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國立台灣大學微生物與生化學研究所營養科學組專題討論

國立台灣大學微生物與生化學研究所營養科學組專題討論. The effectiveness of house dust mite avoidance and dietary fatty acid modification in asthma prevention 指導教授 ： 潘文涵 學 生：李淑貞 中華民國九十四年四月十一日. ARTICLE 1 題目： Eighteen-month outcomes of house dust mite

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國立台灣大學微生物與生化學研究所營養科學組專題討論

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  1. 國立台灣大學微生物與生化學研究所營養科學組專題討論國立台灣大學微生物與生化學研究所營養科學組專題討論 The effectiveness of house dust mite avoidance and dietary fatty acid modification in asthma prevention 指導教授：潘文涵 學 生：李淑貞 中華民國九十四年四月十一日

  2. ARTICLE 1 題目：Eighteen-month outcomes of house dust mite avoidance and dietary fatty acid modification in the Childhood Asthma Prevention Study (CAPS).作者： Mihrshahi, S., Peat, J. K., Marks, G. B., Mellis,C. M., Tovey, E. R., Webb, K., Britton, W. J., Leeder, S. R.; Childhood Asthma Prevention Study. 出處： J Allergy Clin Immunol. 2003 Jan;111(1):162-8. ARTICLE 2 題目：Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study 作者：Peat, J. K., Mihrshahi, S., Kemp, A. S., Marks, G. B., Tovey, E. R., Webb, K., Mellis, C. M., Leeder, S. R. 出處：J Allergy Clin Immunol. 2004 Oct; 114(4): 807-813.

  3. Introduction

  4. Asthma • Asthma prevalence: • 87year: 16% 91year: 19% • Risk factor: • Exposure to allergens • Environmental tobacco smoke • Respiratory infections in early life • Dietary factor: sodium, antioxidant • Preventive strategies: • Allergen avoidance • Avoidance of Environmental tobacco smoke exposure • Prolongation of breast-feeding • Beneficial food: fish (oil)

  5. Asthma & ω-3 fatty acid • Epidemiological studies: • National Health and Nutrition Examination survey: High fish intake, ↓asthma (Schwartz, J. et al 1990) • High intake of ω-6 fatty acid, ↑asthma risk (Haby, M. M. et al. 2001) • Controlled dietary ω-6 fatty acid intake, ↑ω-3 fatty acid supplement: ↓ biochemical markers (Hodge, L. et al. 1998) • A double-blind, randomized trial in children: 24-38mg/kg/d of EPA / DHA → improvement asthma symptoms, ↓airway responsiveness (Nagakura, T. ea al. 2000) • high marine fatty acid intake may have beneficial effects on inflammatory conditions such as rheumatoid arthritis, psoriasis, and asthma (Kremer, J. M. ea al. 2000; Bittiner, S. B. et al. 1988; Black, P. N. et al. 1997)

  6. Fatty acid metabolism and eicosanoids • ↑ ω-3 fatty acid supplement an inhibitory and competitive effect ↓ arachidonic acid-derived inflammatory mediators (leukotrienes; LT) LTC4, D4, E4: slow-reacting substance of anaphlaxis induces bronchoconstriction, ↑vascular permeability, mucus secretion LTB4 recruits neutrophils, ↑vascular permeability, attracts inflammatory cells modulate airway inflammation

  7. Asthma & House dust mite allergen • Epidemiological studies: • In humid region, HDM allergen is a stronger risk factor for asthma (Sporik, R. et al. 1992) • New South Wales study in children: ↑HDM allergen, ↑current asthma, dose-response relation (Peat, J. K, et al. 1996) • A randomized trials (n=23): Chemical and physical methods of HDM allergen avoidance → improvement asthma symptom, medication use, peak flow (Hammarquist, C. et al. 2000)

  8. Objective

  9. To measure the effects of dietary supplementation with ω-3 fatty acid and house dust mite allergen avoidance in children with a family history of asthma

  10. Research Design and Methods

  11. Study population • Childhood Asthma Prevention Study (CAPS) • A randomized controlled trial • Participants：Pregnant women • unborn children • high risk of developing asthma • place： 6 hospitals in Sydney, Australia. • Recruitment time：1997.9 ~1999.12

  12. Women assessed for eligibility at 6 antenatal clinics n=7171 FIG 1. CAPS trial profile Excluded n=5076 Met entry criteria n=2095 enrollment Verbally agreed to participate n=616 Declined to participate n=1479 Reasons for non-participation recorded n=1303 randomization Informed consent obtained at 34-37 weeks pregnant 616 women randomized Group A N=149 Placebo diet supplements No house dust mite reduction Group B N=155 Placebo diet supplements Active house dust mite reduction Group C N=159 Active diet supplements No house dust mite reduction Group D N=153 Active diet supplements Active house dust mite reduction

  13. Inclusion criteria for CAPS • At least one parent or sibling with symptoms of asthma as assessed by screening questionnaire • Reasonable fluency in English • Telephone at home • Reside within 30 km from center of recruitment

  14. Exclusion criteriafor CAPS • Pet cat at home • Families on strict vegetarian diet • Multiple births • Babies born earlier than 36 weeks gestation

  15. Interventions

  16. Dietary intervention

  17. Intervention group Control group FIG 2. Dietary intervention flow chart Families supplied with canola based margarines and cooking oils Families supplied with polyunsaturated margarines and cooking oils Birth Birth Breastfed Bottlefed Breastfed Bottlefed Tuna fish oil supplements added to formula Sunola oil supplements added to formula If formula is introduced before 6 months If formula is introduced before 6 months 6 months Sunola oil supplements added to favourite foods and beverages 6 months Tuna fish oil supplements added to favourite foods and beverages 5 years 5 years

  18. Table 1. comparison of DHA and EPA content in infant formula supplemented with Tuna fish oil and in breast milk

  19. Antenatal home visit (36 weeks gestation) FIG 3. House dust mite intervention flow chart. randomization Active group playmats, Acaril and covers provided with special information Control group standard information provided Acaril wash Birth Normal washing routine 1 month home visit dust collected Acaril wash 3 month home visit dust collected Acaril wash 6 month hime visit dust collected Acaril wash Washing procedure and dust collection repeated every 3 months until the child is 5 years old

  20. FIG 1. CAPS trial profile Withdrawn (18month, n=62; 3 years, n=90) Follow up home visits At 1,3,6,9,12 months and every 6 months thereafter Symptoms and illness questionnaire Home environment questionnaire Diet questionnaire Dust collection Medical assessments At 18 months, 3 years, 5 years Skin prick tests Assessment of symptoms and diagnosis Blood tests 3 day weighed food record

  21. Withdrawal criteria for CAPS(after randomization) • Birth weight below 2.5 kg • Babies requiring surgery • Babies requiring hospitalization for more than 1 weeks • Babies with significant neonatal disease • Babies with congenital malformations

  22. Symptoms and illness questionnaire • Respiratory history • Allergic symptoms • Common childhood illnesses • Significant medical and surgical problem • Immunization status • Growth rates

  23. Home environment questionnaire • Home structural • Infants sleeps room • Type of bedding • Indoor and outdoor temperature and humidity

  24. Diet questionnaire • Breast-feeding • Infant formula • Infant’s first solid foods • Eating habits • Compliance with the diet intervention

  25. Measuring instruments: analysis

  26. Assessment of symptoms and diagnosis: 18 months • Atopy: ≧1 skin prick teats, ≧2mm • symptoms diagnosis: wheeze, cough, eczema

  27. Assessment of symptoms and diagnosis: 3 years Asthma was defined by patterns of wheeze agreed in the International Consensus Guidelines Adopted by the National Asthma Council of Australia.

  28. Statistical analysis • χ2 test: whether the interventions had an independent effect on outcome • Pearson χ2 : was used for 3×2 tables • Continuity corrected χ2 : was used for 2×2 tables • Logistic regression: interaction between interventions

  29. Results--- 18 months

  30. Table 2. Demographic data for all groups(1)

  31. Table 2. Demographic data for all groups(2)

  32. Intervention effectiveness • House dust mite intervention • Participants’ beds (mean): placebo: 15.4μg/g Active group: 4.6 μg/g ↓70% (95% CI, 64%-75%) • Playroom floor (mean): placebo : 15.11μg/g (95% CI, 12.27-18.60) Active group: 10.45 μg/g (95% CI, 8.39-12.88) • Diet intervention • ω-3 plasma fatty acid: placebo: 5.0% (95% CI, 4.8-5.2) Active group: 6.7% (95%CI, 6.5-7.0; P<0.0001) ↑ • ω-6 plasma fatty acid: placebo: 35.0% (95% CI, 34.6-35.4) Active group: 32.5% (95%CI, 32.1-32.9; P<0.0001) ↓ • ω-3/ω-6: placebo: 1:7.14 Active group: 1:5.00 (P<0.0001)

  33. IgE concentrations: • placebo diet group: 22.4 IU/L (95% CI, 15.6-22.7) • Active diet group: 18.8 UL/L (95% CI, 18.1-27.6) (P=.23) • placebo HDM group: 22.4 IU/L (95% CI, 18.6-27.2) • Active HDM avoidance group: 18.6 IU/L (95% CI, 15.1-23.0) (P=.19) No difference • Cytokines: • IL-4, IL-5, IFN-γ: no data • IL-10: no difference

  34. Table 3 . Sensitization to inhaled and ingested allergens by skin prick testing at 18 months of age * The prevalence of sensitization to cockroach, Alternaria,rye grass, grass mix, cow’ milk, salmon, and tuna was<5% and did not differ between groups.

  35. Table 4. Symptoms of wheeze, cough, and eczema at 18 months of age(1)

  36. Table 4. Symptoms of wheeze, cough, and eczema at 18 months of age(2)

  37. Table 5. Medication use at 18 months of age(1) * Albuterol, terbutaline, and/or ipratropium bromide. ** Beclomethasone, budesonide, or fluticasone.

  38. Table 5. Medication use at 18 months of age(2) * Albuterol, terbutaline, and/or ipratropium bromide. ** Beclomethasone, budesonide, or fluticasone.

  39. Conclusion and discussion 1. Intervention effectiveness: achieved the expect 2. The diet and HDM interventions: no difference IgE concentrations cytokine (IL-10) specific sensitization 3. The diet interventions: symptoms: ↓ wheeze prevalence (9.8%) ↓>1 wheeze prevalence (7.8%) Medication: no difference Because symptoms of asthma cannot be reliably categorized or diagnosed in the period. increasing ω-3 fatty acid in the diet might have a beneficial effect on wheeze in high risk infant. 4. The HDM interventions: symptoms: ↑reported eczema prevalence (8.2%) ↑visible eczema prevalence (6.9%) Medication: ↓Oral steroid prevalence Required to determine these findings 5. No significant interaction between interventions was observed.

  40. Results--- 3 years

  41. Table 6. Baseline characteristics of each study groups

  42. Intervention effectiveness • House dust mite intervention • child’s bed (mean): Placebo: 16.6μg/g (95% CI, 14.8-18.1) Active group: 5.5 μg/g (95% CI, 4.9-6.2) ↓3 –fold • Diet intervention • ω-3 plasma fatty acid: Placebo: 4.9% (95% CI, 4.7-5.1) Active group: 6.3% (95%CI, 6.1-6.6; P<0.0001) ↑ • ω-6 plasma fatty acid: Placebo: 35.7% (95% CI, 35.3-36.0) Active group: 33.3% (95%CI, 32.9-33.7; P<0.0001) ↓ • ω-3/ω-6: Placebo: 1:7.7 Active group: 1:5.6 (P<0.0001)

  43. IgE concentrations (Mean): • Placebo diet group: 40.1 kIU/L (95% CI, 32.5-49.5) • Active diet group: 31.0 kUL/L (95% CI, 25.0-38.4) (P=.09) • Placebo HDM group: 38.3 kIU/L (95% CI, 31.1-47.2) • Active HDM avoidance group: 32.3 kIU/L (95% CI, 26.0-40.1) (P=.26) No difference

  44. Table 7. Prevalence of respiratory and allergic outcomes by dietary intervention group

  45. Table 8. Prevalence of respiratory and allergic outcomes by house dust mite intervention group

  46. Conclusion and discussion 1. Intervention effectiveness: achieved the expect 2. The diet and HDM interventions: no difference IgE concentrations asthma and wheeze prevalence 3. The diet interventions: ↓mild cough prevalence (7.1%) ↓moderate cough prevalence (4.1%) ↓atopic cough prevalence (10.0%) cough in children has sometimes been regarded as synonymous with asthma. A possible mechanism for the protective effect of ω-3 fatty acid supplementation is a reduction in arachidonic acid-derived inflammatory mediators, such as leukotrienes (LT). 4. The HDM interventions: ↓atopy to inhaled allergens prevalence (7.8%) ↓HDM atopy prevalence (7.2%) 5. No significant interaction between interventions was observed. 6. Potential confounders were equally distributed among the group. 7. Breast-feeding might a effect-modifiers in the study.

  47. summary 1. The results of those study suggest that increasing ω-3 fatty acid in the diet might have a beneficial effect on asthma prevention. 2. Primary preventive interventions may have significant long-term rather than early effect.

  48. Reference 1. Mihrshahi, S. et al.（2003）Eighteen-month outcomes of house dust mite avoidance and dietary fatty acid modification in the Childhood Asthma Prevention Study (CAPS). J Allergy Clin Immunol. 111:162-168. 2. Peat, J. K. et al.（2004）Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study. J Allergy Clin Immunol. 114: 807-813. 3. Schwartz, J. & Weiss, S. T.（1990）Dietary factors and their relation to respiratory symptoms. The second National Health and Nutrition Examination survey. Am J Epidemiol. 132: 67-76. 4. Kremer, J. M.（2000）n-3 fatty acid supplements in rheumatoid arthritis. Am J Clin Nutr. 71: 349S-351S. 5. Bittiner, S. B. et al.（1988）A double blind, randomized, placebo-controlled trial of fish oil in psoriasis. Lancet 1: 3. 6. Black, P. N. & Sharpe, S.（1997）Dietary fat and asthma: Is there a connection? Eur Respir J. 10: 6-12. 7. Haby, M. M. et al.（2001）Asthma in preschool children: Prevalence and risk factors. Thorax. 56: 589-595. 8. Hodge, L. et al.（1998）Effect of dietary intake of omega-3 and omega-6 fatty acid on severity of asthma in children. Eur Respir J. 1: 361-365. 9. Nagakura, T. et al.（2000）Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acid in children with bronchial asthma. Eur Respir J. 16: 861-865. 10. Peat, J. K. et al.（1996）House dust mite allergens: A major risk factor for children asthma in Australia. Am J Respir Crit Care Med. 153: 141-146. 11. Mihrshahi, S. et al.（2001）The Childhood Asthma Prevention Study (CAPS): design and research protocol of a randomized trial for the primary prevention of asthma. Control Clin Trials. 22: 333-354.

  49. Thanks for your attention

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