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The radiological manifestations of pulmonary nocardiosis are very diverse, and include non-segmental consolidation and pulmonary nodule(s). Cavitary nodules most commonly appear in AIDS patients, and are uncommon in non-AIDS patients. We report a case of pulmonary nocardiosis with bilateral multiple cavitary nodules in a HIV-negative 60-year-old man with nephrotic syndrome who was receiving corticosteroid treatment. It is suggested that pulmonary nocardiosis should be considered in the differential diagnosis of multiple cavitary nodules on chest radiographs, even in non-AIDS immunocompromised patients.

Introduction Although previous studies have reported etiologies, diagnostic strategies, and outcomes of acute respiratory failure (ARF) in cancer patients, few studies investigated ARF in cancer patients presenting with diffuse pulmonary infiltrates. Methods This was a retrospective observational study of 214 consecutive cancer patients with diffuse pulmonary infiltrates on chest radiography admitted to the oncology medical intensive care unit for acute respiratory failure between July 2009 and June 2011. Results After diagnostic investigations including bronchoalveolar lavage in 160 (75%) patients, transbronchial lung biopsy in 75 (35%), and surgical lung biopsy in 6 (3%), the etiologies of diffuse pulmonary infiltrates causing ARF were identified in 187 (87%) patients. The most common etiology was infection (138, 64%), followed by drug-induced pneumonitis (13, 6%) and metastasis (12, 6%). Based on the etiologic diagnoses, therapies for diffuse pulmonary infiltrates were subsequently modified in 99 (46%) patients. Diagnostic yield (46%, 62%, 85%, and 100%; P for trend < 0.001) and frequency of therapeutic modifications (14%, 37%, 52%, and 100%; P for trend < 0.001) were significantly increased with additional invasive tests. Patients with therapeutic modification had a 34% lower in-hospital mortality rate than patients without therapeutic modification (38% versus 58%, P = 0.004) and a similar difference in mortality rate was observed up to 90 days (55% versus 73%, Log-rank P = 0.004). After adjusting for potential confounding factors, therapeutic modification was still significantly associated with reduced in-hospital mortality (adjusted OR 0.509, 95% CI 0.281-0.920). Conclusions Invasive diagnostic tests, including lung biopsy, increased diagnostic yield and caused therapeutic modification that was significantly associated with better outcomes for diffuse pulmonary infiltrates causing ARF in cancer patients.

Background. There are limited data on the performance of the pneumonia severity index (PSI) and CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥65) score, which were originally developed for communityacquired pneumonia (CAP), for patients with healthcare-associated pneumonia (HCAP). Methods. The performances of PSI and CURB-65 were retrospectively evaluated in patients with HCAP compared to patients with CAP using prospectively collected data between January 2008 and December 2010. Results. In total, 938 patients hospitalized with pneumonia were eligible for this study, consisting of 519 (55%) with CAP and 419 (45%) with HCAP. The PSI and CURB-65 scores had similar trends of increasing mortality with worsening risk class in both the HCAP and CAP groups. In the HCAP group, however, the low-risk patients identified using CURB-65 had a higher aggregate 30-day mortality compared with the low-risk patients identified using PSI. Although the performances of PSI and CURB-65 in the HCAP group showed similar trends to those observed in the CAP group, the estimated areas under the receiver operating characteristic curve for PSI (0.679, 95% confidence interval [CI], .619–.739) and CURB-65 (0.599, 95% CI, .522–.675) in the HCAP group were significantly lower than those in the CAP group (0.835, 95% CI, .768–.759 for PSI and .686–.832 for CURB-65). Conclusions. The performances of PSI and CURB-65 for predicting 30-day mortality in patients with HCAP were comparable to those in patients with CAP. However, the discriminatory powers of PSI and CURB-65 for 30-day mortality were significantly lower in the HACP group than those in the CAP group.

Procurement of tumor tissue is mandatory for a mutation analysis in patients with non-small cell lung cancer. The purpose of this study was to evaluate the usefulness of bronchoscopic biopsy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy for detecting epidermal growth factor receptor (EGFR) and KRAS mutations in routine practice.Tumor DNA was extracted from formalin-fixed paraffin-embedded tissues, and amplifications of exons 18-21 of EGFR and codons 12, 13 and 61 of KRAS were performed using polymerase chain reaction (PCR). PCR products were subjected to direct sequencing in both directions.Of 211 consecutive specimens, 201 (95.3%) were available for EGFR mutation analysis, and 196 (92.9%) were adequate for KRAS mutation analysis. EGFR and KRAS mutations were detected in 14.9% and 5.4%, respectively. A median of 16 days was spent from biopsy to the final report for either EGFR or KRAS mutation status. The detection rates for both mutations were similar between bronchoscopic biopsy and EBUS-TBNA (P0.05). Female gender (53.3%), never smoker (63.3%), and adenocarcinoma (96.7%) were predominant in patients with EGFR mutations. Among patients with adenocarcinoma (n = 104), the frequencies of EGFR and KRAS mutations were 27.9% and 10.6%, respectively.Small tissue samples obtained by bronchoscopic biopsy and EBUS-TBNA are sufficient for detecting EGFR and KRAS mutations in routine practice. Therefore, concurrent mutational analyses of small tissue samples should be considered at the time of initial diagnosis.

We report a 54-year-old woman who presented with a well-defined, homogeneous, and non-enhancing mass in the retrobronchial region of the bronchus intermedius. The patient underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for histological confirmation. Serous fluid was aspirated by EBUS-TBNA. Cytological examination identified an acellular smear with negative microbiological cultures. The patient was finally diagnosed with bronchogenic cysts by chest computed tomography (CT) and EBUS-TBNA findings. However, 1 week after EBUS-TBNA, the patient developed bronchogenic cyst rupture and pneumonia. Empirical antibiotics were administered, and pneumonia from the bronchogenic cyst rupture had resolved on follow-up chest CT. To our knowledge, this is the first reported case of pneumonia from bronchogenic cyst rupture after EBUS-TBNA.

Epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC) is a strong predictive factor for a favorable response to EGFR tyrosine kinase inhibitors, however, its prognostic role in locally advanced stage is unclear. The aim of this study was to analyze the association of EGFR mutational status and clinical outcome after neoadjuvant chemoradiotherapy (CRT) followed by surgical resection in mediastinoscopically proven N2(+) NSCLC patients. We retrospectively identified 168 patients diagnosed between 1998 and 2006. EGFR mutational status was identified in 107 patients. Response and survival after neoadjuvant CRT followed by surgery were compared according to EGFR mutational status. 83 patients (77.6%) were found to have wild type EGFR, while exon 19 deletions or L858R missense mutations in the EGFR gene were detected in 19 patients. There was no significant difference in overall survival; however, the 5-year PFS rate in EGFR mutant patients (8.4%) were significantly lower than in the EGFR wild-type patients (33.6%; p=0.005). In multivariate analysis, EGFR mutation was a significant prognostic factor for a higher risk of distant recurrence/progression than the EGFR wild type (HR=7.183, p=0.005). In locally advanced mediastinoscopic N2-positive NSCLC, EGFR mutation was associated with more frequent distant relapses and worse 5-year PFS rate after neoadjuvant CRT followed by surgery, which might suggest that systemic control might be important in patients with the EGFR mutation. Therefore, the role of TKI for adjuvant EGFR TKI to decrease disease recurrence in distant sites should be further investigated.

Acute respiratory failure that requires invasive mechanical ventilation is a leading cause of death in critically ill cancer patients. The aim of this study was to evaluate the outcome and prognostic factors of patients requiring invasive mechanical ventilator for acute respiratory failure, within 1 month of ambulatory chemotherapy for solid cancer.A retrospective observational study of patients who underwent ambulatory chemotherapy at Samsung Medical Center, between January of 2007 and April of 2009, was employed for this study.A total of 51 patients met the inclusion criteria and were included in the study. The median age was 65 years (25-87) and the majority of the patients were male (n = 38, 74.5%). There were 42 patients (82.3%) with lung cancer. The most common cause of acute respiratory failure was pneumonia (n = 24, 47.1%), followed by acute respiratory failure due to extra-pulmonary infection, drug-induced pneumonitis, alveolar hemorrhage, and cancer progression. The intensive care unit (ICU) mortality was 68.6% and the most common cause of death in the ICU was uncorrected cause of acute respiratory failure. Before adjustment for others factors, prechemotherapy Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) (P = 0.03), Sequential Organ Failure Assessment score (P = 0.01), and anemia (P = 0.04) were significantly associated with ICU mortality. However, when adjusted for age, sex, and Acute Physiologic and Chronic Health Evaluation II score, only poor ECOG PS (≥2) was significantly associated with ICU mortality [OR 6.36 (95% CI (1.02-39.5))].The outcome of patients with acute respiratory failure needing invasive mechanical ventilation during ambulatory chemotherapy for solid cancer is poor. Prechemotherapy performance status is an independent predictor of mortality.

Mycobacterium avium and Mycobacterium intracellulare are grouped together as the M avium complex; however, little is known about the clinical impact of this species differentiation. This study compared the clinical features and prognoses of patients with M avium and M intracellulare lung disease.From 2000 to 2009, 590 patients were given a new diagnosis of M avium complex lung disease; 323 (55%) had M avium lung disease, and 267 (45%) had M intracellulare lung disease.Compared with the patients with M avium lung disease, the patients with M intracellulare lung disease were more likely to have the following characteristics: older age (64 vs 59 years, P = .002), a lower BMI (19.5 kg/m² vs 20.6 kg/m², P.001), respiratory symptoms such as cough (84% vs 74%, P = .005), a history of previous treatment for TB (51% vs 31%, P.001), the fibrocavitary form of the disease (26% vs 13%, P.001), smear-positive sputum (56% vs 38%, P.001), antibiotic therapy during the 24 months of follow-up (58% vs 42%, P.001), and an unfavorable microbiologic response after combination antibiotic treatment (56% vs 74%, P = .001).Patients with M intracellulare lung disease exhibited a more severe presentation and had a worse prognosis than patients with M avium lung disease in terms of disease progression and treatment response. Therefore, species differentiation between M avium and M intracellulare may have prognostic and therapeutic implications.

We evaluated effective treatments of broncholithiasis based on its radiographical and bronchoscopic features.This retrospective study conducted at Samsung Medical Center, Korea enrolled patients who were suspected of having broncholithiasis based on chest computed tomography (CT). The broncholiths were classified as intraluminal, mixed (both intraluminal and extraluminal) and extraluminal based on chest CT and bronchoscopic findings.The study enrolled 46 patients between 1995 and 2009. Symptoms included cough (n = 21, 45.7%), hemoptysis (n = 19, 41.3%) and purulent sputum (n = 11, 23.9%). Cough was more common in intraluminal boncholiths than in other type of broncholiths (P = 0.03). Based on chest CT, there were 15 (32.6%) intraluminal, 15 (32.6%) mixed and 16 (34.8%) extraluminal broncholiths. All 15 intraluminal broncholiths were removed completely via flexible (n = 2) or rigid (n = 13) bronchoscopy. For the 15 mixed broncholiths, seven (46.7%) bronchoscopic interventions were performed, but complete removal of the broncholiths was not accomplished. Six (40%) mixed and four (25%) extraluminal broncholiths were treated by surgical resection for symptom control. None of the patients who underwent surgical resection suffered morbidity or postoperative mortality.The treatment of broncholithiasis should be based on chest CT and bronchoscopic findings. Intraluminal broncholiths can be removed via bronchoscopy, while surgery should be considered for symptomatic mixed or extraluminal broncholiths.

This study was designed to investigate the incidence, causes, and outcomes of new-onset thrombocytopenia (NOT) in Korean intensive care units (ICUs). A prospective cohort study was conducted in medical ICUs of Samsung Medical Center between August 2010 and February 2011. All newly admitted patients were included if they stayed in the ICU for more than 48 hr and did not have thrombocytopenia upon admission. A total of 186 patients were included. NOT developed in 37.1%. Most common cause of NOT was sepsis with disseminated intravascular coagulation (66.7%), followed by drug-induced thrombocytopenia (18.8%), and heparin-induced thrombocytopenia (2.9%). IgG-specific antibody to platelet factor 4/heparin was positive in 2.4% among patients treated with heparin, and thrombosis occurred in two patients. Twenty eight-day mortality was higher in patients that developed NOT compared to those that did not develop NOT (39.1% vs 12%, P < 0.001). NOT increased the odds ratio of 28-day mortality and was an independent risk factor for mortality (OR 3.52; 95% CI 1.32-9.38; P = 0.012). In conclusion, NOT is common and is an independent risk factor for mortality in Korean ICU patients. Therefore, clinicians should make every effort to correct the causes of NOT.

To correlate the results of histopathologic subtyping and grading of lung adenocarcinoma with maximum standardized uptake values (SUVmax) on positron emission tomography (PET)/computed tomography and apparent diffusion coefficient (ADC) values on diffusion-weighted MRI (DWI).Forty-three patients were included. The SUVmax and mean ADC values of tumors were measured and correlated with the histologic subtypes and grades of lung adenocarcinomas based on the IASLC/ATS/ERS classification scheme. Disease-free survival (DFS) was estimated by using the Kaplan-Meier method, and the log-rank test was used to evaluate differences among three histologic grades or subgroups classified with imaging biomarker study results.Five (12.5%) tumors belonged to low grade, 30 (70%) to intermediate grade, and 8 (18.5%) to high grade, and patients with low-grade histology had lower risk of recurrence than those with intermediate- or high-grade histology (P = 0.048). A significant difference in SUVmax and mean ADC values was observed among three histologic grades (Ps0.001). Regarding DFS, lower metabolic (PET) activity or higher functional (DWI) diffusivity showed longer DFS. When patients (n = 30; 70% of patients) with intermediate histologic grade were subgrouped in consideration of both SUVmax and mean ADC results, combining metabolic and functional criteria helped stratify patients more precisely (P = 0.006).SUVmax and mean ADC value correlate well with the histologic grades in lung adenocarcinomas, and combining both imaging biomarker study results leads to more useful stratification of patients into different prognostic subsets than the results of each study.

Linezolid may be an effective treatment for multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). The objective was to evaluate the efficacy, tolerability and adverse events of a 300 mg daily dose of linezolid in the treatment of MDR/XDR-TB.We retrospectively reviewed the medical records of 51 MDR-TB patients, including 26 patients (51%) with XDR-TB, to evaluate the safety, tolerability and efficacy of therapy with 300 mg/day linezolid. All patients had failed previous treatments with second-line anti-TB drugs.Patients were treated with linezolid for a median of 413 days (IQR 237-622 days). Favourable treatment outcome (treatment success or still on treatment after culture conversion) was achieved in 40 patients (78%) with culture conversion at a median of 55 days (IQR 41-91 days) from the start of linezolid therapy. Eleven patients (22%) had unfavourable outcomes (treatment failure or death) and 14 (27%) discontinued treatment due to neurotoxicity (peripheral or optic neuropathy) after a median of 278 days (IQR 174-412 days).Our findings suggest that linezolid at a daily dose of 300 mg is effective against intractable MDR/XDR-TB, and may be associated with fewer neuropathic side effects than a daily dose of 600 or 1200 mg.

To evaluate whether air pockets (tracheobronchial air columns in the space between the outer surface of the stent and the adjacent airway wall) discernible at computed tomography (CT) can help optimize the time of stent removal in patients with posttuberculosis tracheobronchial stenosis (PTTS).The study was approved by the institutional review board, and informed consent was obtained from all patients. Data from 41 patients (five men, 36 women) with a median age of 39 years (range, 21-64 years) who underwent silicone stent placement owing to PTTS, followed by CT and stent removal 6-12 months after clinical stabilization, were investigated retrospectively. Two radiologists determined whether the extent of air pockets on CT scans was associated with clinical success, which was defined as maintenance of a prosthesis-free airway for more than 2 years after stent removal. Radiologic features were compared for outcome by using a Wilcoxon two-sample test or Fisher exact test.Stents were removed successfully in 31 patients (76%). Air pockets longer than 1 cm or longer than 2 cm were associated with successful stent removal (P = .04 and P = .006, respectively). The sensitivity and specificity of air pocket length in the prediction of successful stent removal were 84% and 50%, respectively, for air pockets longer than 1 cm and 68% and 70% for air pockets longer than 2 cm.The extent of air pockets at chest CT shows correlation with the success of stent removal, indicates regression of stenosis, and may help guide the optimal time for stent removal.

Purpose: Vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) are major mediators of angiogenesis and are induced by tissue inflammation and hypoxia. The purpose of this study was to investigate whether serum VEGF and Ang-2 are associated with the presence of hemoptysis and the extent of systemic inflammation in patients with inflammatory lung diseases. Materials and Methods: We prospectively enrolled 52 patients with inflammatory lung disease be tween June 2008 and October 2009. Results: The median values of VEGF and Ang-2 were 436 pg/mL and 2383 pg/mL, respectively. There was a significant positive correlation between serum Ang-2 and VEGF levels. VEGF levels were not significantly different according to the presence of hemoptysis. C-reactive pro tein (CRP) and Ang-2 level were significantly higher in patients without hemopty sis (n=26) than in those with hemoptysis (n=26; p

N -Acetyltransferase 2 (NAT2) metabolizes arylamines and hydrazines. The substrates of NAT2 include many therapeutic drugs, such as isoniazid (INH), as well as chemicals and carcinogens (1)(2)(3). For that reason, N-acetylation activity is associated with drug effects or toxicities and susceptibility to various cancers. The ability of NAT2 to N-acetylate arylamines is subject to a genetic polymorphism in the NAT2 gene. The acetylation rate and NAT2 genotype distribution are quite different among various populations. The genetic polymorphism in NAT2 has not been studied extensively in the Korean population. Previous reports were based only on phenotyping or restriction fragment length polymorphism analysis, leading to possible misclassification of genotypes. We therefore decided to investigate NAT2 allelic variability and genotype distributions in the Korean population by complete sequencing. We also evaluated the relationship between genotype and phenotype to understand N-acetylation pharmacogenetics. One thousand Korean individuals who visited the health promotion center at Samsung Medical Center were anonymously studied. An additional 23 healthy volunteers and 18 patients with pulmonary tuberculosis participated in this study. DNA was extracted from peripheral blood leukocytes. We amplified a 1211-bp fragment that included an 870-bp protein-coding region of the NAT2 gene and performed full sequencing analysis (4) on an ABI Prism 377 DNA Sequencer (Perkin-Elmer). We then checked nucleotide substitutions by combined use of allele-specific-PCR (AS-PCR) and restriction enzyme digestion. Specific primers (5) for the wild-type and mutant alleles were used in separate PCRs to detect C282T, T341C, and G590A substitutions. The nucleotides at positions 190, 481, 590, 803, and 857 were explored by digesting the 1211-bp PCR fragment or AS-PCR product carrying the wild-type or mutant allele with Nci I, Kpn I, Taq I, Dde I, and Bam HI, respectively. For phenotyping, the healthy volunteers and patients gave informed …

To evaluate the prognostic significance of maximum standardized uptake value (SUVmax) at (18)F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography in patients with stage IIIA non-small-cell lung cancer (NSCLC) who underwent surgical resection after neoadjuvant chemoradiotherapy, focused on the relationship between SUVmax values and tumor histology.We retrospectively evaluated the initial SUVmax of 205 patients (112 adenocarcinomas, 82 squamous cell carcinomas [SCCs], and 11 of other histology) with a stage IIIA NSCLC who underwent surgical resection after neoadjuvant chemoradiotherapy, and who were followed for up to 6 years. Clinical data, including histologic type, pathologic response, and treatment, were reviewed, and the relationship between the SUVmax and patient overall survival was examined.Overall, the 2-year survival rate was 68%. Between the two histologic subtypes of adenocarcinoma and SCC, we noted significant differences in all variables of gender (male predominance in SCC), initial SUVmax (greater in SCC), pathologic response (more complete remission in SCC), and overall survival (better in SCC) (all P values,.05). SUVmax remained as a sole independent factor for survival in multivariate analysis in whole series (SUVmax cutoff, 13; median survival, 3.0 years vs. 4.0 years; P = .016) and in adenocarcinomas (SUVmax cutoff, 11.5; median survival, 2.6 years vs. 3.6 years; P = .045), but not in SCCs.The initial SUVmax is a sole significant prognostic factor in patients with a surgically resected NSCLC after neoadjuvant chemoradiotherapy, particularly in patients with an adenocarcinoma.

There are no accurate data on the relationship between nodal station and diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). We evaluated the impact of nodal station and size on the diagnostic performance of EBUS-TBNA in patients with non-small cell lung cancer (NSCLC). Consecutive patients who underwent EBUS-TBNA of mediastinal or hilar lymph nodes for staging or diagnosis of NSCLC were included in this retrospective study. Between May 2009 and February 2010, EBUS-TBNA was performed in 373 mediastinal and hilar lymph nodes in 151 patients. The overall diagnostic sensitivity, specificity, accuracy and negative predictive value (NPV) of EBUS-TBNA were 91.6%, 98.6%, 93.8%, and 84.3%, respectively. NPV of the left side nodal group was significantly lower than those of the other groups (P = 0.047) and sensitivity of the left side nodal group tended to decrease (P = 0.096) compared with those of the other groups. Diagnostic sensitivity and NPV of 4L lymph node were 83.3% and 66.7%, respectively. However, diagnostic performances of EBUS-TBNA did not differ according to nodal size. Bronchoscopists should consider the impact of nodal stations on diagnostic performances of EBUS-TBNA.

Silicone airway stents are used to widen narrowed airways in patients with post-tuberculosis tracheobronchial stenosis (PTTS). After mechanical stabilization, stents can be removed from the majority of patients leaving restored airway patency. However, in a significant minority re-stenosis develops post-sten removal thus necessitating surgical intervention or long-term stenting. In this study, we sought to establish prognostic factors for successful airway intervention in PTTS.We retrospectively investigated 71 patients who underwent silicone stenting due to PTTS. After stenting, bronchoscopic toileting and/or repositioning was performed during follow up. At 6-12 months after clinical stabilization, stents were planned to be removed. Patients with patent airways were followed if no further intervention was required. If restenosis developed, patients underwent re-stenting or operation. Clinical parameters were analysed to determine favourable prognostic factors.Stents were successfully removed in 40 patients at a median 12.5 months after insertion. In 27 patients, stent re-insertion was carried out and four patients underwent surgical management. Multivariate logistic regression analysis revealed that successful stent removal was independently associated with atelectasis1 month before bronchoscopic intervention, and absence of complete lobar atelectasis.Airway intervention, including silicone stenting, can be successful in patients with PTTS, when the intervention is performed within 1 month of atelectasis and before complete lobar atelectasis.

A novel duplex PCR method based on variable-number tandem-repeat targets to discriminate among Mycobacterium abscessus complex isolates was developed and evaluated in 85 clinical isolates. The assay accuracy was confirmed by a multiple-target sequence analysis. The duplex PCR assay is a one-step, reliable, and accurate assay for discriminating M. abscessus species.

The aim of this study was to evaluate the annual incidence of tuberculosis infection among newly employed doctors and nurses in Korea. The annual incidence of tuberculosis infection ranged from 3.3% to 5.7%, based on the definition of conversion of an interferon-γ release assay, which suggests that stricter preventive strategies against nosocomial TB infection should be employed. Follow-up interferon-γ levels measured after 3 months of isoniazid and rifampicin treatment showed considerable variation. Therefore, serial testing with interferon-γ release assays after treatment of latent TB infection may be insufficient for evaluating the effects of treatment due to the variable responses.

Mycobacterium massiliense has been recognized as a separate species from Mycobacterium abscessus; however, little is known regarding the clinical impact of this differentiation.To compare clinical features and treatment outcomes between patients with M. abscessus lung disease and those with M. massiliense lung disease.We performed molecular identification of stored clinical isolates of M. abscessus complex and compared clinical characteristics and treatment outcomes between 64 patients with M. abscessus lung disease and 81 patients with M. massiliense lung disease.The clinical and radiographic manifestations of disease caused by each species were similar. Standardized combination antibiotic therapy, including a clarithromycin-containing regimen in combination with an initial 4-week course of cefoxitin and amikacin, was given to 57 patients (24 with M. abscessus and 33 with M. massiliense) for more than 12 months. The proportion of patients with sputum conversion and maintenance of negative sputum cultures was higher in patients with M. massiliense infection (88%) than in those with M. abscessus infection (25%; P0.001). Inducible resistance to clarithromycin (minimal inhibitory concentrations ≥ 32 μg/ml) was found in all tested M. abscessus isolates (n = 19), but in none of the M. massiliense isolates (n = 28).Treatment response rates to combination antibiotic therapy including clarithromycin were much higher in patients with M. massiliense lung disease than in those with M. abscessus lung disease. The inducible resistance to clarithromycin could explain the lack of efficacy of clarithromycin-containing antibiotic therapy against M. abscessus lung disease.

The introduction of ¹⁸F-FDG PET/CT has enhanced the diagnostic accuracy of nodal staging for non-small cell lung cancer (NSCLC). We analysed risk factors for occult nodal metastasis in patients with clinical stage IA NSCLC as determined by ¹⁸F-FDG PET/CT.Data for 147 patients diagnosed as clinical stage IA NSCLC by PET/CT from 2005 to 2007 were retrospectively reviewed. All study patients underwent ¹⁸F-FDG PET/CT for lung cancer staging. They also underwent cervical mediastinoscopy or systematic lymph node dissection.Cervical mediastinoscopy was performed in 78 patients (53.1%), and N2 involvement was detected in 3.8% (3/78) of these patients. Thoracotomy with systematic lymph node dissection was done in 144 patients. Four patients (2.8%, 4/144) were diagnosed with N2 disease after systematic lymph node dissection. Total N2 involvement was 4.8% (7/147). As 9.5% (14/147) of study patients had N1 disease, 14.3% (21/147) of patients had occult nodal (N1 or N2) metastasis. In univariate analyses, larger tumour size and a higher primary tumour maximum standardized uptake value7.3 (SUV(max)) were associated with occult nodal metastasis. Multivariate analysis demonstrated that a primary tumour SUV(max)7.3 was an independent predictor of occult nodal metastasis (odds ratio: 7.574; P = 0.001).Preoperative PET/CT scans contribute to reduce the frequency of occult nodal metastasis compared with those reported in the pre-PET/CT era. The higher SUV(max) in primary tumour was an independent predictor of occult nodal metastasis in patients with clinical stage IA NSCLC by PET/CT.

Objective: To describe the radiographic findings of primary pulmonary tubercu-losis (TB) in previously healthy adolescent patients.Materials and Methods: The Institutional Review Board approved this retro-spective study, with a waiver of informed consent from the patients. TB outbreaksoccurred in 15 senior high schools and chest radiographs from 58 students withidentical strains of TB were analyzed by restriction fragment length polymorphismanalysis by two independent observers. Lesions of nodule(s), consolidation, orcavitation in the upper lung zones were classified as typical TB. Mediastinallymph node enlargement; lesions of nodule(s), consolidation, or cavitation inlower lung zones; or pleural effusion were classified as atypical TB. Inter-observ-er agreement for the presence of each radiographic finding was examined bykappa statistics.Results: Of 58 patients, three (5%) had normal chest radiographs. Cavitarylesions were present in 25 (45%) of 55 students. Lesions with upper lung zonepredominance were observed in 27 (49%) patients, whereas lower lung zone pre-dominance was noted in 18 (33%) patients. The remaining 10 (18%) patients hadlesions in both upper and lower lung zones. Pleural effusion was not observed inany patient, nor was the mediastinal lymph node enlargement. Hilar lymph nodeenlargement was seen in only one (2%) patient. Overall, 37 (67%) students hadthe typical form of TB, whereas 18 (33%) had TB lesions of the atypical form. Conclusion: The most common radiographic findings in primary pulmonary TBby recent infection in previously healthy adolescents are upper lung lesions,which were thought to be radiographic findings of reactivation pulmonary TB byremote infection.ulmonary tuberculosis (TB) has been classified into primary and reactiva-tion (post-primary) forms (1). In about 5% of individuals infected by

Introduction The development of synchronous multiple primary non-small cell lung cancer (NSCLC) is not rare. Nevertheless, the diagnosis, treatment and outcome are controversial. The purposes of this study were to assess the treatment outcomes for patients with synchronous multiple primary NSCLC and to analyze the factors related to this outcome. Methods We retrospectively analyzed clinical characteristics and treatment outcomes of 32 patients with synchronous multiple primary NSCLC who underwent surgical resection between 1995 and 2008. Results A total of 68 separate tumors were identified in 32 patients. Fifteen (46.9%) patients underwent lobectomy or pneumonectomy with mediastinal lymph node dissection, and 17 (53.1%) patients underwent at least one limited resection or photodynamic therapy. The rate of immediate postoperative mortality was 9.4% (N = 3). The five-year progression-free survival (PFS) and overall survival (OS) rates were 46.0% and 60.9%, respectively. Small tumor size, similar histology, pN0, and pT1 were associated with better PFS in univariable analyses. Female gender, young age, non-smoker, FEV1/FVC ≥70%, small tumor size, similar histology, and highest pT1 were associated with better OS in univariable analyses. Conclusions An aggressive surgical approach offers the greatest chance for long-term survival in patient with synchronous multiple primary NSCLC and several clinical factors were associated with survivals. However, the decision of aggressive surgical treatments for synchronous MPLC should be made carefully in the patients with old age and underlying comorbidities due to poor OS and increased surgical mortality.

The advent of computed tomography (CT) screening with or without the help of computer-aided detection systems has increased the detection rate of solitary pulmonary nodules (SPNs), including that of early peripheral lung cancer. Helical dynamic (HD)CT, providing the information on morphologic and hemodynamic characteristics with high specificity and reasonably high accuracy, can be used for the initial assessment of SPNs. (18)F-fluorodeoxyglucose PET/CT is more sensitive at detecting malignancy than HDCT. Therefore, PET/CT may be selectively performed to characterize SPNs when HDCT gives an inconclusive diagnosis. Serial volume measurements are currently the most reliable methods for the tissue characterization of subcentimeter nodules. When malignant nodule is highly suspected for subcentimeter nodules, video-assisted thoracoscopic surgery nodule removal after nodule localization using the pulmonary nodule-marker system may be performed for diagnosis and treatment.

SummaryBackgroundHealth care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection. ATS/IDSA guidelines state that all patients with HCAP should receive empirical therapy directed at multidrug-resistant pathogens. However, recent data from other countries have reported a different picture of HCAP.MethodsWe conducted a retrospective observational study of patients with HCAP and CAP who were hospitalized through the emergency department in January–December 2008 at Samsung Medical Center, Seoul, Korea, and compared clinical characteristics, severity, distribution of pathogen, and outcomes.ResultsIn total, 345 patients hospitalized with pneumonia were eligible, 182 (52.8%) with HCAP and 163 (47.2%) with CAP. Patients with HCAP had greater comorbidity and higher Pneumonia Severity Index (PSI) score (P

We evaluated the usefulness of interferon-gamma release assays (IGRAs) in the diagnosis of active tuberculosis (TB) in routine clinical practice. We retrospectively assessed the diagnostic usefulness of the QuantiFERON-TB Gold In-Tube (QFT-IT) test in 519 consecutive patients who were suspected of having active pulmonary TB and had QFT-IT test results. Active pulmonary TB was diagnosed in 242 patients (47%). The sensitivity in the diagnosis of active pulmonary TB was higher with the QFT-IT test (84%) than with the tuberculin skin test (TST; 74%; p=0.003). The negative predictive value in the diagnosis of active pulmonary TB was also higher with the QFT-IT test (79%) than with the TST (70%; p=0.023). Among 59 patients with non-tuberculous mycobacterial lung disease, the QFT-IT test was positive in 29 patients (49%). In conclusion, the high negative predictive value of the QFT-IT suggests a supplementary role for this test in the diagnostic exclusion of active TB. However, negative QFT-IT test results should not be used alone to exclude active TB. Additionally, the QFT-IT test has limited usefulness in differentiating active pulmonary TB from non-tuberculous mycobacterial lung disease in areas with a high prevalence of latent tuberculosis infection.

The decision to start chemotherapy in critically ill cancer patients is extremely complex in the intensive care unit (ICU). Therefore, this study evaluated the outcomes and prognostic factors in critically ill cancer patients receiving chemotherapy in the ICU.A retrospective analysis was performed using 62 cancer patients who received chemotherapy in the ICU between October 2002 and December 2008. The dataset included 49 hematologic malignancies (79%) and 13 solid tumors (21%).Twenty (32%) patients were admitted to the ICU with septic shock, 15 (24%) with respiratory failure, and 14 (23%) with renal failure. The median SOFA and SAPS II scores at the time of chemotherapy were 10 (interquartile range, 6-14) and 53 (interquartile range, 41-68), respectively. Twenty-three (37%) patients had concomitant infections when chemotherapy was initiated. Thirty-eight (61%) patients received mechanical ventilation, and 19 (31%) patients underwent renal replacement therapy at the moment of chemotherapy. Overall, 25 (40%) patients died in the ICU; death occurred due to septic shock (13, 52%), cancer progression (9, 36%), or bleeding (2, 8%). ICU mortality after chemotherapy was correlated with respiratory failure requiring mechanical ventilation (OR, 6.26; 95% CI, 1.12-34.95) and a SOFA score of ≥10 (OR, 9.66; 95% CI, 1.43-65.47) upon initiating chemotherapy.Chemotherapy in the ICU for critically ill cancer patients can be considered even when infection or organ failure is present. However, the severity of organ failure, including respiratory failure requiring mechanical ventilation, was associated with an increased mortality after chemotherapy during an ICU stay.

Mycobacterium kansasii is a facultative intracellular pathogen causing pulmonary disease in immunocompetent patients. Little is known about the host defense against M. kansasii and its intracellular survival strategy inside macrophages. In the present study, we obtained six clinical isolates from patients with M. kansasii pulmonary disease and investigated the intracellular growth and cytotoxic effects of M. kansasii inside mouse bone marrow-derived macrophages (BMDM) as well as cytokine secretion from BMDM. Interestingly, two isolates, SM-1 and 2693-20, displayed faster growth rates and higher levels of TNF-alpha secretion from macrophages when compared to the other strains. In addition, SM-1 and 2693-20 also induced massive cell death in BMDM and THP-1 acute monocytic leukemia cells, while the slow growing strains induced significantly lower levels of cell death. This cytotoxicity was mainly caused by necrosis, not apoptosis and it was TNF-alpha-independent. Caspase inhibitors failed to block M. kansasii-induced macrophage death. In addition, necrosis caused by the fast growing strains was accompanied by the loss of mitochondrial membrane potential (DeltaPsi(m)). When dissipation of DeltaPsi(m) was inhibited by the classical mitochondrial permeability transition (MPT) inhibitor cyclosporine A (CsA), macrophage necrosis was reduced. These results suggest that clinical isolates of M. kansasii that grow faster in macrophages induce higher levels of necrosis in a DeltaPsi(m) loss-dependent manner.

Few studies have compared the clinical and radiographic findings of tuberculomas to those of solitary pulmonary nodules (SPNs) caused by Mycobacterium avium complex (MAC). We retrospectively analyzed clinical and radiographic findings from 26 patients with tuberculomas and 15 patients with SPNs caused by MAC. Median SPN size was 22 mm. In 26 patients (63%), the SPN was detected during a routine health checkup or evaluation of organs other than lungs. Patients with SPNs due to MAC were slightly older (median = 59 years) compared with those with tuberculomas (median = 50 years; P = 0.044). When we compared computed tomography (CT) features between patients with tuberculomas and patients with MAC, no significant differences were found in SPN location or the presence of calcification, cavitation, central low attenuation, and the satellite lesions. Although the maximum standardized uptake values were slightly higher in patients with SPNs due to MAC (median = 8.5) compared with those with tuberculomas (median = 2.2), this difference was not significant (P = 0.053). Of the 15 patients with SPNs due to MAC, 10 were initially diagnosed with “tuberculoma” and administered antituberculosis medication. MAC pulmonary disease should be considered in the differential diagnosis of SPNs, even when encountered in geographic regions with a high prevalence of pulmonary tuberculosis.

Pulmonary disease caused by nontuberculous mycobacteria (NTM), including Mycobacterium abscessus, can be classified into two distinct types of clinical disease; the upper lobe fibrocavitary (UC) form and nodular bronchiectatic (NB) form. However, the relationship between mycobacterial strain virulence and disease type in the pulmonary M. abscessus diseases has not been reported. To determine the differential virulence between strains causing two forms of disease, we obtained clinical isolates from patients with the UC and NB form of pulmonary disease caused by M. abscessus. In present study, we investigated the intracellular growth of clinical isolates in macrophages and their pathogenicity in C57BL/6 mice. For the isolates from the UC form, intracellular macrophage growth was faster and higher levels of cytokines were induced in macrophages than for those from NB form. Moreover, severe lung inflammation was only observed in mice intranasally infected with the isolate from the UC form with the increase of bacterial load. These findings suggest that M. abscessus isolates from the UC form of pulmonary disease are more virulent than those from NB form. This differential virulence of clinical strains may be one of the important factors involved in the determination of the disease form of pulmonary M. abscessus disease.

Mycobacterium bolletii is a rapidly growing nontuberculous mycobacterium first characterized in 2006. Here, we report a case of disseminated infection caused by M. bolletii in a young adult patient. To our knowledge, this is the first case of disseminated M. bolletii infection in an otherwise healthy young adult.

The optimal therapeutic regimen and duration of treatment for Mycobacterium abscessus lung disease is not well established.To assess the efficacy of a standardized combination antibiotic therapy for the treatment of M. abscessus lung disease.Sixty-five patients (11 males, 55 females, median age 55 yr) with M. abscessus lung disease were treated with clarithromycin, ciprofloxacin, and doxycycline, together with an initial regimen of amikacin and cefoxitin for the first 4 weeks of hospitalization.Treatment response rates were 83% for symptoms and 74% for high-resolution computed tomography. Sputum conversion and maintenance of negative sputum cultures for more than 12 months was achieved in 38 (58%) patients. These rates were significantly lower in patients whose isolates were resistant to clarithromycin (17%, 2/12) compared with those whose isolates were susceptible or intermediate to clarithromycin (64%, 21/33; P = 0.007). Neutropenia and thrombocytopenia associated with cefoxitin developed in 33 (51%) and 4 (6%) patients, respectively. Drug-induced hepatotoxicity occurred in 10 (15%) patients. Because of these adverse reactions, cefoxitin was discontinued in 39 (60%) patients after treatment for a median of 22 days.Standardized combination antibiotic therapy was moderately effective in treating M. abscessus lung disease. However, frequent adverse reactions and the potential for long-duration hospitalization are important problems that remain to be solved.

Background Although previous studies have suggested that linezolid may be effective for treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), the optimal dose of linezolid for intractable MDR/XDR-TB is not clear. Methods Twenty-four patients with intractable MDR/XDR-TB were treated with a daily 300 mg dose of linezolid as part of their anti-TB drug regimen. Results The patients were treated with linezolid for a median duration of 359 days [interquartile range (IQR) 268-443 days]. Seventeen (71%) patients received 300 mg of linezolid once daily from the beginning of treatment for a median duration of 289 days (IQR 233-405 days). Of these patients, four developed peripheral neuropathy, one of whom discontinued linezolid. In seven (29%) patients, 600 mg/day linezolid was administered initially for a median duration of 104 days (IQR 26-145 days) followed by 300 mg/day linezolid for a median duration of 348 days (IQR 298-427 days). In five of these seven patients, the reason for changing from 600 to 300 mg/day was due to side effects of 600 mg/day linezolid (peripheral neuropathy in four patients and leucopenia in one patient). After reducing the dose to 300 mg/day, linezolid could be continued in six of the seven patients. Negative sputum conversion was achieved in 22 (92%) patients after a median of 89 days from the start of linezolid treatment (IQR 48-160 days). Conclusions A daily 300 mg dose of linezolid may be useful for increasing the chances of culture conversion in the treatment of patients with intractable MDR/XDR-TB and might have fewer side effects, especially neurotoxicity, compared with a daily 600 mg dose of linezolid therapy. The present results encourage further research into the use of a 300 mg dose of linezolid for MDR/XDR-TB patients.

Background: Pulmonary paragonimiasis is a subacute to chronic inflammatory disease of the lung caused by lung flukes that result in prolonged inflammation and mechanical injury to the bronchi. However, there are few reports on the bronchoscopic findings of pulmonary paragonimiasis. This report describes the bronchoscopic findings of pulmonary paragonimiasis. Methods: The bronchosocpic findings of 30 patients (20 males, median age 50 years) with pulmonary paragonimiasis between May 1995 and December 2007 were reviewed retrospectively. Results: The diagnoses were based on a positive serologic test results for Paragonimus-specific antibodies in 13 patients (43%), or the detection of Paragonimus eggs in the sputum, bronchial washing fluid, or lung biopsy specimens in 17 patients (57%). The bronchoscopic examinations revealed endobronchial lesions in 17 patients (57%), which were located within the segmental bronchi in 10 patients (59%), lobar bronchi in 6 patients (35%) and main bronchi in 1 patient (6%). The bronchoscopic characteristics of endobronchial lesions were edematous swelling of the mucosa (16/17, 94%) and mucosal nodularity (4/17, 24%), accompanied by bronchial stenosis in 16 patients (94%). Paragonimus eggs were detected in the bronchial washing fluid of 9 out of the 17 patients with endobronchial lesions. The bronchial mucosal biopsy specimens showed evidence of chronic inflammation with eosinophilic infiltration in 6 out of 11 patients (55%). However, no adult fluke or ova were found in the bronchial tissue. Conclusion: Bronchial stenosis with mucosal changes including edematous swelling and mucosal nodularity is the most common bronchoscopic finding of pulmonary paragonimiasis.

Background The optimal treatment for non-small cell lung cancer (NSCLC) patients with asymptomatic brain metastasis is still controversial. This study aimed to analyze the outcome for various treatment modalities including chemotherapy only, upfront whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) in NSCLC patients with asymptomatic brain metastases. Methods We retrospectively reviewed the medical records of patients with histopathologically proven NSCLC and synchronous asymptomatic brain metastasis between January 2003 and December 2007. Results From the database, 741 NSCLC patients were identified to have been diagnosed of brain metastases during initial staging or follow-up between January 2003 and December 2007. Of 741 NSCLC patients, 135 (18%) NSCLC patients were identified to have synchronous brain metastasis without associated symptoms. Of the 129 patients included in the analysis, 78 (57.8%) patients received systemic chemotherapy only, 27 (20.0%) upfront WBRT followed by chemotherapy and 24 (17.8%) patients received upfront SRS and chemotherapy. There was no significant difference in overall survival among three groups (systemic chemotherapy alone, 13.9 versus upfront SRS followed by chemotherapy, 22.4 versus upfront WBRT followed by chemotherapy, 17.7 months, respectively; P = 0.86). Subset analysis of 110 adenocarcinoma patients showed that the median OS for patients treated with upfront SRS was longer than those of upfront WRBT (29.3 months versus 17.7 months; P = 0.01) or chemotherapy alone (29.3 months versus 14.6 months; P = 0.04). Conclusion This study suggested a potential role of systemic chemotherapy alone or upfront SRS followed by chemotherapy instead of WBRT as an initial treatment of NSCLC patients with synchronous, asymptomatic brain metastases. The optimal treatment modality, however, needs to be defined in prospective trials for this subset of patients.

Dark-blue pigmentation has been thought to be related to smoking or occupational exposure and has been regarded as anthracotic pigmentation. It is also frequently observed in non-smokers without occupational exposure, but there is no proven mechanism of pigmetation. To investigate clinical features and to find other causes of dark-blue pigmentaion, retrospective analysis was done in 59 patients who showed anthracotic pigmentation on bronchoscopy during recent 5 years in Seoul National University Hospital. The results were as follows; 1) Forty cases were non-smokers, while smokers were 19 cases. 2) Fifteen cases had history of tuberculosis, but there was no history of environmental exposure. 3) Mediastinal calcification was observed in 89.7%. 4) There was significant bleeding without exception when biopsy was done at the pigmentation site. 5) In patients with pigmentation only, hemoptysis and productive cough were main chief complaints, and chest X-ray showed atelectasis, infiltration, mass, or pleural change. 6) The number of patients whose lesion of X-ray corresponds to pigmentation site were 19/30 in tuberculosis, 4/30 in DILD and 7/30 in other diseases.

It has been well known that the integrity of airway epithelium is important in developing of bronchial hyperreactivity or bronchial asthma. But the mechanisms underlying this nonspecific airway hyperresponsiveness are not yet determined. To evaluate the ability of guinea pig trachea to release an epithelium derived relaxing factor (EpDRF) which relax rat vascular smooth muscle, we performed the coaxial bioassay using guinea pig trachea and rat aorta. And to evaluate the nature of EpDRF we investigate the influence of methylene blue and indomethacin on the coaxial bioassay. Results were as follows. 1) Vascular smooth muscle mounted into the epithelium intact trachea which was precontracted with phenylephrine was relaxed by addition of histamine or acetylcholine. But vascular smooth muscle mounted into epithelium denuded trachea failed to be relaxed. 2) Epithelium dependent relaxation of vascular smooth muscle was not affected by pretreatment of methylene blue or indomethacin. These results strongly suggests that guinea pig tracheal epithelium releases EpDRF which is able to relax rat vascular smooth muscle. And EpDRF released by airway epithelium is not related to endothelium derived relaxing factor (EDRF) or cyclooxygenase products.

It has been well known that the integrity of airway epithelium is important in development of bronchial hyperreactivity and bronchial asthma. But the mechanisms involved are still unclear. To evaluate that airway epithelium is able to modulate the contraction of guinea pig tracheal smooth muscle, we investigated the responsiveness of intact and epithelium-denuded tracheal strips to histamine and acetylcholine. And to evaluate whether cyclooxgenase products play a role in this modulatory mechanism, we also investigated the effect of indomethacin pretreatment on the tracheal responsiveness to histamine. Results were as follows: 1) In guinea pig tracheal smooth muscle the presence of airway epithelium significantly reduced the response to histamine. 2) In the presence of indomethacin dose-response curves and values were similar between intact and epithelium-denuded tracheal strips, that is, indomethacin abolished the influence of epithelium on the contracion of tracheal smooth muscle. 3) The response of tracheal smooth muscle to acetylcholine was similar both in the presence and absence of epithelium. These results suggest that airway epithelium of guinea pig may generate an inhibitory signal to decrease the response of tracheal smooth muscle to histamine and cyclooxygenase products may contrbute to the modulation of airway epithelium on the contracion of tracheal smooth muscle.

The purpose of the present study was to evaluate outcomes and identify prognostic factors in patients with acute leukemia who were admitted to the intensive care unit (ICU) with septic shock. Medical records of 50 patients with acute leukemia who were treated for septic shock in the Medical ICU of Samsung Medical Centre between September 2001 and June 2006 were retrospectively reviewed. The data were analysed for patient outcomes and for predictors of ICU mortality. ICU mortality and in-hospital mortality were 60% and 68%, respectively. The need for mechanical ventilation (p