氧化壓力在慢性阻塞性肺病(COPD)的疾病發展上扮演重要的角色。越來越多的證據顯示，攝取較多的抗氧化營養素，如維生素C、維生素E、維生素A及各種類胡蘿蔔素可維持較好的肺功能，但在台灣COPD病人的情形是否如此知道的不多。因此本研究比較COPD病患與健康人維生素A及各種類胡蘿蔔素的飲食攝取量及血漿濃度，並且探討血漿中抗氧化營養素與白血球內生性及H2O2誘發的DNA傷害之相關性。此外，我們也研究COPD病患是否會因避免攝取“冷性”蔬果的飲食習慣，進而影響此類營養素的攝取。我們招募的受試者中有32名COPD病患(年齡≧50歲)，其FEV1％＜80％，FEV1/FVC＜0.7，另有43名(年齡≧50歲)肺功能正常的健康人作為對照組。首先利用24小時回憶法及食物頻率問卷，評估受試者膳食攝取的營養素量及攝食蔬果的習慣。我們同時收集受試者血液樣本，分析血漿維生素A、α-胡蘿蔔素、β-胡蘿蔔素、葉黃素、茄紅素的濃度。結果顯示，除了α-胡蘿蔔素外，COPD病患維生素A、β-胡蘿蔔素、葉黃素、茄紅素及總類胡蘿蔔素(α-胡蘿蔔素、β-胡蘿蔔素、葉黃素、茄紅素的總和)的膳食攝取量或加入補充劑後總攝取量的平均值顯著較健康人低。另一方面，除了葉黃素和茄紅素外，COPD病患血漿的維生素A、α-胡蘿蔔素、β-胡蘿蔔素及總類胡蘿蔔素的濃度比健康人低。此外，根據我們之前的研究顯示，COPD病人的白血球內生性及由H2O2誘發DNA傷害，顯著高於健康人，因此，我們進一步研究這些營養素與白血球DNA傷害的相關性。在所有受試者血漿中total carotenoids與H2O2誘發DNA傷害呈現顯著負相關連性(β= -5.343, p = 0.043)，但在調整干擾因子後，則無統計上的顯著相關。此外，COPD病人總蔬果攝取量顯著低於健康人，尤其是冷性蔬果。在病人及健康人組中發現膳食中維生素A、β-carotene、lutein、total carotenoids的攝取量與蔬果總攝取量呈顯著正相關性，在調整干擾因子後，COPD組維生素A的攝取量與冷性蔬果攝取量接近顯著正相關性。以羅吉斯回歸分析危險因子發現，總蔬果攝取量，可以減少COPD的罹患率，但個別分析抗氧化營養素則無此結果。總合以上，本研究結果顯示，在台灣COPD病患維生素A及多種類胡蘿蔔素膳食攝取量和血漿濃度比健康人低，病人攝取“冷性”蔬果的頻率與總蔬果的攝取量成正相關，而總蔬果攝取量則會影響許多抗氧化營養素的攝取量。

Oxidative stress is thought to play a key role in the pathogenesis of COPD. Increasing evidence suggested that individuals with a high intake of antioxidative nutrients, such as vitamins C, E, A, and carotenoids tend to maintain better lung function. However, little has been known about the intakes status of these nutrients in COPD patients in Taiwan. Therefore, this case-controlled study elucidated the differences in plasma and intake levels of vitamin A and various carotenoids as well as the association of the plasma concentration of these nutrients and endogenous and H2O2-induced white blood cells (WBC) DNA damage. In addition, we investigated whether the dietary habits of avoiding “cooling” vegetables and fruits affect the intake of these nutrients. Thirty-two COPD patients, who satisfied the criteria with forced expiratory volume in 1 second (FEV1) % predicted less than 80% and a ratio of FEV1 to forced vital capacity (FVC) less than 0.7, were recruited in this study; whereas, forty-three healthy people, who were ≧ 50 years old and with normal lung function, were recruited as control group. We compared the dietary habits and nutrient intakes using a food frequency questionnaire and a 24-h food recall. Blood samples were collected to measure the level of vitamin A, α-carotene, β-carotene, lutein and lycopene. The results showed that the mean intakes of vitamin A, individual carotenoid except for α-carotene or total carotenoids in COPD patients were significantly lower than those of healthy people. On the other hand, the mean plasma concentrations of vitamin A, individual carotenoid except for lutein and lycopene, or total carotenoids were also significantly lower in COPD patients than those of healthy individuals. Furthermore, we investigated the associations between these nutrients with DNA damage in white blood cells (WBC), because the previous study in our lab showed that the endogenous and H2O2-induced WBC DNA damage of COPD patients were significantly higher than those of healthy people. Pooling the data of the two groups showed that total carotenoids concentration was significantly inversely correlated with the H2O2-induced WBC DNA damage (β= -5.343, p=0.043).However, after adjusted for confounders, the inverse association was not statistically significant. In addition, the sum vegetable and fruit intakes frequency of COPD patients was significantly lower than that of healthy people, especially in cooling items. In both COPD and healthy groups, the total consumption of vegetables and fruits was significantly positively associated with the intake of dietary vitamin A,β-carotene, lutein, and total carotenoids; whereas the consumption of cooling items were positively associated, with a borderline significance, with the intake of vitamin A in both groups after adjustment for confounders. After adjusting for confounders, the total consumption vegetables and fruits, rather than each individual nutrient, reduced the OR for COPD. In summary, COPD patients in Taiwan have lower levels of plasma and of intake of vitamin A and several carotenoids than healthy people. The consumption of cooling foods was positively associated with the total consumption of vegetables and fruits which affect the intake of several antioxidative nutrients.

目錄 ......................................... 2
縮寫表 …………………………………………………. 4
中文摘要 ………………………………………………. 5
英文摘要 ………………………………………………. 7
一、 前言 …………………………………………. 9
1. 慢性阻塞性肺病 ……………………………. 9
2. 維生素A ………………………………………10
3. 類胡蘿蔔素 …………………………….....11
3.1 α-carotene ……………………………....12
3.2 β-carotene ……………………………....13
3.3 Lutein ……………………………………..14
3.4 Lycopene ……………………………………15
4. 食物性質 …………………………………..16
5. 研究動機 …………………………………..17
6. 試驗架構 …………………………………..19
二、 方法 ………………………………………….20
1. 研究設計 …………………………………..20
1.1.研究對象 ………………………………………...20
1.2.飲食問卷設計 …………………………………...20
1.2.1. 24小時飲食回憶法 …………………………..20
1.2.2. 蔬果飲食頻率問卷 …………………………..22
1.3.試驗期間 ………………………………………….22
2. 材料 ………………………………………..22
2.1.儀器 …………………………………...........22
2.2.藥品 ……………………………………………...23
3. Retinol和carotenoids分析方法 ………..23
4. 統計分析 …………………………………..24
三、 結果 ……………………………………....25
1. 受試者基本資料 …………………………..25
2. 每日維生素A、α-胡蘿蔔素、β-胡蘿蔔素、葉黃素、
茄紅素及總類胡蘿蔔素的攝取 ……………………...25
3. 血漿中維生素A、α-胡蘿蔔素、β-胡蘿蔔素、葉黃素、
茄紅素及總類胡蘿蔔素的濃度 ……………………...26
4. 血漿中維生素A、α-胡蘿蔔素、β-胡蘿蔔素、葉黃素、
茄紅素及總類胡蘿蔔素濃度與DNA傷害的複回
歸分析 ........................................27
5. 食物的選擇 ……………….…...........28
6. COPD危險因子分析 ……………….….....30
四、 討論 …………………………………………31
五、 圖表 ………………………………….…...35
六、 參考文獻 ………………………………...…61
七、 附錄 ………………………………….…...73

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