- 學位論文
貧血對兒童社區型肺炎的影響
The Association of Anemia with the Clinical Outcomes of Community-Acquired Pneumonia in Children
摘要
背景：貧血與感染症的關係一直是個重要的公共衛生議題。在開發中國家，根據WHO 2019年的調查，有六成的兒童有貧血的情形，而且缺鐵性貧血的兒童有較高的比例得到肺炎或其他下呼吸道感染。在已開發國家，缺鐵性貧血常發生在嬰兒、學齡前兒童和青春期的女生；一篇以色列的世代研究發現，貧血的兒童容易反覆發生中耳炎，而且血紅素越低，復發的次數越多。2020年台灣的研究發現有沙門桿菌(nontyphoidal Salmonella)菌血症的病童比起單純沙門桿菌腸炎的病童，血紅素值比較低，也有較高比例的小球性貧血(microcytic anemia)和地中海型貧血帶因合併貧血(thalassemia trait with anemia)。因此想探討：貧血，尤其是兒童常見的缺鐵性貧血和地中海型貧血帶因，會不會造成兒童容易得到社區型肺炎，或是有較高的嚴重度。 方法：這篇研究使用「小兒呼吸道感染決策輔助系統計畫案」之臺大醫院醫療整合資料庫，做回溯性分析研究。研究對象是年齡6個月以上至17歲兒童，自2010年到2019年，在臺大醫院診斷為社區型肺炎並且住院治療的病人；社區型肺炎定義為符合：1) 入院時有呼吸道感染的症狀加上入院48小時內理學檢查紀錄有肺炎的呼吸音(rales or crackles)或是入院48小時內胸部X光報告有肺炎相關徵象，2) 出院ICD診斷碼有肺炎相關診斷碼。資料收集病人入院24小時內的入院病歷摘要、全血細胞計數(hemogram)、C反應蛋白[C-reactive protein level (CRP)]、48小時內的胸部X光報告、住院過程的醫療處置代碼和病原菌檢查報告、出院時的ICD診斷碼；用不同年齡層的血紅素值[hemoglobin (Hb)]把病人分成有貧血和沒貧血兩組，再用不同年齡層的平均紅血球容積[mean corpuscular volume (MCV)]和Mentzer index(MCV/RBC)把貧血組分成缺鐵性貧血、地中海型貧血帶因合併貧血和正球性貧血(normocytic anemia)，沒貧血組分成地中海型貧血帶因(thalassemia trait without anemia)和對照組；嚴重臨床結果包含：加護病房照護、氣管插管、膿胸、使用升壓劑、葉克膜支持和死亡。分析有貧血和沒貧血組，以及不同貧血組有嚴重臨床結果比例的差異；接著使用多變項分析，校正年齡、生命徵象[vital signs (tachypnea, hypoxemia, hypotension)]、WBC、CRP、胸部X光有實質化(consolidation)或是有肋膜積水(pleural effusion)這些在過去文獻和臨床實務上常用來預測病人嚴重度的因子，來檢視貧血是否能獨立預測肺炎的嚴重度。 結果：研究收案3,601人，年齡中位數2.9歲(四分位距1.7–4.6歲)，男女比1.09:1；貧血的盛行率是11.6% (418/3601)，缺鐵性貧血、地中海型貧血帶因合併貧血、地中海型貧血帶因和正球性貧血的盛行率是1.6%、2.5%、3.8%和7.4%。貧血病人比起沒貧血的病人，有較高的加護病房照護比率(16.8% vs. 3.6%; P <.001)、氣管插管比率(11.0% vs. 1.3%; P <.001)、膿胸比率(8.6% vs. 0.6%; P <.001)；單變項分析有顯著的因子：年齡、低血氧(hypoxemia)、低血壓(hypotension)、WBC、CRP、胸部X光有實質化或肋膜積水放入逐步羅吉斯回歸模型(stepwise logistic regression models)分析，顯示有貧血的病人需要加護病房照顧、需要氣管插管、得到膿胸的機會是沒貧血病人的3倍(adjusted OR, 3.00; 95% CI, 2.03–4.42 )、3.7倍(adjusted OR, 3.79; 95% CI, 2.17–6.63)、4.7倍(adjusted OR, 4.72, 95% CI, 2.30–9.69)；其中，這些嚴重結果跟缺鐵性貧血和正球性貧血與有相關聯，與地中海型貧血帶因沒有相關。 結論：除了WBC和CRP外，貧血也可以做為兒童社區型肺炎嚴重度的生物指標，尤其是有缺鐵性貧血或是正球性貧血的病人，容易有較高的嚴重度和併發症，需要我們小心監測臨床進程和治療。
並列摘要
Background According to the World Health Organization (WHO) survey, 60% of children in the developing countries were anemic, and children with iron-deficiency anemia (IDA) had higher risks of getting lower respiratory tract infections. In developed countries, IDA is frequently found in high-risk groups, such as infants, toddlers, and adolescent females. Research in Israel shows that children with IDA were prone to have recurrent otitis media. Another research in Taiwan found that patients with bacteremia had lower Hb level and higher proportion of thalassemia trait with anemia than patients with isolated Salmonella enterocolitis. Accordingly, the aim of this study was to investigate the association of anemia (especially IDA and thalassemia trait) with the clinical outcomes of pediatric community-acquired pneumonia (CAP). Methods This retrospective cohort study was conducted from 2010 through 2019, in the National Taiwan University Hospital. Inpatients aged 6 months to 17 years who met the criteria for CAP: 1) symptoms of respiratory tract infection at admission plus rales or crackles presented within 48 hours of admission or abnormal chest X-ray findings related to pneumonia presented within 48 hours of admission and 2) diagnosed pneumonia at discharge were enrolled. Patients with major underlying diseases were excluded. Each subject’s hemogram data within 24 hours of admission was collected. Anemia was defined by age-specific hemoglobin level and further classified into IDA, thalassemia trait with anemia and normocytic anemia, according to the age-specific mean corpuscular volume and Mentzer index. Nonanemic patients were further classified into thalassemia trait without anemia and nonanemic control. The primary outcome measures were rates of requiring intensive care, requiring endotracheal intubation, empyema, use of inotropic agents, extracorporeal membrane oxygenation, and mortality. We compared these rates between anemic and nonanemic patients, as well as among different types of anemia. The associations of anemia with these adverse outcomes were assessed by multivariable analysis, adjusted with factors associated with clinical outcomes. Results In this study of 3,601 cases [median age (interquartile range), 2.9 years (1.7–4.6 years); male to female ratio, 1.09], the prevalence of anemia was 11.6% (418/3601). Anemic cases had higher rates of intensive care (16.8% vs. 3.6%; P <.001), endotracheal intubation (11.0% vs. 1.3%; P <.001), and empyema (8.6% vs. 0.6%; P <.001) than nonanemic cases. Multivariable analysis showed that anemia was independently associated with intensive care [adjusted odds ratio (OR), 3.00; 95% CI, 2.03–4.42], endotracheal intubation (adjusted OR, 3.79; 95% CI, 2.17–6.63), and empyema (adjusted OR, 4.72; 95% CI, 2.30–9.69). IDA and normocytic anemia were associated with these adverse outcomes but not with anemia due to thalassemia trait. Conclusion Anemia is a biomarker associated with poor outcomes in pediatric CAP, and patients with IDA or normocytic anemia should be carefully monitored and managed since they may have higher disease severity.