소아 알레르기질환의 발생 및 예방 성균관의과대학 삼성서울병원 소아과 안 강 모 성균관대학교 대학원 소아과 (2009 년 2 학기 )

알레르기 행진 나이 ( 세 ) 알레르기비염식품알레르기천식아토피피부염 증상 중증도

위생가설 (Hygiene Hypothesis) (New Engl J Med 2002;347:911-20)

알레르기 질환의 면역상태 Th1Th2

알레르기 질환의 면역상태 Th1 Th2

출생 전후의 Th2 면역 상태의 변화

Development of Allergic disease Genetic factor Environmental factor Allergic diseases

알레르기질환 가족력 : 아토피피부염 발생 위험 증 가 아토피피부염 발생률 (%) 알레르기질환 가족력이 없는 경우 아버지가 알레 르기질환 있는 경우 어머니가 알레 르기질환 있는 경우 부모가 모두 알 레르기질환 있 는 경우 14.7% (49/333) 22.2% (18/81) 30.7% (32/104) 41.7% (10/24)

Pathogenesis of AD Genetic factor Environmental factor Atopic dermatitis Allergy (Th2 immunity) Skin Barrier Dysfunction

Pathogenesis of AD Biological and Genetic Risk - Immune - Skin Environment - Allergens - Infections - Microbes - Pollutants - Stress Age Atopic Dermatitis Innate and Adaptive Immune Development (Atopy)

Environmental factor Biologic Non-biologic Allergen Irritant / Toxin Indoor Outdoor Inhalation Ingestion Contact Pollutant Non-pollutant Allergic diseases Causative factor exacerbating factor CURE / Prevention CARE

(J Allergy Clin Immunol 2005;116:657-61)

(J Am Acad Dermatol 2001;45:520-7)

BMF duration is a risk factor for AD Bergmann RL, et al. Clin Exp Allergy 2002;32:205-9 Methods; In an observational birth cohort study 1314 infants born in 1990 were followed-up for 7 years. Results; the prevalence of atopic eczema in the first 7 years increased with each year of age(OR 1.05), with each additional month of breastfeeding (1.03), with history of parental AD(2.06), and if other atopic signs and symptoms appeared, esp. specific sensitization(1.53), and asthma(1.41).

Extensively hydrolyzed formula Amino acid-based formula

(Han YS, et al. J Korean Med Sci 2003;18: ) Preventive effect of Partially Hydrolyzed formula Prevalence (%) p < /1519/329/22 Cumulative incidence (%) p < /1525/3215/22

Preventive effect of hydrolyzed infant formulas persists until age 6 years: Long-term results from the German Infant Nutritional Intervention Study(GINI) J Allergy Clin Immunol 2008;121: RCT in 2252 newborns with atopic heredity Randomly assigned at birth to receive one of 4 blinded formulas as milk substitute for the first 4 months when BMF was insufficient

Maternal and infant diets for prevention of allergic disease J Allergy Clin Immunol 2008;122:29-33 Approaches that are generally effective: - BMF for the first 4-6 mo of life - if not breast-feeding, or if supplementing, for the first 4- 6 mo, using an eHF(casein) - delaying introduction of solid foods until 4-6 mo of age Approaches that remain unproven: - dietary allergen restriction during pregnancy - dietary allergen restriction during lactation - avoidance of allergenic foods for months and years beyond 6 mo of age

Isle of Wight Prevention Study J Allergy Clin Immunol 2007;119: Subjects : infants at high risk (n=120) Design : prospective, randomized study Intervention : Prophylactic group (n=58), Control (n=62) - feeding ; either breastfed with mother on a low allergen diet or eHF - exposure to HDM ; reduced by the use of an acaricide and mattress covers F/U : 8 years

(J Allergy Clin Immunol 2007;119:307-13)

Canadian Asthma Primary Prevention Study J Allergy Clin Immunol 2005;116:49-55 Subjects : high-risk infants with an immediate family history of asthma and allergies (n=545) Design : prospective, randomized study Intervention : before birth and during the 1 st year of life Prophylactic group (n=58) vs Control group (n=62) : - avoidance of HDM, pets, and ETS - encouragement of BMF and delayed introduction of solid foods F/U : 7 years

(J Allergy Clin Immunol 2005;116:49-55)

Probiotics in primary prevention of atopic disease : 2 year f/u (Lancet 2001;357:1076-9) 15/64 (23%) 31/68 (46%) placeboLactobacillus GG Proportion of 2 year-old children with atopic eczema (%)

Probiotics in primary prevention of atopic disease : 4 year f/u (Lancet 2003;361: ) 14/53 (26%) 25/54 (46%) placeboLactobacillus GG placeboLactobacillus GG 10/50 (20%) 9/50 (18%) Proportion of AD (%) Proportion of SPT positivity (%)

Probiotics in primary prevention of atopic disease : 7 year f/u (J Allergy Clin Immunol 2007;119: ) LGG vs Placebo RR 0.64 (95% CI ) OR 0.58 (95% CI )

Probiotics in primary prevention of atopic disease : 7 year f/u placeboLactobacillus GG 16/52 (31%) 19/57 (33%) Proportion of SPT positivity (%) LGG vs Placebo RR 0.92 (95% CI ) (J Allergy Clin Immunol 2007;119: )

Probiotics in primary prevention of atopic disease : 7 year f/u 12/53 (22.6%) 6/62 (9.7%) placeboLactobacillus GG Proportion of AR (%) 9/53 (17.0%) 3/62 (4.8%) placeboLactobacillus GG Proportion of BA (%) LGG vs Placebo RR 2.30 (95% CI ) LGG vs Placebo RR 3.44 (95% CI ) (J Allergy Clin Immunol 2007;119: )

Bifidobacterium bifidum BGN4 in allergic animal model (Biotechnol Lett 2005;27:1361-7)

Subjects; mothers who had at least one first-degree relative with AD, AR, or BA and their infants Feeding; BMF or AMF Design; randomized, DB-PC trial Probiotics; MIXTURE (Bifidobacterium bifidum BGN4, B. Longum, L. acidophilus) for 1 Mo prenatally and for 6 Mo postnatally Preventive effect of B. bifidum BGN4

프로바이오틱스의 아토피피부염 예방효과 위약군비피도박테리움 투여군 생후 1 년시 아토피피부염 유병률 (%) 14/35 (40%) 6/33 (18%) p < 0.05

결론 알레르기 질환은 소아에서 발생하여 알레르기 행진이라는 자연경과를 거친다. 소아 알레르기질환의 자연경과는 나이에 따른 면역계의 발달과 관련있다. 발생기전은 다양하다. 예방 : 모유, 가수분해유, 원인물질 회피, 프로 바이오틱스