Hyun Kyung Lee

Serial interferon-gamma release assays after rifampicin prophylaxis in a tuberculosis outbreak

Even though some studies have reported the results of serial interferon-gamma release assays (IGRAs) during isoniazid prophylactic treatment, serial results have not been reported after rifampicin prophylaxis. A contact investigation was conducted after a tuberculosis (TB) outbreak in an accommodation facility. The tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) test were performed in 214 contacts with normal chest radiographs. Rifampicin prophylaxis was initiated in TST+/QFT-GIT+ subjects, and the QFT-GIT test was repeated upon completion of 4 months of rifampicin treatment. Among the 214 contacts, the TST and QFT-GIT test results were positive in 67.7% and 56.7%, respectively, and the agreement between the two tests was fair-to-good (78.3%, kappa=0.55, p<0.001). The QFT-GIT test was positive in 77% (97/126) of contacts with positive TST results. Rifampicin prophylaxis was completed in 81 subjects with good compliance. Among 74 subjects with valid serial QFT-GIT test results, IFN-gamma levels decreased in 97.3% (72/74) of the subjects and QFT-GIT test reversion (positive to negative) was achieved in 31 subjects (41.9%). Subjects without QFT-GIT test reversion had a significantly higher baseline TST induration sizes (18.3+/-4.8 vs. 14.9+/-3.4mm, p<0.01) and IFN-gamma levels (18.6+/-17.9 vs. 3.2+/-7.5IU/mL, p<0.01) than the subjects with QFT-GIT test reversion. Thus, IGRAs may be useful in evaluating the therapeutic response to rifampicin prophylaxis in TB contacts. However, considering that this was not a controlled study, a prospective controlled study is needed to determine whether rifampicin prophylaxis truly affects QFT-GIT reversion.

Risk factors for hospital-acquired pneumonia caused by carbapenem-resistant Gram-negative bacteria in critically ill patients: a multicenter study in Korea

We performed a case-control study to identify risk factors of carbapenem-resistant Gram-negative bacteria (CRGNB) as an increasing cause of hospital-acquired pneumonia (HAP). The study included critically ill adult patients with HAP whose microbial etiology was identified at eight tertiary centers in Korea between June 2008 and December 2009. Eighty two patients with 86 isolates of CRGNB (62 Acinetobacter baumannii, 14 Pseudomonas aeruginosa, and 10 Stenotrophomonas maltophilia) were included in the case group, and 122 patients with carbapenem-susceptible Gram-negative bacteria were included in the control group. Diabetes mellitus (adjusted odds ratio [aOR] 2.82, 95% confidence interval [95% CI] 1.25-6.38), radiologic score ≥5 (aOR 4.56, 95% CI 2.36-8.81), prior fluoroquinolone (aOR 2.39. 95% CI = 1.07-5.35), or carbapenem usage (aOR 2.82, 95% CI 1.75-17.83) were found to be independent risk factors. Fluoroquinolone and carbapenem should be cautiously used to avoid HAP caused by CRGNB.

Association Between Occupational Dust Exposure and Prognosis of Idiopathic Pulmonary Fibrosis

BACKGROUND Previous studies have investigated the relationship between occupational and environmental agents and idiopathic pulmonary fibrosis (IPF). However, there have been few studies regarding the prognosis of patients with IPF according to patient occupation. METHODS We investigated whether occupational dust exposure was associated with clinically decreased lung function and poor prognosis. The Korean Interstitial Lung Disease Research Group conducted a national survey to evaluate the clinical, physiologic, radiologic, and survival characteristics of patients with IPF. A total of 1,311 patients with IPF were stratified into five groups according to their occupation: (1) unemployed or homemakers (n = 628); (2) farmers, fishers, or ranchers (n = 230); (3) sales or service personnel (n = 131); (4) clerical or professional personnel (n = 151); and (5) specific dust-exposed workers (n = 171). RESULTS The mean age of subjects at diagnosis, was 67.5 ± 9.7 years. Current smokers were 336 patients, 435 were exsmokers, and 456 were never smokers. Dust-exposed workers showed early onset of IPF (61.3 ± 8.6 years; P < .001) and a longer duration of symptoms at diagnosis (17.0 ± 28.2 months; P = .004). Aging (P = .001; hazard ratio [HR], 1.034; 95% CI, 1.014-1.054), FVC % predicted at diagnosis (P = .004; HR, 0.984; 95% CI, 0.974-0.995), and dust-exposure occupation (P = .033; HR, 1.813; 95% CI, 1.049-3.133) were associated with mortality. CONCLUSIONS These findings indicate that occupational dust may be an aggravating factor associated with a poor prognosis in IPF.

Mortality of Community-Acquired Pneumonia in Korea: Assessed with the Pneumonia Severity Index and the CURB-65 Score

The pneumonia severity index (PSI) and CURB-65 are widely used tools for the prediction of community-acquired pneumonia (CAP). This study was conducted to evaluate validation of severity scoring system including the PSI and CURB-65 scores of Korean CAP patients. In the prospective CAP cohort (participated in by 14 hospitals in Korea from January 2009 to September 2011), 883 patients aged over 18 yr were studied. The 30-day mortalities of all patients were calculated with their PSI index classes and CURB scores. The overall mortality rate was 4.5% (40/883). The mortality rates per CURB-65 score were as follows: score 0, 2.3% (6/260); score 1, 4.0% (12/300); score 2, 6.0% (13/216); score 3, 5.7% (5/88); score 4, 23.5% (4/17); and score 5, 0% (0/2). Mortality rate with PSI risk class were as follows: I, 2.3% (4/174); II, 2.7% (5/182); III, 2.3% (5/213); IV, 4.5% (11/245); and V, 21.7% (15/69). The subgroup mortality rate of Korean CAP patients varies based on the severity scores and CURB-65 is more valid for the lower scores, and PSI, for the higher scores. Thus, these variations must be considered when using PSI and CURB-65 for CAP in Korean patients.

Choice between Levofloxacin and Moxifloxacin and Multidrug-Resistant Tuberculosis Treatment Outcomes

RATIONALE We previously showed that the choice of levofloxacin or moxifloxacin for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-TB) did not affect sputum culture conversion at 3 months of treatment. OBJECTIVES To compare final treatment outcomes between patients with MDR-TB randomized to levofloxacin or moxifloxacin. METHODS A total of 151 participants with MDR-TB who were included for the final analysis in our previous trial were followed through the end of treatment. Treatment outcomes were compared between 77 patients in the levofloxacin group and 74 in the moxifloxacin group, based on the 2008 World Health Organization definitions as well as 2013 revised definitions of treatment outcomes. In addition, the time to culture conversion was compared between the two groups. MEASUREMENTS AND MAIN RESULTS Treatment outcomes were not different between the two groups, based on 2008 World Health Organization definitions as well as 2013 definitions. With 2008 definitions, cure was achieved in 54 patients (70.1%) in the levofloxacin group and 54 (73.0%) in the moxifloxacin group (P = 0.72). Treatment success rates, including cure and treatment completed, were not different between the two groups (87.0 vs. 81.1%, P = 0.38). With 2013 definitions, cure rates (83.1 vs. 78.4%, P = 0.54) and treatment success rates (84.4 vs. 79.7%, P = 0.53) were also similar between the levofloxacin and moxifloxacin groups. Time to culture conversion was also not different between the two groups (27.0 vs. 45.0 d, P = 0.11 on liquid media; 17.0 vs. 42.0 d, P = 0.14 on solid media). Patients in the levofloxacin group had more adverse events than those in the moxifloxacin group (79.2 vs. 63.5%, P = 0.03), especially musculoskeletal ones (37.7 vs. 14.9%, P = 0.001). CONCLUSIONS The choice of levofloxacin or moxifloxacin made no difference to the final treatment outcome among patients with fluoroquinolone-sensitive MDR-TB. Clinical trial registered with www.clinicalrials.gov (NCT01055145).

Low Serum Concentrations of Moxifloxacin, Prothionamide, and Cycloserine on Sputum Conversion in Multi-Drug Resistant TB

Purpose Low serum concentrations of drugs used to treat multi-drug resistant tuberculosis (MDR-TB) have occasionally been associated with treatment failure. We determined the frequencies of low serum concentrations of anti-MDR-TB drugs, and assessed the effects of these concentrations on 2-month sputum conversion. Materials and Methods The serum levels of moxifloxacin (MF), prothionamide (PTH), and cycloserine (CS) were determined for 89 serum samples by high-pressure liquid chromatography-tandem mass spectrometry. Results Low serum concentrations of MF, PTH, and CS below the minimal levels of the normal ranges were 83.3% (20/24), 59.2% (29/49), and 71.2% (47/66), respectively. There were no significant differences between the 2-month sputum conversion group (n=25) and the 2-month sputum non-conversion group (n=4) in median drug concentrations (µg/mL) of MF (1.46 vs. 1.60), PTH (0.91 vs. 0.70), and CS (14.90 vs. 14.90). However, a poor compliance rate was significantly greater in the 2-month sputum non-conversion group (75.0%, 3/4) than in the 2-month sputum conversion group (0%, 0/25) (p=0.001). Conclusion The frequency of low serum concentrations of anti-MDR-TB drugs was substantial and might not affect the 2-month sputum conversion rate. Larger prospective studies with timely sampling are needed to investigate the role of therapeutic drug monitoring in MDR-TB.

Predicting survival of patients with idiopathic pulmonary fibrosis using GAP score: a nationwide cohort study.

BackgroundThe clinical course of idiopathic pulmonary fibrosis (IPF) varies widely. Although the GAP model is useful for predicting mortality, survivals have not yet been validated for each GAP score. We aimed to elucidate how prognosis is related to GAP score and GAP stage in IPF patients.MethodsThe Korean Interstitial Lung Disease Study Group conducted a national survey to evaluate various characteristics in IPF patients from 2003 to 2007. Patients were diagnosed according to the 2002 criteria of the ATS/ERS. We enrolled 1,685 patients with IPF; 1,262 had undergone DLCO measurement. Patients were stratified based on GAP score (0–7): GAP score Group 0 (n = 26), Group 1 (n = 150), Group 2 (n = 208), Group 3 (n = 376), Group 4 (n = 317), Group 5 (n = 138), Group 6 (n = 39), and Group 7 (n = 8).ResultsHigher GAP score and GAP stage were associated with a poorer prognosis (p < 0.001, respectively). Survival time in Group 3 was lower than those in Groups 1 and 2 (p = 0.043 and p = 0.039, respectively), and higher than those in groups 4, 5, and 6 (p = 0.043, p = 0.032, and p = 0.003, respectively). Gender, age, and DLCO (%) differed significantly between Groups 2 and 3. All four variables in the GAP model differed significantly between Groups 3 and 4.ConclusionThe GAP system showed significant predictive ability for mortality in IPF patients. However, prognosis in IPF patients with a GAP score of 3 were significantly different from those in the other stage I groups and stage II groups of Asian patients.

Prevention of Venous Thromboembolism in Medical Intensive Care Unit: A Multicenter Observational Study in Korea

Patients admitted to medical intensive care unit (MICU) are at increased risk for venous thromboembolism (VTE); and prophylaxis is recommended. However, the actual range and frequency of VTE prophylaxis administered to MICU patients are not well defined. Patients over 40 yr of age and expected MICU stay of more than 48 hr were eligible for this observational cohort study of 23 MICUs in Korea. Patients already on anticoagulation therapy or those requiring anticoagulation for reasons other than VTE were excluded. Among 830 patients, VTE prophylaxis was given to 560 (67.5%) patients. Among 560 patients, 323 (38.9%) received pharmacoprophylaxis, 318 (38.4%) received mechanical prophylaxis and 81 (9.8%) received both forms of prophylaxis. About 74% of patients in the pharmacoprophylaxis group received low molecular weight heparin and 53% of the patients in the mechanical prophylaxis group used intermittent pneumatic compression. Most of the patients (90%) had more than one risk factor for VTE and the most common risk factor was old age, followed by heart and respiratory failure. In this observational cohort study of 23 MICUs in Korea, 67.5% of patients received thromboprophylaxis. Further studies are needed to clarify the role and efficacy of VTE prophylaxis in Korean critically ill patients.

Asthma and severity of the 2009 novel H1N1 influenza: a case-control study

Abstract Objective: Previous studies reported that the most common chronic condition found among hospitalized patients due to the novel 2009 H1N1 influenza was asthma. However, these studies did not include a concurrent control group. Thus, we investigated the association of asthma status and severity of H1N1 influenza in adults. Methods: The study was designed as a multi-site case-control study. Cases were patients who had positive PCR for H1N1 influenza and were admitted to the ICU or general ward with a diagnosis of H1N1 influenza from 1 January 2009 to 31 December 2009. Controls were patients who had positive PCR for H1N1 influenza, but were not admitted to hospitals. Results: There were 91 H1N1 cases admitted to either ICU (n = 41) or general hospital ward (n = 50), and 56 controls who met the matching criteria were available. Of the 91 cases, the mean age was 47.3 years, 59% were female, and 38% had comorbid conditions. Of the 91 cases, 12 (13%) had asthma. Stratified analysis by comorbid conditions showed that among those without any comorbid conditions, 8 of 56 cases (14%) and 2 of 49 controls (4%) had asthma, (OR: 3.92, 95% CI: 0.79–19.42, p = 0.095) whereas, among the 39 subjects with one or more comorbid conditions, one of 7 controls (14%) had asthma and 4 of 35 (11%) cases had asthma (p = 0.83). Conclusions: Asthma may be associated with severity of H1N1 influenza among those without any non-asthma comorbid conditions. However, the limited sample size did not allow this study to fully establish statistical significance. We still recommend asthmatics as a priority group for influenza vaccination and treatment.

Comparisons of Prognosis between Surgically and Clinically Diagnosed Idiopathic Pulmonary Fibrosis Using Gap Model: A Korean National Cohort Study.

AbstractAlthough a multidisciplinary approach has become an important criterion for an idiopathic pulmonary fibrosis (IPF) diagnosis, lung biopsies remain crucial. However, the prognosis of patients with surgically diagnosed IPF (sIPF) is uncertain. We aimed to investigate the prognosis of patients with clinically diagnosed IPF (cIPF) and sIPF.In this retrospective observational study, the Korean Interstitial Lung Disease Study Group conducted a national survey to evaluate the clinical, physiological, radiological, and survival characteristics of patients with IPF from January 1, 2003 to December 31, 2007. Patients were recruited from 54 universities and teaching hospitals across the Republic of Korea. IPF diagnoses were established according to the 2002 American Thoracic Society (ATS)/European Respiratory Society criteria (ERS) guideline. A total of 1685 patients with IPF (1027 cIPF and 658 sIPF) were enrolled.Patients with sIPF were significantly younger, predominantly female, and nonsmokers (all P < 0.001). sIPF group had significantly better initial pulmonary function. The proportion of computed tomography-based honeycomb findings of patients with cIPF was higher than in those with sIPF (P < 0.001). A Kaplan-Meier analysis showed that the sIPF group had a better prognosis (P = 0.001). A survival analysis showed that age, pulmonary function parameters, pulmonary oxygen tension, honeycombing change, and combined lung cancer had a significant influence on patient prognosis. However, there was no significant difference in prognosis between the cIPF and sIPF groups after adjusting for GAP (gender, age, physiology) stage.The patients with sIPF had better clinical features than those with cIPF. However, after adjusting for GAP stage, the sIPF group showed similar prognoses as the cIPF group. This study showed that after adjusting for GAP stage, the prognosis of patients with IPF is the same regardless of the diagnostic method used.