9 Respiratory System

2015201 Outbreak of six cases of nosocomial Legionella pneumophila pneumonia.LI Yan（李嫣），et al. Dept Respir&Critical Care Med，Med Edu Dept，Affil Hosp，Logistics Univ，PAPF，Tianjin 300162.Chin J Tuberc Respir Dis 2015；38（4）：294-297.

Objective To describe the clinical characteristics，diagnosis，treatment and the causes of outbreak of nosocomial pneumonia due to Legionella pneumophila.Methods The medical records of 6 cases of nosocomial Legionella pneumophila pneumonia were retrospectively reviewed，and the clinical data of clinical presentation，treatment，and etiologic diagnosis were analyzed.Results The 6 patients were staff of the Department of Respiratory and Critical Care Medicine of the Affiliated Hospital of Logistics University of PAPF.There were 5 female and 1 male patients，aged 23 to 27 years.The diagnosis of Legionella pneumophila was made based on a positive Legionella urinary I antigen test.In all the 6 cases，the disease was attributable to inhaling contaminated aerosols produced by the air conditioning system in our hospital.All the 6 patients presented with fever of 37.5-39℃，and productive cough.One patient had anorexia，dyspnoea，and pleuritic chest pain，while headache was reported in 3 patients.Physical examination s revealedlung rales in 3 patients.Single or multiple patchy infiltrates were found on Chest CT in all patients.However，the typical extrapulmonary manifestations of Legionnaires' disease，including relative bradycardia，hyponatremia，hypophosphatemia and diarrhea，were not present in the 6 patients.Neither neurological abnormalities nor renal involvement were observed.Conclusion Our data demonstrated that Legionella pneumonia may be mild with atypical laboratory findings and clinical manifestations，with fever，cough，chest tightness，headache，etc.The radiologic manifestations of Legionella pneumonia were single or multiple patchy infiltrates，similar to those of viral pneumonia，and therefore their differential diagnosis wasneeded.Legionellapneumophilacanoutbreak through the respiratory tract，in public places with central air-conditioning system，hot water piping systems and hospitals，andthereforemicrobiologicalmonitoring，cleaning and disinfection of the water system was required for prevention of the outbreaks of Legionnaires' disease.

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2015202 The effect of MTB antigens on the NFAT5 expression in monocytes from human peripheral blood.LIU Yanhua（刘艳华），et al.Army Tuberc Prev &Contr Key Lab，Beijing 100091.Chin J Tuberc Respir Dis 2015；38（9）：290-293.

Objective To study the effect of Mycobacterium tuberculosis antigens early secretory antigen target 6/culture filtrate protein 10（ESAT-6/CFP-10）on nuclear factor of activated T-cells 5（NFAT5）mRNA in monocytes from human peripheral blood.Methods Fifteen patients with active pulmonary tuberculosis（age range：33-42 y，mean：37 y，male/female：9/6）were recruited from the Institute of Tuberculosis in 309 Hospital，and 15 healthy subjects（age range：37-42 y，mean：40 y，male/female：9/6）were recruited from Medical Examination Center of the hospital.Monocytes were isolated from peripheral blood and stimulated with whole cell lysate of H37Rv strain and peptide pool of ESAT-6/CFP-10.Fluorescence quantitative PCR was used to detect the mRNA expression of NFAT5，and differences of NFAT5 mRNA between unstimulated and stimulated monocytes were analyzed by paired t test statistic method.Results The expression of NFAT5 mRNA in monocytes from patients with active pulmonary tuberculosis was significantly decreased when stimulated with peptide pool of ESAT-6/ CFP-10 compared with unstimulated monocytes（0.18± 0.12 vs.0.23±0.15）（t=2.591，P＜0.05）.Similarly，the expression of NFAT5 mRNA in monocytes from healthy subjects was also significantly decreased when stimulated with peptide pool of ESAT-6/CFP-10 compared with unstimulated monocytes（0.17±0.09 vs 0.21± 0.09）（t=2.828，P＜0.05）.However，the expression of NFAT5 mRNA in monocytes stimulated with whole cell lysate was not significantly changed（t=1.142，P＞0.05），which was 0.28±0.25 and 0.23±0.15 in stimulated and unstimulated monocytes，respectively. Similarly，the expression of NFAT5 mRNA in monocytes from healthy subjects was also not significantly changed when stimulated with whole cell lysate（t=0.451，P＞0.05），which was 0.20±0.12 and 0.21±0.09 in stimulated and unstimulated monocytes，respectively. Conclusion The MTB antigen ESAT-6/CFP-10 can inhibit NFAT5 expression in human monocytes in vitro.

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2015203 Evaluation of a mouse model of chronic obstructive pulmonary disease induced by intraperitoneal injections of cigarette smoke extract.ZHANG Qian（张倩），et al.Dept Respir Med，Beijing Tongren Hosp，Capital Med Univ，Beijing 100730.Chin J Tuberc Respir Dis 2015；38（4）：279-285.

Objective To evaluate a mouse model of chronic obstructive pulmonary disease（COPD）induced by intraperitoneal injections of cigarette smoke extract（CSE），and to study the potential mechanisms.Methods Mice were injected intraperitoneally with CSE at different time points to establish a mouse model of COPD.Mouse lung mechanics parameters were measured，and the total numbers and differentials of cells in bronchoalveolar lavage fluid（BALF）were counted.Pathological changes of lung tissue were observed and mean linear intercept（MLI）and alveolar destructive index（DI） were measured.Theexpressions of matrix metalloproteinases-12（MMP12），neutrophil elastase（NE），tissue inhibitor of metalloproteinase-1（TIMP1），pro-inflammatory cytokines（TNF-α，IL-1β，IL-6），Th1 cytokines（IFN-γ），Th2 cytokines （IL-5，IL-13）and the neutrophil chemokine KC were determined in the lungs of all mice.Results Significant increase of total lung capacity（TLC）［（0.73±0.02），（0.83±0.04），（0.97±0.02）ml］was found in the CSE group as compared with the PBS control group［（0.65±0.01），（0.67±0.02），（0.71±0.04）ml，t=4.109，3.666，5.994，P＜0.01］at day 21，41，61.Lung compliance was higher in the CSE group［（0.041±0.002）ml/cmH2O（1 cmH2O=0.098 kPa），（0.039±0.001）ml/cmH2O］than the PBS control group［（0.030±0.001）ml/cmH2O，（0.032± 0.003）ml/cmH2O，t=4.788，2.508，P＜0.05］at day 41，61，but airway resistance in the lungs（R）was lower in the CSE group［（0.959±0.016）cmH2O·s· ml-1，（0.976±0.020）cmH2O·s·ml-1］than the PBS control group［（1.043±0.022）cmH2O·s· ml-1，（1.085±0.043）cmH2O·s·ml-1］（t= 2.928，2.321，P＜0.05）.The total numbers of BALF cells in the CSE group［（23.83±2.63）×104，（20.67± 1.69）×104，（18.67±1.56）×104］were increased compared with the PBS control group［（7.33±0.61）× 104，（7.67±0.76）×104，（6.67±0.88）×104，t= 6.119，7.027，6.685，P＜0.01］at day 21，41，61，predominantly with neutrophils and macrophages.Typical COPD pathological changes of lung tissue were evident，including inflammatory cell infiltration in the lung parenchyma and increased mean linear intercept（MLI）in the CSE group［（48.0±1.4），（56.1±2.4），（59.3± 3.3）μm］as compared with the PBS control group［（40.5±1.2），（43.7±1.2），（43.5±1.2）μm，t= 4.015，4.695，4.612，P＜0.01］as well as increased alveolar destructive index（DI）in the CSE group［（15.2± 1.3）%，（22.4±1.3）%，（23.8±1.0）%］as compared with the PBS control group［（11.1±0.9）%，（10.8±1.0）%，（12.4±0.7）%，t=2.532，7.225，8.471，P＜0.05］at the 3 time points.The expressions of MMP12 and NE increased significantly in the CSE-treated mice.Pro-inflammatory cytokines（TNF-α，IL-1β，L-6），Th1 cytokine IFN-γ and KC all increased significantly in the CSE-treated mice as compared with the PBS-control mice.Conclusion A mouse model of COPD was successfully established by repeated intraperitoneal injections of CSE in a shorter period of time.Local inflammation and proteinase/anti-proteinase imbalance as a result of CSE-induced immunological responses may be the underlying mechanisms.

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2015204 Effects of 17-AAG on the proliferation and apoptosis of human lung cancer A549 and H446 cells.NIU Ben（牛奔），et al.Dept Respir Med，Centr Hosp，Shengli Oil Field，Dongying 257034.Chin J Tuberc Respir Dis 2015；38（4）：267-272.

Objective To observe the effect of 17-（allylamino）-17-demethoxygeldanamycin（17-AAG）on the apoptosis of human lung cancer cell lines A549 and H446，and to investigate the potential mechanisms.Methods Proliferation inhibition and apoptosis assays，and the cell cycles were detected by MTT and flow cytometry respectively. Western blot was used to determine the expression level of proteins such as Hsp90，Hsp70，Akt，Her-2，Bcl-2 and Bax.Results After treated with 17-AAG，the proliferation of both A549 and H446 cells was inhibited significantly in a dose-dependent manner；as the concentration of 17-AAG was from 50 to 500 nmol/L，the IC50values to A549 and H446 cell lines were（222±13）nmol/L and（189±7）nmol/L respectively at 48 h.Cell cycle assays showed that 17-AAG was able to arrest cell cycles of A549 and H446 cell lines at the G2/M phase.Apoptosis assay showed that 17-AAGwas capable of inducing apoptosis in A549 and H446 cell lines.After treated with 17-AAG for 48 h，there were significant differences between the 400 nmol/L groups（46.3%for A549 cell line and 56.9%for H446 cell line）and the control group （11.9%for A549 cell line and 6.9%for H446 cell line，P＜0.01）.Western blot results showed that the relative proteins of the Hsp90 signal pathway in both A549 and H446 cell lines underwent similar changes after 17-AAG treatment：Akt and Her-2 decreased significantly while the expression of Hsp70 increase d.Mean-while，the expression of Bcl-2 decreased but that of Bax increased，indicating that 17-AAG was able to promote apoptosis mode in A549 and H446 cells.Conclusion 17-AAG can regulate the expression level of apoptosis-related proteins such as Bax and Bcl-2 by Hsp90 signaling pathway in A549 and H446 cells，and ultimately inhibit cell proliferation and induce apoptosis.

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2015205 Application and validity evaluation of fatfree mass index in malnutrition screening in patients with stable chronic obstructive pulmonary disease. CHEN Lian（陈炼），et al.Gaduate Sch，South Med Univ，Guangzhou 510515.Chin J Geriatr 2015；34（4）：387-390.

Objective To evaluate the validity of fat-free mass index in malnutrition screening in patients with stable chronic obstructive pulmonary disease（COPD）.Methods A total of 235 patients with stable COPD were enrolled from out-patient department，and each of them was measured for anthropometric indicators，urine creatinine and blood biochemical indicators.Body composition was assessed by bioelectrical impedance analysis and their body mass index（BMI）and fat-free mass index（FFMI）were calculated.Body composition assessment（BCA），BMI，FFMI and mini-nutritional assessment（MNA）were used for screening malnutrition in enrolled patients.U-sing BCA as the diagnosis standard of malnutrition，the sensitivity，specificity，Youden's index（YI）and consistency of FFMI，BMI，MNA with BCA were compared. Results The incidence of malnutrition screened by BCA，FFMI，BMI and MNA were 47.6%，48.5%，8.3%，53.2%respectively.The sensitivity of FFMI，BMI and MNA screening for malnutrition was 92%，33%，and 86%，the specificity was 91%，95%and 75%，the Youden's index（YI）was 0.83，0.28 and 0.38 and Kappa value were 0.84，0.29，0.60 respectively（all P＜0.01）.Conclusion Compared with BMI and MNA，FFMI shows higher sensitivity，specificity，YI and agreement with BCA，which is suitable for patients with stable COPD in screening malnutrition.

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2015206 Prognostic factors and response of chemotherapy including amrubicin in small cell lung cancer patients.WANG Yuyan（王玉艳），et al.Dept Thoracic Oncol，Beijing Cancer Hosp，Beijing Univ Oncol Coll，Beijing 100142.Chin J Tuberc Respir Dis 2015；38（4）：261-266.

Objective To evaluate the response，toxicity and prognostic factors of amrubicin in the therapy of small cell lung cancer（SCLC）.Methods Thirty-one SCLC patients treated with amrubicin in Beijing Cancer Hospital from Dec.2008 to Arp.2013，including 21 males and 10 females，aged from 32 to 75 years，were enrolled in this study.Amrubicin was injected intravenously with 40 mg/m2d1-3，Q21 d or combined with cisplatin 60 mg/ m2d1，Q 21 d.The first line chemotherapy regiments included amrubicin plus cisplatin in 11 cases，etopside plus platin in 18 cases and other drugs in 2 cases.The second and more line chemotherapy treatments included amrubicin in 20 cases，topotican in 14 cases and others in 28 cases.SPSS 16.0 statistical analysis software was used to analyze the clinical characteristics and survivals. Results The median progression free survival（PFS）of patients receiving amrubicin plus cisplatin and single amrubicin were 7.5 months（95%CI：6.2 to 8.8）and 4.1 months（95%CI：1.2 to 7.0）respectively（P= 0.090）.There were 16 refractory patients whose disease progressed within 3 months after first line chemotherapy and 15 sensitive patients who had tumor progression after more than 3 months；the median survival time（MST）were 14.2 months（95%CI 11.1-17.3）and 21.3 months（95%CI 15.7-26.9）respectively（P= 0.018）.Patients treated with amrubicin plus cisplatin as first line therapy had a prolonged median PFS compared with etopside plus platin，which were 7.5 months（95% CI：6.2-8.8）vs.4.6 months（95%CI：1.7-7.5）（P=0.055）.Patients received amrubicin，topotican or other drugs as second or other line therapy had median PFS of 4.1 months（95%CI：1.2-7.0），1.4 months （95%CI：0.8-2.0）and 1.6 months（95%CI：1.2-1.9）respectively（P=0.013），while the median PFS was 5.6 months（95%CI：2.0-9.2），1.4 months （95%CI：0.6-2.2）and 1.4 months（95%CI：0.8-2.0）（P=0.005 and 0.003）in refractory patients. Conclusion Amrubicin as second or other line treatment was shown to be an effective and safe drug for SCLC patients with a significant survival benefit compared with other drugs，especially in refractory patients.It suggested that amrubicin might be one of the preferred therapies for refractory SCLC.

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2015207 Correlation of thin-section CT morphologic features and pathological vascular invasion in the clinical stage IA peripheral lung adenocarcinoma. ZHOU Ying（周莹），et al.Dept Radiol&Nucl Med，ChangzhengHosp，2ndMilit MedUniv，Shanghai 200003.Chin J Radiol 2015；49（4）：259-263.

Objective To evaluate the correlation between thinsection CT morphologic features and pathological vascular invasion in the clinical stage IA peripheral lung adenocarcinoma.Methods The preoperative thin-section CT images，clinical and pathological characteristics of 102 nodules in 98 patients were retrospectively analyzed and divided into two groups according to pathological vascular invasion.Variables including the diameter of tumor（T）and consolidation part（C）in the mix ground glass nodule（mGGN），C/T ratio，morphology and pathological classification were analyzed by two-independent samples Mann-Whitney U test or t test and χ2test or Fisher exact probability test.Variables with significant difference in the univariate analyses were entered into multivariate analysis to explore predictors for vascular invasion.The correlation between these measurements and vascular invasion was evaluated by a ROC analysis.Results All of 102 nodules，36 had pathological vascular invasion and 66 without.The numbers of two groups with speculation，air bronchogram，abnormal vein，vascular convergence，pleural indentation were 30，30；26，26；3；35，39；32，29 and the median diameter of tumors were 2.1（1.0-3.0），1.2（0.5-3.0）cm respectively.By univariate analysis，spiculation，air bronchogram，abnormal vein，vascular convergence，pleural indentation，and diameter of tumor were significantly associated with pathological vascular invasion（P＜0.01）.By multivariate logistic analysis，statistically significant differences were found in speculation and abnormal vein（OR=33.867，8 161.063，P＜0.05）.The ROC analysis showed the area under curve，cut-off value，sensitivity and specificity ofthe diameter of tumor and consolidation part of mGGN and C/T ratio were 0.784，2.05 cm，66.7%，78.8%，0.886，1.08 cm，82.4%，90.0%and 0.861，0.65，79.4%，85.0%respectively in differentiating tumors with pathological vascular invasion.Conclusion The spiculation sign and abnormal vein are independent predictors for vascular invasion in stage IA peripheral lung adenocarcinoma.

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2015208 Relationship between histopathologic characteristics and epidermal growth factor receptor mutation in lung adenocarcinoma.WANG Kai（王凯），et al.Dept Pathol，1st Affil Hosp，Med Coll，Xi'an Jiaotong Univ，Xi'an 710061.Chin J Pathol 2015；44（3）：170-174.

Objective To correlate morphological features with mutations of epidermal growth factor receptor（EGFR）in lung adenocarcinomas.Methods According to 2011 International Association for the Study of Lung Cancer/A-merican Thoracic Society/European Respiratory Society InternationalMultidisciplinaryLungAdenocarcinoma Classification，a total of 72 surgically resected lung adenocarcinomas were collected and classified into different histological subtypes and different cell types（hobnail，columnar and polygonal）.EGFR gene mutation was detected with the amplification refractory mutation method provided by the EGFR mutation test kit.The correlation between these subtypes and EGFR mutations were evaluated.Results Mutations of EGFR were detected in 48.6% （35/72）of lung adenocarcinomas；19del and L858R were major mutational types（88.6%，31/35）.EGFR mutations were associated with female gender，non-smoking status，and well to moderately differentiated tumor histology.EGFR mutation types were not associated with age，smoking index，lymph node metastasis，stage.Correlations were observed between acinar and papillary adenocarcinoma subtypes and EGFR mutations acco rding tothe new classification.EGFR mutation was rare in the subtype of solid adenocarcinoma with mucin production and almost never observed in special subtypes（mainly mucinous and colloid adenocarcinoma）.In addition，EGFR mutation was associated with the hobnail cell type.Conclusion Lung adenocarcinomas of predominate acinar and papillary histological subtypes with hobnail cell morphology are good predictors for EGFR mutations.

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