Mediated Cell Activation Signals. Cell 85(7): 985-95.
Lin YC, Lu CC, Su HJ, Shen CY, Lei HY, et al. (2002a). The Association between Tumor Necrosis Factor, Hla-Dr Alleles, and IgE-Mediated Asthma in Taiwanese Adolescents. Allergy 57(9): 831-4.
Lin YC, Su HJ, Hsiue TR, Lee CH, Chen CW, et al. (2002b). Levels of House Dust Mite-Specific IgE and Cockroach-Specific IgE and Their Association with Lower Pulmonary Function in Taiwanese Children. Chest 121(2): 347-53.
Lin YC, Wen HJ, Lee YL and Guo YL (2004). Are Maternal Psychosocial Factors Associated with Cord Immunoglobulin E in Addition to Family Atopic History and Mother Immunoglobulin E? Clin Exp Allergy 34(4): 548-54.
Litonjua AA, Carey VJ, Burge HA, Weiss ST and Gold DR (1998). Parental History and the Risk for Childhood Asthma. Does Mother Confer More Risk Than Father? Am J Respir Crit Care Med 158(1): 176-81.
Lofroth G (1989). Environmental Tobacco Smoke: Overview of Chemical Composition and Genotoxic Components. Mutat Res 222(2): 73-80.
Magnusson CG (1986). Maternal Smoking Influences Cord Serum IgE and IgD Levels and Increases the Risk for Subsequent Infant Allergy. J Allergy Clin Immunol 78(5 Pt 1): 898-904.
Magnusson CG (1988). Cord Serum IgE in Relation to Family History and as Predictor of Atopic Disease in Early Infancy. Allergy 43(4): 241-51.
Malerba G, Trabetti E, Patuzzo C, Lauciello MC, Galavotti R, et al. (1999). Candidate Genes and a Genome-Wide Search in Italian Families with Atopic Asthmatic Children. Clin Exp Allergy 29 Suppl 4: 27-30.
Marsh DG, Neely JD, Breazeale DR, Ghosh B, Freidhoff LR, et al. (1994). Linkage Analysis of IL4 and Other Chromosome 5q31.1 Markers and Total Serum Immunoglobulin E Concentrations. Science 264(5162): 1152-6.
Maurer D, Ebner C, Reininger B, Petzelbauer P, Fiebiger E, et al. (1997). Mechanisms of FcRI-IgE-Facilitated Allergen Presentation by Dendritic Cells. Adv Exp Med Biol 417: 175-8.
Maziak W, Behrens T, Brasky TM, Duhme H, Rzehak P, et al. (2003). Are Asthma and Allergies in Children and Adolescents Increasing? Results from Isaac Phase I and Phase Iii Surveys in Munster, Germany. Allergy 58(7): 572-9.
Mendell MJ (2007). Indoor Residential Chemical Emissions as Risk Factors for Respiratory and Allergic Effects in Children: A Review. Indoor Air 17(4): 259-77.
Mitchell EB, Crow J, Chapman MD, Jouhal SS, Pope FM, et al. (1982). Basophils in Allergen-Induced Patch Test Sites in Atopic Dermatitis. Lancet 1(8264): 127-30.
Moffatt MF and Cookson WO (1997). Linkage and Candidate Gene Studies in Asthma. Am J Respir Crit Care Med 156(4 Pt 2): S110-2.
Muranaka M, Suzuki S, Koizumi K, Takafuji S, Miyamoto T, et al. (1986). Adjuvant Activity of Diesel-Exhaust Particulates for the Production of Ige Antibody in Mice. J Allergy Clin Immunol 77(4): 616-23.
Murray CS, Woodcock A, Smillie FI, Cain G, Kissen P, et al. (2004). Tobacco Smoke Exposure, Wheeze, and Atopy. Pediatr Pulmonol 37(6): 492-8.
Newman-Taylor A (1995). Environmental Determinants of Asthma. Lancet 345(8945): 296-9.
Nimmagadda SR and Evans R, 3rd (1999). Allergy: Etiology and Epidemiology. Pediatr Rev 20(4): 111-5; quiz 116.
Nishiyama C, Akizawa Y, Nishiyama M, Tokura T, Kawada H, et al. (2004). Polymorphisms in the FcRI  Promoter Region Affecting Transcription Activity: A Possible Promoter-Dependent Mechanism for Association between Fc Epsilon Ri Beta and Atopy. J Immunol 173(10): 6458-64.
Norback D, Wieslander G, Nordstrom K and Walinder R (2000). Asthma Symptoms in Relation to Measured Building Dampness in Upper Concrete Floor Construction, and 2-Ethyl-1-Hexanol in Indoor Air. Int J Tuberc Lung Dis 4(11): 1016-25.
Oie L, Hersoug LG and Madsen JO (1997). Residential Exposure to Plasticizers and Its Possible Role in the Pathogenesis of Asthma. Environ Health Perspect 105(9): 972-8.
Omenaas E, Bakke P, Elsayed S, Hanoa R and Gulsvik A (1994). Total and Specific Serum IgE Levels in Adults: Relationship to Sex, Age and Environmental Factors. Clin Exp Allergy 24(6): 530-9.
Orgel HA, Hamburger RN, Bazaral M, Gorrin H, Groshong T, et al. (1975). Development of IgE and Allergy in Infancy. J Allergy Clin Immunol 56(4): 296-307.
Oryszczyn MP, Annesi-Maesano I, Campagna D, Sahuquillo J, Huel G, et al. (1999). Head Circumference at Birth and Maternal Factors Related to Cord Blood Total Ige. Clin Exp Allergy 29(3): 334-41.
Oryszczyn MP, Annesi-Maesano I, Charpin D, Paty E, Maccario J, et al. (2000). Relationships of Active and Passive Smoking to Total IgE in Adults of the Epidemiological Study of the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy (Egea). Am J Respir Crit Care Med 161(4 Pt 1): 1241-6.
Oryszczyn MP, Godin J, Annesi I, Hellier G and Kauffmann F (1991). In Utero Exposure to Parental Smoking, Cotinine Measurements, and Cord Blood IgE. J Allergy Clin Immunol 87(6): 1169-74.
Overberger PA, Wadowsky RM and Schaper MM (1995). Evaluation of Airborne Particulates and Fungi During Hospital Renovation. Am Ind Hyg Assoc J 56(7): 706-12.
Ozaki K, Ohnishi Y, Iida A, Sekine A, Yamada R, et al. (2002). Functional SNPs in the Lymphotoxin-α Gene That Are Associated with Susceptibility to Myocardial Infarction. Nat Genet 32(4): 650-4.
Peat JK, Salome CM and Woolcock AJ (1990). Longitudinal Changes in Atopy During a 4-Year Period: Relation to Bronchial Hyperresponsiveness and Respiratory Symptoms in a Population Sample of Australian Schoolchildren. J Allergy Clin Immunol 85(1 Pt 1): 65-74.
Peden DB (2000). Development of Atopy and Asthma: Candidate Environmental Influences and Important Periods of Exposure. Environ Health Perspect 108 Suppl 3: 475-82.
Pesonen M, Kallio MJ, Siimes MA, Elg P, Bjorksten F, et al. (2009). Cord Serum Immunoglobulin E as a Risk Factor for Allergic Symptoms and Sensitization in Children and Young Adults. Pediatr Allergy Immunol 20(1): 12-8.
Prescott SL, Macaubas C, Holt BJ, Smallacombe TB, Loh R, et al. (1998). Transplacental Priming of the Human Immune System to Environmental Allergens: Universal Skewing of Initial T Cell Responses toward the Th2 Cytokine Profile. J Immunol 160(10): 4730-7.
Purvis DJ, Thompson JM, Clark PM, Robinson E, Black PN, et al. (2005). Risk Factors for Atopic Dermatitis in New Zealand Children at 3.5 Years of Age. Br J Dermatol 152(4): 742-9.
Qiao HL, Yang J and Zhang YW (2004). Specific Serum IgE Levels and FcRI- Genetic Polymorphism in Patients with Penicillins Allergy. Allergy 59(12): 1326-32.
Raap U and Kapp A (2005). Neuroimmunological Findings in Allergic Skin Diseases. Curr Opin Allergy Clin Immunol 5(5): 419-24.
Rhodes HL, Sporik R, Thomas P, Holgate ST and Cogswell JJ (2001). Early Life Risk Factors for Adult Asthma: A Birth Cohort Study of Subjects at Risk. J Allergy Clin Immunol 108(5): 720-5.
Rosenwasser LJ and Borish L (1997). Genetics of Atopy and Asthma: The Rationale Behind Promoter-Based Candidate Gene Studies (IL-4 and IL-10). Am J Respir Crit Care Med 156(4 Pt 2): S152-5.
Rosenwasser LJ, Klemm DJ, Dresback JK, Inamura H, Mascali JJ, et al. (1995). Promoter Polymorphisms in the Chromosome 5 Gene Cluster in Asthma and Atopy. Clin Exp Allergy 25 Suppl 2: 74-8; discussion 95-6.
Sadeghnejad A, Karmaus W, Davis S, Kurukulaaratchy RJ, Matthews S, et al. (2004). Raised Cord Serum Immunoglobulin E Increases the Risk of Allergic Sensitisation at Ages 4 and 10 and Asthma at Age 10. Thorax 59(11): 936-42.
Sandford AJ, Chagani T, Zhu S, Weir TD, Bai TR, et al. (2000). Polymorphisms in the IL4, IL4Rα, and FcRI Genes and Asthma Severity. J Allergy Clin Immunol 106(1 Pt 1): 135-40.
Sandford AJ, Shirakawa T, Moffatt MF, Daniels SE, Ra C, et al. (1993). Localisation of Atopy and  Subunit of High-Affinity IgE Receptor (FcRI) on Chromosome 11q. Lancet 341(8841): 332-4.
Sator PG, Schmidt JB and Honigsmann H (2003). Comparison of Epidermal Hydration and Skin Surface Lipids in Healthy Individuals and in Patients with Atopic Dermatitis. J Am Acad Dermatol 48(3): 352-8.
Scalabrin DM, Bavbek S, Perzanowski MS, Wilson BB, Platts-Mills TA, et al. (1999). Use of Specific Ige in Assessing the Relevance of Fungal and Dust Mite Allergens to Atopic Dermatitis: A Comparison with Asthmatic and Nonasthmatic Control Subjects. J Allergy Clin Immunol 104(6): 1273-9.
Shirakawa T, Hashimoto T, Furuyama J, Takeshita T and Morimoto K (1994). Linkage between Severe Atopy and Chromosome 11q13 in Japanese Families. Clin Genet 46(3): 228-32.
Soto-Quiros ME, Silverman EK, Hanson LA, Weiss ST and Celedon JC (2002). Maternal History, Sensitization to Allergens, and Current Wheezing, Rhinitis, and Eczema among Children in Costa Rica. Pediatr Pulmonol 33(4): 237-43.
Spergel JM and Paller AS (2003). Atopic Dermatitis and the Atopic March. J Allergy Clin Immunol 112(6 Suppl): S118-27.
Stetter F and Kupper S (1998). Autogenes Training - Qualitative Meta-Analyse Kontrollierter Klinischer Studien Und Beziehungen Zur Naturheilkunde. Forsch Komplementarmed 5(5): 211-223.
Sublett JL (2005). The Environment and Risk Factors for Atopy. Curr Allergy Asthma Rep 5(6): 445-50.
Sutton BJ and Gould HJ (1993). The Human Ige Network. Nature 366(6454): 421-8.
Takafuji S, Suzuki S, Koizumi K, Tadokoro K, Ohashi H, et al. (1989). Enhancing Effect of Suspended Particulate Matter on the Ige Antibody Production in Mice. Int Arch Allergy Appl Immunol 90(1): 1-7.
Takano H, Yoshikawa T, Ichinose T, Miyabara Y, Imaoka K, et al. (1997). Diesel Exhaust Particles Enhance Antigen-Induced Airway Inflammation and Local Cytokine Expression in Mice. Am J Respir Crit Care Med 156(1): 36-42.
Takenaka H, Zhang K, Diaz-Sanchez D, Tsien A and Saxon A (1995). Enhanced Human IgE Production Results from Exposure to the Aromatic Hydrocarbons from Diesel Exhaust: Direct Effects on B-Cell Ige Production. J Allergy Clin Immunol 95(1 Pt 1): 103-15.
Tariq SM, Arshad SH, Matthews SM and Hakim EA (1999). Elevated Cord Serum IgE Increases the Risk of Aeroallergen Sensitization without Increasing Respiratory Allergic Symptoms in Early Childhood. Clin Exp Allergy 29(8): 1042-8.
Tariq SM, Matthews SM, Hakim EA, Stevens M, Arshad SH, et al. (1998). The Prevalence of and Risk Factors for Atopy in Early Childhood: A Whole Population Birth Cohort Study. J Allergy Clin Immunol 101(5): 587-93.
Trabetti E, Patuzzo C, Malerba G, Galavotti R, Martinati LC, et al. (1999). Association of a Lymphotoxin α Gene Polymorphism and Atopy in Italian Families. J Med Genet 36(4): 323-5.
Tsuang HC, Su HJ, Kao FF and Shih HC (2003). Effects of Changing Risk Factors on Increasing Asthma Prevalence in Southern Taiwan. Paediatr Perinat Epidemiol 17(1): 3-9.
Vailes LD, Perzanowski MS, Wheatley LM, Platts-Mills TA and Chapman MD (2001). IgE and IgG Antibody Responses to Recombinant Alt a 1 as a Marker of Sensitization to Alternaria in Asthma and Atopic Dermatitis. Clin Exp Allergy 31(12): 1891-5.
von Bubnoff D, Novak N, Kraft S and Bieber T (2003). The Central Role of FcRI in Allergy. Clin Exp Dermatol 28(2): 184-7.
von Mutius E (1998). The Rising Trends in Asthma and Allergic Disease. Clin Exp Allergy 28 Suppl 5: 45-9; discussion 50-1.
Wahn U, Lau S, Bergmann R, Kulig M, Forster J, et al. (1997). Indoor Allergen Exposure Is a Risk Factor for Sensitization During the First Three Years of Life. J Allergy Clin Immunol 99(6 Pt 1): 763-9.
Walker C, Kagi MK, Ingold P, Braun P, Blaser K, et al. (1993). Atopic Dermatitis: Correlation of Peripheral Blood T Cell Activation, Eosinophilia and Serum Factors with Clinical Severity. Clin Exp Allergy 23(2): 145-53.
Walley AJ and Cookson WO (1996). Investigation of an Interleukin-4 Promoter Polymorphism for Associations with Asthma and Atopy. J Med Genet 33(8): 689-92.
Wang IJ, Guo YL, Weng HJ, Hsieh WS, Chuang YL, et al. (2007). Environmental Risk Factors for Early Infantile Atopic Dermatitis. Pediatr Allergy Immunol 18(5): 441-7.
Wang IJ, Hsieh WS, Guo YL, Jee SH, Hsieh CJ, et al. (2008). Neuro-Mediators as Predictors of Paediatric Atopic Dermatitis. Clin Exp Allergy 38(8): 1302-8.
Wang M, Xing ZM, Lu C, Ma YX, Yu DL, et al. (2003). A Common IL-13 Arg130Gln Single Nucleotide Polymorphism among Chinese Atopy Patients with Allergic Rhinitis. Hum Genet 113(5): 387-90.
Warner JA and Warner JO (2000). Early Life Events in Allergic Sensitisation. Br Med Bull 56(4): 883-93.
Wen HJ, Chen PC, Chiang TL, Lin SJ, Chuang YL, et al. (2009). Predicting Risk for Early Infantile Atopic Dermatitis by Hereditary and Environmental Factors. Br J Dermatol 161(5): 1166-72.
Wollenberg A and Bieber T (2000). Atopic Dermatitis: From the Genes to Skin Lesions. Allergy 55(3): 205-13.
Worm M, Ebermayer K and Henz B (1998). Lymphotoxin-α Is an Important Autocrine Factor for CD40 + Interleukin-4-Mediated B-Cell Activation in Normal and Atopic Donors. Immunology 94(3): 395-402.
Wright RJ, Cohen RT and Cohen S (2005). The Impact of Stress on the Development and Expression of Atopy. Curr Opin Allergy Clin Immunol 5(1): 23-9.
Wright RJ, Cohen S, Carey V, Weiss ST and Gold DR (2002). Parental Stress as a Predictor of Wheezing in Infancy: A Prospective Birth-Cohort Study. Am J Respir Crit Care Med 165(3): 358-65.
Wright RJ, Visness CM, Calatroni A, Grayson MH, Gold DR, et al. (2010). Prenatal Maternal Stress and Cord Blood Innate and Adaptive Cytokine Responses in an Inner-City Cohort. Am J Respir Crit Care Med 182(1): 25-33.
Zhu S, Chan-Yeung M, Becker AB, Dimich-Ward H, Ferguson AC, et al. (2000). Polymorphisms of the IL-4, TNF-α, and FceRI-b Genes and the Risk of Allergic Disorders in at-Risk Infants. Am J Respir Crit Care Med 161(5): 1655-9.