空氣污染與孩童呼吸道健康效應研究

Abstract

前言：空氣汙染暴露為重要的環境議題，而真菌孢子為環境中主要過敏原。人體暴露到空氣汙染與真菌孢子等吸入性過敏原所可能造成之呼吸道健康影響有進行研究加以探討的必要。本研究透過問卷調查，瞭解過敏性呼吸道疾病的季節性發作特性及其可能之個人及環境危害因子，並評估疾病季節性對生活品質的影響。研究亦執行長期追蹤以評估環境空氣汙染與吸入性過敏原暴露對學齡孩童肺功能與鼻腔發炎的影響。 方法：研究以國小及國中學童為對象，經受訪學校及學生父母同意於2007年9月進行學齡孩童呼吸系統健康問卷調查，研究對象就所述問卷可區分為患有氣喘組、患有過敏性鼻炎及健康對照組。患有過敏性呼吸道疾病之學童以主成分分析來區分其疾病的季節發作型態；使用多變項邏輯斯迴歸分析造成過敏性疾病季節性發作的個人及環境危害因子；另比較疾病在不同季節性發作型態下其疾病嚴重度與疾病相關生活品質的分布變異。研究後續於2007年10月至2009年11月間，每月到校追蹤學童肺功能表現與鼻腔發炎情形。研究期間由環保署新莊空氣品質監測站及超級測站提供主要空氣汙染物與粒狀空氣汙染物的每日連續監測值；每月亦於學童肺功能及鼻腔發炎檢測當週進行為期一周的真菌孢子採集，提供每日真菌孢子暴露總量。使用混合效果模式（Mixed-effects model）評估空氣汙染及真菌孢子的暴露和肺功能及鼻腔發炎的相關性。本研究經台大醫院研究倫理委員會審查通過。 結果：計有4221名學童完成問卷調查，其中133位患有氣喘、1059位患有過敏性鼻炎（未患氣喘）、另2745位為健康對照。氣喘個案可區分為夏季發作、秋季發作、春冬發作及全年發作四組；過敏性鼻炎個案則可區分為春季發作、夏秋發作、冬季發作及全年發作四組。年齡、性別、父母教育程度、母親懷孕期間二手菸暴露、母乳哺育及家中牆壁霉斑可發現會造成過敏性呼吸道疾病的不同季節性發作型態。全年發作及春季發作過敏性呼吸道疾病的個案其疾病嚴重度較高，疾病相關生活品質亦較差。 研究進一步邀請33位患有氣喘、30位患有過敏性鼻炎及37位健康對照學童進行10次之到校呼吸道健康檢測。肺功能檢測分析結果發現檢測前一日之細懸浮微粒（particulate matter with an aerodynamic diameter of 2.5 μm or less, PM2.5）暴露與用力呼氣肺活量（forced vital capacity, FVC）有負相關（下降0.16 L，95%信賴區間為-0.23至-0.08 L）。前一日之真菌孢子暴露與FVC（下降0.12 L，95%信賴區間為-0.21至-0.03 L）及用力呼氣第一秒容積（forced expiratory volume in 1 second, FEV1）（下降0.10 L，95%信賴區間為-0.17至-0.02 L）皆呈現負相關。前一日之臭氧暴露則與在25%、50%、75%的FVC處時的瞬間用力吐氣流量（forced expiratory flow at 25%, 50%, and 75% of forced vital capacity, FEF25%, FEF50%, and FEF75%）及25%至50%的FVC間的平均用力吐氣流量（average expiratory flow over the middle half of forced vital capacity, FEF25-75%）呈現負相關（FEF25%下降0.39 L/s，95%信賴區間為-0.51至-0.27 L/s；FEF50%下降0.32 L/s，95%信賴區間為-0.41至-0.24 L/s；FEF75%下降0.21 L/s，95%信賴區間為-0.26至-0.15 L/s；FEF25-75%下降0.30 L/s，95%信賴區間為-0.38至-0.22 L/s）。鼻腔發炎分析結果則發現檢測當日之PM2.5暴露與總發炎細胞比例、嗜中性血白球細胞比例及細胞白介素第八因子濃度（Interleukin-8, IL-8）皆成正相關（總發炎細胞比例上升3.51%，95%信賴區間為0.78至6.23%；嗜中性血白球細胞比例上升3.45%，95%信賴區間為0.89至6.01%；IL-8上升29.98 pg/ml，95%信賴區間為3.26至56.69 pg/ml）。 結論：綜合問卷調查結果可知過敏性呼吸道疾病確實具不同季節發作型態，造成疾病發作的個人及環境危害因子也有所不同。針對不同季節發作特性來主動避免相關過敏原及進行症狀治療將可有效提升患有過敏性呼吸道疾病學童的生活品質。長期追蹤研究世代則可發現PM2.5暴露會造成鼻腔發炎及影響肺部容積；真菌孢子暴露亦會對肺部容積造成不良影響；臭氧暴露則對細小呼吸道具有不良效應。藉本研究結果可知有必要審視現有環境空氣污染物的標準以避免暴露對人體所造成之潛在危害。

Background and Objective: It is important to know whether adverse respiratory response can be detected and associated with levels of air pollutants that expose to children. We conducted questionnaire and longitudinal follow-up study to examine whether respiratory atopic disease-related risk factors and quality of life (QOL) were different among children with respiratory atopic disease by seasonal patterns. We also investigated whether exposure to air pollutants and fungal spores affected children’ lung function and inflammatory cells and mediators from nasal lavage. Method: Study participants were elementary and middle-school students in New Taipei City, Taiwan. A structured respiratory health questionnaire was administered to each participant in September 2007, followed by monthly measurements of lung function and nasal inflammation from October 2007 to November 2009. Using moving average and principal component analysis, children with respiratory atopic disease were grouped by attack seasons. The association between disease seasonality and personal and environmental factors on were assessed using logistic regression models. Disease severity and disease-related QOL were compared among seasons by the subtype of disease. Complete daily concentrations of air pollutants during the follow-up period were obtained from the Environmental Protection Administration monitoring station and Aerosol Supersite. Fungal spores were measured from Sunday to Saturday in the week of conducting lung-function measurements. Mixed-effects models were applied to examine whether air pollution and fungal spores were associated with lung function and nasal inflammatory cells and mediators, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow at 25%, 50%, and 75% of forced vital capacity (FEF25%, FEF50%, and FEF75%), average expiratory flow over the middle half of forced vital capacity (FEF25-75%), percentages of neutrophils, eosinophils, and monocytes in lavaged cells, and interleukin (IL)-8. The study was approved by the Institutional Review Board of the National Taiwan University Medical Center. Result: Among 4221 children with the completed questionnaire, 133, 1059, and 2745 children were divided into three groups: “ having current asthma”, “having current allergic rhinitis (AR) but not asthma”, and “healthy control”, respectively. Four asthma (perennial, summer, fall, and spring/winter) and four AR subtypes (perennial, spring, summer/fall, and winter) were categorized. Age, gender, parental education, maternal passive smoking during pregnancy, breast feeding, and mouldy walls were found to contribute differentially to different AR subtypes. Children suffering from perennial and winter AR were found to have more severe symptoms and significantly lower QOL score compared with other subtypes. In longitudinal follow-up, a total of 824 measurements from 100 participants over 10 months were obtained. The levels of particulate matter with an aerodynamic diameter of 2.5 μm or less (PM2.5) measured 1 day before the lung function tests were negatively associated with FVCs (β= -0.16 L, 95% Confidence intervals (CI)= -0.23, -0.08 L). The fungal spore levels were negatively associated with measures of both FVC (β= -0.12 L, 95% CI= -0.21, -0.03 L) and FEV1 (β= -0.10 L, 95% CI= -0.17, -0.02 L). Ozone (O3) levels were negatively associated with measures of FEF25% (β= -0.39 L/s, 95% CI= -0.51, -0.27 L/s), FEF50% (β= -0.32 L/s, 95% CI= -0.41, -0.24 L/s), FEF75% (β= -0.21 L/s, 95% CI= -0.26, -0.15 L/s), and FEF25-75% (β= -0.30 L/s, 95% CI= -0.38, -0.22 L/s). In addition, the levels of PM2.5 were found associated with percentages of neutrophils (β= 3.45%, 95% CI= 0.89, 6.01%) and level of IL-8 (β= 29.98 pg/mL, 95% CI= 3.26, 56.69) in the nasal lavage on the day of exposure. Conclusion: Specific personal and environmental risk factors could contribute to different seasonal subtypes of respiratory atopic disease. Active allergen avoidance and symptomatic treatment should be the focus of management aiming to improve the QOL among children with perennial and winter subtype. In a longitudinal schoolchildren cohort, exposure to PM2.5 might induce nasal inflammation. Exposure to PM2.5 and fungal spores might cause adverse effects on the vital capacity of schoolchildren. Decrement of small airway function was associated with exposure to O3. Our results emphasize the continued need to examine the existing standards of ambient air pollutants by documenting potential human adverse effects.