Investigation Of Predicting The Influenza A(H1N1) Pneumonia In Clinnical Early And Effectiveness Of Treatment With Convalescent Plasma For Inlfuenza A(H1N1) Pneumonia

Influenza, an acute respiratory infection caused by influenza virus, is oneof public concerns to human health. Influenza viruses are classified as types A,B and C, identified by antigenic differences in nucleocapside proteins(NP) andmatrixproteins(MP). Influenza A is most harmful to human. Influenza Aviruses are further classified, based on structures and genetic properties ofsurface hemagglutinin(HA) and neuraminidase(NA). Influenza A occurs inlocalized outbreak every1-2years through antigentic drift and may evolveinto a wordwide influenza pandemic every10-20years through antigenticshift. In the20th century, there have been four pandemics of influenza,including two influenza A(H1N1) pandemics.In2009, influenza A pandemic caused by reassortant H1N1influenza Aviruses again. A large number of patients with influenza appeared within avery short period of time. Most of the patients showed mild upper respiratorytract illness and could recover in1-2weeks, but the complications of thedisease appeared in part of the patients with influenza A(H1N1). The mostcommon complication of this outbreak was pneumonia, which became theprimary cause of critical illness such as severe pneumonia, acute respiratorydistress syndrome, shock, and death. The current study have proved thatunderlying disease, infants and young children, the elderly, pregnancy, obesity,onset-to-treatment interval longer, elevated liver enzymes are the risk factorsfor incidence of pneumonia in patients with influenza A(H1N1), butinvestigation of the initial symptoms and occupation as risk factors is barelyseen in the past reports. Human convalescent plasma against influenzaA(H1N1) was reported to be beneficial in reducing clinical mortality during the1918Spanish influenza pneumonia and in severe2009H1N1infections,but its efficacy in patients with2009pandemic influenza A(H1N1) pneumoniaremained unknown in Chengde area. It can improve clinical efficacy ofpassive immunotherapy in theory that high neutralizing antibody titer(NAT)plasma against influenza A viruse treat critically ill patients with influenza Ain early disease, but the people with high NAT plasma against influenza Aviruse remain unknown. The difference of neutralizing antibody titer isuncertainty between different conditions.To investigate the risk factors for influenza A(H1N1) pneumonia and themethod improving ability to predict the patients of susceptibility influenza A(H1N1) pneumonia in clinical early, the clinical features of patients withinfluenza A H1N1hospitalized at Chengde Hospital for Infections Diseasesfrom September to December of2009were retrospectively analyzed; To studythe effectiveness of treatment with convalescent plasma for influenza A(H1N1)pneumonia,7patients with pneumonia of influenza A(H1N1) hospitalized atChengde Hospital for Infections Diseases, who were given the convalescentplasma treatment, were retrospectively analyzed. To investigate the methodimproving the clinnical effect treatment with convalescent plasma forinfluenza A(H1N1) pneumonia, the plasma samples against2009influenza A(H1N1) recruited in Chengde city blood bank were tested throughhemagglutination inhibition test. Our study covers two parts:Part I: Investigation of predicting the influenza A(H1N1) pneumonia inclinical earlyPart II: Investigation of the effectiveness of treatment with convalescentplasma for influenza A(H1N1) pneumoniaPart I: Investigation of predicting the influenza A(H1N1) pneumonia inclinical earlyObjective:To investigate the risk factors for influenza A(H1N1) pneumonia and the method improving ability to predict the patients of susceptibility influenza A(H1N1) pneumonia in clinical early.Methods:All the patients who were diagnosed with novel influenza A(H1N1) inChengde area between September and December of2009were concentrated inChengde Hospital for Infectious Diseases for free treatment; the basis fordefinite diagnosis of the totally206patients was consistent with the “Protocolfor Diagnosis and Treatment of Influenza A (H1N1)(2009Third Edition)”issued by the General Office of Ministry of Health; A retropective study ofearly clinical situation of206cases with difinit diagonosis was conducted.Based on the final imaging findings, these patients were divided intopneumonia group(51cases) and non-pneumonia group(155cases). A casecontrol study, including statistical analysis, on the clinical characteristics ofthe2groups of patients was carried out. Unicariate analysis and multivariatelogistic regression analysis were used to identify independent predictors ofpneumonia; Goodness of Fit test was performed on an estabished clinicalpredicting scoring system.Results:1. Univariate analysis1.1Comparison of clinical features between two groups of patientsInitial symptoms including cough and expectoration and dyspnea,onset-to-treatment interval>48hours, Postpartum, Underlying diseases,Occupation including Preschool children, Farmers, Unemployed and retiredurban residents, Other professions were higher in pneumonia group than innon-pneumonia group, with difference of statistical significance (all P<0.05).Above factors are the risk factors for influenza A(H1N1) pneumonia. Thedifference in Age distribution had statistical significance between the twogroups (P＜0.001). The difference in gender, initial symptoms sore throat,BMI had no statistical significance between the two groups (P>0.05). Initialsymptoms including fever, headache were lower in pneumonia group than innon-pneumonia group, with difference of statistical significance (all P<0.05). 1.2Comparison of blood routine and biochemical indexes between twogroups of patients on admissionWhite cell count<4×10~9cells/l, White cell count>10×10~9cells/l,Lymphocyte count<0.8×10~9cells/l, Thrombocytopenia<100×10~9cells/l,Hemoglobin<110g/L, Serum albumin<35g/L, Aspartate aminotransferase>40U/L, Alanine aminotransferase>40U/L, Lacticdehydrogenase>250U/L,Creatine kinase>195U/L, Creatine kinase-MB>40U/L, Potassiu<3.5mmol/L, Sodium<135mmol/L, Calcium<1.75mmol/L, Fasting bloodglucose>6.4mmol/L were higher in pneumonia group than in non-pneumoniagroup, with difference of statistical significance (all P<0.05). Above factorsare the risk factors for influenza A(H1N1) pneumonia.2. Multivariate logistic regression analysisForward multivariate logistic regression analysis was performed usingprogression into pneumonia as dependent variable and factors of statisticalsignificance in the above univariate analysis as independent variables.Multivariate logistic regression analysis of the statistically significant factorsshowed that: expectoration as initial symptom [relative odds ratio(OR)=3.537,95%confidence interval (95%CI)(1.016~12.311)], onset-to-treatmentinterval>48hours[OR=19.525,95%CI(4.576~83.309)],LDH>250U/L[OR=16.717,95%CI(5.484~34.417), k<3.5mmol/L[OR=7.332,95%CI(1.763~49.709)],AST>40U/L[OR=3.809,95%CI(1.008~12.460)], presence of underlyingdiseases[OR=61.003,95%CI(2.808~1325.304)] are the independent riskfactors for influenza A (H1N1) pneumonia (all P <0.05).3. The prignostic criteris had a good discriminstive ability[area underreceiver operating characteristic curve(AUC)was0.965(95%CI0.939~0.992),P<0.001].4. Prediction scoring system of pneamonia was established according thelevel of six high risk factors. Low risk(score0-2), intermediate risk(score3-4),high risk(score5-6) and very high risk(score7) were categorized for predictingthe occurrence of pneamonia illness.and the Goodness of fit test was good(R~2=0.916, P=0.043). Conclusion:1.The independent risk factors for influenza A (H1N1) pneumonia areexpectoration as initial symptom， interval>48hours，LDH>250U/L，k<3.5mmol/L，AST>40U/L，presence of underlying diseases.2. During future epidemic of influenza A (H1N1), relevant physicians canpredict the susceptibility pneumonia in patients with influenza A(H1N1) byusing initial symptom, onset-to-treatment interval time, level of serumPotassiu and Aspartate aminotransferase, presence of underlying diseasesand it is helpful in making clinical decision qucikly. Part II: Investigation of the effectiveness of treatment with convalescentplasma for influenza A(H1N1) pneumoniaObjective:To investigate the effectiveness of treatment with convalescent plasmafor influenza A(H1N1) pneumonia in Chengde area and the method improvingthe clinnical treatment effect with convalescent plasma for influenza A(H1N1)pneumonia.Methods:7patients with pneumonia (1sever ill patient and6critical ill patients) ofinfluenza A H1N1hospitalized at Chengde Hospital for Infections Diseases,who were given the convalescent plasma treatment, and19critical ill patientswithout the convalescent plasma treatment, were retrospectively analyzed. Acase control study, including statistical analysis, on the clinical characteristicsbetween6critical ill patients with the treatment group with convalescentplasma and the control group without the convalescent plasma treatment group.195antibody plasma samples against influenza A(H1N1)2009were recruitedin Chengde city blood bank, including165vaccine recipients and30 convalescents, in addition20plasma samples donated during influenza A(H1N1)2009epidemic were recruited from the normal population. Thehemagglutination inhibition test was conducted to detect antibody titersagainst influenza A (H1N1)2009.Results:1. Detailed information of7patients offered treatment with convalescentplasmaThis study included7patients including5men and2women who wereaged between0.6and79years without underlying diseases and withpneumonia of influenza A H1N1. Of them,1patient was sever ill patient and6patients were critical ill patients. APACHE II score were between10and19.The time from manifestation of symptoms to Oseltamivir treatment was4-7days; The time from admission to convalescent plasma treatment was7-36hours. All of them were given treatment with antibiotics,Glucocorticoid,Immunoglobulin. Of them,1patient combined myocarditisand4patients combined ARDS, receiving mechanical ventilation. Finally,1deceased, the rest patients were cured and discharged.2. Comparison of demographic and clinical factors between the treatmentgroup and the control groupThe difference in gender, age, Leukocyte count, Lymphocyte count,Lactic dehydrogenase, Aspartate am inotransferase, Alanine aminotransferase,Creatine kinase-MB, PaO2/FIO2, APACHE II score, Interval from onset toantivira, Use of corticosteroids, Duration of fever after admission,Hospitalization time, death had no statistical significance(all P>0.05). Themedian age, Underlying diseases, Creatine kinsewere lower in convalescentplasma treatment group than in no convalescent plasma treatment group, withdifference of statistical significance (all P<0.05). Combined ARDS,Mechanical ventilation(IPPV), use of Immunoglobulin were higher inconvalescent plasma treatment group than in no convalescent plasmatreatment group, with difference of statistical significance (all P<0.05).3. Comparison of NAT≥1:320and GMT among the three groups The difference in gender had no statistical significance among the threegroups(χ~2=1.199P=0.549). The difference in average age had statisticalsignificance(F=11.657，P<0.001). The average age in convalescents groupwas lower than in the vaccine recipients group and the normal population,with difference of statistical significance(all P<0.001). There were significantdifferences on rates of high NAT and Geometiic mean titers(GMTS) amongthree groups plasma samples (all P<0.001). The rate of high NAT ofvaccinationg group was significantly higher than convalescent group andnormal population(all P<0.0125). GMTS: vaccinationg group>convalescentgroup>normal population, the differernces were statistically significant (allP<0.05).4. Comparison of NAT≥1:320and GMT in different gender, age anddifferent donation time after vaccination in vaccine recipientsIn vaccination group,there were no significant differences in the rates ofhigh NAT and GMTS between males and females(P=0.657and0.234respectively). the rates of high NAT and GMTS in defferent age gpoups:18~27years>28~37years>38~48years, but no significantdifferences(P=0.227and0.063respectively). There was difference ofstatisticlly significant in rates of high NAT of defferent donation times aftervaccination(P=0.024),31~50days and51~70days were both significantlyhigher than71~90days(P=0.012and0.011respectively). there was nosignificant differences between31~50days and51~71days(P=0.603). Thedifference in GMTS had no statistical significance among defferent donationtimes after vaccination(P=0.276).5. Comparison of NAT≥1:320and GMT between the sever ill groupsand the mild illThe difference in gender had no statistical significance between the twogroups (χ~2=0.151P=1.0). The difference in average age had no statisticalsignificance(t=-0.599P=0.544). In convalescent, the rates of high NAT andGMT in sever ill patients were both significantly higher than in mild illpatients(P=0.011and0.034respectively). Conclusion:During influenza A pandemic in a future, it can improve the efficiency ofrecruitment antibody plasma that antibody plasma for treating critically illpatients with influenza A will be drawn from convalescent donors with severeinfluenza A and31~70days donors after vaccination old during influenza Apandemic in a future.