蔬菜、水果、魚油、益生菌濃縮物添加對氣喘學童症狀改善效果之評估

Abstract

國際上與台灣學界研究均指出氣喘盛行率逐年上升，此現象可能與基因、環境及飲食因子之間的交互作用有關。而根據流行病學研究指出蔬菜、水果攝取量，或蔬果中富含多種的維生素與氣喘發生呈逆相關，且與肺功能成正相關，但單一營養素的補充卻對氣喘症狀改善並無明顯成效；又許多臨床試驗顯示魚油的補充可改善氣喘病患的肺功能或減少發炎介質的產生；亦有研究指出益生菌可能具有調節免疫力的功效。由於飲食中多種化合物的潛在交互作用極為重要，近年來，飲食型態觀察性研究或以健康飲食型態介入的研究受到重視，著名的DASH飲食（Dietary Approaches to Stop Hypertension diet）結合多種保護因子而能有效得降低血壓是一極好的例子。因此，本研究的目的為以食物導向（food-base）的設計原則，結合執行容易的概念，給予國小學童有益氣喘食物的濃縮物（蔬果濃縮物、魚油及益生菌）的補充，以實證方式探討對氣喘病患的影響。此試驗以隨機雙盲實驗設計進行，以192 位10-12 歲氣喘學童為研究對象，分別給予蔬果濃縮膠囊、益生菌膠囊及魚油軟膠囊的補充是為補充劑組，或安慰劑補充是為安慰劑組，實驗為期16週。研究在基線、第8週及第16週進行飲食頻率問卷、肺功能、藥物記錄問卷、氣喘生活品質問卷（PAQLQ score）、常規血液生化值、血漿總抗氧化力、紅血球細胞膜之脂肪酸組成、尿液中isoprostances、嗜伊紅性白血球百分比、IgE與eotaxin評估分析；每4週進行氣喘控制問卷評估（CACT score）；每週完成氣喘週誌的紀錄；每日進行尖峰呼氣流速檢測及每日記錄本。研究結果顯示在介入16週後，補充劑組的肺功能指標獲得改善，強制呼氣之全肺活量（FVC）及一秒吐氣量（FEV1）分別增加178ml及107ml，顯著高於安慰劑組的91ml與40ml（P = 0.01），且支氣管擴張劑（P < 0.01）、吸入性類固醇（P < 0.001）及抗組織胺用藥（P < 0.05）的使用人數，吸入性類固醇（P = 0.01）及抗組織胺用藥的使用次數（P < 0.05）均顯著低於安慰劑組，但氣喘症狀評估問卷分數、氣喘生活品質問卷及週誌記錄之氣喘症狀則兩組之間無顯著差異。在血液生化值部分，發現補充劑組之紅血球細胞膜上之EPA與DHA含量比例顯著高於安慰劑組（P < 0.05），∑n-6/∑n-3不飽和脂肪酸比值、及花生四烯酸與EP比值則顯著低於安慰劑組（P < 0.05），但其他的生化檢測值則未見兩組之間有顯著差異。未來尚須進行單獨給予三種補充劑的研究來確定可能的作用機轉，及其所扮演的角色。但此以食物為導向的複合食物濃縮劑補充模式可有效的改善氣喘學童的肺功能，減少急救用藥（短效支氣管擴張劑）及常規氣喘控制用藥（吸入性類固醇）的使用，對氣喘控制有助益，可作為臨床上在常規的藥物醫療之外的另一非藥物治療的參考依據，由飲食修正幫助氣喘患者做好良好的氣喘控制。

The prevalence of asthma is increasing in Taiwan and worldwide. This could be related to interactions among dietary factors, environment and genetic factors. Ample evidence from cross-sectional and case-control observational studies suggested that consumption levels of fruits, vegetables, and potentially vitamins A, C, E from foods are negatively associated with asthma risk, and positively with lung function. However, single nutrient supplementation did not consistenly improved asthma symptoms. Some studies had shown probiotics could modulate human immunity. A number of trials have suggested that fish oil supplement improves lung function and reduces inflammatory mediator. The potential interactions and synergism among multiple components in foods have been neglected in the past. Recently, observational studies on dietary pattern analyses or intervention trials modifying the overall dietary composition have caught tremendous scientific attentions. Therefore, we designed an intervention trial with food-based principle to investigate the joint effect of several beneficial dietary components on asthma symptoms and medications. For practicality and efficiency, concentrates of vegetable plus fruit, fish oil, and probiotics were provided as supplements to asthmatic children. Total of 192 asthmatic children aged 10-12 yrs were recruited into a 16-week parallel, double-blind, randomized, and placebo-controlled trial. During the intervention, supplement group received multiple capsules of vegetable plus fruit, fish oil, and probiotics; while control group received placebos. Food frequency questionnaire, pulmonary functions (FVC, FEV1), medicine usage, pediatric asthma quality of life questionnaire score (PAQLQ score), plasma total antioxidant capacity, RBC fatty acid composition, urinary isoprostances, eosinophil, IgE and eotaxin were evaluated at baseline and after 8 and 16 weeks of intervention. Children asthma control test (CACT ) score was evaluated wvwry 4 week and weekly diary was kept. Peak expiratory flow rate was measured every day. Supplement group had significantly greater improvement in pulmonary function than placebo group (FVC: 178 ml vs. 91 ml, P = 0.01 and FEV1: 107 ml vs. 40 ml, P = 0.01), and the proportion of children using bronchodilator (P < 0.01), inhaled steroids (P < 0.001) and antihistamine (P < 0.05) over 16 weeks were also significantly decreased in the supplement group. CACT score, PAQLQ score and asthma symptoms were not significantly different between the two groups. Compared to controls, the supplement group has higher proportion of eicosapentaenoic acid (EPA) and docosahexaenoic acid (P < 0.05); but lower ratio of ∑n-6/∑n-3 polyunsaturated fatty acid (P < 0.05), and arachidonic acid and EPA (P < 0.05). Plasma total antioxidant capacity, urinary isoprostances, eosinophil, IgE and eotaxin were not significantly different between two groups. Future, clinical trials should be carried out to understand the specific roles of vegetable and fruit, fish oil, and probiotics. Our study results provide a direction for dietary modification in asthma children.