Pneu-monia and Chronic Heart Failure
Vladyslav BEREZNYAKOV1, Oleksii KORZH1, Maryna LEBEDYNSKA1, Igor BEREZNYAKOV1 Kharkiv Medical Academy of Postgraduate Education, Ukraine1
Background: Step-down therapy is well-established option in management of hospi-talized patients with community-acquired pneumonia (CAP) but it is not the same in cases of combination of CAP and chronic heart failure (HF).
Methods: A total of 139 pts with CAP aged 44-73 years were divided into 3 groups.
73 pts with CAP and HF were included in step-down therapy group (1-st gr.), 36 pts with CAP and HF formed parenteral antimicrobial therapy (AMT) group (2-nd gr.), the 3-rd group on step-down therapy consisted of 30 pts with CAP and no co-morbidities.
Step-down therapy was implemented in accordance with national CAP management protocol after achieving of clinical stability on 3 to 5 days after beginning of AMT. An effectiveness of treatment was evaluated in 12±2 days after starting of AMT and was classified as positive results (recovery + improvement), clinical failure or “impossible to evaluate”. Length of stay (LOS) in hospital and duration of AMT were studied also.
Results: There was no difference between groups in frequency of positive results (97.3% in the 1-st group, 91.7% in the 2-nd group and 96.7% in the 3-rd group) and clinical failures (2.7% vs. 8.3% vs. 0, respectively). LOS and duration of AMT in the 1-st group did not differ from the same indices in the 2-nd and 3-rd groups. Decrease in frequency of pts suffering from cough and dyspnoea in the 1-st group was docu-mented earlier than in the 2-nd group (in 7±1 and 12±2 days after starting of AMT, respectively).
Conclusions: An effectiveness of step-down therapy in hospitalized patients with non-severe CAP and HF did not differ from traditional parenteral AMT. There are some clinical indices in favor of step-down therapy in such kind of pts.
OS-RES-02 Respiratory Medicine Clinical Features of 46 Cases with Organizing Pneumo-nia Diagnosed by Transbronchial Lung Biopsy
Masako AMANO1, Tomotaka NISHIZAWA1, Tomohiro OHBA1, Kojirou HONDA1, Ryo OKUDA1, Hidekazu MATSUSHIMA1
Saitama Red Cross Hospital, Japan1
Background: Generally, organizing pneumonia (OP) responds well to steroid therapy with good prognosis. However, relapses sometimes occur, thus a treatment policy based on the cause and background of each case should be carefully considered.
Methods: The medical records of 46 patients with biopsy-proved OP were retrospec-tively reviewed. Their clinical presentations, radiographic studies, bronchoalveolar lavage (BAL) findings, treatment, and outcomes were analyzed. Cases where the final diagnosis was eosinophilic pneumonia were excluded from this study.
Results: The mean age at presentation was 64±13.9 years. Nineteen patients were diagnosed with Cryptogenic organizing pneumonia (COP), 6 patients had drug induced OP, 6 patients were associated with collagen disease, 7 patients had post pneumonia, 4 were post-radiation therapy patients, 3 patients were finally diagnosed with nonspe-cific interstitial pneumonia (NSIP) and 1 patient was associated with radiofrequency ablation (RFA) for hepatocellular carcinoma. Twenty nine patients were treated with systemic steroid therapy. The mean duration of steroid therapy was 7.2 months. The relapse rate was 10% for COP and 75% for post-radiation therapy patients. The ster-oid-refractory cases were patients with NSIP who needed immunosuppressant drugs for treatment.
Conclusions: The relapse rate was high among radiation therapy patients. Although patients were given more than 6 months to taper off of steroid therapy, relapse still occurred. If the patient is refractory to steroid therapy, then we need to consider that the diagnosis could be NSIP, instead of OP.
OS-RES-03 Respiratory Medicine Characteristics of Patients with Multidrug Resistant MBT
Elena TORKATUIK2, Goar BALASANYANS1, Peter YABLONSKIY2, Pavel GAVRILOV1, Boris VISHNEVSKIY1, Olga NARVSKAYA3
Saint Petersburg Research Institute of Phthisiopulmonology, Russia1, Saint Petersburg State University, Russia2, Saint Petersburg Pasteur Institute, Russia3
Background: To study clinical radiological symptoms and microbiological tests of tu-berculosis with multidrug resistant MBT (MDR-TB).
Methods: 43 patients of MDR-TB treated in Saint-Petersburg Research Institute of Phthisiopulmonology in 2011 year aged from 21 to 64 (34M/9F) were examined by laboratory, radiological, microbiological tests. New cases of tuberculosis were deter-mined at 28% of them, at other patients disease’s duration made from 2 to 8 years.
Results: 76% patients complained of cough. Weakness, fever, a weight loss were in 64% cases. Radiologically at all patients tuberculosis involved both lungs, in 100% of cases were cavities with various sizes and 54% of cavities were multiple.
MDR MBT was found in all patients: in 42% of cases it was first episode of MDR-TB, 1/3 of them had primary resistance of MBT. At 58% cases MDR MBT was detected 1-2 years before and these patients had in past one ineffective course at least. Except resistance to isoniazid and rifampicin second-line drug resistance was identified.
Primary second-line drug resistance to ethionamide was found in 55% of patients’
culture, 45% - to ofloxacine, 55% - to kanamicine. At patients with TB history resist-ance to ethionamide was detected in 73% cases, to ofloxacine – in 28%, to kanami-cine – in17%. 12% of patients had extensively drug-resistant tuberculosis (XDR-TB).
The predominant spoligotypes of MBT were Beijing (25-58% MBT isolates), LAM (8-18% MBT isolates) and Haarlem (4-9% MBT isolates).
Conclusions: MDR-TB characterized by severe currency of tuberculosis with expressed clinical and radiological symptoms. Only 13% cases with MDR MBT had primary MDR-TB, in the most of them MDR MBT followed earlier treatment. Beijing family MBT dominated among patients and associated with MDR-TB. It is necessary also to carry out drug sensibility test to second- line TB drugs as for new cases of tuberculosis and earlier treated.
WCIM 2014 SEOUL KOREA 41
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OS-RES-04 Respiratory Medicine Prevalence of Latent Tuberculosis Infection Among Health Care Workers in Primary Health Care Settings in South Korea
Kyung Hyun OH1, Hee Jin KIM1, Soo Yon OH1, Jin Beom LEE1, Gyung Ho LEE1 Korean Institute of Tuberculosis, Korea1
Background: Tuberculosis (TB) is an important occupational risk for health care work-ers (HCWs). The objective of the study was to estimate prevalence of latent tubercu-losis infection (LTBI) using tuberculin skin test (TST) and interferon-γ release assay (IGRA), to evaluate the agreement between two tests, and to determine risk factors associated with LTBI among HCWs in primary health care settings.
Methods: A cross-sectional study was conducted among HCWs at six health centers of Jeju province in December 2013. Self-administered questionnaire was used to ob-tain relevant information, and IGRA and TST were performed to determine LTBI in the order named.
Results: TST was positive in 52.1% with a 10-mm induration cutoff and IGRA was positive in 17.6% of the HCWs. Agreement between two tests was poor (61.1%, kappa
= 0.24, 95%CI 0.20-0.28). Increasing age and smoking were significant risk factors for TST while increasing age and history of previous TB treatment were significant ones for IGRA. Health profession, duration of employment and experience in TB-related department had little impact on both tests.
Conclusions: Experience in TB-related department in health centers was found not to be associated with increased risk of LTBI, which is presumably attributed to decreased TB burden in South Korea and reduced role of primary health care in TB management.
Therefore, it is critical to assess the TB risk in health-care settings and to prepare the appropriate measures according to the risk assessment.
OS-RES-05 Respiratory Medicine Comparison of the Infectivity of TB and MDR-TB in Non-Familial Contacts
Seung Chul LEE1, Tae Sun SHIM2
National Masan Hospital, Korea1, University of Ulsan College of Medicine, Asan Medical Center, Korea2 Background: Multidrug-resistant tuberculosis (MDR-TB) has recently become one of the major concerns in tuberculosis control programs. However, there is almost no information yet on its infectivity and virulence, especially in non-familial contact.
Methods: In 2013, 391 cases of TB contact investigation in schools and military units were accomplished by local public health care centers under the supervision of the KCDC Tuberculosis Epidemic Investigation Service (KTEIS). All the TST (N = 104,949) and IGRA (N = 5,848) tests enrolled in this study were performed by skilled KTEIS members. We estimated the infectivity by measuring the LTBI ratio of the TB patient contacts. LTBI was diagnosed using either the dual screening strategy (with simulta-neously positive TST and IGRA test results) or the two-step TST test (with TST positive conversion).
Results: Of the 61,369 total contacts, 59,632 were drug-susceptible TB (DS-TB) con-tacts and 1,737 were MDR-TB concon-tacts. The overall incidence of LTBI in the MDR-TB contacts group (9.3%) was higher than that in the DS-TB contacts group (6.1%, p <
0.001). To eliminate the different environmental factors such as the contact strength, we analyzed only the close contacts of the high school students who had shared a same classroom with a student with contagious TB (N = 8,732). We also found that the MDR-TB close contacts group (12.0%) had a higher LTBI incidence than the DS-TB close contacts group (8.7%, p < 0.001). Among the various risk factors of TB infection, MDR TB (OR = 1.53, 95% CI = 1.28-1.84, p < 0.001) was found to be an important risk factor.
Conclusions: In group facilities such as schools and military units, the infectivity of MDR-TB could be stronger than that of DS-TB.
OS-RES-06 Respiratory Medicine Two Consecutive Intrapleural Injection of Cisplatin for Complicated Malignant Pleural Effusion
Yong Hoon KIM1, Ki Hyon SEO1, Ju Ok NA1, Jae Sung CHOI1, Ho Sung LEE1, Ji Won RYOU1
Soon Chun Hyang University Hospital Cheonan, Korea1
Background: Chemical pleurodesis is usually not effective for MPE accompanied with atelectasis, loculation and pleural invasion which need another approaches. Recently intrapleural chemotherapy with cisplatin has not been recommanded firstly because of low yields and high recurrence of MPE. However, most trials of intrapleural cisplatin were done one time with low doses. We expected more than one intrapleural cisplatin injection with higher dose might be better for complicated MPE.
Methods: Patients were enrolled from 1 July 2013 to 30 June 2014. Intrapleural cisplatin (50 mg) injections were done two times via chest tube at 24hr interval after complete drainage of PE. Following each injection, chest tube was clamped for 6hrs.
If there was no shfting on decubitus x ray or daily amount of drainage reduced by <
30 ml, chest tube was removed. Between one and two weeks after injections, CT or decubitus view was taken to evaluate early response. Late response was determined monthly thereafter. CR: no residual PE or no shifting on CT/x ray. PR: presence of min-imal PE (subpleural fluid = 1 cm in width). Stable: decreased but more than minmin-imal.
Failure or Relapse: no decreased or more increased PE in 2wks or progression after early response.
Results: 22 complicated MPE (11 atelectasis, 8 pleural invasion, 2 loculation and 1 re-fractory to previous pleurodesis) in 20 patients were included. Early responses showed 14 CR (63.6%) and 8 PR (36.4%) (100% RR). Mean duration of overall response was 101ds. Late response was determined in 19 MPEs. Two (10.5%) were relapsed at 42 and 281ds and 2 (10.5%) were changed to stable from early CR/PR. RR of late reponse was 78.9% (15/19).
Conclusions: Two consecutive intrapleural injection of cisplatin was highly effective for complicated MPE in both early and late periods.
OS-RES-07 Respiratory Medicine Progastrin-Releasing Peptide as a Diagnostic and Ther-apeutic Biomarker of Small Cell Lung Cancer
Hyuong Ju OH1, Hong-Jun SHIN1, Chul-Kyu PARK1, Bo-Ram LEE1, Hee-Jung BAN1, In-Jae OH1, Yong-Soo KWON1, Kyu-Sik KIM1, Yu-Il KIM1, Sung-Chul LIM1, Young-Chul KIM1, Duck CHO2, Soo-Hyun KIM2, Myung-Geun SHIN2
Chonnam National University Medical School, Korea1, Chonnam National University Medical School, Korea2
Background: Progastrin-releasing peptide (proGRP) is a recently identified biomarker of small cell lung cancer (SCLC). We aimed this study for evaluating the usefulness of automated proGRP measurement as a tumor marker for diagnosis and treatment monitoring in patients with SCLC.
Methods: From January 2011 to December 2013, plasma samples were prospectively collected from 452 [213 non-small cell lung cancer (NSCLC), 104 SCLC, 135 other diseases] patients who visit for tissue diagnosis and tested by two-step automated immunoassay using the ARCHITECT® proGRP assay kit (Abbott Diagnostics, USA). The cutoff level of proGRP was set at 63 pg/mL.
Results: The mean proGRP was higher in SCLC (1830.4 ± 2706.7 pg/mL) than in NS-CLC (74.0 ± 365.4 pg/mL) and other diseases (61.7 ± 271.7 pg/mL, p<0.001). Among the cancer group, the sensitivity of proGRP was 85.6% (89/104) in SCLC and 12.2%
(26/213) in NSCLC. The specificity was 87.8%, positive predictive value was 77.4%, and negative predictive value was 92.6% at 63 pg/mL in SCLC patients. The mean proGRP was higher in extensive disease (2166.8 ± 2999.5 pg/mL) than in limited dis-ease (901.4 ± 1216.0 pg/mL, p=0.033). Among the 39 patients with SCLC who could be followed, the mean proGRP levels of 23 responders were significantly decreased after chemotherapy (from 1651.5 ± 1386.4 pg/mL to 290.0 ± 524.8 pg/mL, p<0.001), whereas those of the 16 non-responders were not significantly different between before and after chemotherapy (from 572.5 ± 790.3 pg/mL to 494.4 ± 610.9 pg/mL, p=0.583).
Conclusion: Plasma proGRP could be a useful biomarker of SCLC for diagnosis and treatment monitoring. And the initial level may represent the tumor extent of SCLC.
42 32nd World Congress of Internal Medicine (October 24-28, 2014) OS-RES-08 Critical Care Medicine Ventilator Associated Pneumonia - Incidence, Antibio-gram of Pathogens Isolated and Clinical Outcome
ARJUN KHANNA1
VMMC And Safdarjang Hospital, India1
Background: Ventilator associated pneumonia (VAP) is an important cause of mor-bidity and mortality in mechanically ventilated patients globally. The aim of this study was to find out the incidence of VAP at our institution, to evaluate the antibiotic sen-sitivity pattern of microorganisms isolated and to assess clinical outcome in VAP.
Methods: A total of 107 patients who were not having pneumonia at presentation and who were mechanically ventilated for more than 48 hours for various indications were included in the study. APACHE II score of first day was recorded. The diagnosis of VAP was established using clinical pulmonary infection score of more than 6. Gram staining and culture sensitivity using Kirby –Bauer disc diffusion method was per-formed on all endotracheal aspirates and antibiotic therapy modified accordingly. The results were analysed to determine the incidence and clinical outcome in VAP.
Results: 30 out of 107 patients (28.03%) developed VAP.25 patients developed late onset VAP while 5 developed early onset VAP. Most common isolates were Pseu-domonas aeruginosa (9 isolates) followed by MRSA (8isolates), Klebsiella pnueumo-niae(7 isolates) and Acinetobacter baumanii(6 isolates). Klebsiella pnueumoniae and Acinetobacter baumanii were found to be most lethal. Most isolates of Klebsiella were extended spectrum Beta Lactamase producing and all Acinetobacter were carbape-nem resistant. Mortality in VAP was 46.67% and correlated well with a higher mean APACHE II score of 18.3 as compared to a mortality of 28.57 in non VAP group with a low mean APACHE II score of 13.1.
Conclusion: The development of VAP was associated with increased morbidity and mortality and a higher mean APACHE II score at admission. The incidence of multidrug resistant pathogens is rising and therefore it is important to identify them as this in-formation will help in the selection of an appropriate antibiotic regimen and decrease the treatment costs and improve outcome.
OS-RES-10 Critical Care Medicine Intensive Care Unit Admission is Associated with Poor Outcome in Patients with Mitochondrial DNA M.3243a>g Mutation: A Multicenter Retrospective Study
Emily Han-Chung HSIUE1,2, Ni-Chung LEE3, Pei-Lin LEE1
Department of Interminal Medicine, National Taiwan University Hospital, Taiwan R.O.C1, Department of Oncology, National Taiwan University Hospital, Taiwan R.O.C2, Department of Pediatrics, National Taiwan University Hospital, Taiwan R.O.C3
Background: Mitochondrial DNA 3243A>G, one of the most common pathogenic mitochondrial mutations, often presents in adulthood and is associated with mito-chondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and other syndromes. Due to multi-organ involvement, patients with m.3243A>G frequently require critical care, but the diagnosis often remains unrecognized. This multicenter study aimed to evaluate the prognostic factors of m.3243A>G in Taiwan, and focused on those who had been admitted to ICU.
Methods: Patients diagnosed with m.3243A>G from January 1st 1997 to August 1st 2014 at the National Taiwan University Hospital were identified. Clinical features, laboratory study results, and outcomes were recorded. ICU admission course was reviewed. Prognostic factors for ICU admission, severe disability (defined by modified Rankin Scale, mRS≧4), and death were analyzed.
Results: A total of 33 patients were identified, with 19 patients (58%) demonstrating the MELAS phenotype. Thirteen patients (39%) had been admitted to ICU, and 7 (54%) were diagnosed with the mutation after ICU admission. Seizure was the most common cause for ICU admission (n=8), followed by lactic acidosis (n=2), diabetic ketoacidosis (n=1), stroke (n=1), and respiratory failure (n=1). In total, 6 patients (18%) died while 11 patients (33%) developed mRS≧4. Logistic regression analysis identified sympto-matic CNS involvement as a significant predictor of both ICU admission (OR 8.25, 95%
CI 1.43-47.58, p=0.018) and development of mRS≧4 (OR 14.44, 95% CI 1.56-133.58, p=0.019); while Kaplan Meier analysis showed that ICU admission was significantly associated with mortality (log-rank test p=0.012, Fig.).
Conclusions: Patients with m.3243A>G often remained undiagnosed until severe complications requiring critical care have developed. Investigation for possible mito-chondrial disease is warranted in cases of unexplained seizure, stroke, lactic acidosis, and respiratory failure.
OS-RES-11 Respiratory Medicine Tetrahdrobiopterin(BH4): Novel Treatment for Pulmo-nary Hypertension
Bahaa FRANCIS1 Rivka Ziv Medical Centre, Israel1
Background: Pulmonary Hypertension (PH) is characterized by pulmonary vaso-constriction, vascular remodeling, right heart failure and death. The pathogenesis is multifactorial. The integrity of the pulmonary vascular endothelium, particularly its en-dothelial nitric oxide synthase (eNOS), is a key factor in maintaining normal pulmonary vascular homeostasis. While enzymatically coupled, eNOS produces nitric oxide (NO), otherwise eNOS activation may lead to increased superoxide production. The cofactor tetrahydrobiopterin (BH4) is an important regulator of eNOS function; by ‘recoupling’
eNOS and enhancing its enzymatic activity, BH4 increases NO bioavailability and de-creases superoxide production. Thus pharmacological supplementation with BH4 may be a novel treatment in PH.
Methods: Isolated perfused lung studies were used to explore the acute pharmacolog-ical effects of BH4 in regulating pulmonary vascular tone. Animal studies were used to evaluate the pharmacological effects of BH4 treatment and to clarify its molecular mechanism using biochemical and histological experiments.
Results: In acute ex-vivo studies, BH4 was found to regulate hypoxic pulmonary vasoconstriction. Its effects are mediated via enhancing NO and H2O2 secretion and its antioxidant properties, all leading to pulmonary vasodilation. Superoxide dismutase co-administration with BH4 enhanced its vasodilatory effect. In chronic studies, BH4 prevented the development of PH in monocrotaline model and ameliorated established PH when administered to recover the disease. BH4 partially reversed PH in hypoxia model. In both models, BH4 reduced pulmonary vascular muscularization and reversed right ventricular hypertrophy. BH4 effect was evidenced by enhancing the activity and protein levels of eNOS, recoupling eNOS activity to produce more NO, and its second messenger cGMP, and lowering the levels of superoxide.
Conclusions: BH4 bioavailability is essential for maintaining pulmonary vascular ho-meostasis, and plays a major role in the pathophysiology of PH. This study establishes a firm basis to explore the therapeutic potential of BH4 in human PH.
WCIM 2014 SEOUL KOREA 43
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OS-RES-12 Respiratory Medicine The Dysregulated Autophagy Induced by Graphene Oxides in A549 Cells
Jong Wook SHIN1, In Won PARK1, Chang Seok PARK1, Jae Woo JUNG1, Jae Cheol CHOI1, Jae Yeol KIM1, Byoung Whui CHOI1, Kyung Soon CHOI2, Soo Young KIM2 Chung-Ang University Hospital, Korea1, Chung-Ang University, Korea2
The graphene, an allotrope of carbon, has the honeycombing structure of one-atom-thick planar sheets, is widely used for the modern electronics, informative technol-ogies including medical devices. Because GO may affect on the respiratory tract by inhalation during the manufacture, we tested GO materials in A549 cells to check the cell viability and injuring mechanism especially for autophagy. A549 cells were treated with GO, reduced GO(rGO), SDS-rGO, dodecyl amine(DA)-GO. MTT assay and West-ern blotting for LC3-A/B-I/II, NBR1 and p62/sequestosome-1. The light microscopy showed the injured cellular morphology of A549 cells. The vitality of A549 cells were decreased with four GO materials in 24 and 48 hours. The expression of LC3-A/B-I,II was induced or changed differently to the four kinds of GO’s. NBR1 and p62/sequesto-some-1, the cargo proteins for autophagosome formation, were oppositely expressed after GO treatment in this cells.Taken together, GO materials may be harmful to res-piratory epithelial cells by mechanism includ
ing the dysregulated autophagy.