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Role of probiotics in allergic
disease prevention in children
益生菌在兒童過敏疾病預防
所扮演的角色
高雄榮總 兒童醫學部
兒童過敏免疫風濕科
邱益煊
1/95
前言
➢ Allergic diseases (including atopic dermatitis, respiratory
allergies and food allergies) are increasing in prevalence
worldwide, affecting up to 30% of the world population,
and pose a significant impacts on the quality of life in
atopic individual and on society, both economically and
psychosocially.
➢ Allergic diseases are now classified as the 4th most
common global disease by the World Health Organization.
➢ Allergic diseases are also the earliest onset non
communicable diseases (NCDs) and a clear manifestation
of the vulnerability of the immune system to modern
environmental changes.
➢ 根據研究報告顯示,過敏性疾病可能發生於不同年齡
,若發生時間愈早,其嚴重性就愈大,因此,預防過
敏的工作應盡早開始,才能將影響降到最低。
何謂過敏?
➢ 免疫系統失去平衡
– 接觸無害外來物(過敏原)時產生過度免疫反應
過敏體質形成後,
目前無法根治
過敏反應
(致敏化)
KD Yang at al. Clinical Immunology
過敏疾病的致病機轉 ?
過敏進行曲–The allergic march
◼不同年齡層,過敏症狀的相對盛行率
◼許多兒童會同時出現二種以上的過敏症狀
過敏的成因 – 多重因數
➢ 免疫系統的…
– 先天不足:
• 遺傳(基因)
– 後天失調:
• 環境 (城市 / 過度清潔 / 獨生子多 / 空汙嚴重…)
• 飲食 (以配方奶取代母奶 / 兒童肥胖 /加工食品…)
• 行為 (剖腹產取代自然產 / 抗生素使用…)
• 腸道菌相不健全
父 + 母 →子女30%
父 + 母 →子女50%
父 + 母 →子女80%
→ 免疫反應失衡 → 過敏
(Coolson & Hopkin, Lancet 23:957, 1989; Marsh et al., Science 264:1152. 1994)
常見的過敏原
過敏性鼻炎
過敏性結膜炎
異位性皮膚炎
過敏性氣喘
(濕疹)
塵蟎
花粉
雞蛋
牛奶
堅果
海鮮
寵物
空汙
PM2.5
昆蟲
黴菌
蟑螂
常見的刺激物來源
刺激物(非過敏原)
上呼吸道感染:病毒感染
氣候劇烈變化:溫度、濕度、風速、氣壓
空氣污染:打掃、工廠或車輛廢氣、PM2.5
刺激味道:蚊香、香煙、香水、油漆、殺蟲劑
哭、笑等心理及情緒因素、壓力
劇烈運動
冷熱變化:洗澡、冷氣房、冰冷引料及水果
過敏疾病的治療
➢改善環境,避免接觸過敏原:減少致敏化
➢藥物治療:正確使用藥物可以減緩過敏症
狀,降低過敏疾病的發作頻率
– 急性期緩解藥物
– 症狀緩解藥物
– 長期保養改善藥物
➢減敏療法:
– 皮下過敏原注射
– 舌下過敏原滴劑
9/95
Life style and environment
➢ These allergic conditions linked to environmental and lifestyle
changes driving the dysfunction of three interdependent
biological systems: microbiota, epithelial barrier, and immune
system.
➢ Dietary changes are of particular interest in the altered
establishment and maturation of the microbiome, including the
associated profile of metabolites that modulate immune
development and barrier function.
➢ The primary prevention of allergic airway diseases focuses on
offspring’s gestational and childhood environment, such as
maternal smoking and diet during pregnancy and breast feeding
as well as exposure to environmental microbes and irritants.
➢ Rapid action needs to be taken to restrain smoking among
children and adolescents in order to prevent burden of allergic
airway diseases.
➢ Exposure to pollution and environmental issues concerning
hygiene and lifestyle would also need to be actively addressed.
10Nutrients 2019, 11, 1841
Curr Treat Options Allergy (2018) 5:347–355
如何阻斷過敏進程?
(三段五級防治)
過敏性疾病三級防治:
初級預防:(primary prevention)去除引發過敏進程的致敏因素
的積極方法,是最為有效的預防措施
二級預防:(cure)針對已致敏個體,在臨床症狀出現之前採取
的積極預防方法,或治癒
三級預防:(care)出現過敏臨床症狀後,延緩過敏進程和減輕
嚴重程度,並積極治療急性過敏症的方法,一般通
過藥物實現
崔玉濤, 等, 中華圍產醫學雜誌, 2007, 10 (3): 211-213
(不要被致敏化sensitize)
(已被致敏者,如何不發病)
(已發病者之疾病控制,推遲進行)
如何預防兒童過敏?
預防寶寶過敏建議
從懷孕開始
過敏疾病的預防
準媽媽在懷孕的第四個月起:
(高過敏遺傳性懷孕婦女)
⚫應避免攝取易引起過敏的食物:如
牛奶、蛋白、有殼海鮮、花生堅果類、
豆類、麥類、柑橘類、巧克力、、等
⚫去除環境中的過敏原
⚫懷孕情緒
• 生活飲食
– 至少6個月的母乳哺育→水解配方奶粉
– 飲食均衡/避免油膩及冰冷食物
– 補充抗過敏益生菌
• 懷孕後期食用/產後哺乳食用
• 新生寶寶食用(研究持續進行中)
➢ 環境控制
– 避免接觸過敏原 /塵蟎/二手煙/花粉/空汙(PM 2.5)…
– 維持適當溫濕度 /夏天穿著透氣/冬天注重保濕
– 不須過度清潔–免疫系統需要適當訓練
如何預防兒童過敏體質產生?
Primary prevention of allergy
➢Probiotics issues
➢Environments and life style issues
15
Primary prevention of allergy
➢Probiotics issues
➢Environments and life style issues
16
Probiotics(益生菌)
– 應用於預防醫學的觀念是1907年Eli Metchnikoff (梅
契尼可夫) 提出,他假設一些巴爾幹半島居民的長壽
是因為經常食用發酵乳中含有特定乳酸稈菌所造成。
– Fuller在1989年提議將益生菌(Probiotics)定義為能經
由改善腸道菌叢平衡而讓宿主得到健康之活菌添加物
➢ 人類腸道中的內生型Probiotics(益生菌)
重要屬種如下:
– 乳酸菌(LAB): Lactobacillus (乳酸桿菌屬)
Bifidobacterium (雙岐桿菌屬)
Enterococcus (球菌屬)
– 非乳酸菌: Clostridium butyricum (酪酸菌)
(Non-LAB) Bacillus mesentericus (醣化菌)
Saccharomyces Boulardii (酵母菌)
… etc
What are Probiotics?
FAO/WHO Definition
人類與細菌共生共存
人體內外有許多細菌常駐
人體內外有許多細菌常駐
100 兆細菌在人體上: 口腔, 腸道, 陰道, 皮膚
10x 人體細胞總數的10倍
>500 不同的細菌種類在腸道
不同時期的人體菌相變化
20
胎兒期
無菌
嬰兒期
母乳餵養
雙歧桿菌為主
學童期
斷奶後菌群多
樣性增加
成年期
以厚壁菌門、擬桿
菌門和放線菌門細
菌為主
老年期
以厚壁菌和雙歧桿
菌減少、擬桿菌和
變形菌增加
母乳餵養
奶粉餵養
固體食物 健康
健康
肥胖
65~80歲
厚壁菌門
擬桿菌門
放線菌門
變形菌門
其他
抗生素治療
營養不良
腸道菌相與人體健康
60 kg的健康成人大約有1.5 kg重的腸道菌
➢ 健康的腸道菌相有助於
免疫系統的發育
腸道菌
腸道免疫細胞
Nat Rev Immunol. 2010 Feb;10(2):131-44.
小腸內側
皮膚狀態也與腸道健康平衡有關
- 腸道與皮膚發炎的關聯
異位性皮膚炎
NATURE REVIEWS | MICROBIOLOGY VOLUME
15 | MAY 2017 | 259
24
Nature Medicine 2016 22:1079-89
Metabolites
Organs
Gut microbiota associated with diseases
25
Nature Medicine 2016 22:1079-89
神經系統疾病 精神疾病 呼吸系統疾病
心血管疾病 胃腸道疾病 肝病
自身免疫性疾病 代謝性疾病 腫瘤
Nature Medicine 2016 22:1079-89
腸道正常菌相的功能
Functions of the Intestinal Flora
Therap Adv Gastroenterol. 2013 Jan; 6(1): 39–51
益生菌在腸道作用的機轉
自然產&有兄姐的兒童較不易得到過敏
Gut Microbes.2014 Mar-Apr;5(2):239-44.
雙歧桿菌
乳酸桿菌
預防過敏性疾病
自然產
有兄姐
梭狀芽孢桿菌
類桿菌(中性常駐菌)
嬰兒的腸道好菌變多!
壞菌減少!
母乳哺育與嬰兒配方奶
Breast milk supplies more than just nutrients for baby
母乳不只提供營養,還包括嬰兒腸道菌相的建立
健康的腸道菌相
天然的營養
母親的腸道菌相
可「傳遞」給子女
Trends Mol Med.2014 Sep;20(9):509-18.
生產前 生產後
食用益生菌
飲食組成
食用益生菌
胎盤
喂母乳
母親腸道菌
母親腸道菌 影響免疫 /
代謝 /神經系
統發育
益生菌的菌株特異性
特定菌株
特定菌種
一般益生菌
平衡免疫/神經/內分泌系統
幫助物質代謝
特殊營養生成…
抑制有害菌生長
一般腸道保健…
(功能性益生菌)
益生源 (Prebiotics)
– 是指腸道益生菌所需的某些特殊營養素,可幫助益菌的生長。
– 不被小腸所消化吸收,但可以被腸內菌發酵利用的物質。
– 主要來源:碳水化合物(醣類)
– 如膳食纖維、不被消化的澱粉、寡糖類......
➢ 常見富含益生源的食物如下:
– 五穀類:未精製穀類、蕎麥、燕麥、糙米、薏仁
– 塊莖類:地瓜、馬鈴薯、芋頭
– 根莖類:洋蔥、牛蒡、菊苣、蘆筍、南瓜
– 蔬菜類:青花菜、花椰菜
– 海藻類:海帶、紫菜、裙帶菜
– 水果類:香蕉、木瓜、蘋果
– 蕈 類:香菇、白木耳、黑木耳
– 豆 類:黃豆、毛豆、乾豆類
– 寡糖類:果寡糖、異麥芽寡糖、菊糖
素食者,
生機飲食
Synbiotics (共生菌) =
Probiotics + Prebiotics + Symbiosis(共生增值)
◆ 2000年英國學者Burns & Rowland更指出共生
菌比一般的益生菌更能有效的改善腸道的生態環
境,並更有效率的提升腸道益菌數。
( Curr Issues Intest Microbiol 2000 Mar; 1(1): 13-24 )
統整678例的臨床人體試驗資料分析,益生菌對於減輕異位性皮膚
炎症狀是有效果的。
臨床研究證實益生菌能夠
減輕異位皮膚炎症狀
美國賴特派特森醫療中心
Gary M. Onady醫師
臨床研究證實益生菌能夠減輕過敏性
鼻炎症狀與減少藥物的使用
統整12篇隨機分組的臨床人體試驗資料,多數的臨床研究證實益生菌
對於減輕過敏性鼻炎症狀與減少藥物的使用有顯著的效果,但對於後
期較嚴重的氣喘症狀則無顯著差異。
波士頓塔夫斯大學醫學院
Matthew E. Falagas醫師
the Canadian Healthy Infant Longitudinal Development (CHILD)
Study
嬰兒早期微生物及代謝改變影響兒童哮喘的風險
嬰兒早期微生物及代謝改變影響兒童哮喘的風險
The relative abundance of the
bacterial genera Lachnospira,
Veillonella, Faecalibacterium, and
Rothia was significantly decreased
in children at risk of asthma
根據臺灣全民健保資料庫,以1998年全部新生兒共
263,620人,及2003年百萬人樣本中的新生兒 9,910人,
各追蹤五年,來看在周歲前使用過抗生素及
acetaminophen 對在後來連續四年中發生過敏性皮膚炎,
鼻炎及哮喘的影響。
International Journal of Epidemiology 2013;42:1087–1099
人體菌相的保護與重建可以減少
過敏性呼吸道疾病的發展風險
過敏性的呼吸道疾病經科學研究證實與嬰幼兒時期的抗生素過度使用
及接觸的微生物過少有關,導致之後出現呼吸道過敏的疾病。
因此,人體菌相的保護與重建可以減少過敏性呼吸道疾病的發展風險。
悉尼大學
Dianne E. Campbell
教授
Paediatric Respiratory Reviews 2016;19:69-74
Seventeen studies from PubMed, Embase and Cochrane Library were
searched for randomized controlled trials evaluating the use of probiotics
during pregnancy or early infancy for prevention of allergic diseases,
reporting data from 4755 children (2381 in the probiotic group and 2374 in
the control group), were included in the meta-analysis.
17篇針對懷孕期及早期嬰兒使用益生菌預防過敏性疾病的研究,共收案4755名兒
童(2381名為益生菌組,2374名為對照組)進行資料分析
益生菌應用於預防兒童過敏性疾病
Allergy Eur J Allergy Clin Immunol 2015;70:1356-1371
補充益生菌組的孩子和對照組相比,較少發展成濕疹(672 [28.22%]
vs 847 [35.67%], respectively).顯示補充益生菌可顯著降低濕疹的發
生率(RR 0.78 [95% CI 0.69–0.89], P = 0.0003)
Forest plot showing the association between probiotics and eczema
森林圖顯示益生菌和濕疹間之關聯性
Fewer children in the probiotic group developed eczema compared
to those in the control group (672 [28.22%] vs 847 [35.67%],
respectively). The RR was significantly lower in children treated with
probiotics (RR 0.78 [95% CI 0.69–0.89], P = 0.0003)
Forest plot showing the association between
probiotics and eczema in the studies which used
森林圖顯示益生菌和濕疹間之關聯性
A). Lactobacillus
P =0.18
B). Bifidobacterials
P =0.23
Forest plot showing the association between
probiotics and eczema in the studies which used
森林圖顯示益生菌和濕疹間之關聯性
C). Probiotics mixture with Lactobacillus
and Bifidobacteria
Test for overall effects Z =5.34
(P < 0.00001)
< 12 mon,
p =0.008
< 24 mon,
p =0.008
> 2 yrs,
p =0.13
No significant difference in terms of prevention of asthma
(RR 0.99 [95% CI: 0.77–1.27], P = 0.95), wheezing (RR 1.02
[95% CI: 0.89–1.17], P = 0.76) or rhinoconjunctivitis (RR
0.91 [95% CI: 0.67–1.23], P = 0.53) was documented
The results of the present meta-analysis show that
probiotic supplementation prevents infantile eczema, thus
suggesting a new potential indication for probiotic use in
pregnancy and infancy.
本結果顯示,益生菌補充劑可預防嬰兒濕疹,建議在懷孕期和嬰
兒期即可補充益生菌
Allergy Eur J Allergy Clin Immunol 2015;70:1356-1371
➢ 29 randomized-controlled trials that examined probiotic
supplementation in pregnant women, breastfeeding mothers,
infants, and children.
➢ Of the 29 studies, 15 trials (n = 3509) evaluated probiotic use
during pregnancy. Exploration of the data showed a reduced risk
of eczema in infants (RR 0.72; 95% CI: 0.61–0.85) with probiotic
use during pregnancy.
➢ Thirteen studies (n = 1595) evaluating the use of probiotics in
breastfeeding mothers also revealed a reduced risk of eczema
(RR 0.61; 95% CI: 0.50–0.74).
➢ Fifteen trials (n = 3447) evaluating the use of probiotics in infants
reported a reduced risk of eczema (RR 0.81;95% CI: 0.70–0.94).
J. Allergy Clin. Immunol. 2015, 136, 952–961.
Results: Currently available evidence does not indicate that probiotic
supplementation reduces the risk of developing allergy in children. However,
considering all critical outcomes in this context, the WAO guideline panel
determined that there is a likely net benefit from using probiotics resulting
primarily from prevention of eczema.
The WAO guideline panel suggests:
世界過敏組織指南建議
a) using probiotics in pregnant women at high risk for having an allergic child;
過敏高遺傳性懷孕婦女可使用益生菌
b) using probiotics in women who breastfeed infants at high risk of developing
allergy
有過敏兒之哺乳婦女可使用益生菌
c) using probiotics in infants at high risk of developing allergy.
高過敏危險之嬰兒可使用益生菌
All recommendations are conditional and supported by very low quality evidence
➢ A total of 28 studies met the inclusion criteria.
➢ Compared with controls, probiotic treatment was associated with
a reduced risk of AD (OR 0.69;95% CI 0.58-0.82, P < 0.0001).
➢ The use of probiotics during both the prenatal and the postnatal
period significantly reduced the incidence of AD (OR 0.67; 95% CI 0.54-0.82)
➢ Analysis of studies of probiotics given prenatally or postnatally only
did not reach statistical significance.
➢ Conclusions: Our meta-analysis showed that probiotic
supplementation during both the prenatal and the postnatal
period reduced the incidence of AD in infants and children.
➢ Our findings suggest that starting probiotic treatment during
gestation and continuing through the first 6 months of the
infant's life may be of benefit in the prevention of AD 53
➢ A recent mini-review by Mennini et al. highlights that in asthma,
MMP9 levels were significantly increased, and treatment with
LGG was shown to decrease MMP9 expression in lung tissue and
inhibit inflammatory cell infiltration.
➢ Furthermore, in OVA-sensitized mice, LGG suppressed the airway
hyper-responsiveness to methacholine and reduced the number
of infiltrating inflammatory cells and Th2 cytokines in
bronchoalveolar lavage fluid and serum.
➢ LGG has previously been reported to reduce the concentration of
exhaled nitric oxide among 4- to 7-year-olds in pediatric asthma
54
Front. Pediatr. 2017, 5:1–5
Children 2019, 6:24
Current evidence does not support the use
of probiotics in the prevention of asthma
➢ Azad M.B., a meta-analysis including nine different trials and a
total of 3257 children showed an RR of 0.99 (95% CI: 0.81–1.21)
of asthma in children receiving probiotics.
➢ The previously described randomized-controlled trial by Cabana
et al. evaluated probiotics and the incidence of asthma at 5
years of age as a secondary outcome.
– The study did not show a significant reduction in asthma development
following the use of probiotics, with an incidence of asthma at 17.4% in
the control arm (n = 92) and 9.7% in the LGG arm (n = 92) (HR 0.88; 95%
CI: 0.41–1.87; log rank p = 0.25)
➢ Zuccottti et al. and Cuello-Garcia et al., which also did not show
any significant effect of probiotics on asthma
55
1. BMJ 2013, 347, f6471
2. Pediatrics 2017, 140, 1–9.
3. Allergy Eur. J. Allergy Clin. Immunol. 2015, 70, 1356–1371
4. J. Allergy Clin. Immunol. 2015, 136, 952–961
Probiotics in allergic rhinitis
➢ Allergic rhinitis affects between 10 and 30% of the population,
and the management of this disease is costly, both in the amount
spent on medications and in the loss of time away from work.
➢ Currently, there is no strong evidence that probiotics have an
effect on the development of allergic rhinitis.
➢ Peldan et al. administered questionnaires to the parents of their
study patients (at the time between 5 and 10 years of age)
investigating the presence of atopy, including allergic rhinitis, in
those children.
➢ Analysis of the lifetime prevalence of allergic rhinitis was the
same in both placebo and probiotic group; however, the
prevalence of allergic rhino-conjunctivitis at age 5–10 years was
greater in the probiotic group compared to the placebo group
(36.5% versus 29.0%, OR: 1.43, 95% CI:1.06–1.94, p = 0.03). 56
Clin. Exp. Allergy 2017, 47, 975–979.
2004年LP33經臨床實驗證實
改善過敏性鼻炎症狀
期刊:Pediatric Allergy
Immunology
2004 Apr; 15(2):152-8.
圖中負值表示改善狀況,負值
愈高,表示改善效果愈好。
不論是過敏性鼻炎症狀發作頻
率或困撓程度,服用
Lactobacillus paracasei 33的組
別對於過敏性鼻炎等症狀至整
體生活品質而言,改善效果都
優於安慰劑組。 57
58
2014年425例大型臨床實驗證實LP33對歐洲人
花粉過敏有改善效果
(歐洲氣喘過敏協會認證實驗)
✓全球第一株臨床證實可有效輔助抗組織胺治療的益生菌
✓法國醫學大學證實LP-33可顯著改善過敏鼻炎患者的生活品質
✓抗組織胺的治療效果不佳時,配合LP33可增強治療效果,甚至停藥後持
續服用LP33,可持續改善效果!!!
59
Nutrients 2018, 10, 1678
60
Safety of probiotics
➢ Probiotics are generally considered safe; however,
they may not be completely innocuous. While there
are some probiotic products that are considered
medicinal, most are classified as commercial
food/dietary supplements or natural health
products.
➢ The authors rightfully recommend that patients
should always read labels closely and use commercial
probiotics with caution.
61
益生菌對於兒童過敏疾病有效果
並且安全性高、副作用低
嬰兒從出生的那一刻就由大量的微生物的定殖。這些微生物可能賦
予人們許多好處,尤其是腸道問題、泌尿道感染與過敏性疾病。諸
多證據顯示益生菌的輔助治療是安全且極少副作用的。
史丹佛大學 醫師
Michael Harrison Hsieh
➢ Hassan, a more recent systematic review examining the efficacy
and safety of probiotics in people with cancer included 25 studies
(n = 2242 participants) in their safety analysis.
– Five case reports were identified involving probiotic-associated infections
including bacteremia and fungemia. Two deaths were reported in patients
receiving probiotics; however, these were not attributed to the probiotic
intervention.
➢ Brunser reports of sepsis due to lactobacillus or bifidobacterium,
these species are generally not considered pathogenic. Relevant
case reports are usually associated with an underlying comorbidity
resulting in immunocompromise.
➢ Overall, the risk with probiotic administration appears low in non-
immunocompromised patients, but good clinical judgment is still
important in making the decision of whether to administer
probiotics or not in different clinical settings. 63
Safety of probiotics
Care Cancer 2018, 26, 2503–2509.
Rev. Chil. Pediatr. 2017, 88, 534–540
Conclusion
➢ Current evidence does not support the routine use of probiotics
as an intervention for preventing any form of allergic disease,
with the exception of eczema in high-risk infants (World Allergy
Organization WAO recommendation)
➢ The WAO does favor probiotic supplementation in
pregnant/lactating women and in infants with a family history of
allergic disease
➢ As a result of the previously studies, lack of homogeneity in
specific probiotic strains, many trials are now carefully recording
the specific strains of probiotics that are being used
➢ However, research in this area is ongoing and will hopefully
provide better insights into how probiotics may contribute to the
prevention or treatment of atopic diseases.
➢ The optimal strains, dosages, timing, and duration of probiotic
administration remain unknown. 64
➢哪一種菌種好?
➢哪一種產品?
➢何種情況下使用?
➢劑量?
➢使用週期?
➢是否有副作用?
➢價格?
Primary prevention of allergy
➢Probiotics issues
➢Environments and life style issues
67
68
Curr Treat Options Allergy (2018) 5:347–355
Smoking
➢ Smoking during pregnancy is common, and estimated
rates vary from 17 to 30%.
➢ Cigarette smoking is the single largest modifiable risk
for all pregnancy-related morbidity and mortality.
➢ Numerous studies have confirmed the effect of
external tobacco smoke on the risk of asthma and also
on the severity of bronchial inflammation.
➢ This risk may be even transmitted by possible
epigenetic mechanisms over the generation from
grandmothers to grandchildren.
69
Curr Treat Options Allergy (2018) 5:347–355
➢ A recent meta-analysis found that on adults, active smoking did
not increase risk of AR, but increased the risk for rhinitis.
➢ In children and adolescents, both active and passive smoking
increased the incidence of AR.
➢ The study group estimated that 14% of the AR is due to active
smoking, therefore eliminating smoking among young and
children, every seventh case of AR could be prevented.
➢ Reduction of smoking remains the easiest and one of the most
concrete ways of practical asthma prevention.
➢ Studies have shown that maternal smoking during pregnancy
increases the risk for wheezing in childhood or asthma among
offspring during early childhood [19], in preschool-age children,
in adolescents, and in adults.
➢ Conclusion: encourage women of childbearing age and parents
having children to permanently cease smoking in order to
decrease AR and asthma risk of offspring.
70
Curr Treat Options Allergy (2018) 5:347–355
Smoking
Allergen avoidance as
prevention of airway allergy
➢ It is not clear whether airway allergy can be prevented by
allergen avoidance in families having risk for allergic diseases.
➢ Most studies aiming to reduce risk of asthma or allergy
through controlling environmental exposure to allergens are
inconsistent and have failed.
➢ The Isle of Wight study examined the effect of diets and
extensive measures to reduce exposure to house dust mite
(HDM). This study with a relatively small number of children
(n = 120) considered at high risk for allergic disorders is the
only trial which has shown reduction of mite sensitization and
asthma persisting until the age of 18 years.
➢ The much larger and more comprehensive Manchester study
reported an opposite effect on mite sensitization. 71
Curr Treat Options Allergy (2018) 5:347–355
➢ An impaired lung function was shown to develop on
children with high exposure to indoor allergens early
in life compared to children without sensitization.
➢ High amount of viral upper respiratory tract
infections in the first years of life may reduce the
onset of asthma later in life.
➢ It is clear that if an anaphylaxis has happened, then
avoidance is recommendable. Also, in secondary
prevention, avoidance seems to have a role.
72
Curr Treat Options Allergy (2018) 5:347–355
Allergen avoidance as
prevention of airway allergy
Inhaled indoor factors
➢ HDM has been the most studied of indoor air particles in
association with AR prevention.
➢ A Cochrane review was conducted in 2010, in which
seven reports concluded that HDM load can be reduced
with combination of acaricides and bedroom
environmental control programs. Reduction of AR
symptoms is poorly assessed in these reports, and more
specific studies are in request.
➢ Also, other factors as excessive moisture and volatile
organic compounds may play a role in airway allergy, but
taken together, controversial knowledge exists of the
effect of indoor particles to development of AR or
asthma.
73
Curr Treat Options Allergy (2018) 5:347–355
Outdoor environment factors
➢ Climate change and air pollution is one of the main reasons for
increase of allergic diseases. Especially, sulfur dioxide (SO2) is
shown to increase AR.
➢ In a cross-sectional questionnaire study, the authors concluded
that increase in the levels of SO2 increased the prevalence in AR
in Taiwanese school children.
➢ Also, exposure to traffic-related pollutant during pregnancy is
shown to increase the incidence of AR, as well as asthma and
eczema.
➢ Exposure to extreme heat has speculated to increase the
incidence of hay fever.
➢ Taken together, evidence exists that outdoor air pollution is
associated with airway allergy.
74
Curr Treat Options Allergy (2018) 5:347–355
Outdoor environment factors
➢ Several studies reported nearly 20 years ago that children grown
up in farm environment develop less asthma and allergies. This
effect is now contributed to contact with farm animals and their
microbes.
➢ The most recent studies from Amish and Hutterite populations
demonstrated that Amish children have much lower prevalence
of asthma than Hutterite children, despite the similarities in
ancestry and most lifestyle factors associated with asthma risk.
➢ At the moment, the data suggest that airborne substances likely
derived from animals and their microbes shape innate immune
pathways to finally produce protection from asthma.
➢ Several trials are now underway to examine whether for example
bacterial lysates could prevent development of asthma.
75
Vit D and obesity
➢ In a recent systematic review, the role of vitamin D in
primary prevention of allergic diseases was assessed
in four populations: pregnant and breastfeeding
mothers, infants, and older children. No clear
association between D vitamin and prevention of
airway allergy was found.
➢ There is lacking knowledge of the association
between obesity and AR.
➢ In a Chinese survey study (n = 4132), the prevalence
of allergic rhinitis and atopic dermatitis was higher
among obese children compared to children with
normal weight . 76
Perinatal dietary factors
➢ During the breastfeeding-period and first months of life,
nutrition of the baby is regarded as a major factor in
development of allergic diseases.
➢ There is not enough evidence on AR with dietary
consumption of the mom during the pregnancy or the
breastfeeding period.
➢ It is shown that if milking is not sufficient, highly
hydrolyzed formulas of cow milk decrease the incidence
of atopic eczema, but not asthma or AR.
➢ Polyunsaturated fatty acids (omega-3- and 6) were
tested in a randomized controlled trial in Australia and
no significant difference on allergic disease onset was
found between the study groups. 77
Perinatal dietary factors
➢ Numerous follow-up cohorts have addressed the
significance of breastfeeding on development of
asthma. The results have been often inconsistent and
the studies are often confounded by selection bias and
reverse causality.
➢ Even several meta-analysis studies done over the years
have not been able to solve the dilemmas and do not
demonstrate a consistent protection from asthma.
➢ It is, however, obvious that breastfeeding should be
recommended in all guidelines for many other health
benefits.
78
Maternal nutrition
➢ The nutrition of mothers during pregnancy: dietary patterns
and selective supplementation as well as levels of iron,
vitamin D, folic acid, and other nutrients may have protective
as well as adverse effects on the evolution of atopic diseases
in the offspring.
➢ However, only one published trial on nutritional intervention
of mothers has been able to show a clear decrease in asthma
risk.
➢ In a Danish study, pregnant mothers received fish oil or
placebo and their offsprings were followed for 3 years. The
risk of the children’s persistent wheeze and infections of the
lower respiratory tract infections was reduced by
approximately one third.
79
Conclusions
➢ Current knowledge of primary prevention of allergic
airway diseases is limited, except for smoking
cessation.
➢ Childhood AR and asthma risk are increased by
exposure to smoking. Hence, asthma and AR
offspring could be reduced and airway health could
be improved by encouraging parents to permanently
cease smoking.
➢ There is limited or controversial knowledge of other
environmental factors and their effect on airway
allergies
80
Curr Treat Options Allergy (2018) 5:347–355
Future needs
➢ Western urbanization and lifestyle changes are claimed
to be the main reason for the increase of airway
allergy.
➢ There is a global need of prevention of the current
epidemics of chronic allergic respiratory diseases.
Studies on prediction and prevention of allergic
diseases are needed.
➢ Programs of better education and successes of
children and adults in the case of the prevalence and
burden of allergic airway diseases are needed, such as
allergy programs.
➢ This would increase airway health and also general
health and wellbeing. 81
Curr Treat Options Allergy (2018) 5:347–355
1090904- 益生菌在兒童過敏疾病預防所扮演的角色

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