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Background: The role of interferon-gamma release assay (IGRA) in monitoring responses to anti-tuberculosis (TB) treatment is not clear. We evaluated the results of the QuantiFERON-TB Gold In-tube (QFT-GIT) assay over time during the anti-TB treatment of adults with no underlying disease. Methods: We enrolled soldiers who were newly diagnosed with active TB and admitted to the central referral military hospital in South Korea between May 1, 2008 and September 30, 2009. For each participant, we preformed QFT-GIT assay before treatment (baseline) and at 1, 3, and 6 months after initiating anti-TB medication. Results: Of 67 eligible patients, 59 (88.1%) completed the study protocol. All participants were males who were human immunodeficiency virus (HIV)-negative and had no chronic diseases. Their median age was 21 years (range, 20-48). Initially, 57 (96.6%) patients had positive QFT-GIT results, and 53 (89.8%), 42 (71.2%), and 39 (66.1%) had positive QFT-GIT results at 1, 3, and 6 months, respectively. The IFN-gamma level at baseline was 5.31 +/- 5.34 IU/ml, and the levels at 1, 3, and 6 months were 3.95 +/- 4.30, 1.82 +/- 2.14, and 1.50 +/- 2.12 IU/ml, respectively. All patients had clinical and radiologic improvements after treatment and were cured. A lower IFN-gamma level, C-reactive protein >= 3 mg/dl, and the presence of fever (>= 38.3 degrees C) at diagnosis were associated with negative reversion of the QFT-GIT assay. Conclusion: Although the IFN-gamma level measured by QFT-GIT assay decreased after successful anti-TB treatment in most participants, less than half of them exhibited QFT-GIT reversion. Thus, the reversion to negativity of the QFT-GIT assay may not be a good surrogate for treatment response in otherwise healthy young patients with TB. ; Lee SSJ, 2009, INFECTION, V37, P96, DOI 10.1007/s15010-008-8082-3 ; Kobashi Y, 2009, J INFECTION, V58, P197, DOI 10.1016/j.jinf.2008.08.009 ; Katiyar SK, 2008, INT J TUBERC LUNG D, V12, P1146 ; Kobashi Y, 2008, CHEST, V133, P1196, DOI 10.1378/chest.07-1995 ; Nishimura T, 2008, INT J TUBERC LUNG D, V12, P269 ; Kobashi Y, 2008, INTERNAL MED, V47, P1957, DOI 10.2169/internalmedicine.47.1313 ; RABY E, 2008, PLOS ONE, V3, pNI529 ; Vincenti D, 2007, CLIN EXP IMMUNOL, V150, P91, DOI 10.1111/j.1365-2249.2007.03462.x ; Kang YA, 2007, CHEST, V132, P959, DOI 10.1378/chest.06-2805 ; Dheda K, 2007, J INFECTION, V55, P169, DOI 10.1016/j.jinf.2007.02.005 ; Pai M, 2007, INFECTION, V35, P98, DOI 10.1007/s15010-007-6114-z ; Menzies D, 2007, ANN INTERN MED, V146, P340 ; Dewan PK, 2007, CLIN INFECT DIS, V44, P69 ; Kobashi Y, 2006, CLIN INFECT DIS, V43, P1540 ; Lee JY, 2006, EUR RESPIR J, V28, P24, DOI 10.1183/09031936.06.00016906 ; Goletti D, 2006, CLIN MICROBIOL INFEC, V12, P544, DOI 10.1111/j.1469-0691.2006.01391.x ; Kim HJ, 2006, CHEST, V129, P1253 ; AIKEN AM, 2006, BMC INFECT DIS, V6, pNIL1 ; Kang YA, 2005, JAMA-J AM MED ASSOC, V293, P2756 ; MAZUREK GH, 2005, MMWR RECOMM REP, V54, P49 ; Carrara S, 2004, CLIN INFECT DIS, V38, P754 ; Seung KJ, 2003, INT J TUBERC LUNG D, V7, P912 ; *WHO, 2003, TREATM TUB GUID NAT, V3 ; 2000, AM J RESP CRIT CAR 2, V161, pS221 ; Foulds J, 1998, INT J TUBERC LUNG D, V2, P778 ; IM JG, 1995, CRIT REV DIAGN IMAG, V36, P227 ; COOPER AM, 1993, J EXP MED, V178, P2243 ; FLYNN JL, 1993, J EXP MED, V178, P2249 ; IM JG, 1993, RADIOLOGY, V186, P653 ; IM JG, 1991, RADIOLOGY, V178, P727 ; LANDIS JR, 1977, BIOMETRICS, V33, P159 ; APICELLA MA, 1969, J CLIN INVEST, V48, P250 ; LECKIE WJH, 1965, CLIN SCI, V29, P339 ; *WHO, GLOB TUB CONTR SURV ; 3

Abstract Background The role of interferon-γ release assay (IGRA) in monitoring responses to anti-tuberculosis (TB) treatment is not clear. We evaluated the results of the QuantiFERON-TB Gold In-tube (QFT-GIT) assay over time during the anti-TB treatment of adults with no underlying disease. Methods We enrolled soldiers who were newly diagnosed with active TB and admitted to the central referral military hospital in South Korea between May 1, 2008 and September 30, 2009. For each participant, we preformed QFT-GIT assay before treatment (baseline) and at 1, 3, and 6 months after initiating anti-TB medication. Results Of 67 eligible patients, 59 (88.1%) completed the study protocol. All participants were males who were human immunodeficiency virus (HIV)-negative and had no chronic diseases. Their median age was 21 years (range, 20-48). Initially, 57 (96.6%) patients had positive QFT-GIT results, and 53 (89.8%), 42 (71.2%), and 39 (66.1%) had positive QFT-GIT results at 1, 3, and 6 months, respectively. The IFN-γ level at baseline was 5.31 ± 5.34 IU/ml, and the levels at 1, 3, and 6 months were 3.95 ± 4.30, 1.82 ± 2.14, and 1.50 ± 2.12 IU/ml, respectively. All patients had clinical and radiologic improvements after treatment and were cured. A lower IFN-γ level, C-reactive protein ≥ 3 mg/dl, and the presence of fever (≥ 38.3°C) at diagnosis were associated with negative reversion of the QFT-GIT assay. Conclusion Although the IFN-γ level measured by QFT-GIT assay decreased after successful anti-TB treatment in most participants, less than half of them exhibited QFT-GIT reversion. Thus, the reversion to negativity of the QFT-GIT assay may not be a good surrogate for treatment response in otherwise healthy young patients with TB.

Woo Jin Kim,1 Jae-Joon Yim,2 Deog Kyeom Kim,3 Myung Goo Lee,4 Anne L Fuhlbrigge,5 Pawel Sliwinski,6 Iwona Hawrylkiewicz,6 Emily S Wan,7,8 Michael H Cho,7,8 Edwin K Silverman7,8 1Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, Chuncheon, 2Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul National University College of Medicine, Seoul, 3Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, 4Division of Pulmonary, Allergy and Critical Care Medicine, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon, Korea; 5Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA; 62nd Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland; 7Channing Division of Network Medicine, 8Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA Purpose: Chronic obstructive pulmonary disease (COPD), characterized by irreversible airflow obstruction, is a major cause of morbidity and mortality worldwide. However, geographic differences in the clinical characteristics of severe COPD patients have not been widely studied. Methods: We recruited a total of 828 severe COPD cases from three continents. Subjects in Poland were enrolled by the Institute of Tuberculosis and Lung Diseases in Warsaw; subjects in Korea participated at several university hospitals in Korea; and subjects in USA were enrolled at two clinics affiliated with academic medical centers. All subjects were over the age of 30 with at least 10 pack-years of cigarette smoking history. Cases manifested severe to very severe airflow obstruction with post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted and FEV1/forced vital capacity <0.7. All subjects completed a detailed questionnaire and underwent standardized pre-bronchodilator and post-bronchodilator spirometry. Subjects with known tuberculosis (TB)-associated lung parenchymal destruction were excluded. Univariate and multivariate assessments of the impact of the country of origin on respiratory symptoms and respiratory illness were performed. Results: In both univariate and multivariate analyses, a history of TB (38.7%) and physician-diagnosed asthma (43.9%) were significantly more common in subjects with severe COPD from Korea than USA or Poland, while attacks of bronchitis (64.2%) were more common in subjects with severe COPD from Poland. COPD subjects from Poland had more severe dyspnea (modified Medical Research Council 3.3±1.0) and more frequently reported symptoms of chronic bronchitis (52.2%). A history of TB was also more common in Poland (10.8%) than in USA (0.3%) severe COPD patients. Conclusion: Respiratory symptoms and other respiratory illnesses associated with severe COPD differed widely among three continents. Keywords: COPD, epidemiology, respiratory symptoms, tuberculosis

Objective: To describe detailed clinical and radiological features of the pandemic H1N1 2009 influenza viral infection among healthy young males in a semi-closed institutionalized setting. Materials and Methods: A total of 18 patients confirmed with the pandemic H1N1 2009 influenza virus infection from July 18 to July 30, 2009 were enrolled in this study. Each patient underwent an evaluation to determine detailed clinical and radiological features. Results: All patients presented with high fever (> 38.0 degrees C), with accompanying symptoms of cough, rhinorrhea, sore throat, myalgia and diarrhea, and increased C-reactive protein (CRP) values with no leukocytosis nor elevated erythrocyte sedimentation rate (ESR). All patients, including one patient who progressed into acute respiratory distress syndrome, were treated with oseltamivir phosphate and quickly recovered from their symptoms. Chest radiographs showed abnormalities of small nodules and lobar consolidation in only two out of 18 patients. However, six of 12 patients who underwent thin-section CT examinations showed abnormal findings for small ground-glass opacities (GGOs) in addition to poorly-defined nodules with upper lobe predominance. Conclusion: In a population of healthy young adults, elevated CRP with normal ESR and white blood cell levels combined with GGOs and nodules on thin-section CT scans may indicate early signs of infection by the pandemic H1N1 2009 influenza virus. ; Agarwal PP, 2009, AM J ROENTGENOL, V193, P1488, DOI 10.2214/AJR.09.3599 ; Ajlan AM, 2009, AM J ROENTGENOL, V193, P1494, DOI 10.2214/AJR.09.3625 ; Lee CW, 2009, KOREAN J RADIOL, V10, P531, DOI 10.3348/kjr.2009.10.6.531 ; Chowell G, 2009, NEW ENGL J MED, V361, P674, DOI 10.1056/NEJMoa0904023 ; Perez-Padilla R, 2009, NEW ENGL J MED, V361, P680, DOI 10.1056/NEJMoa0904252 ; Dawood FS, 2009, NEW ENGL J MED, V360, P2605, DOI 10.1056/NEJMoa0903810 ; Shinde V, 2009, NEW ENGL J MED, V360, P2616, DOI 10.1056/NEJMoa0903812 ; Belshe RB, 2009, NEW ENGL J MED, V360, P2667, DOI 10.1056/NEJMe0903995 ; 2009, MMWR MORB MORTAL WKL, V58, P536 ; *WHO, 2009, WKLY EPIDEMIOL REC, V84, P185 ; *US CDCP, 2009, INT WHO GUID SURV HU ; Hansell DM, 2008, RADIOLOGY, V246, P697 ; DOLIN R, 2008, HARRISONS PRINCIPLES, P1127 ; Grinblat L, 2003, RADIOLOGY, V228, P802, DOI 10.1148/radiol.2283030671 ; Wong KT, 2003, RADIOLOGY, V228, P395, DOI 10.1148/radiol.2283030541 ; *WHO, WORLD NOW START 2009 ; *WHO, INFL A H1N1 UPD 68 ; 3

Ha Youn Lee,1,2 Sun Mi Choi,1,2 Jinwoo Lee,1,2 Young Sik Park,1,2 Chang-Hoon Lee,1,2 Deog Kyeom Kim,2,3 Sang-Min Lee,1,2 Ho Il Yoon,2,4 Jae-Joon Yim,1,2 Young Whan Kim,1,2 Sung Koo Han,1,2 Chul-Gyu Yoo1,2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 4Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Background: Tiotropium failed to slow the annual rate of forced expiratory volume in 1 second (FEV1) decline in chronic obstructive pulmonary disease (COPD) patients with <70% predicted FEV1. However, the rate of FEV1 decline is known to be faster at early stages, which suggests that the effects of tiotropium may be more prominent in early-stage of COPD patients. The aim of this study was to test the hypothesis that tiotropium modifies the rate of FEV1 decline in COPD patients with an FEV1≥70%.Methods: We retrospectively reviewed the records of COPD patients diagnosed between January 1, 2004, and July 31, 2012, at Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul Metropolitan Government-Seoul National University Boramae Medical Center. The inclusion criteria were as follows: age ≥40 years, postbronchodilator (BD) FEV1≥70% of predicted and FEV1/FVC (forced vital capacity) <0.70, and spirometry more than two times at certain times of the year. Conversely, the exclusion criteria were as follows: asthma, lung cancer, pulmonary tuberculosis, pulmonary resection, or long-term use of a short-acting muscarinic antagonist. The annual lung function decline in patients using tiotropium was compared with that in patients not using the drug.Results: Of the 587 patients enrolled in the study, 257 took tiotropium. Following propensity score matching, 404 patients were included in the analysis. The mean annual rate of post-BD FEV1 decline was 23.9 (tiotropium) and 22.5 (control) mL/yr (P=0.86); corresponding pre-BD values were 30.4 and 21.9 mL/yr (P=0.31), respectively. Mean annual rate of post-BD FVC decline was 55.1 (tiotropium) and 43.5 (control) mL/yr (P=0.33); corresponding pre-BD values were 37.1 and 33.3 mL/yr (P=0.13).Conclusion: Therefore, tiotropium does not reduce the rate of lung function decline in COPD patients with FEV1≥70%. Keywords: tiotropium, chronic obstructive pulmonary disease, lung function decline