Novel Immunomodulatory Strategies for the Prevention of Atopy and Asthma

  • Susan L. Prescott
Part of the Allergy Frontiers book series (ALLERGY, volume 5)

As asthma and allergic diseases reach epidemic proportions, there is an urgent need to identify early the logical targets for strategies to reverse this trend. The frequent onset of disease within the first months of life necessitates early interventions. While it has been well recognized that allergic disease is multifactorial, conventional allergy prevention strategies have largely centered around avoidance of allergens and irritants with disappointing results. More recently, there has been a shift in focus to the role of immunomodulatory factors both as aetiologic factors and as possible avenues of early treatment and/or prevention [88].

Preliminary studies suggest that other environmental exposures (such as infection [1], maternal diet [2, 3], and smoking [3, 4]) can modify early immune function, although the mechanisms are not clear (Fig. 1). While potential genetic polymorphisms are of great importance in understanding the complex gene-environmental interactions during this period, genomic programming cannot account for the rising rates of disease. There has been a consequential shift in interest to environmental factors that may influence early immune development potentially through epige-netic modification in gene expression. This includes potentially environment-driven changes in the patterns of DNA methylation in proximal gene promoters, chromatin remodeling, histone modifications, and/or non-coding RNA interactions that can alter the patterns of gene expression and clinical phenotype (Fig. 1) [89].


Atopic Dermatitis Allergic Disease Allergy Clin Immunol Sublingual Immunotherapy Maternal Vitamin 
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  1. 1.
    T Matsuoka, T Matsubara, K Katayama, K Takeda, M Koga, S Furukawa. Increase of cord blood cytokine-producing T cells in intrauterine infection. Pediatr Int 2001;43(5):453–7.CrossRefPubMedGoogle Scholar
  2. 2.
    J Dunstan, TA Mori, A Barden, LJ Beilin, A Taylor, PG Holt, SL Prescott. Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomised controlled trial. J Allergy Clin Immunol 2003;112:1178–84.CrossRefPubMedGoogle Scholar
  3. 3.
    G Devereux, RN Barker, A Seaton. Antenatal determinants of neonatal immune responses to allergens. Clin Exp Allergy 2002;32(1):43–50.CrossRefPubMedGoogle Scholar
  4. 4.
    PS Noakes, PG Holt, SL Prescott. Maternal smoking in pregnancy alters neonatal cytokine responses. Allergy 2003;58(10):1053–8.CrossRefPubMedGoogle Scholar
  5. 5.
    SL Prescott, ML Tang. The Australasian Society of Clinical Immunology and Allergy position statement: summary of allergy prevention in children. Med J Aust 2005;182(9):464–7.PubMedGoogle Scholar
  6. 6.
    A Woodcock, LA Lowe, CS Murray, BM Simpson, SD Pipis, P Kissen, A Simpson, A Custovic. Early life environmental control: effect on symptoms, sensitization, and lung function at age 3 years. Am J Respir Crit Care Med 2004;170(4):433–9.CrossRefPubMedGoogle Scholar
  7. 7.
    MLK Tang, AS Kemp, J Thorburn, D Hill. Reduced interferon gamma secretion in neonates and subsequent atopy. Lancet 1994;344:983–85.CrossRefPubMedGoogle Scholar
  8. 8.
    JA Warner, EA Miles, AC Jones, DJ Quint, BM Colwell, JO Warner. Is deficiency of interferon gamma production by allergen triggered cord blood cells a predictor of atopic eczema? Clin Exp Allergy 1994;24: 423–30.CrossRefPubMedGoogle Scholar
  9. 9.
    F Martinez, D Stern, A Wright, C Holberg, L Taussig, M Halonen. Association of interleukin-2 and interferon-g production by blood mononuclear cells in infancy with parental allergy skin tests and with subsequent development of atopy. J Allergy Clin Immunol 1995;96:652–60.CrossRefPubMedGoogle Scholar
  10. 10.
    N Kondo, Y Kobayashi, S Shinoda et al. Reduced interferon gamma production by antigen-stimulated cord blood mononuclear cells is a risk factor of allergic disorders-6-year follow-up study. Clin Exp Allergy 1998;28(11):1340–4.CrossRefPubMedGoogle Scholar
  11. 11.
    S Prescott, C Macaubas, T Smallacombe, B Holt, P Sly, R Loh, P Holt. Development of allergen-specific T-cell memory in atopic and normal children. Lancet 1999;353(9148):196–200.CrossRefPubMedGoogle Scholar
  12. 12.
    SL Prescott, C Macaubas, T Smallacombe, BJ Holt, PD Sly, R Loh, PG Holt. Reciprocal age-related patterns of allergen-specific T-cell immunity in normal vs. atopic infants. Clin Exp Allergy 1998;28 Suppl 5:39–44; discussion 50–1.CrossRefPubMedGoogle Scholar
  13. 13.
    JP Allam, O Zivanovic, Berg C., U Gembruch, T Bieber, N Novak. In search for predictive factors for atopy in human cord blood. Allergy 2005;60:743–50.CrossRefPubMedGoogle Scholar
  14. 14.
    DW Hide, SH Arshad, R Twiselton, M Stevens. Cord serum IgE: an insensitive method for prediction of atopy. Clin Exp Allergy 1991;21:739–43.CrossRefPubMedGoogle Scholar
  15. 15.
    RL Bergmann, G Edenharter, KE Bergmann et al. Predictability of early atopy by cord blood IgE and parental history. Clin Exp Allergy 1997;27:752–60.CrossRefPubMedGoogle Scholar
  16. 16.
    LG Hansen, S Halken, A Host, K Møller, O Østerballe. Prediction of allergy from family history and cord blood IgE levels. Pediatr Allergy Immunol 1993;4(1):34–40.CrossRefPubMedGoogle Scholar
  17. 17.
    S Croner, N-I Kjellman. Predictors of atopic disease: cord blood IgE and month of birth. Allergy 1986;41:68–70.CrossRefPubMedGoogle Scholar
  18. 18.
    SL Prescott, J Irvine, J Dunstan, C Hii, A Ferrante. Protein kinase-C zeta: a novel “protective” neonatal T cell marker that can be up-regulated by allergy prevention strategies. J Allergy Clin Immunol 2007; (accepted February 2007).Google Scholar
  19. 19.
    P Black, S Sharpe. Dietary fat and asthma: Is there a connection? Eur Respir J 1997;10: 6–12.CrossRefPubMedGoogle Scholar
  20. 20.
    M Makrides, K Simmer, M Neumann, R Gibson. Changes in the polyunsaturated fatty acids of breast milk from mothers of full-term infants over 30 wk of lactation. Am J Clin Nutr 1995;61(6):1231–3.PubMedGoogle Scholar
  21. 21.
    J Peat, C Salome, A Woolcock. Factors associated with bronchial hyper-responsiveness in Australian adults and children. Eur Respir J 1992;5:921–9.PubMedGoogle Scholar
  22. 22.
    L Poysa, M Korppi, K Remes, K Juntunen-Backman. Atopy in childhood and diet in infancy. A nine-year follow-up study. Allergy Proc 1991;12(2):107–11.CrossRefPubMedGoogle Scholar
  23. 23.
    L Hodge, C Salome, J Peat, M Haby, W Xuan, A Woolcock. Consumption of oily fish and childhood asthma risk. Med J Aust 1996;164:137–40.PubMedGoogle Scholar
  24. 24.
    Y Takemura, Y Sakurai, S Honjo, A Tokimatsu, M Gibo, T Hara, A Kusakari, N Kugai. The Relationship between Fish Intake and the Prevalence of Asthma: The Tokorozawa Childhood Asthma and Pollinosis Study. Prev Med 2002;34(2):221.CrossRefPubMedGoogle Scholar
  25. 25.
    WH Oddy, NH de Klerk, GE Kendall, S Mihrshahi, JK Peat. Ratio of omega-6 to omega-3 fatty acids and childhood asthma. J Asthma 2004;41(3):319–26.CrossRefPubMedGoogle Scholar
  26. 26.
    S Sausenthaler, S Koletzko, B Schaaf et al. Maternal diet during pregnancy in relation to eczema and allergic sensitization in the offspring at 2 y of age. Am J Clin Nutr 2007;85(2):530.PubMedGoogle Scholar
  27. 27.
    MT Salam, YF Li, B Langholz, FD Gilliland. Maternal fish consumption during pregnancy and risk of early childhood asthma. J Asthma 2005;42(6):513–8.PubMedGoogle Scholar
  28. 28.
    RB Newson, SO Shaheen, AJ Henderson, PM Emmett, A Sherriff, PC Calder. Umbilical cord and maternal blood red cell fatty acids and early childhood wheezing and eczema. J Allergy Clin Immunol 2004;114(3):531–7.CrossRefPubMedGoogle Scholar
  29. 29.
    DR Gold, BM Willwerth, KG Tantisira et al. Associations of cord blood fatty acids with lymphocyte proliferation, IL-13, and IFN-g. J Allergy Clin Immunol 2006;in press.Google Scholar
  30. 30.
    PC Calder. N-3 polyunsaturated fatty acids and inflammation: from molecular biology to the clinic. Lipids 2003;38(4):343–52.CrossRefPubMedGoogle Scholar
  31. 31.
    JA Dunstan, TA Mori, A Barden, LJ Beilin, AL Taylor, PG Holt, SL Prescott. Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy. Clin Exp Allergy 2003;33(4):442–8.CrossRefPubMedGoogle Scholar
  32. 32.
    SL Prescott, J Irvine, JA Dunstan, C Hii, A Ferrante. Protein kinase-C zeta: a novel “protective” neonatal T cell marker that can be up-regulated by allergy prevention strategies. J Allergy Clin Immunol 2007; (accepted February 2007).Google Scholar
  33. 33.
    S Mihrshahi, JK Peat, GB Marks, CM Mellis, ER Tovey, K Webb, WJ Britton, SR Leeder. Eighteen-month outcomes of house dust mite avoidance and dietary fatty acid modification in the Childhood Asthma Prevention Study (CAPS). J Allergy Clin Immunol 2003;111(1):162–8.CrossRefPubMedGoogle Scholar
  34. 34.
    JK Peat, S Mihrshahi, AS Kemp, GB Marks, ER Tovey, K Webb, CM Mellis, SR Leeder. Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study. J Allergy Clin Immunol 2004;114.Google Scholar
  35. 35.
    GB Marks, S Mihrshahi, AS Kemp et al. Prevention of asthma during the first 5 years of life: a randomized controlled trial. J Allergy Clin Immunol 2006;118(1):53–61.CrossRefPubMedGoogle Scholar
  36. 36.
    FD Gilliland, KT Berhane, Y-F Li, WJ Gauderman, R McConnell, J Peters. Children's lung function and antioxidant vitamin, fruit, juice, and vegetable intake. Am J Epidemiol 2003;158(6):576–84.CrossRefPubMedGoogle Scholar
  37. 37.
    C Bodner, D Godden, K Brown, J Little, S Ross, A Seaton. Antioxidant intake and adults onset wheeze: a case control study. Eur Respir J 1999;13:22–30.CrossRefPubMedGoogle Scholar
  38. 38.
    F Forastiere, R Pistelli, P Sestini et al. Consumption of fresh fruit rich in vitamin C and wheezing symptoms in children. SIDRIA Collaborative Group, Italy (Italian Studies on Respiratory Disorders in Children and the Environment). Thorax 2000;55(4):283–8.CrossRefPubMedGoogle Scholar
  39. 39.
    B Okoko, P Burney, R Newson, J Potts, S Shaheen. Childhood asthma and fruit consumption in South London. Eur Respir J 2007;1–24.Google Scholar
  40. 40.
    G Devereux, SW Turner, LCA Craig, G McNeill, S Martindale, PJ Harbour, PJ Helms, A Seaton. Low maternal vitamin E intake during pregnancy is associated with asthma in 5-year-old children. Am J Respir Crit Care Med 2006;174(5):499–507.CrossRefPubMedGoogle Scholar
  41. 41.
    F Nja, W Nystad, KC Lodrup Carlsen, O Hetlevik, K-H Carlsen. Effects of early intake of fruit or vegetables in relation to later asthma and allergic sensitization in school-age children. Acta Paediatr 2005;94(2):147–54.CrossRefPubMedGoogle Scholar
  42. 42.
    PH Tan, P Sagoo, C Chan et al. Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells. J Immunol 2005;174(12):7633–44.PubMedGoogle Scholar
  43. 43.
    M Utsugi, K Dobashi, T Ishizuka, K Endou, J Hamuro, Y Murata, T Nakazawa, M Mori. c-Jun N-terminal kinase negatively regulates lipopolysaccharide-induced IL-12 production in human macrophages: role of mitogen-activated protein kinase in glutathione redox regulation of IL-12 production. J Immunol 2003;171(2):628–35.PubMedGoogle Scholar
  44. 44.
    S Martindale, G McNeill, G Devereux, D Campbell, G Russell, A Seaton. Antioxidant intake in pregnancy in relation to wheeze and eczema in the first two years of life. Am J Respir Crit Care Med 2005;171(2):121–8.CrossRefPubMedGoogle Scholar
  45. 45.
    G Devereux, AA Litonjua, SW Turner et al. Maternal vitamin D intake during pregnancy and early childhood wheezing. Am J Clin Nutr 2007;85:853–9.PubMedGoogle Scholar
  46. 46.
    AA Litonjua, SL Rifas-Shiman, NP Ly et al. Maternal antioxidant intake in pregnancy and wheezing illnesses in children at 2 y of age. Am J Clin Nutr 2006;84(4):903–11.PubMedGoogle Scholar
  47. 47.
    S Farchi, F Forastiere, N Agabiti, G Corbo, R Pistelli, C Fortes, V Dell'Orco, CA Perucci. Dietary factors associated with wheezing and allergic rhinitis in children. [see comment]. Eur Respir J 2003;22(5):772–80.CrossRefPubMedGoogle Scholar
  48. 48.
    BE Lee, YC Hong, KH Lee et al. Influence of maternal serum levels of vitamins C and E during the second trimester on birth weight and length. Eur J Clin Nutr 2004;58(10):1365–71.CrossRefPubMedGoogle Scholar
  49. 49.
    AR Scaife, G McNeill, DM Campbell, S Martindale, G Devereux, A Seaton. Maternal intake of antioxidant vitamins in pregnancy in relation to maternal and fetal plasma levels at delivery. Br J Nutr 2006;95(4):771–8.CrossRefPubMedGoogle Scholar
  50. 50.
    C Murr, K Schroecksnadel, C Winkler, M Ledochowski, D Fuchs. Antioxidants may increase the probablility of developing allergic disease and asthma. Med Hypotheses 2005;64:973–7.CrossRefPubMedGoogle Scholar
  51. 51.
    WL Stone, I LeClair, T Ponder, G Baggs, BB Reis. Infants discriminate between natural and synthetic vitamin E. Am J Clin Nutr 2003;77(4):899–906.PubMedGoogle Scholar
  52. 52.
    N Sudo, S Sawamura, K Tanaka, Y Aiba, C Kubo, Y Koga. The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. J Immunol 1997;159(4):1739–45.PubMedGoogle Scholar
  53. 53.
    B Björkstén. Effects of intestinal microflora and the environment on the development of asthma and allergy. Springer Semin Immunopathol 2004;25(3–4):257–70.CrossRefPubMedGoogle Scholar
  54. 54.
    M Kalliomäki, P Kirjavainen, E Eerola, P Kero, S Salminen, E Isolauri. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol 2001;107(1):129–34.CrossRefPubMedGoogle Scholar
  55. 55.
    M Kalliomäki, S Salminen, H Arvilommi, P Kero, P Koskinen, E Isolauri. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 2001;357(9262):1076–9.CrossRefPubMedGoogle Scholar
  56. 56.
    M Kalliomäki, S Salminen, T Poussa, H Arvilommi, E Isolauri. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003;361(9372):1869–71.CrossRefPubMedGoogle Scholar
  57. 57.
    PM Matricardi. Probiotics against allergy: data, doubts, and perspectives Allergy 2002;57:185–7.CrossRefPubMedGoogle Scholar
  58. 58.
    AL Taylor, JA Dunstan, SL Prescott. Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial. J Allergy Clin Immunol 2007;119(1):184–91.CrossRefPubMedGoogle Scholar
  59. 59.
    KK Kukkonen, KE Savilahti, KT Haahtela, KK Juntunen-Backman, KR Korpela, KT Poussa, KT Tuure, KM Kuitunen. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial. J Allergy Clin Immun 2007;119(1):192–8.CrossRefPubMedGoogle Scholar
  60. 60.
    T Abrahamsson, T Jakobsson, M Böttcher, M Fredriksson, M Jenmalm, N Björkstén, G Oldaeus. Probiotics in prevention of IgE associated eczema; a double blind randomised placebo-controleld trial. J Allergy Clin Immunol 2007; in press.Google Scholar
  61. 61.
    TT Lee, M Morisset, C Astier et al. Contamination of probiotic preparations with milk allergens can cause anaphylaxis in children with cow's milk allergy. J Allergy Clin Immunol 2007;119(3):746–7.CrossRefPubMedGoogle Scholar
  62. 62.
    G Moro, S Arslanoglu, B Stahl, J Jelinek, U Wahn, G Boehm. A mixture of prebiotic oligosac-charides reduces the incidence of atopic dermatitis during the first six months of age. Arch Dis Child 2006;91(10):814–9.CrossRefPubMedGoogle Scholar
  63. 63.
    HL Mueller, M Lanz. Hyposensitization with bacterial vaccine in infectious asthma. A double- blind study and a longitudinal study. Jama 1969;208(8):1379–83.CrossRefPubMedGoogle Scholar
  64. 64.
    BK Choudhury, JS Wild, R Alam, DM Klinman, I Boldogh, N Dharajiya, WJ Mileski, S Sur. In vivo role of p38 mitogen-activated protein kinase in mediating the anti-inflammatory effects of CpG oligodeoxynucleotide in murine asthma. J Immunol 2002;169(10):5955–61.PubMedGoogle Scholar
  65. 65.
    S Sur, JS Wild, BK Choudhury, N Sur, R Alam, DM Klinman. Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J Immunol 1999;162(10):6284–93.PubMedGoogle Scholar
  66. 66.
    JN Kline, K Kitagaki, TR Businga, VV Jain. Treatment of established asthma in a murine model using CpG oligodeoxynucleotides. Am J Physiol Lung Cell Mol Physiol 2002;283(1):L170–9.PubMedGoogle Scholar
  67. 67.
    H Tighe, K Takabayashi, D Schwartz et al. Conjugation of immunostimulatory DNA to the short ragweed allergen amb a 1 enhances its immunogenicity and reduces its allergenicity. J Allergy Clin Immunol 2000;106(1 Pt 1):124–34.CrossRefPubMedGoogle Scholar
  68. 68.
    IT Tobagus, WR Thomas, PG Holt. Adjuvant costimulation during secondary antigen challenge directs qualitative aspects of oral tolerance induction, particularly during the neonatal period. J Immunol 2004;172(4):2274–85.PubMedGoogle Scholar
  69. 69.
    R Beasley, P Shirtcliffe, JL Harper, S Holt, G Le Gros. Mycobacterium-based vaccines for the prevention of allergic disease: a progress report. Clin Exp Allergy 2002;32(8):1128–30.CrossRefPubMedGoogle Scholar
  70. 70.
    MT Hopfenspirger, DK Agrawal. Airway hyperresponsiveness, late allergic response, and eosinophilia are reversed with mycobacterial antigens in ovalbumin-presensitized mice. J Immunol 2002;168(5):2516–22.PubMedGoogle Scholar
  71. 71.
    JJ Tsai, YH Liu, HD Shen, SH Huang, SH Han. Prevention of Der p2-induced allergic airway inflammation by Mycobacterium-bacillus Calmette Guerin. J Microbiol Immunol Infect 2002;35(3):152–8.PubMedGoogle Scholar
  72. 72.
    T Major, G Wohlleben, B Reibetanz, KJ Erb. Application of heat killed Mycobacterium bovis-BCG into the lung inhibits the development of allergen-induced Th2 responses. Vaccine 2002;20(11–12):1532–40.CrossRefPubMedGoogle Scholar
  73. 73.
    X Yang, Y Fan, S Wang, X Han, J Yang, L Bilenki, L Chen. Mycobacterial infection inhibits established allergic inflammatory responses via alteration of cytokine production and vascular cell adhesion molecule-1 expression. Immunology 2002;1.Google Scholar
  74. 74.
    C Zuany-Amorim, E Sawicka, C Manlius et al. Suppression of airway eosinophilia by killed Mycobacterium vaccae- induced allergen-specific regulatory T-cells. Nat Med 2002;8(6):625–9.CrossRefPubMedGoogle Scholar
  75. 75.
    GP Cavallo, M Elia, D Giordano, C Baldi, R Cammarota. Decrease of specific and total IgE levels in allergic patients after BCG vaccination: preliminary report. Arch Otolaryngol Head Neck Surg 2002;128(9):1058–60.PubMedGoogle Scholar
  76. 76.
    MO Ota, J Vekemans, SE Schlegel-Haueter et al. Influence of Mycobacterium bovis bacillus Calmette-Guerin on antibody and cytokine responses to human neonatal vaccination. J Immunol 2002;168(2):919–25.PubMedGoogle Scholar
  77. 77.
    IB Barlan, F Tukenmez, NN Bahceciler, MM Basaran. The impact of in vivo Calmette-Guerin Bacillus administration on in vitro IgE secretion in atopic children. J Asthma 2002;39(3):239–46.CrossRefPubMedGoogle Scholar
  78. 78.
    IS Choi, YI Koh. Therapeutic effects of BCG vaccination in adult asthmatic patients: a randomized, controlled trial. Ann Allergy Asthma Immunol 2002;88(6):584–91.PubMedCrossRefGoogle Scholar
  79. 79.
    PD Arkwright, TJ David. Intradermal administration of a killed Mycobacterium vaccae suspension (SRL 172) is associated with improvement in atopic dermatitis in children with moderate-to-severe disease. J Allergy Clin Immunol 2001;107(3):53CrossRefGoogle Scholar
  80. 80.
    JS Alm, G Lilja, G Pershagen, A Scheynius. Early BCG vaccination and development of atopy. Lancet 1997;350(9075):400–3.CrossRefPubMedGoogle Scholar
  81. 81.
    IL Strannegård, LO Larsson, G Wennergren, Ö Strannegård. Prevalence of allergy in children in relation to prior BCG vaccination and infection with atypical mycobacteria. Allergy 1998;53(3):249–54.CrossRefPubMedGoogle Scholar
  82. 82.
    E von Mutius, C Braun-Fahrländer, R Schierl, J Riedler, S Ehlermann, S Maisch, M Waser, D Nowak. Exposure to endotoxin or other bacterial components might protect against the development of atopy. Clin Exp Allergy 2000;30(9):1230–4.CrossRefGoogle Scholar
  83. 83.
    G Bolte, W Bischof, M Borte, I Lehmann, HE Wichmann, J Heinrich. Early endotoxin exposure and atopy development in infants: results of a birth cohort study. Clin Exp Allergy 2003;33(6):770–6.CrossRefPubMedGoogle Scholar
  84. 84.
    M Baldini, IC Lohman, M Halonen, RP Erickson, PG Holt, FD Martinez. A Polymorphism in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. Am J Respir Cell Mol Biol 1999;20(5):976–83.PubMedGoogle Scholar
  85. 85.
    W Eder, W Klimecki, L Yu, E von Mutius, J Riedler, C Braun-Fahrlander, D Nowak, FD Martinez. Toll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol 2004;113(3):482–8.CrossRefPubMedGoogle Scholar
  86. 86.
    SM Sopo, M Macchiaiolo, G Zorzi, S Tripodi. Sublingual immunotherapy in asthma and rhinoconjunctivitis; systematic review of paediatric literature. Arch Dis Child 2004;89(7):620–4.CrossRefPubMedGoogle Scholar
  87. 87.
    E Novembre, E Galli, F Landi et al. Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol 2004;114(4):851–7.CrossRefPubMedGoogle Scholar
  88. 88.
    SL Prescott, VL Clifton. Asthma and Pregnancy: emerging evidence of epigenetic interactions in utero. Curr Opin Allergy Clin Immunol 2009;9(5):417–26.CrossRefPubMedGoogle Scholar
  89. 89.
    D Martino, SL Prescott. Silent mysteries: epigenetic paradigms could hold the key to conquering the epidemic of allergy and immune disease. Allergy 2009; in press.Google Scholar
  90. 90.
    C Furuhjelm, K Warstedt, J Larsson, M Fredriksson, MF Bottcher, K Falth-Magnusson, et al. Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy. Acta Paediatr 2009;98(9):1461–7.CrossRefPubMedGoogle Scholar
  91. 91.
    SF Olsen, ML Osterdal, JD Salvig, LM Mortensen, D Rytter, NJ Secher, et al. Fish oil intake compared with olive oil intake in late pregnancy and asthma in the offspring: 16 y of registry-based follow-up from a randomized controlled trial. Am J Clin Nutr 2008;88:167–75.PubMedGoogle Scholar
  92. 92.
    H Johannsen, SL Prescott. Practical prebiotics, probiotics and synbiotics for allergists: how useful are they? Clin Exp Allergy 2009; in press.Google Scholar
  93. 93.
    SL Prescott, B Björkstén. Probiotics for the prevention or treatment of allergic diseases. J Allergy Clin Immunol 2007;120:255–62.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Susan L. Prescott
    • 1
    • 2
  1. 1.School Paediatrics and Child Health ResearchUniversity of Western AustraliaPerthAustralia
  2. 2.Princess Margaret HospitalPerthAustralia

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