探讨SAA联合CRP在慢性阻塞性肺疾病急性加重期的临床应用
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摘要
目的本研究旨在探讨血清淀粉样蛋白A(serum amyloid A,SAA)联合C-反应蛋白(C-reactive protein,CRP)在慢性阻塞性肺疾病急性加重期(acute exacerbationof chronic obstructive pulmonary disease,AECOPD)的临床应用价值。
     方法在昆明医学院第一附属医院呼吸内科招募患者参加我们的研究,经过病史询问、体格检查、胸片和肺功能检查。符合纳入标准的中一极重度慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者112例(GOLDⅡ—Ⅳ级)(因中—重度极易反复急性加重),其中男67例,女45例;AECOPDⅠ级、AECOPDⅡ/Ⅲ级患者各56例[依据2004年美国胸科学会/欧洲呼吸学会(ATS/ERS)的COPD诊治指南:Ⅰ级,不需住院治疗;Ⅱ级,需住院治疗;Ⅲ级,存在呼吸衰竭。并以此标准作为判断住院与否的金标准]。AECOPDⅠ级患者在急性加重期、稳定期测血清SAA、CRP水平;AECOPDⅡ/Ⅲ级患者在急性加重期、恢复期、稳定期测血清SAA、CRP水平,其中9例于用糖皮质激素24小时后再检测SAA、CRP水平,且住院后至少做3次痰涂片及培养;被纳入的所有患者均检测肺炎支原体抗体;并随机抽取同期我院体检的健康对照者20例,其中男13人,女7人,测血清SAA、CRP水平。
     结果纳入的AECOPD患者血清SAA水平明显高于CRP水平,差异有统计学意义(P<0.05)。根据接收者工作特征(the receiver operatingcharacteristic,ROC)曲线分析,SAA、CRP均不能很好地将AECOPDⅠ级同COPD稳定期区分开,因为其ROC曲线下面积(AUC)分别为0.69、0.63;SAA与CRP相比能更好地将AECOPDⅡ/Ⅲ级同COPD稳定期区分开,因为其AUC值分别为0.91、0.80。糖皮质激素治疗前后血清SAA、CRP水平无统计学差异(P>0.05)。有脓痰或痰培养阳性者血清SAA、CRP水平明显升高。细菌感染组SAA、CRP水平高于肺炎支原体感染组,肺炎支原体感染组SAA、CRP水平高于急性加重的其他诱因组(P<0.05)。SAA、CRP水平均升高时,静滴抗生素5天左右后症状明显好转者,出院后继续口服抗生素3天组和住院静滴抗生素10-14天组,12个月随访的再住院次数、急性加重次数在两组间差异无统计学意义(P>0.05)。CRP基本正常、SAA升高时,用与不用抗生素组预后差异无统计学意义(P>0.05)。
     结论在AECOPD中SAA是较CRP更敏感的一个炎症标志物,有利于疾病的诊断与病情观察和治疗的判断,且SAA联合CRP有利于指导抗生素的应用,使用糖皮质激素治疗对患者的血清CRP、SAA水平无影响。
Objective To probe clinical application of serum amyloid A combinating C-reactive protein in acute exacerbation of chronic obstructive pulmonary disease.
     Methods Through disease history inquiry,physical examination,chest X-ray and pulmonary function test,we recruited 112 patients admitted to the Department of Respiratory Medicine,the First Affiliated Hospital of Kunming Medical College.Patients with COPD(GOLDⅡ-Ⅳlevel)include fifty six patients of AECOPDⅠlevel and fifty six patients AECOPDⅡ/Ⅲ(according to 2004 year ATS/ERS guide:levelⅠ,treated at home;levelⅡ,requires hospitalization;levelⅢ,leads to respiratory failure.The criteria is regarded golden criteria to decide wether patients require hospitalization.).There are 67 male patients,45 female patients.The concentrations of SAA and CRP in the serum were measured in patients with levelⅠAECOPD both acute exacerbation and stable stage and in twenty healthy volunteers(13 male,7 female);they were also measured in patients with AECOPD of levelⅡ/Ⅲamong acute exacerbation,stage of recovery,stable stage.The concentrations of SAA and CRP in the serum were measured again after twenty-four hours using glucocorticoid.And sputum smear and cluture were done three times at least after hospitalization.A11 AECOPD patients were measured antibody of Mycoplasma pneumoniae.
     Results The concentration of SAA was significantly higher than that of CRP in patients with AECOPD(P<0.05).According to the receiver operating characteristic curves(ROC curves) analysis principle,both SAA and CRP modestly distinguished levelⅠAECOPD from stable COPD,as ROC analysis generated AUC values of 0.69 for SAA and 0.63 for CRP;SAA was significantly better at differentiating levelⅡ/ⅢAECOPD from stable COPD with an AUC value of 0.91 versus CRP with an AUC value of 0.80(P<0.05). The concentrations of SAA and CRP before and after using glucocorticoid are not different in statistics.The concentrations of SAA and CRP in the serum were significantly higher when sputum was purulent or bacteria found. The concentrations of SAA and CRP in group of bacterial infection are higher than those of group of Mycoplasma pneumoniae infection,the concentrations of SAA and CRP in group of Mycoplasma pneumoniae infection are higher than those of group of other incentives(P<0.05).When SAA and CRP were both higher than normal level,one group used ivtravenous antibiotic about five days and symptom was significantly improved,then altered oral antibiotic using three days and the other group used ivtravenous antibiotic about 10-14 days in hospital.Times of hospitalization and acute exacerbation were not significantly different between the two groups after twelve months follow-up visit (P>0.05).Wether using antibiotic was not significantly different by twelve months follow-up visit when SAA was high and CRP was normal(P>0.05).
     Conclusion SAA is more sensitive inflammation marker than CRP in AECOPD,and is availed to diagnose disease and estimate therapy.Moreover, SAA combinating CRP can profit to direct application of antibiotic.The concentrations of SAA and CRP will not be affected by using glucocorticoid.
引文
1 Celli BR,MacNee W,ATS/ERS Task Force.Standards for the diagnosis and treatment of patients with COPD:a summary of the ATS/ERS position paper.Eur Respir J,2004,23:932-946.
    2 中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性废疾病诊治指南(2007年修订版).中华结核和呼吸杂志,2007,30(1):8-17.
    3 Roche N,Huchon G.Epidemiology of chronic obstructive pulmonary disease.Rev Prat,2004,54(13):1408-1413.
    4 梅长林等主编.内科学教程.慢性阻塞性肺疾病.北京:人民卫生出版社,2003:84-96.
    5 National center for Health statistics.Current estimates from the Nati-onal Health interview survey,United states,1995,Washington,DC:Department of Health and Human Services,Public Health Service,Vital and Health statistics,1995,Publica-tion No,1496-1527.
    6 丁乐杰,何权瀛.慢性阻塞性肺疾病诊治进展J.中华结核和呼吸杂志,1995,18(5):277-281.
    7 Paggiaro PL,Dahle R,Bakran I,et al.Multicentre randomized placeto controlled trial of inhaled disease,Lancet,1998,351:73-80.
    8 Steven Bozinovski,Anastasia Hutchinson,Michelle Thompson,et al.Serum amyloid is a biomarker of acute exacerbations of chronic obstructive pulmonary disease.Am J Respir CritCare Med,2008,177:269-278.
    9 Hill AT,Campbell EJ,Hill SL,et al.Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis.Am J Med,2000,109:288-295.
    10 Eller J,Ede A,Schaber G,et al.Infective exacerbations of chronic bronchitis.Relation between bacteriologic etiology and lung function.Chest,1998,113:1542-1548.
    11 Yamada T.Serum amyloid A(SAA):a concise review biology,assay methods and clinical usefulness.Clin Chem Lab Med,1999,37:381-388.
    12 Enguix A,Rey C,Concha A,et al.Comparison of procalcitonin with C-reactive protein and serum amyloid A for the early diagnosis of bacterial sepsis in critically ill neonates and children.Intensive Care Med,2001,27:211-215.
    13 Falsey A,Walsh C,Francis C,et al.Response of C-reactive protein and serum amyloid A to influenza A infection in old adults.J Infection Dis,2001,183:995-999.
    14 向玉成,温先勇,林燕英.4种急性时相蛋白在化疗患者真菌感染诊治中的价值.现代医药 卫生,2006,22(1):19-20.
    15 Murphy TF,Sethi S.Chronic obstructive pulmonary disease.Drugs Aging,2002,19(10):761-763.
    16 Husby G;Natvig JB.A serum component related to nonimmunoglobulin amyloid protein AS,a possible precursor of the fibrils.J Clin Invest,1974,53(4):1054-1061.
    17 Levin M,Pars M,Franklin EC.Immunologic studies of the major nonimmuno-globulin protein of the amyloid I identification and partial characte-rization of a related serum component.J Exp Med,1973,138:373-380.
    18 Whitehead AS,Debeer FC,Stell DM,et al.Identification of novel members of theserum amyloid A protein superfamily as constitutive apolipoproteins of high density lipoprotein.J Biol Chem.1998,267:3862-3867.
    19 Jensen LE,Whitehead AS.Regulation of serum amyliod A protein express-ion during the acute-phase response.Bio Chem J.1998,334:489-503.
    20 Rajeeta Hari-Dass,Chandrabala Shah,David J.Meyer et al.Serum amyloid A protein binds to outer membrane protein A of gram-negative bacteria.JBC Papers in Press,2005,280,18562-18567.
    21 Uragarin N,Landman WJ,Gaastra W,et al.Extrahepatic production of acute phase serum amyloid A.Histol Histopathol.2005,20(4):1295-1307.
    22 Urieli-Shoval S,Linke RP,Matzmer Y.Expression and function of serum amyloid A,a major acute phase protein,in normal and disease states.J Curt Opin Hematol,2001,7:64-69.
    23 Calabro P,Willerson JT.Inflammatiry eytokines stimulated C-reactive protein production by human coronary,artery smooth muscle cells[J].Circulation,2003,108(16):1930-1932.
    24 Jals WJ,Logering BA,Cerke P,et al.The kidney as a second site of human C-reactive protein formation in vivo[J].Eur J Immunol,2003,33(1):152-161.
    25 Could JM,Weiser JN.Expression of C-reactive protein in the human respiratory tract[J].Infect Immun.2001,69(3):1747-1754.
    26 何礼贤主编.肺部感染性疾病.上海医科大学出版社,1996,34-40.
    27 Hurst JR,Perera WR,Wilkinson TM,et al.Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease.Am J Respir Crit Care Med.2006,173:71-78.
    28 余立清,余铭鹏.血清淀粉样蛋白A——种新的载脂蛋白 ApoSAA.中华病理学杂志,1995, 24(2):113-115.
    29 Franciosi LG,Page CP,Celli BR,et al.Markers of exacerbation severity in chronic obstructive pulmonary disease.Respir Res,2006,7:74.
    30 Pinto-Plata V,Toso J,Lee K,et al.Profiling serum biomarkers in patients with COPD:associations with clinical parameters.Thorax,2007,62:595-601.
    31 Pinto-Plata VM,Livnat G,Girish M,et al.Systemic cytokines,clinical and physiological changes in patients hospitalized for exacerbation of COPD.Chest,2007,131:137-143.
    32 Dev D,Wallace E,Sankaran R,et al.Value of C-reactive protein measurements in exacerbations of chronic obstructive pulmonary disease.Respir Med,1998,92:664-667.
    33 Hurst JR,Donaldson GC,Perera WR,et al.Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2006,174:867-874.
    34 S Arnon,I Litmanovitz,RH Reyev,et al.Serum amyloid A:an early and accurate marker of neonatal early-onset sepsis.Joural of Perinatology,2007,27:297-302.
    35 Engui A,Rey C,Concha A,et al.Comparison of procalcitonin with C-reactive protein and serum amyloid for the earlydiagnosis of bacterial sepsis in critically ill neonates and children.Intensive Care Med,2001,27(1):211-215.
    36 Buyukozturk S,Gelincik AA,Kocak H,et al.Acute phase reactants in allergic airway disease.Tohoku J Exp Med,2004,204(3):209-213.
    37 Jousilahti P,Salomaa V,Hakala K,et al.The association of sensitive systemic inflammation markers with bronchial asthma.Ann.Allergy.Asthma Immunol,89,381-385.
    38 Steel DM.Donoghue FC,O'Neill RM.et al.Expression and regulation of constitutive and acute phase serum amyloid A mRNAs in hepatic and non-hepatic cell lines.Scand J Immunol,1996,44:493-500.
    39 O'Hara R,Murphy EP,Whitehead AS,et al.Local expression of the serum amyloid A and formy Ⅰ peptide receptor-like I genes in synovial tissue is associated with matrix metalloproteinase production in patients with inflammatory arthritis.Arthritis Rheum,2004,50:1788-1799.
    40 Sha Q,Truong-Tran AQ,Plitt JR,et al.Activation of airway epithelial cells by Toll-like receptor agonists.Am J Respir cell Mol Biol,2004,31:358-364.
    41 Pipa A,Bellettato CM,Braccioni F,et al.Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations.Am J Respir Crit Care Med,2006,173:1114-1121.
    42 Agusti AG.Systemic effects of chronic obstructive pulmonary disease.Proc Am Thorac Soc,2005,2:367-370.
    43 Thorn CF,Lu Z-Y,Whitehead AS.Regulation of the human acute phase serum amyloid A genes by tumour necrosis factor-a,interleukin-6 and glucocorticoids in hepatic and epithelial cell lines.Scand J Immunol,2004,59:152-158.
    44 Fyfe AI,Rothenberg LS,Debeer FC.et al.Association between serum amyloid A proteins and coronary artery disease:evidence from two distinct arteriosclerotic processes.Circulation,1997,96:2914-2919.
    45 施国华,刘兵,谭鹤龙等.C反应蛋白检测在监测慢性阻塞性肺疾病急性加重期使用糖皮质激素治疗临床研究[J].医学理论与实践,2006,19(11),1269-1270.
    46 Man SF,Sin DD.Effects of corticosteroids on systemic inflammation in chronicy obstructive pulmonar disease.Proc Am Thorac Soc,2005,2(1):78-72.
    47 Woodhead M,Blasi F,Ewig S,et al.Guidelines for the man agement of adult lower respiratory tract infections.Eur Respir J 2005;26(6):1138-1180.
    48 Blasi F,Damato S,Cosentini R,et al.Chlamydia pneumoniae and chronic bronchitis:association with severity and bacterial clearance following treatment.Thorax 2002;57(8):672-676.
    49 Alamoudi OS Bacterial infection and risk factors in outpatients with acute exacerbation of chronic obstructive pulmonary disease:a 2-year prospective study.Respirology.2007,12(2):283-287.
    50 Burley CJ,Masterton RG,Lovell DP.Indicators of bacterial infection in patients with acute exacerbation of chronic bronchitis for application in clinical trails of antibacterial drugs.J Infect.2007,55(3):226-232.
    51 熊彬,王荣丽,曹乃清等.慢性阻塞性肺疾病急性加重期痰细菌培养与肺功能关系探讨.实用心脑肺血管病杂志,2004,12(2):83-85.
    52 王秀香,杨敬平,孙得俊等.COPD急性加重的诱因及病原.临床肺科杂志,2006,11(2):176-177.
    53 Soler N.Ewing S,Torres A,et al.Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease.Eur Respir J,1999,14:1015-1022.
    54 Cabello H,Torres A,Celis R,et al.Bacterial colonization of distal airway in healthy subjects and chronic lung diseases:a bronehoscopic study.Eur Respir J,1997,10:1137-1144.
    55 Hanlon GW.The emergence of multidrug resistant Acinetobacter species:a major concern in the hospital setting.Lett Appl Microbiol,2005,41:375-378.
    56 刘玲,李晓静.老年慢性阻塞性肺疾病急性加重期肺部真菌感染的临床分析[J].中国临床保健杂志,2007,10(6):597-599.
    57 赵舰,刘锋,李秀珍.老年慢性阻塞性肺疾病继发真菌感染的危险因素[J].临床肺科杂志,2005,10(6):787.
    58 Monso E,Rosell A,Bonet Get al.Risk factors for lower airway bacterial colonization in chronic bronchitis.Eur Respir J.1999,13:338-342.
    59 Paterson DL,Singh N.Invasive aspergillosis in transplant recipients.Medicine(Baltimore),1999,78:123-138.
    60 Muquim A,Dial S,Menzies D.Invasive aspergillosis in patients with chronic obstructive pulmonary disease.Can Respir J,2005,12(4):199-204.
    61 徐凌、蔡柏蔷.浅析2006年慢性阻塞性肺疾病全球创议修订版.国际呼吸杂志,2007,27(3):161-165.
    62 Seemungal T,Harper-owen R,Bhowmik A,et al.Respiratory viruses,symptoms and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.Am J,Respir Crit Care Med,2001,164:1618-1623.
    63 Stolz D,Christ-Crain M,Bingisser R,et al.Antibiotic treatment of exacerbations of COPD:a randomized.controlled trial comparing procalcitonin-guidence with standard therapy.Chest.2007,131:9-19.
    64 Christ-Crain M,Jaccard-Stolz D,Bingisser R,et al.Effect of procalcition-guided treatment on antibiotic use and outcome in lower respiratory tract infections:cluster-randomised,single-blinded intervention trial.Lacet 2004,363:600-607.
    65 Muller B,Morgenthaler N,Stolz D,et al.Circulating levels of copeptin,a novel biomarker,in lower respiratory tract infections.Eur J Clin Invest,2007,37:145-152.
    66 Stolz D.Christ-Crain M,Morgenthaler NGet al.Copeptin,C-reactive protein and procalcitonin as prognostic biomarkers in acute exacerbation of COPD.Chest,2007,131:1058-1067.
    67 戴利成,沈水荣,吴阶明,等.联合检测 SAA 和 CRP 对小儿感染性疾病的早期鉴别诊断价值. 上海医学检验科杂志,2003,18(4):227-228.
    68 温先勇,郑燕,向成玉,等.医院感染诊治中急性时相蛋白的变化研究.中华医院感染学杂志,2006,16(12):1343-1346.
    69 Tasbakan Ms,Sayiner AA,Sayiner A.Role of atypical pathogens in infections in infectiousexacerbations of COPD.Tuberk Toraks,2007,55(4):336-341.
    70 Lieberman D,Ben-Yaakov M,Shmarkov O,et al.Serological evidence of Mycoplasma pneumoniae infection in acute exacerbation of COPD.Diagn Microbiol Infect Dis,2002,44(1):1-6.
    71 诸彭伟,葛婷婷,沈南平.肺炎支原体感染与C-反应蛋白的测定与临床意义[J].中国优生与遗传杂志,2003,11(5):35-41.
    72 陈小杰,汪相武,汪天林.非细菌性肺炎血 CRP 临床意义[J].中国微生态学杂志,2003,15(4):230.
    73 陈蕾,闻平.呼吸道感染患者血清 MP-IgM、Cpn-IgM 和 CRP 检测的临床意义[J].世界感染杂志,2006,6(4):303-305.
    74 张琳,徐建国.C反应蛋白与白细胞检测在小儿哮喘合并感染的应用[J].中国误诊学杂志,2009,9(7):1549-1550.
    75 徐华,毕淑英,郑春茜等.超敏C-反应蛋白在儿童不同病原感染中的诊断意义[J].空军总医院学报,2008,24(2):78-80.
    76 储德节,孙书明,胡志雄等.肺炎衣原体与慢性阻塞性肺疾病相关性[J]。中国感染与化疗杂志,2008,8(4):260-265.
    1 Whitehead AS,Debeer FC,Stell DM,et al.Identification of novel members of the serum amyloid A protein superfamily as constitutive apolipoproteins of high density lipoprotein.J Biol Chem.1998,267:3862-3867.
    2 Jensen LE,Whitehead AS.Regulation of serum amyliod A protein expression during the acute-phase response.Bio Chem J.1998,334:489-503.
    3 Ranjeeta Hari-Dass,Chandrabala Shah,David J.Meyer et al.Serum amyloid A protein binds to outer membrane protein A of gram-negative bacteria.JBC Papers in Press,2005,280,18562-18567.
    4 Upragarin N,Landman WJ,Gaastra W,et al.Extrahepatic production of acute phase serum amyloid A.Histol Histopathol.2005,20(4):1295-1307.
    5 Urieli-Shoval S,Linke RP,Matzmer Y.Expression and function of serum amyloid A,a major acute phase protein,in normal and disease states.J Curr Opin Hematol,2001,7:64-69.
    6 Yamada T.Serum amyloid A(SAA):a concise review biology,assay methods and clinical usefulness.Clin Chem Lab Med,1999,37:381-388.
    7 Enguix A,Rey C,Concha A,et al.Comparison of procalcitonin with C-reactive protein and serum amyloid A for the early diagnosis of bacterial sepsis in critically ill neonates and children.Intensive Care Med,2001,27:211-215.
    8 Falsey A,Walsh C,Francis C,et al.Response of C-reactive protein and serum amyloid A to influenza A infection in old adults.J Infection Dis,2001,183:995-999.
    9 Valle RP.Chavany C,Zhukov TA,et al.New approaches for biomarker discovery in lung cancer.Expert Rev Mol Diagn.2003,3:55-67.
    10 向玉成,温先勇,林燕英.4种急性时相蛋白在化疗患者真菌感染诊治中的价值.现代医药卫生,2006.22(1):19-20.
    11 温先勇,郑燕,向成玉,等.医院感染诊治中急性时相蛋白的变化研究.中华医院感染学杂志,2006,16(12):1343-1346.
    12 Renckens R,Renchers,Roelofs JJ,Knapp S,et al.The acute-phase response and serum amyloid A inhibit the inflammatory response to Acinetobacter baumannii pneumonia.J Infect Dis,2006,193(2):187-195.
    13 Lannergard A,Larsson A,Kragsbierg P,et al.Correlation between serum amyloid A and C-reactive protein in infectious diseases.Scand J Clin Lab Invest,2003.63(4):267-272.
    14 戴利成,沈水荣,吴阶明,等.联合检测SAA和CRP对小儿感染性疾病的早期鉴别诊断价值.上海医学检验科杂志,2003,18(4):227-228.
    15 Huttunen T,Teppo AM,Lupisan S,et al.Correlation between the severity of infectious diseases in children and the ratio of serum amyloid A protein and C-reactive protein.Scand J Infec Dis,2003,35(8):488-490.
    16 S Arnon,I Litmanovitz,RH Reyev,et al.Serum amyloid A:an early and accurate marker of neonatal early-onset sepsis.Joural of Perinatology,2007,27:297-302.
    17 Engui A,Rey C,Concha A,et al.Comparison of procalcitonin with C-reactive protein and serum amyloid for the earlydiagnosis of bacterial sepsis in critically ill neonates and children.Intensive Care Med,2001,27(l):211-215.
    18 Dai S,Wang X,Liu J,et al.Discovery and identification of serum amyloid A protein elevated in lung cancer serum.Sci China C Life Sci,2007,50(3):305-311.
    19 Khan N,Cromer CJ,Campa M,et al.Clinical utility of serum amyloid A and macrophage migrant inhibitory factor as a serum biomarkers for the detection of nonsmall cell lung carcinoma.Cancer,2004,101(2):379-384.
    20 Cho W,Yip T,Yip C,et al.Identification of serum amyloid A protein as a potential useful biomarkers to monitor relapse of nasopharyngeal cancer by serum proteomic profiling.Clin Cancer Res,2004,10:42-43.
    21 Liu DH,Wang XM,Zhang LJ,et al.Serum amyloid A protein:a potential biomarker correlated with clinical stage of lung cancer.Biomed Environ Sci,2007,20(1):33-40.
    22 Buyukozturk S.Gelincik AA.Kocak H.et al.Acute phase reactants in allergic airway disease.Tohoku J Exp Med.2004.204(3):209-213.
    23 Jousilahti P,Salomaa V,Hakala K,et al.The association of sensitive systemic inflammation markers with bronchial asthma.Ann.Allergy.Asthma Immunol,89,381-385.
    24 Steven Bozinovski,Anastasia Hutchinson,Michelle Thompson,et al.Serum amyloid is a biomarker of acute exacerbations of chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2008,177:269-278.
    25 Murphy TF.Sethi S.Chronic obstructive pulmonary disease.Drugs Aging,2002,19(10):761-763.
    26 Christine Poito MD,Muriel Coupaye MD,Jean-Pierre Laaban et al.Serum amyloid A and obstructive sleep apnea syndrome before and after surgically-induced weight loss in morbidly obese subjects.Obesity Surgery,2006,16:1475-1481.
    27 Rothkrantz-kos S,Van Dieijen-Visser MP,Mulder PG,et al.Potential usefulness of inflammatory markers to monitor respiratory functional impairment in sarcoidosis.Clin.Chem,49:1510-1517.
    28 Dan Agranoff,Delmiro,Fernandez-Reyes,et al.Identification of diagnostic markers for tuberculosis by proteomic finger printing of serum.Lancet,2006,368:1012-1021.

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