小儿甲型H1N1流感重症与危重症比较
摘要
目的：
研究小儿甲型H1N1流感重症与危重症的不同临床特点及患儿发展成为重症、危重症的相关因素,以指导预防和治疗。
方法：
1.一般资料
本研究收集了2009年10月1日至2010年01月15日期间我院确诊并收治入院的76例甲型H1N1流感患儿的临床资料,男46例,女30例,平均年龄3.29±2.90岁,0～1岁25例(32.9%),～3岁17例(22.4%),～5岁18例(23.7%),～16岁16例(21.1%)。参照卫生部《甲型H1N1流感诊疗方案第三版》诊断标准,将76例患儿分成两组：重症组60例,危重症组16例。
2.方法
设计统一的表格,在住院期间收集填写各项资料：患儿一般资料、生命体征和评分；血尿粪常规、血气分析、生化、体液免疫和细胞免疫等检查结果；各种药物的使用情况；使用呼吸机的患儿定时记录呼吸机参数和患儿呼吸循环指标。
动态胸部X线或CT检查,按两肺病变累及范围不同将胸片肺部病变程度划分为轻、中、重三度；按照病灶的形态、大小、分布以及肺纹理的改变,将其分为3种类型：实变型、间质浸润型和混合型。
通过咽拭子采集呼吸道分泌物标本,送苏州市疾病控制中心,采用RT-PCR进行甲型H1N1流感病毒RNA检测。
结果：
1.重症组平均年龄2.91±2.26岁,显著低于危重症组4.68±4.35岁(P<0.05),重症患儿3岁以下占60.0%,危重症患儿3岁以下占37.5%；住院时间重症组7.75±3.06 d显著短于危重症组19.6±7.72 d(P<0.05),重症组第3代小儿死亡危险评分(PRISMⅢ)低于危重症组(P<0.05),小儿危重病例评分(PCIS)高于危重症组(P<0.05)。
2.两组都以发热、咳嗽为主要症状,喘息在重症组发生率高于危重症组,吸气性凹陷、ARDS、抽搐、昏迷和胃肠道出血在危重症组发生率高于重症组。
3.重症组混合其他病原体感染率68.3%显著高于危重症组的37.5%(P<0.05),重症组混合细菌感染以肺炎链球菌为主,次之为流感嗜血杆菌和卡他莫拉菌；危重症组则为金黄色葡萄球菌为主。
4.重症组有31.6%并存基础疾病显著少于危重症组56.3%(P<0.05),重症组并存基础疾病以哮喘多见,危重症组以营养性缺铁性贫血多见,次之是脑性瘫痪和先天性心脏病。
5.重症组PaO2／FiO2(氧合指数)为307.18±55.73 mmHg,显著高于危重症组的187.50±73.62 mmHg(P<0.05),重症组的PA(血清前白蛋白)和A(白蛋白)显著高于危重症组(P<0.05),而CK(肌酸激酶)、AST(谷草转氨酶)、LDH(乳酸脱氢酶)、α-HBDH(α-羟丁酸)和CRP(C反应蛋白)显著低于危重症组(P<0.05)。
6.重症组与危重症组肺部病变X线分型均以实变型为主,分别占70.0%和81.3%,重症组1.7%合并肺气漏征群少于危重症组的31.3%(P<0.05),肺部病变X线分度重症组以轻度、中度为主,而危重症组则以中度、重度为主。
7.重症组的患儿预后均好转出院,无后遗症改变,而危重症组2例(12.5%)死亡,分别为8月和3岁；有3例(18.8%)出现肺部纤维化；2例(12.5%)出现脑萎缩；追踪重症组RT-PCR检测甲型H1N1核酸呈阳性时间3～14 d,平均6.96±3.01 d,危重症组为10～27 d,平均17.27±5.57 d,重症组显著短于危重症组(P<0.05)。
结论：
1.相对于甲型H1N1流感重症患儿,危重症患儿发病年龄较大,受损器官数目较多,更容易发生严重的低氧血症,甚至ARDS和MODS,更易出现死亡或者脑萎缩、肺纤维化等后遗症改变；
2.早期的PaO2／FiO2、CK等指标、影像学检查及PRISMⅢ、PCIS评分有助于临床医生对甲型H1N1流感患儿病情危重程度尽早作出正确判断；
3.警惕有缺铁性贫血、脑性瘫痪和先天性心脏病等基础疾病的患儿发展成为危重症;
4.在选择抗生素时要考虑到重症和危重症患儿混合感染细菌谱的异同。
Objectives:
To study different clinical characteristics and risk factors of severe and critical ill children with novel H1N1 influenza, then to guide prophylaxis and therapy.
Methods:
1.General data
Seventy-six children with novel H1N1 influenza were admitted to our hospital from Oct 1st 2009 to Dec 15th 2009, and their clinical data were collected. These cases consisted of 46 males and 30 females, the mean(SD) age was 3.29±2.90 years,25 cases (32.9%) were distributed in 0～1 years,17 cases (22.4%) in～3 years,18 cases (23.7%) in～5 years,16 cases (21.1%) in～16 years. According to《The third edition diagnosis and treatment program of novel H1N1 influenza》issued by the Health Department, the 76 cases were divided into 2 groups:severe group and critical group.
2. Methods
All the data collected by hand with uniform form included:physical data, vital signs, two kinds of scores, routine tests of blood, urine and stool, blood gas analysis, biochemistry, tests of cytoimmunity and humoral immunity and etc, all kinds of drugs, mechanical ventilation parameters and index of respiratory and circulation if mechanical ventilation received are also included.
Dynamic checks of X-ray or CT were required to observe the imaging changes. According to the extent of the lesion involvement at the early phase of admission, the lesion was classified as three grade:mild (1～2 lung fields involved), moderate (3～41ung fields involved), and severe (5～6 lung fields involved). According to the lesion pattern, size, distribution and changes of lung marking, the lesion was classified as three types: consolidation type, interstitial infiltration type, mixed type.
Cases of novel H1N1 influenza were confirmed by testing throat swabs with the use of a real time reverse transcriptase polymerase chain reaction (RT-PCR) assay at laboratory of SuZhou Center for Disease Control and Prevention (CDC).
Results:
1. The average age of severe cases (2.91±2.26 y) was significantly younger than that of critical cases (4.68±4.35 y)(P<0.05),60.0% of severe cases were younger than 3 years but in critical cases it is 37.5%, The median length of stay of severe cases (7.75±3.06 d) was significantly shorter than that of critical cases (19.6±7.72 d) (P<0.05), The severe cases had lower admission Pediatric Risk of Mortality ScoreⅢ(PRISMⅢScore) and higher Pediatrics Critical Illness Score (PCIS) than critical cases (P<0.05)
2. Fever and cough were the common manifestations of the two groups, wheeze often occurred in severe cases, while inspiratory depression sign, ARDS, convulsion, coma and gastrointestinal bleeding were more often in critical cases.
3. The proportion of coinfections in severe cases (68.3%) was higher than that in critical cases (37.5%) (P<0.05), SP (Streptococcus pneumoniae) was found common in severe cases, followed by Haemophilus influenzae and Moraxelle catarrhalis, while SA (Staphylococcus aureus) was found common in critical cases.
4. Severe cases with pre-existing disease (31.6%) were less than critical cases (56.3%) (P<0.05), Asthma was the most common pre-existing disease in severe cases, followed by iron deficiency anemia, iron deficiency anemia was most common pre-existing disease in critical cases, followed by cerebral palsy and congenital heart disease.
5. Oxygenation index (PaO2/FiO2) in severe cases (307.18±55.73) was significantly higher than those in critical cases (187.50±73.62)(P<0.05), Serum prealbumin (PA) and albumin (A) was significantly higher than those in critical cases (P<0.05), while the creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), a-hydroxybutyrate dehydrogenase (α-HBDH) and C-reactive protein (CRP) of severe cases were significantly lower than those of critical cases (P<0.05).
6. Consolidation type are the main type of severe cases and critical cases, Air leak sign occurred more likely in critical cases than severe cases, the extent of lesion in severe cases presented as mild to moderate, and moderate to severe in critical cases.
7. All the severe cases were improved and charged without any sequela, while in critical group,2 case died who were eight months and 3 years,3 cases were found pulmonary fibrosis and 2 cases found encephalatrophy at return visit, The median length of severe cases with positive real-time RT-PCR test results (6.96±3.01 d) was significantly shorter than that of critical cases (17.27±5.57 d) (P<0.05).
Conclusion
1. Critically ill children with novel H1N1 influenza were commonly older than severe cases, and usually have more organs being damaged.
2. Laboratory tests (such as PaO2/FiO2, CK), imaging examination, PRISM III and PCIS score are helpful for severity and prognosis judgment.
3. Children with iron deficiency anemia, cerebral palsy or congenital heart disease are easier to become critical cases.
4. Different antibiotics should be chosen according to different bacteria spectrum of severe and critical cases.
研究小儿甲型H1N1流感重症与危重症的不同临床特点及患儿发展成为重症、危重症的相关因素,以指导预防和治疗。
方法：
1.一般资料
本研究收集了2009年10月1日至2010年01月15日期间我院确诊并收治入院的76例甲型H1N1流感患儿的临床资料,男46例,女30例,平均年龄3.29±2.90岁,0～1岁25例(32.9%),～3岁17例(22.4%),～5岁18例(23.7%),～16岁16例(21.1%)。参照卫生部《甲型H1N1流感诊疗方案第三版》诊断标准,将76例患儿分成两组：重症组60例,危重症组16例。
2.方法
设计统一的表格,在住院期间收集填写各项资料：患儿一般资料、生命体征和评分；血尿粪常规、血气分析、生化、体液免疫和细胞免疫等检查结果；各种药物的使用情况；使用呼吸机的患儿定时记录呼吸机参数和患儿呼吸循环指标。
动态胸部X线或CT检查,按两肺病变累及范围不同将胸片肺部病变程度划分为轻、中、重三度；按照病灶的形态、大小、分布以及肺纹理的改变,将其分为3种类型：实变型、间质浸润型和混合型。
通过咽拭子采集呼吸道分泌物标本,送苏州市疾病控制中心,采用RT-PCR进行甲型H1N1流感病毒RNA检测。
结果：
1.重症组平均年龄2.91±2.26岁,显著低于危重症组4.68±4.35岁(P<0.05),重症患儿3岁以下占60.0%,危重症患儿3岁以下占37.5%；住院时间重症组7.75±3.06 d显著短于危重症组19.6±7.72 d(P<0.05),重症组第3代小儿死亡危险评分(PRISMⅢ)低于危重症组(P<0.05),小儿危重病例评分(PCIS)高于危重症组(P<0.05)。
2.两组都以发热、咳嗽为主要症状,喘息在重症组发生率高于危重症组,吸气性凹陷、ARDS、抽搐、昏迷和胃肠道出血在危重症组发生率高于重症组。
3.重症组混合其他病原体感染率68.3%显著高于危重症组的37.5%(P<0.05),重症组混合细菌感染以肺炎链球菌为主,次之为流感嗜血杆菌和卡他莫拉菌；危重症组则为金黄色葡萄球菌为主。
4.重症组有31.6%并存基础疾病显著少于危重症组56.3%(P<0.05),重症组并存基础疾病以哮喘多见,危重症组以营养性缺铁性贫血多见,次之是脑性瘫痪和先天性心脏病。
5.重症组PaO2／FiO2(氧合指数)为307.18±55.73 mmHg,显著高于危重症组的187.50±73.62 mmHg(P<0.05),重症组的PA(血清前白蛋白)和A(白蛋白)显著高于危重症组(P<0.05),而CK(肌酸激酶)、AST(谷草转氨酶)、LDH(乳酸脱氢酶)、α-HBDH(α-羟丁酸)和CRP(C反应蛋白)显著低于危重症组(P<0.05)。
6.重症组与危重症组肺部病变X线分型均以实变型为主,分别占70.0%和81.3%,重症组1.7%合并肺气漏征群少于危重症组的31.3%(P<0.05),肺部病变X线分度重症组以轻度、中度为主,而危重症组则以中度、重度为主。
7.重症组的患儿预后均好转出院,无后遗症改变,而危重症组2例(12.5%)死亡,分别为8月和3岁；有3例(18.8%)出现肺部纤维化；2例(12.5%)出现脑萎缩；追踪重症组RT-PCR检测甲型H1N1核酸呈阳性时间3～14 d,平均6.96±3.01 d,危重症组为10～27 d,平均17.27±5.57 d,重症组显著短于危重症组(P<0.05)。
结论：
1.相对于甲型H1N1流感重症患儿,危重症患儿发病年龄较大,受损器官数目较多,更容易发生严重的低氧血症,甚至ARDS和MODS,更易出现死亡或者脑萎缩、肺纤维化等后遗症改变；
2.早期的PaO2／FiO2、CK等指标、影像学检查及PRISMⅢ、PCIS评分有助于临床医生对甲型H1N1流感患儿病情危重程度尽早作出正确判断；
3.警惕有缺铁性贫血、脑性瘫痪和先天性心脏病等基础疾病的患儿发展成为危重症;
4.在选择抗生素时要考虑到重症和危重症患儿混合感染细菌谱的异同。
Objectives:
To study different clinical characteristics and risk factors of severe and critical ill children with novel H1N1 influenza, then to guide prophylaxis and therapy.
Methods:
1.General data
Seventy-six children with novel H1N1 influenza were admitted to our hospital from Oct 1st 2009 to Dec 15th 2009, and their clinical data were collected. These cases consisted of 46 males and 30 females, the mean(SD) age was 3.29±2.90 years,25 cases (32.9%) were distributed in 0～1 years,17 cases (22.4%) in～3 years,18 cases (23.7%) in～5 years,16 cases (21.1%) in～16 years. According to《The third edition diagnosis and treatment program of novel H1N1 influenza》issued by the Health Department, the 76 cases were divided into 2 groups:severe group and critical group.
2. Methods
All the data collected by hand with uniform form included:physical data, vital signs, two kinds of scores, routine tests of blood, urine and stool, blood gas analysis, biochemistry, tests of cytoimmunity and humoral immunity and etc, all kinds of drugs, mechanical ventilation parameters and index of respiratory and circulation if mechanical ventilation received are also included.
Dynamic checks of X-ray or CT were required to observe the imaging changes. According to the extent of the lesion involvement at the early phase of admission, the lesion was classified as three grade:mild (1～2 lung fields involved), moderate (3～41ung fields involved), and severe (5～6 lung fields involved). According to the lesion pattern, size, distribution and changes of lung marking, the lesion was classified as three types: consolidation type, interstitial infiltration type, mixed type.
Cases of novel H1N1 influenza were confirmed by testing throat swabs with the use of a real time reverse transcriptase polymerase chain reaction (RT-PCR) assay at laboratory of SuZhou Center for Disease Control and Prevention (CDC).
Results:
1. The average age of severe cases (2.91±2.26 y) was significantly younger than that of critical cases (4.68±4.35 y)(P<0.05),60.0% of severe cases were younger than 3 years but in critical cases it is 37.5%, The median length of stay of severe cases (7.75±3.06 d) was significantly shorter than that of critical cases (19.6±7.72 d) (P<0.05), The severe cases had lower admission Pediatric Risk of Mortality ScoreⅢ(PRISMⅢScore) and higher Pediatrics Critical Illness Score (PCIS) than critical cases (P<0.05)
2. Fever and cough were the common manifestations of the two groups, wheeze often occurred in severe cases, while inspiratory depression sign, ARDS, convulsion, coma and gastrointestinal bleeding were more often in critical cases.
3. The proportion of coinfections in severe cases (68.3%) was higher than that in critical cases (37.5%) (P<0.05), SP (Streptococcus pneumoniae) was found common in severe cases, followed by Haemophilus influenzae and Moraxelle catarrhalis, while SA (Staphylococcus aureus) was found common in critical cases.
4. Severe cases with pre-existing disease (31.6%) were less than critical cases (56.3%) (P<0.05), Asthma was the most common pre-existing disease in severe cases, followed by iron deficiency anemia, iron deficiency anemia was most common pre-existing disease in critical cases, followed by cerebral palsy and congenital heart disease.
5. Oxygenation index (PaO2/FiO2) in severe cases (307.18±55.73) was significantly higher than those in critical cases (187.50±73.62)(P<0.05), Serum prealbumin (PA) and albumin (A) was significantly higher than those in critical cases (P<0.05), while the creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), a-hydroxybutyrate dehydrogenase (α-HBDH) and C-reactive protein (CRP) of severe cases were significantly lower than those of critical cases (P<0.05).
6. Consolidation type are the main type of severe cases and critical cases, Air leak sign occurred more likely in critical cases than severe cases, the extent of lesion in severe cases presented as mild to moderate, and moderate to severe in critical cases.
7. All the severe cases were improved and charged without any sequela, while in critical group,2 case died who were eight months and 3 years,3 cases were found pulmonary fibrosis and 2 cases found encephalatrophy at return visit, The median length of severe cases with positive real-time RT-PCR test results (6.96±3.01 d) was significantly shorter than that of critical cases (17.27±5.57 d) (P<0.05).
Conclusion
1. Critically ill children with novel H1N1 influenza were commonly older than severe cases, and usually have more organs being damaged.
2. Laboratory tests (such as PaO2/FiO2, CK), imaging examination, PRISM III and PCIS score are helpful for severity and prognosis judgment.
3. Children with iron deficiency anemia, cerebral palsy or congenital heart disease are easier to become critical cases.
4. Different antibiotics should be chosen according to different bacteria spectrum of severe and critical cases.
引文
[1]WHO. http://www.who.int/csr/disease/swineflu/coe_hearing/zh/index.html.
[2]Smith GJ, Vijaykrishna D, Bahl J, et al. Origins and evolutionary genomics of 2009 swine-origin H1N1 influenza A epidemic [J]. Nature,2009,459(7250):1122-1125.
[3]Zimmer SM, Burke DS. Historical perspective-emergence of influenza A (H1N1) viruses [J]. N Engl J Med,2009,361(3):279-285.
[4]Scholtissek C, Rohde W, Von Hoyningen V, et al. On the origin of the human influenza virus subtypes H2N2 and H3N2 [J]. Virology,1978,87(1):13-20.
[5]Kilbourne ED. Influenza pandemic of 20th century [J]. Emerg Infect Dis,2006, 12(1):9-14.
[6]WHO.Human infection with new influenza A(H1N1) virus:Clinical observations from Mexico and other affected countries[J]. Wkly Epidemiol Rec,2009,84(21):185-196.
[7]Bernard G, Artigas A, Brigham K, et al. Report of the American—European consensus conference on ARDS:Definition, mechanisms, relevant outcomes and clinical trial coordination. The Consensus Committee[J]. Intensive Care Med,1994,20(3): 225-232.
[8]曾庆思,陈苓,蔡欣等.SARS的胸部X线与CT诊断[J].中华放射学杂志,2003,37(7)：600-603.
[9]Libster R,Bugna J,Coviello S,et al.Pediatric Hospitalizations Associated with 2009 Pandemic Influenza A (H1N1) in Argentina[J]. N Engl Med,2010,362(l):45-55.
[10]CDC. Surweillance for pediatric deaths associated with 2009 pandemic influenza A(H1N1) virus infection-United States,April-August 2009[J]. MMWR Morb Mortal Wkly Rep,2009,58(34):941-947.
[11]Hackett S, Hill L, Patel J, et al. Clinical characteristics of paediatrics H1N1 admissions in Birmingham, UK [J]. Lancet,2009,374(9690):605.
[12]O'Riordan S, Barton M, Yau Y, et al.Risk factors and outcomes among children admitted to hospital with pandemic H1N1 influenza [J]. CMAJ,2010,182(1):39-44.
[13]Cao B, Li XW, Mao Y, et al. Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China [J]. N Engl J Med,2009,361(26): 2507-2517.
[14]Ling LM, Chow AL, Lye DC, et al. Effects of early Oseltamivir therapy on viral shedding in 2009 pandemic influenza A (H1N1) virus infection [J]. Clin infect Dis, 2010,50(7):963-969.
[15]Klimov AI, Rocha E, Hayden FG, et al. Prolonged shedding of amantadine-resistant influenza A viruses by immunodeficient patients:detection by polymerase chain reaction-restriction analysis [J]. J Infect Dis,1995,172(5):1352-1355.
[16]Ison MG, Gubareva LV, Atmar RL. Recovery of drug-resistant influenza virus from immunocompromised patients:a case series [J]. J infect Dis,2006,193(6):760-764.
[17]Kumar A, Zarychanski R, Pinto R, et al. Critically ill patients with 2009 influenza A(H1N1) infection in Canada [J]. JAMA,2009,302(17):1872-1879.
[18]Soto-Abraham MV, Soriano-Rosas J, Diaz-Quinonez A, et al. Pathological changes associated with the 2009 H1N1 virus [J]. N Engl J Med,2009,361 (20):2001-2003.
[19]Taubenberger JK, Morens DM. The pathology of influenza virus infection [J]. Annu Rev Pathol,2008,3:499-522.
[20]Guarner J, Paddock CD, Shieh WJ, et al. Histopathologic and immunohistochemical features of fatal influenza virus infection in children during the 2003-2004 season [J]. Clin Infect Dis,2006,43(2):132-140.
[21]Korteweg C, Gu J. Pathology, molecular biology, and pathogenesis of avian influenza A (H5N1) infection in humans [J]. Am J Pathol,2008,172(5):1155-1170.
[22]Chowell G, Bertozzi SM, Colchero MA, et al. Severe respiratory disease concurrent with the circulation of H1N1 Influenza[J]. N Engl J Med,2009,361 (7).674-679.
[23]CDC.Hospitalized patients with novel influenza A(H1N1) virus infection-California, April-May,2009[J]. MMWR Morb Mortal Wkly Rep,2009,58(19):536-441.
[24]CDC. Neurologic complications associated with novel influenza A(H1N1) virus infection in children-Dallas,Texas,May 2009[J]. MMWR Morb Mortal Wkly Rep, 2009,58(28):773-778.
[25]Studahl M. Influenza virus and CNS manifestations [J]. J Clin Virol 2003, 28(3):225-232.
[26]Ito Y, Ichiyama T, Kimura H, et al. Detection of influenza virus RNA by reverse transcription-PCR and proinflammatory cytokines in influenza-virus-associated encephalopathy [J]. J Med Virol,1999,58(4):420-425.
[27]Lyon JB, Remigio C, Milligan T, et al. Acute necrotizing encephalopathy in a child with H1N1 influenza infection [J]. Pediatr Radiol,2009,40(2):200-205.
[28]汤正珍,何颜霞,郑跃杰等.儿童2009甲型H1N1流感相关神经系统并发症报道[J].中国实用儿科杂志,2010,25(2)：129-131.
[29]Lister P, Reynolds F, Parslow R, et al. Swine-origin influenza virus H1N1, seasonal influenza virus, and critical illness in children [J]. Lancet,2009,374 (9690):605-607.
[30]中华医学会儿科学分会呼吸学组.儿童社区获得性肺炎管理指南(试行)(上)[J].中华儿科杂志,2007,45(2)：83-90.
[31]中华医学会儿科学分会呼吸学组.儿童社区获得性肺炎管理指南(试行)(下)[J].中华儿科杂志,2007,45(3)：223-230.
[32]CDC. Bacterial coinfections in lung tissue specimens from cases of 2009 pandemic influenza A(H1N1)-United States, May-August 2009[J]. MMWR Morb Mortal Wkly Rep,2009,58(38):1071-1074.
[33]Brundage JF, Shanks GD.Deaths from bacteria pneumonia during 1918-19 influenza pandemic[J]. Emerg Infect Dis,2008,14(8):1193-1199.
[34]CDC.Intensive-care patients with severe novel influenza A(H1N1) virus infection Michigan, June 2009[J]. MMWR Morb Mortal Wkly Rep,2009,58 (27):749-752.
[35]Bernstein LH. The systemic inflammatory response syndrome C-reactive protein and transthyretin conundrum[J]. Clin Chem Lab Med,2007,45(3):419-426.
[36]Pinilla JC, Hayes P, Laverty W, et al.The C-reactive protein to prealbumin ratio correlates with the severity of multiple organ dysfunction[J]. Surgery,1998,124(4): 799-805.
[37]Kaiser L, Fritz RS, Straus SE, et al. Symptom pathogenesis during acute influenza: interleukin-6 and other cytokine responses [J]. J Med Vorol,2001,64(3):262-268.
[38]Greaves K, Oxford JS, Price CP, et al. The prevalence of myocarditis and skeletal muscle inlury during acute viral infection in adults:measurement of cardiac troponins I and T in 152 patients with acute influenza infection[J]. Arch intern Med,2003, 163(2):165-168.
[39]Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease:a systematic review [J]. Lancet Infect Dis,2009,9(10):601-610.
[40]Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza a (H1N1) in Mexico[J]. N Engl Med, 2009,361(7):680-689.
[41]Marchiori E, et al. High-resolution computed tomogtaphy findings from adult patients with Influenza A(H1N1)virus-associated pneumonia. Eur J Radiol (2009),doi:10.1016/j.ejrad.2009.11.005].
[42]任晓旭,宋国维.第3代小儿死亡危险评分和小儿危重病例评分的应用[J].实用儿科临床杂志,2006,21(6)：382-384.
[43]Bilan N, Galehgolab BA, Emadaddin A, et al. Risk of mortality in pediatric intensive care unit, assessed by PRISM-Ⅲ[J]. Pak J Biol Sci,2009,12(6):480-485.
[44]Choi KM, Ng DK, Wong SF, et al. Assessment of the Pediatric index of Mortality (PIM) and the Pediatric Risk of Mortality (PRISM) Ⅲ score for prediction of mortality in a pediatric intensive care unit in Hong Kong [J]. Hong Kong Med J, 2005,11(2):97-103.
[45]小儿危重病例评分使用协作组.小儿危重病例评分法(草案)临床应用评价[J].中华儿科杂志,1998,36(10)：579-582.
[46]张剑珲,曾其毅,陶建平.小儿死亡危险评分的临床应用[J].实用儿科临床杂志,2005,20(6)：569-570.
[1]WHO. http://www.who.int/csr/disease/swineflu/coe_hearing/zh/index.html.
[2]WHO. Human infection with new influenza A(H1N1) virus:Clinical observations from Mexico and other affected countries [J]. Wkly Epidemiol Rec,2009,84(21):185-196.
[3]Smith GJ, Vijaykrishna D, Bahl J, et al. Origins and evolutionary genomics of 2009 swine-origin H1N1 influenza A epidemic [J]. Nature,2009,459(7250):1122-1125.
[4]Nicas M, Jones RM. Relative contributions of four exposure pathways to influenza infection risk. Risk Anal,2009,29(9):1292-1303.
[5]Cao B, Li XW, Mao Y, et al. Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China [J]. N Engl J Med,2009,361(26): 2507-2517.
[6]WHO. New influenza A (H1N1) virus:global epidemiological situation, June 2009 [J]. Wkly Epidemiol Rec,2009,84(25):249-257.
[7]Ling LM, Chow AL, Lye DC, et al. Effects of early Oseltamivir therapy on viral shedding in 2009 pandemic influenza A (H1N1) virus infection [J]. Clin infect Dis, 2010,50(7):963-969.
[8]Klimov AI, Rocha E, Hayden FG, et al. Prolonged shedding of amantadine-resistant influenza A viruses by immunodeficient patients:detection by polymerase chain reaction-restriction analysis [J]. J Infect Dis,1995,172(5):1352-1355.
[9]Ison MG, Gubareva LV, Atmar RL. Recovery of drug-resistant influenza virus from immunocompromised patients:a case series [J]. J infect Dis,2006,193(6):760-764.
[10]CDC. Intensive-care patients with severe novel influenza A(H1N1) virus infection-Michigan, June 2009 [J]. MMWR Morb Mortal Wkly Rep,2009,58(27): 749-752.
[11]Kumar A, Zarychanski R, Pinto R, et al. Critically ill patients with 2009 influenza A(H1N1) infection in Canada [J]. JAMA,2009,302(17):1872-1879.
[12]O'Riordan S, Barton M, Yau Y, et al.Risk factors and outcomes among children admitted to hospital with pandemic H1N1 influenza [J]. CMAJ,2010,182(1):39-44.
[13]Libster R,Bugna J,Coviello S,et al.Pediatric Hospitalizations Associated with 2009 Pandemic Influenza A (H1N1) in Argentina [J]. N Engl Med,2010,362(1):45-55.
[14]Hackett S, Hill L, Patel J, et al. Clinical characteristics of paediatrics H1N1 admissions in Birmingham, UK [J]. Lancet,2009,374(9690):605.
[15]CDC. Surweillance for pediatric deaths associated with 2009 pandemic influenza A(H1N1) virus infection-United States,April-August 2009 [J]. MMWR Morb Mortal Wkly Rep,2009,58 (34):941-947.
[16]Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic Influenza:Implications for pandemic Influenza preparedness [J]. J Infect Dis,2008,198(7):962-970.
[17]Brundage JF, Shanks GD.Deaths from bacteria pneumonia during 1918-19 influenza pandemic [J]. Emerg Infect Dis,2008,14(8):1193-1199.
[18]Rothberg MB, Haessler SD. Complications of seasonal and pandemic influenza [J]. Crit Care Med,2010,38(3):1-7.
[19]CDC. Bacterial coinfections in lung tissue specimens from cases of 2009 pandemic influenza A(H1N1)-United States, May-August 2009 [J]. MMWR Morb Mortal Wkly Rep,2009,58(38):1071-1074.
[20]Soto-Abraham MV, Soriano-Rosas J, Diaz-Quinonez A, et al. Pathological changes associated with the 2009 H1N1 virus [J]. N Engl J Med,2009,361 (20):2001-2003.
[21]Taubenberger JK, Morens DM. The pathology of influenza virus infection [J]. Annu Rev Pathol,2008,3:499-522.
[22]Guarner J, Paddock CD, Shieh WJ, et al. Histopathologic and immunohistochemical features of fatal influenza virus infection in children during the 2003-2004 season [J]. Clin Infect Dis,2006,43(2):132-140.
[23]Korteweg C, Gu J. Pathology, molecular biology, and pathogenesis of avian influenza A (H5N1) infection in humans [J]. Am J Pathol,2008,172(5):1155-1170.
[24]Lee EY, McAdam AJ, Chaudry G, et al. Swine-origin influenza a (H1N1) viral infection in children:initial chest radiographic findings [J]. Radiology,2010,254(3): 934-941.
[25]Ajlan AM, Quiney B, Nicolaou S, et al. Swine-origin influenza A (H1N1) viral infection:radiographic and CT findings [J]. AJR,2009,193(6):1494-1499.
[26]Chowell G, Bertozzi SM, Colchero MA, et al. Severe respiratory disease concurrent with the circulation of H1N1 Influenza [J]. N Engl J Med,2009 361 (7):674-679.
[27]Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza a (H1N1) in Mexico [J]. N Engl Med, 2009,361 (7):680-689.
[28]Lister P, Reynolds F, Parslow R, et al. Swine-origin influenza virus H1N1, seasonal influenza virus, and critical illness in children [J]. Lancet,2009,374(9690):605-607.
[29]Greaves K, Oxford JS, Price CP, et al. The prevalence of myocarditis and skeletal muscle inlury during acute viral infection in adults:measurement of cardiac troponins I and T in 152 patients with acute influenza infection [J]. Arch intern Med,2003,163 (2):165-168.
[30]Kaiser L, Fritz RS, Straus SE, et al. Symptom pathogenesis during acute influenza: interleukin-6 and other cytokine responses [J]. J Med Vorol,2001,64(3):262-268.
[31]Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease:a systematic review [J]. Lancet Infect Dis,2009,9(10):601-610.
[32]汤正珍,何颜霞,郑跃杰等.儿童2009甲型H1N1流感相关神经系统并发症报道[J].中国实用儿科杂志,2010,25(2)：129-131.
[33]Lyon JB, Remigio C, Milligan T, et al. Acute necrotizing encephalopathy in a child with H1N1 influenza infection [J]. Pediatr Radiol,2009,40(2):200-205.
[34]Studahl M. Influenza virus and CNS manifestations [J]. J Clin Virol 2003,28 (3): 225-232.
[35]Jamieson B, Jain R, Carleton B, et al. Use of oseltamivir in children [J]. Can Fam Physician,2009,55(12):1199-1201.
[36]CDC. Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-2010 season. http://www.cdc.gov/h1n1flu/recommendations.htm.
[37]Matheson NJ, Harnden AR, Perera R, et al. Neuraminidase inhibitors for preventing and treating influenza in children [J]. Cochrane Database Syst Rev,2007,24(1): CD002744.
[38]CDC. Oseltamivir-resisitant 2009 pandemic influenza A (H1N1) virus infection in two summer campers receiving prophylaxis-North Carolina [J]. MMWR Morb Mortal Wkly Rep,2009,58(35):969-972.
[39]Alert letter.[US Food and Drug Administration web site]. December,2003. Available at:http://www.fda.gov/medwatch/SAFETY/2003/tamiflu_deardoc.pdf. Accessed January 14,2005.
[40]Okamoto S, Kamiya L, Kishida K, et al. Experience with oseltamivir for infants younger than 1 year old in Japan [J]. Pediatr Infect Dis J,2005,24(6):575-576.
[41]Mandell LA, Wunderink RG, Anzueto A, et al. Infectious diseases society of America/American Thracic Society consensus guidelines on the management of community-acquired pneumonia in adults [J]. Clin Infect Dis,2007,44(Suppl 2): S27-S72.
[42]Bernard GR,Luce JM, Sprung CL, et al. High dose corticosteroids in patients with the adult respiratory distress syndrome [J]. N Engl J Med,1987,317(25):1565-1570.
[43]Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome [J]. N Engl J Med,2006,354(16): 1671-1684.
[44]Griffith JF, Antonio GE, Kumta SM, et al. Osteonecrosis of Hip and Knee in Patients with Severe Acute Respiratory Syndrome Treated with Steroids [J]. Radiology, 2005,235(1):168-175.
[45]Tobin MJ. Culmination of an era in research on the acute respiratory distress syndrome [J]. N Engl J Med,2000,342(18):1360-1361.
[46]Quispe-Laime AM, Bracco JD, Barberio PA, et al. H1N1 influenza A virus-associated acute lung injury:response to combination oseltamivir and prolonged corticosteroid treatment [J]. Intensive Care Med,2010,36(1):33-41.
[47]高恒秒,李峥,陈晖,等.儿童甲型H1N1流感危重症临床特点分析[J].中国小儿急救医学,2009,16(6)：16-19.
[48]The ANZIC Influenza Investigators. Critical care services and 2009 H1N1 influenza in Australia and New Zealand [J]. N Engl J Med,2009,361(20):1925-1934.
[49]Luke TC, Kilbane EM, Jackson JL, et al. Meta-analysis:convalescent blood products for Spanish influenza pneumonia:a future H5N1 treatment? [J]. Ann Intern Med, 2006,145(8):599-609.
[50]Greenberg ME, Lai MH, Hartel GF, et al. Response to a monovalent 2009 influenza A (H1N1) vaccine [J]. N Engl J Med,2009,361(25):2405-2413.
[51]Clark TW, Pareek M, Hoschler K, et al. Trial of 2009 influenza A (H1N1) monovalent MF59-adjuvanted vaccine [J]. N Engl J Med,2009,361(25):2424-2435.
[52]Schonberger LB, Bergman DJ, Sullivan-Bolyai JZ, et al. Guillain-Barre syndrome following vaccination in the National Influenza Immunization Program, United States. 1976-1977 [J]. Am J Epidemiol,1979,110(2):105-123.
[2]Smith GJ, Vijaykrishna D, Bahl J, et al. Origins and evolutionary genomics of 2009 swine-origin H1N1 influenza A epidemic [J]. Nature,2009,459(7250):1122-1125.
[3]Zimmer SM, Burke DS. Historical perspective-emergence of influenza A (H1N1) viruses [J]. N Engl J Med,2009,361(3):279-285.
[4]Scholtissek C, Rohde W, Von Hoyningen V, et al. On the origin of the human influenza virus subtypes H2N2 and H3N2 [J]. Virology,1978,87(1):13-20.
[5]Kilbourne ED. Influenza pandemic of 20th century [J]. Emerg Infect Dis,2006, 12(1):9-14.
[6]WHO.Human infection with new influenza A(H1N1) virus:Clinical observations from Mexico and other affected countries[J]. Wkly Epidemiol Rec,2009,84(21):185-196.
[7]Bernard G, Artigas A, Brigham K, et al. Report of the American—European consensus conference on ARDS:Definition, mechanisms, relevant outcomes and clinical trial coordination. The Consensus Committee[J]. Intensive Care Med,1994,20(3): 225-232.
[8]曾庆思,陈苓,蔡欣等.SARS的胸部X线与CT诊断[J].中华放射学杂志,2003,37(7)：600-603.
[9]Libster R,Bugna J,Coviello S,et al.Pediatric Hospitalizations Associated with 2009 Pandemic Influenza A (H1N1) in Argentina[J]. N Engl Med,2010,362(l):45-55.
[10]CDC. Surweillance for pediatric deaths associated with 2009 pandemic influenza A(H1N1) virus infection-United States,April-August 2009[J]. MMWR Morb Mortal Wkly Rep,2009,58(34):941-947.
[11]Hackett S, Hill L, Patel J, et al. Clinical characteristics of paediatrics H1N1 admissions in Birmingham, UK [J]. Lancet,2009,374(9690):605.
[12]O'Riordan S, Barton M, Yau Y, et al.Risk factors and outcomes among children admitted to hospital with pandemic H1N1 influenza [J]. CMAJ,2010,182(1):39-44.
[13]Cao B, Li XW, Mao Y, et al. Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China [J]. N Engl J Med,2009,361(26): 2507-2517.
[14]Ling LM, Chow AL, Lye DC, et al. Effects of early Oseltamivir therapy on viral shedding in 2009 pandemic influenza A (H1N1) virus infection [J]. Clin infect Dis, 2010,50(7):963-969.
[15]Klimov AI, Rocha E, Hayden FG, et al. Prolonged shedding of amantadine-resistant influenza A viruses by immunodeficient patients:detection by polymerase chain reaction-restriction analysis [J]. J Infect Dis,1995,172(5):1352-1355.
[16]Ison MG, Gubareva LV, Atmar RL. Recovery of drug-resistant influenza virus from immunocompromised patients:a case series [J]. J infect Dis,2006,193(6):760-764.
[17]Kumar A, Zarychanski R, Pinto R, et al. Critically ill patients with 2009 influenza A(H1N1) infection in Canada [J]. JAMA,2009,302(17):1872-1879.
[18]Soto-Abraham MV, Soriano-Rosas J, Diaz-Quinonez A, et al. Pathological changes associated with the 2009 H1N1 virus [J]. N Engl J Med,2009,361 (20):2001-2003.
[19]Taubenberger JK, Morens DM. The pathology of influenza virus infection [J]. Annu Rev Pathol,2008,3:499-522.
[20]Guarner J, Paddock CD, Shieh WJ, et al. Histopathologic and immunohistochemical features of fatal influenza virus infection in children during the 2003-2004 season [J]. Clin Infect Dis,2006,43(2):132-140.
[21]Korteweg C, Gu J. Pathology, molecular biology, and pathogenesis of avian influenza A (H5N1) infection in humans [J]. Am J Pathol,2008,172(5):1155-1170.
[22]Chowell G, Bertozzi SM, Colchero MA, et al. Severe respiratory disease concurrent with the circulation of H1N1 Influenza[J]. N Engl J Med,2009,361 (7).674-679.
[23]CDC.Hospitalized patients with novel influenza A(H1N1) virus infection-California, April-May,2009[J]. MMWR Morb Mortal Wkly Rep,2009,58(19):536-441.
[24]CDC. Neurologic complications associated with novel influenza A(H1N1) virus infection in children-Dallas,Texas,May 2009[J]. MMWR Morb Mortal Wkly Rep, 2009,58(28):773-778.
[25]Studahl M. Influenza virus and CNS manifestations [J]. J Clin Virol 2003, 28(3):225-232.
[26]Ito Y, Ichiyama T, Kimura H, et al. Detection of influenza virus RNA by reverse transcription-PCR and proinflammatory cytokines in influenza-virus-associated encephalopathy [J]. J Med Virol,1999,58(4):420-425.
[27]Lyon JB, Remigio C, Milligan T, et al. Acute necrotizing encephalopathy in a child with H1N1 influenza infection [J]. Pediatr Radiol,2009,40(2):200-205.
[28]汤正珍,何颜霞,郑跃杰等.儿童2009甲型H1N1流感相关神经系统并发症报道[J].中国实用儿科杂志,2010,25(2)：129-131.
[29]Lister P, Reynolds F, Parslow R, et al. Swine-origin influenza virus H1N1, seasonal influenza virus, and critical illness in children [J]. Lancet,2009,374 (9690):605-607.
[30]中华医学会儿科学分会呼吸学组.儿童社区获得性肺炎管理指南(试行)(上)[J].中华儿科杂志,2007,45(2)：83-90.
[31]中华医学会儿科学分会呼吸学组.儿童社区获得性肺炎管理指南(试行)(下)[J].中华儿科杂志,2007,45(3)：223-230.
[32]CDC. Bacterial coinfections in lung tissue specimens from cases of 2009 pandemic influenza A(H1N1)-United States, May-August 2009[J]. MMWR Morb Mortal Wkly Rep,2009,58(38):1071-1074.
[33]Brundage JF, Shanks GD.Deaths from bacteria pneumonia during 1918-19 influenza pandemic[J]. Emerg Infect Dis,2008,14(8):1193-1199.
[34]CDC.Intensive-care patients with severe novel influenza A(H1N1) virus infection Michigan, June 2009[J]. MMWR Morb Mortal Wkly Rep,2009,58 (27):749-752.
[35]Bernstein LH. The systemic inflammatory response syndrome C-reactive protein and transthyretin conundrum[J]. Clin Chem Lab Med,2007,45(3):419-426.
[36]Pinilla JC, Hayes P, Laverty W, et al.The C-reactive protein to prealbumin ratio correlates with the severity of multiple organ dysfunction[J]. Surgery,1998,124(4): 799-805.
[37]Kaiser L, Fritz RS, Straus SE, et al. Symptom pathogenesis during acute influenza: interleukin-6 and other cytokine responses [J]. J Med Vorol,2001,64(3):262-268.
[38]Greaves K, Oxford JS, Price CP, et al. The prevalence of myocarditis and skeletal muscle inlury during acute viral infection in adults:measurement of cardiac troponins I and T in 152 patients with acute influenza infection[J]. Arch intern Med,2003, 163(2):165-168.
[39]Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease:a systematic review [J]. Lancet Infect Dis,2009,9(10):601-610.
[40]Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza a (H1N1) in Mexico[J]. N Engl Med, 2009,361(7):680-689.
[41]Marchiori E, et al. High-resolution computed tomogtaphy findings from adult patients with Influenza A(H1N1)virus-associated pneumonia. Eur J Radiol (2009),doi:10.1016/j.ejrad.2009.11.005].
[42]任晓旭,宋国维.第3代小儿死亡危险评分和小儿危重病例评分的应用[J].实用儿科临床杂志,2006,21(6)：382-384.
[43]Bilan N, Galehgolab BA, Emadaddin A, et al. Risk of mortality in pediatric intensive care unit, assessed by PRISM-Ⅲ[J]. Pak J Biol Sci,2009,12(6):480-485.
[44]Choi KM, Ng DK, Wong SF, et al. Assessment of the Pediatric index of Mortality (PIM) and the Pediatric Risk of Mortality (PRISM) Ⅲ score for prediction of mortality in a pediatric intensive care unit in Hong Kong [J]. Hong Kong Med J, 2005,11(2):97-103.
[45]小儿危重病例评分使用协作组.小儿危重病例评分法(草案)临床应用评价[J].中华儿科杂志,1998,36(10)：579-582.
[46]张剑珲,曾其毅,陶建平.小儿死亡危险评分的临床应用[J].实用儿科临床杂志,2005,20(6)：569-570.
[1]WHO. http://www.who.int/csr/disease/swineflu/coe_hearing/zh/index.html.
[2]WHO. Human infection with new influenza A(H1N1) virus:Clinical observations from Mexico and other affected countries [J]. Wkly Epidemiol Rec,2009,84(21):185-196.
[3]Smith GJ, Vijaykrishna D, Bahl J, et al. Origins and evolutionary genomics of 2009 swine-origin H1N1 influenza A epidemic [J]. Nature,2009,459(7250):1122-1125.
[4]Nicas M, Jones RM. Relative contributions of four exposure pathways to influenza infection risk. Risk Anal,2009,29(9):1292-1303.
[5]Cao B, Li XW, Mao Y, et al. Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China [J]. N Engl J Med,2009,361(26): 2507-2517.
[6]WHO. New influenza A (H1N1) virus:global epidemiological situation, June 2009 [J]. Wkly Epidemiol Rec,2009,84(25):249-257.
[7]Ling LM, Chow AL, Lye DC, et al. Effects of early Oseltamivir therapy on viral shedding in 2009 pandemic influenza A (H1N1) virus infection [J]. Clin infect Dis, 2010,50(7):963-969.
[8]Klimov AI, Rocha E, Hayden FG, et al. Prolonged shedding of amantadine-resistant influenza A viruses by immunodeficient patients:detection by polymerase chain reaction-restriction analysis [J]. J Infect Dis,1995,172(5):1352-1355.
[9]Ison MG, Gubareva LV, Atmar RL. Recovery of drug-resistant influenza virus from immunocompromised patients:a case series [J]. J infect Dis,2006,193(6):760-764.
[10]CDC. Intensive-care patients with severe novel influenza A(H1N1) virus infection-Michigan, June 2009 [J]. MMWR Morb Mortal Wkly Rep,2009,58(27): 749-752.
[11]Kumar A, Zarychanski R, Pinto R, et al. Critically ill patients with 2009 influenza A(H1N1) infection in Canada [J]. JAMA,2009,302(17):1872-1879.
[12]O'Riordan S, Barton M, Yau Y, et al.Risk factors and outcomes among children admitted to hospital with pandemic H1N1 influenza [J]. CMAJ,2010,182(1):39-44.
[13]Libster R,Bugna J,Coviello S,et al.Pediatric Hospitalizations Associated with 2009 Pandemic Influenza A (H1N1) in Argentina [J]. N Engl Med,2010,362(1):45-55.
[14]Hackett S, Hill L, Patel J, et al. Clinical characteristics of paediatrics H1N1 admissions in Birmingham, UK [J]. Lancet,2009,374(9690):605.
[15]CDC. Surweillance for pediatric deaths associated with 2009 pandemic influenza A(H1N1) virus infection-United States,April-August 2009 [J]. MMWR Morb Mortal Wkly Rep,2009,58 (34):941-947.
[16]Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic Influenza:Implications for pandemic Influenza preparedness [J]. J Infect Dis,2008,198(7):962-970.
[17]Brundage JF, Shanks GD.Deaths from bacteria pneumonia during 1918-19 influenza pandemic [J]. Emerg Infect Dis,2008,14(8):1193-1199.
[18]Rothberg MB, Haessler SD. Complications of seasonal and pandemic influenza [J]. Crit Care Med,2010,38(3):1-7.
[19]CDC. Bacterial coinfections in lung tissue specimens from cases of 2009 pandemic influenza A(H1N1)-United States, May-August 2009 [J]. MMWR Morb Mortal Wkly Rep,2009,58(38):1071-1074.
[20]Soto-Abraham MV, Soriano-Rosas J, Diaz-Quinonez A, et al. Pathological changes associated with the 2009 H1N1 virus [J]. N Engl J Med,2009,361 (20):2001-2003.
[21]Taubenberger JK, Morens DM. The pathology of influenza virus infection [J]. Annu Rev Pathol,2008,3:499-522.
[22]Guarner J, Paddock CD, Shieh WJ, et al. Histopathologic and immunohistochemical features of fatal influenza virus infection in children during the 2003-2004 season [J]. Clin Infect Dis,2006,43(2):132-140.
[23]Korteweg C, Gu J. Pathology, molecular biology, and pathogenesis of avian influenza A (H5N1) infection in humans [J]. Am J Pathol,2008,172(5):1155-1170.
[24]Lee EY, McAdam AJ, Chaudry G, et al. Swine-origin influenza a (H1N1) viral infection in children:initial chest radiographic findings [J]. Radiology,2010,254(3): 934-941.
[25]Ajlan AM, Quiney B, Nicolaou S, et al. Swine-origin influenza A (H1N1) viral infection:radiographic and CT findings [J]. AJR,2009,193(6):1494-1499.
[26]Chowell G, Bertozzi SM, Colchero MA, et al. Severe respiratory disease concurrent with the circulation of H1N1 Influenza [J]. N Engl J Med,2009 361 (7):674-679.
[27]Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza a (H1N1) in Mexico [J]. N Engl Med, 2009,361 (7):680-689.
[28]Lister P, Reynolds F, Parslow R, et al. Swine-origin influenza virus H1N1, seasonal influenza virus, and critical illness in children [J]. Lancet,2009,374(9690):605-607.
[29]Greaves K, Oxford JS, Price CP, et al. The prevalence of myocarditis and skeletal muscle inlury during acute viral infection in adults:measurement of cardiac troponins I and T in 152 patients with acute influenza infection [J]. Arch intern Med,2003,163 (2):165-168.
[30]Kaiser L, Fritz RS, Straus SE, et al. Symptom pathogenesis during acute influenza: interleukin-6 and other cytokine responses [J]. J Med Vorol,2001,64(3):262-268.
[31]Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease:a systematic review [J]. Lancet Infect Dis,2009,9(10):601-610.
[32]汤正珍,何颜霞,郑跃杰等.儿童2009甲型H1N1流感相关神经系统并发症报道[J].中国实用儿科杂志,2010,25(2)：129-131.
[33]Lyon JB, Remigio C, Milligan T, et al. Acute necrotizing encephalopathy in a child with H1N1 influenza infection [J]. Pediatr Radiol,2009,40(2):200-205.
[34]Studahl M. Influenza virus and CNS manifestations [J]. J Clin Virol 2003,28 (3): 225-232.
[35]Jamieson B, Jain R, Carleton B, et al. Use of oseltamivir in children [J]. Can Fam Physician,2009,55(12):1199-1201.
[36]CDC. Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-2010 season. http://www.cdc.gov/h1n1flu/recommendations.htm.
[37]Matheson NJ, Harnden AR, Perera R, et al. Neuraminidase inhibitors for preventing and treating influenza in children [J]. Cochrane Database Syst Rev,2007,24(1): CD002744.
[38]CDC. Oseltamivir-resisitant 2009 pandemic influenza A (H1N1) virus infection in two summer campers receiving prophylaxis-North Carolina [J]. MMWR Morb Mortal Wkly Rep,2009,58(35):969-972.
[39]Alert letter.[US Food and Drug Administration web site]. December,2003. Available at:http://www.fda.gov/medwatch/SAFETY/2003/tamiflu_deardoc.pdf. Accessed January 14,2005.
[40]Okamoto S, Kamiya L, Kishida K, et al. Experience with oseltamivir for infants younger than 1 year old in Japan [J]. Pediatr Infect Dis J,2005,24(6):575-576.
[41]Mandell LA, Wunderink RG, Anzueto A, et al. Infectious diseases society of America/American Thracic Society consensus guidelines on the management of community-acquired pneumonia in adults [J]. Clin Infect Dis,2007,44(Suppl 2): S27-S72.
[42]Bernard GR,Luce JM, Sprung CL, et al. High dose corticosteroids in patients with the adult respiratory distress syndrome [J]. N Engl J Med,1987,317(25):1565-1570.
[43]Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome [J]. N Engl J Med,2006,354(16): 1671-1684.
[44]Griffith JF, Antonio GE, Kumta SM, et al. Osteonecrosis of Hip and Knee in Patients with Severe Acute Respiratory Syndrome Treated with Steroids [J]. Radiology, 2005,235(1):168-175.
[45]Tobin MJ. Culmination of an era in research on the acute respiratory distress syndrome [J]. N Engl J Med,2000,342(18):1360-1361.
[46]Quispe-Laime AM, Bracco JD, Barberio PA, et al. H1N1 influenza A virus-associated acute lung injury:response to combination oseltamivir and prolonged corticosteroid treatment [J]. Intensive Care Med,2010,36(1):33-41.
[47]高恒秒,李峥,陈晖,等.儿童甲型H1N1流感危重症临床特点分析[J].中国小儿急救医学,2009,16(6)：16-19.
[48]The ANZIC Influenza Investigators. Critical care services and 2009 H1N1 influenza in Australia and New Zealand [J]. N Engl J Med,2009,361(20):1925-1934.
[49]Luke TC, Kilbane EM, Jackson JL, et al. Meta-analysis:convalescent blood products for Spanish influenza pneumonia:a future H5N1 treatment? [J]. Ann Intern Med, 2006,145(8):599-609.
[50]Greenberg ME, Lai MH, Hartel GF, et al. Response to a monovalent 2009 influenza A (H1N1) vaccine [J]. N Engl J Med,2009,361(25):2405-2413.
[51]Clark TW, Pareek M, Hoschler K, et al. Trial of 2009 influenza A (H1N1) monovalent MF59-adjuvanted vaccine [J]. N Engl J Med,2009,361(25):2424-2435.
[52]Schonberger LB, Bergman DJ, Sullivan-Bolyai JZ, et al. Guillain-Barre syndrome following vaccination in the National Influenza Immunization Program, United States. 1976-1977 [J]. Am J Epidemiol,1979,110(2):105-123.