流行病學研究顯示室內二手菸暴露與氣喘具有明顯的關連性，但是香菸暴露對於兒童氣喘發生的致病機轉，至今仍不清楚。香菸成分中包含著許多反應性氧化產物 (reactive oxygen species [ROS])，這些反應性氧化產物會引發細胞激素的增加，造成支氣管上皮細胞發炎，導致氣喘；此外，抗氧化酵素超氧化物歧解 (superoxide dismutase [SOD]) 也已被證實與氣喘有關。 MnSOD 基因在 mitochondrial targeting sequence 序列上可能產生 T→C 的變異，因而改變酵素活性；進一步地影響對於 ROS 所產生之細胞氧化傷害的清除能力。因此，具有易感受性 MnSOD 基因型之兒童，其氣喘發生之危險可能較高。脂多醣體 (lipopolysaccharide [LPS]) 在室內環境中無所不在；當吸入 LPS 時，會刺激呼吸道產生發炎反應；CD14 是 LPS 的接受器，而氣喘及 CD14/-260 啟動者基因多形性之關係，目前仍不清楚。本計畫嘗試來瞭解具有 MnSOD 易感受性基因型的兒童，暴露於室內二手菸的狀態下，其氣喘發生及相關效應指標之間的關係；亦將針 對 CD14/-260 基因型跟兒童氣喘及其效應指標的關係來進行探討。本研究選取 68 名氣喘兒童為病例組，以及 200 名健康兒童為對照。流行病學的資料是經由面對面的問卷訪視所收集；室內 二手菸累積暴露量是以每天平均暴露的香菸支數計算，亦即父母親於兒童在家時，抽菸支數的總和。 MnSOD 及 CD14/-260 基因型則是以聚合鏈鎖反應 (polymerase chain reaction [PCR]) 進行判定。我們發現父母親有抽菸的習慣中，以每天平均暴露香菸支數大於 10 支以上並且為 MnSOD Val/Val 基因型者為參考族群 (OR = 1.0)，而每天平均暴露香菸支數大於 10 支以上並且 為 MnSOD Ala/Ala 或 Ala/Val 基因型者，被觀察到具有 2.6 倍的兒童氣喘發生之危險 (95% C.I. = 0.6-12.2)。因此，MnSOD 易感受性基因型對於室內二手菸暴露所導致的兒童氣喘發生，可能具有修飾作用。
Epidemiological studies revealed that household smoking exposure was obviously associated with asthma although, the mechanism of cigarette smoke-induced childhood asthma remains indistinct. Cigarette smoke contains a variety of reactive oxygen species (ROS), which may increase the level of cytokines, cause cellular inflammation in bronchial epithelium cells, and then promote the development of asthma. Additionally, antioxidant enzyme superoxide dismutase (SOD) has been demonstrated to be associated with asthma. A possible transition of T---C in the mitochondrial targeting sequence of MnSOD gene may alter enzyme expression, and thus influencing the scavenging capacity for ROS-caused cellular oxidative injury. Therefore, children with susceptible MnSOD genotype may have a higher risk of asthma development. Lipopolysaccharide [LPS] is abundant in our indoor environments. Cellular inflammation in respiratory system may be stimulated when LPS was inhaled into body. CD14 is a receptor that has specificity for LPS, however, the relationship between asthma and CD14/-260 promotor polymorphism remains unclear. In this study, we try to understand the relationship of asthma development and associated indicators among children with household smoking exposure and susceptible MnSOD genotype. The relationship of CD14/-260 genotype and childhood asthma, and associated indicators were also investigated. Study subjects comprised 68 children with asthma and 200 healthy controls. Epidemiological information was obtained by an interviewer-administered questionnaire. Cumulative indoor passive smoking for children was defined as the number of cigarettes smoked daily for household members multiplied by the number of years of lived together until asthma being confirmed. The genotypes of MnSOD and CD14/-260 were identified by the polymerase chain reaction (PCR). We found when children with indoor passive smoking greater than ten cigarettes/day and MnSOD Val/Val genotype was selected as reference group (odd ratio [OR] = 1.0), a 2.6-fold increased asthma risk was observed for those with indoor passive smoking greater than ten cigarettes/day and MnSOD Ala/Ala or Ala/Val genotype (95% confidence interval [CI] = 0.6-12.2). Therefore, MnSOD susceptible genotype could modify the development of childhood asthma elicited by indoor passive smoking.
