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Rationale: While the history of pulmonary tuberculosis (PTB) is a risk factor for developing both chronic obstructive pulmonary disease (COPD) and lung cancer, it remains unclear whether the histor...

This study aimed to investigate the prognostic significance of dynamic contrast-enhanced computed tomography in patients with stage IA non-small cell lung cancer (NSCLC).We retrospectively enrolled 139 patients (77 men, 62 women; mean age, 59 years) with stage IA NSCLC who underwent dynamic contrast-enhanced computed tomography. Data on age, pathologic subtype, peak enhancement, and net enhancement of primary lung cancer were collected and correlated with 5-year survival.Peak enhancement had a significant correlation with overall survival in the univariable analysis (hazard ratio [HR], 1.18, confidence interval [CI], 1.01-1.38; P = 0.04) and in the multivariable analysis (HR, 1.19; CI, 1.01-1.39; P = 0.04). Patients with peak enhancement of 90 Hounsfield unit or higher had a significantly increased risk of death compared with patients with less enhancement after curative surgery (HR, 4.15; CI, 1.23-13.95; P = 0.02).Our study confirmed the prognostic significance of peak enhancement as an indicator for the overall survival of stage IA NSCLC.

Mycobacterium abscessus pulmonary disease (M abscessus-PD) is challenging to treat because of its resistance to antibiotics.What are the outcomes of treatment-naive patients with M abscessus-PD treated with inhaled amikacin-containing multidrug regimens?We identified 82 treatment-naive patients with M abscessus-PD from a prospective observational cohort treated with regimens containing inhaled amikacin with or without clofazimine between March 2015 and June 2018 (ClinicalTrials.gov identifier: NCT00970801). During the initial phase, all patients received IV amikacin, imipenem (or cefoxitin), and oral azithromycin. Oral clofazimine was added in cases of (1) M abscessus subspecies abscessus (here M abscessus) or (2) M abscessus subspecies massiliense (here M massiliense) with cavitary lesions. During the continuation phase, amikacin was changed from an injectional to inhalational form.Of 82 patients, 46 (56%) had M massiliense-PD and 36 (44%) had M abscessus-PD. Among 59 patients with nodular bronchiectatic disease (72%), 23 of 59 had a concurrent cavitary lesion. The remaining 23 patients (28%) had fibrocavitary disease. Twelve months after treatment initiation, cure was achieved in 53 patients (65%): 42 of 46 patients (91%) with M massiliense-PD and 11 of 36 patients (31%) with M abscessus-PD (P .001). Symptomatic and radiologic improvements were observed in 72 patients (88%) and 64 patients (78%), respectively, with significantly greater improvement in patients with M massiliense-PD (symptom improvement, 96% vs 78% [P = .047]; improvement on CT scanning, 93% vs 61% [P = .002]).Inhaled amikacin with or without clofazimine in the regimen provides favorable treatment outcomes in M massiliense-PD. However, more effective treatments are needed for M abscessus-PD.

Mycobacterium avium complex pulmonary disease (MAC-PD) requires long-term treatment. We analyzed the outcomes of 992 MAC-PD patients according to disease severity and compared the outcomes of intermittent and daily therapy for mild disease. Patients were divided into groups according to severity using the body mass index, age, cavity, erythrocyte sedimentation rate, and sex (BACES) system, and culture conversion rates were evaluated. We also evaluated the effects of intermittent treatment on the culture conversion rates in mild disease group. Using the BACES, 992 patients were divided into mild (n=331), moderate (n=503), and severe (n=158) disease groups, and culture conversion at the end of treatment was achieved in 85% (282/331), 80% (403/503), and 61% (97/158), respectively. Differences in culture conversion among the severity groups were significant (pp=0.396), and intermittent antibiotic therapy did not negatively impact culture conversion (adjusted hazard ratio 1.08; confidence interval 0.83–1.15; p=0.552). MAC-PD patients with mild disease had higher culture conversion rates. Daily and intermittent therapy yielded similar culture conversion rates for mild disease. Treatment strategies with lower pill burden may be applicable in mild MAC-PD.

Background Information about the natural history of nontuberculous mycobacterial pulmonary disease (NTM-PD) is limited. The purpose of this study was to evaluate the long-term natural history of non-cavitary nodular bronchiectatic NTM-PD and the factors associated with treatment initiation and the frequency of spontaneous sputum culture conversion after diagnosis of NTM-PD. Methods We evaluated 1,021 patients with newly diagnosed non-cavitary nodular bronchiectatic NTM-PD caused by Mycobacterium avium complex or M. abscessus between 2003 and 2013. Results Of 1,021 patients, 562 (55%) initiated antibiotic treatment and 459 (45%) did not. Young age (adjusted hazard ratio [aHR] = 0.99; 95% confidence interval [CI] = 0.98–0.99), low body mass index (aHR = 0.96; 95% CI = 0.93–0.99), previous history of tuberculosis (aHR = 1.23; 95% CI = 1.01–1.50), respiratory complaints such as cough (aHR = 1.36; 95% CI = 1.05–1.75) and sputum production (aHR = 1.47; 95% CI = 1.13–1.91), and high number of involved lobes on high-resolution computed tomography (aHR = 1.22; 95% CI = 1.14–1.31) were associated with treatment initiation. Of 459 patients who did not initiate treatment, 157 (34%) showed spontaneous sputum culture conversion. None of the clinical factors was associated with spontaneous conversion. After spontaneous culture conversion, 26 of 157 (17%) showed redeveloped NTM-PD caused by a species different from the original species. Conclusions The natural history of non-cavitary nodular bronchiectatic NTM-PD is variable. After diagnosis, the decision to initiate antibiotic therapy should be individualized based on consideration of the risk factors for disease progression. However, for patients who do not start antibiotic therapy, continuous and lifetime follow-up is recommended to manage underlying bronchiectasis and the possibility of late progression of NTM-PD.

Background Mycobacterium kansasii is a major pathogen associated with nontuberculous mycobacterial pulmonary disease. For treatment of M. kansasii pulmonary disease, daily therapy with isoniazid, rifampin, and ethambutol is traditionally recommended. Although a regimen containing a macrolide, instead of isoniazid, has been recently recommended, supporting data are limited. We compared the treatment outcomes of a macrolide-containing regimen (macrolide group) and an isoniazid-containing regimen (isoniazid group) on patients with M. kansasii pulmonary disease. Methods A total of 49 patients were identified between January 2002 and December 2016. Treatment outcomes for the isoniazid group (n = 24) and the macrolide group (n = 25) were compared. Results Baseline characteristics of the isoniazid and macrolide groups were similar. Favorable outcomes did not differ between the isoniazid group (79%, n = 19) and macrolide group (88%, n = 22, P = 0.463). Total treatment duration (median 17.9 months vs. 15.4 months; P = 0.712) and time to culture conversion (median 2.0 months vs. 1.2 months; P = 0.838) were also similar between the isoniazid and macrolide groups. Five patients who completed three-times-weekly intermittent treatment containing a macrolide for non-cavitary M. kansasii pulmonary disease achieved negative sputum culture conversion within 12 months of treatment. Only one patient experienced recurrence of M. kansasii pulmonary disease in the isoniazid group. Conclusions A macrolide-containing regimen appears to be as effective as an isoniazid-containing regimen for treatment of M. kansasii pulmonary disease. Additionally, intermittent therapy containing a macrolide could be an alternative treatment option for non-cavitary M. kansasii pulmonary disease.

BACKGROUND AND OBJECTIVE We evaluated the usefulness of acid-fast bacilli (AFB) culture and Mycobacterium tuberculosis (MTB) polymerase chain reaction (PCR) of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) needle rinse fluid for diagnosing tuberculous lymphadenitis. METHODS EBUS-TBNA needle rinse fluid was routinely used for AFB culture and MTB PCR. The patients were categorized according to the pre-procedural diagnosis (Group A, suspected/histology-confirmed lung cancer; Group B, extrapulmonary malignancy; and Group C, other benign diseases). RESULTS Of the 4672 subjects, 104 (2.2%) were diagnosed with tuberculous lymphadenitis; 1.0%, 4.6% and 12.7% of Group A, B and C, respectively. Tuberculous lymphadenitis was diagnosed in 0.2%, 1.0% and 4.5% Group A, B and C patients, respectively, by histopathology. On addition of AFB culture to histopathology, tuberculous lymphadenitis was diagnosed in 1.0%, 4.4% and 10.3% of Group A, B and C patients, respectively (P

Chronic obstructive pulmonary disease (COPD), an established risk factor for lung cancer, remains largely undiagnosed and untreated before lung cancer surgery. We evaluated the effect of perioperative bronchodilator therapy on lung function changes in COPD patients who underwent surgery for non-small cell lung cancer (NSCLC). From a database including NSCLC patients undergoing lung resection, COPD patients were identified and divided into two groups based on the use of bronchodilator during the pre- and post-operative period. Changes in forced expiratory volume in 1 s (FEV1) and postoperative complications were compared between patients treated with and without bronchodilators. Among 268 COPD patients, 112 (41.8%) received perioperative bronchodilator, and 75% (84/112) were newly diagnosed with COPD before surgery. Declines in FEV1 after surgery were alleviated by perioperative bronchodilator even after adjustments for related confounding factors including surgical extent, surgical approach and preoperative FEV1 (adjusted mean difference in FEV1 decline [95% CI] between perioperative bronchodilator group and no perioperative bronchodilator group; − 161.1 mL [− 240.2, − 82.0], − 179.2 mL [− 252.1, − 106.3], − 128.8 mL [− 193.2, − 64.4] at 1, 4, and 12 months after surgery, respectively). Prevalence of postoperative complications was similar between two groups. Perioperative bronchodilator therapy was effective to preserve lung function, after surgery for NSCLC in COPD patients. An active diagnosis and treatment of COPD are required for surgical candidates of NSCLC.

Although Candida species can cause invasive fungal diseases, such as disseminated infection and pneumonia, they rarely cause tracheobronchitis, which is often fatal. To identify the clinical characteristics of Candida tracheobronchitis, we retrospectively evaluated 8 patients who had pathologically proven Candida tracheobronchitis. Their median age was 64 (range: 51–70) years and 5 were females. Three patients had solid cancers and 5 had hematological malignancies. We classified tracheobronchitis into localized and diffuse types. Of the 8 patients, 5 had localized and 3 had diffuse tracheobronchitis. While all patients with diffuse tracheobronchitis had predisposing risk factors for invasive fungal disease, such as prolonged corticosteroid use, recent use of nucleoside analogues, or recent neutropenia (

Pulmonary disease (PD) due to nontuberculous mycobacteria (NTM) is increasing globally, but specific biomarkers for NTM-PD have not been established. As circulating miRNAs are promising biomarkers for various diseases, we investigated whether miRNAs have potential as NTM-PD biomarkers. Sera from 12 NTM-PD patients due to Mycobacterium avium, M. intracellulare, M. abscessus, or M. massiliense and three healthy controls were initially evaluated via small RNA sequencing. Multiple miRNAs showed significant differences in expression in patients compared to in healthy controls, with some expression differences unique to PD caused by a specific mycobacterial species. Notably, 14 miRNAs exhibited significant expression differences in PD associated with all four mycobacteria. Validation by quantitative reverse-transcription-PCR in an additional 40 patients with NTM-PD and 40 healthy controls confirmed that four differentially expressed miRNAs (hsa-miR-484, hsa-miR-584-5p, hsa-miR-625-3p, and hsa-miR-4732-5p) showed significantly higher serum expressions in NTM-PD patients than in controls. Receiver operating characteristic curve analysis of these four miRNAs supported the discriminative potential for NTM-PD and their combination provided an improved diagnostic value for NTM-PD. Furthermore, bioinformatics analysis revealed their 125 target genes, which were mostly associated with immune responses. Collectively, this study identified four miRNAs as potential biomarkers for NTM-PD and provided insight into NTM-PD pathophysiology.

Aim: Several studies have reported favorable outcomes of nonspecific interstitial pneumonia (NSIP); however, its prognosis and prognostic factors remain unclear. This study aimed to determine the outcomes of fibrotic NSIP and the prognostic factors for progression, relapse, and survival. Methods: In this retrospective study, we reviewed the clinical data of 204 patients diagnosed with fibrotic NSIP by surgical lung biopsy at Samsung Medical Center. The factors associated with survival and disease progression or relapse were determined using Cox proportional hazard analysis. Results: The median age of patients was 54 years and 67 (33%) patients were male. Also, 47 patients (23%) were current or ex-smokers. In all, 141 (69%) patients were diagnosed with idiopathic NSIP, while 63 (31%) patients were associated with connective tissue diseases. Progression or relapse was observed in 100 (49%) patients. The 5-year and 10-year survival rates were 94.6% and 90.4%, respectively. The factors associated with disease progression and relapse were diffusing capacity for carbon monoxide (DLco) 15% (adjusted HR, 0.592; 95% CI, 0.352–0.994; p = 0.047), and treatment with corticosteroid and azathioprine (adjusted HR, 0.556; 95% CI, 0.311–0.955; p = 0.048). Disease progression or relapse was associated with mortality (adjusted HR, 7.135; 95% CI, 1.499–33.971; p = 0.014). Conclusion: Preserved lung function, BAL lymphocytosis, and treatment with corticosteroids and azathioprine were associated with lower risks of disease progression and relapse, which were risk factors for mortality.

Patients with refractory Mycobacterium avium complex lung disease (MAC-LD) undergo long-term macrolide therapy, but macrolide resistance develops infrequently.The aim of this study was to determine whether reinfection was a factor in the low incidence of macrolide resistance in patients with refractory MAC-LD.Among 481 patients with treatment-naive MAC-LD who started antibiotic treatment between January 2002 and December 2013, we identified 72 patients with refractory disease, characterized by persistently positive sputum cultures despite ≥12 months of treatment. Molecular analyses of the 23S ribosomal RNA gene responsible for macrolide resistance and serial mycobacterial genotyping were performed using stored MAC isolates.The median duration of treatment was 32 months (interquartile range, 24-41 mo) in 72 patients. After treatment for a median of 33 months (interquartile range, 21-44 mo), macrolide resistance developed in 16 (22%) patients. Molecular analysis of isolates from 15 patients revealed that 80% (12 of 15) had a point mutation at position 2,058 or 2,059 of the 23S ribosomal RNA gene. Of the 49 patients who had stored pre- and post-treatment isolates, mycobacterial genotyping revealed that reinfection by new MAC strains occurred in 36 (73%) patients. New MAC strains were found in 24 (49%) patients, and mixed infections with original and new strains occurred in 12 (24%) patients. Only 13 (27%) patients had persistent infections with their original MAC strains.Refractory MAC-LD is commonly caused by reinfection with new strains rather than persistence of the original strain, which may explain the infrequent development of macrolide resistance in refractory MAC-LD. Clinical trial registered with www.clinicaltrials.gov (NCT00970801).

Objectives: The aim of this study was to evaluate whether rifabutin can improve treatment outcomes in patients with rifabutin-sensitive MDR-TB. Methods: A retrospective cohort study was performed on 76 patients with rifabutin-sensitive MDR-TB who were treated with or without rifabutin between 2006 and 2011. Results: Overall, 75% (57/76) of patients achieved favorable outcomes, including cure (53/76, 70%) and treatment completion (4/76, 5%). In contrast, 25% (19/76) had unfavorable treatment outcomes, which included treatment failure (6/76, 8%), death (2/76, 3%), loss to follow-up (4/76. 5%), and no evaluation due to transfer to other institutions (7/76, 9%). Rifabutin was given to 52 (68%) of the 76 patients with rifabutin-sensitive MDR-TB. Although favorable treatment outcomes were more frequent in patients who received rifabutin [81% (42/52)] than in those who did not receive rifabutin [63% (15/24)], this difference was not statistically significant (P = 0.154). However, in multivariable regression logistic analysis, use of rifabutin was significantly associated with favorable treatment outcomes in patients with rifabutin-sensitive MDR-TB (adjusted odds ratio = 9.80, 95% confidence interval = 1.65â58.37, P = 0.012). Conclusions: These results suggest that the use of rifabutin can improve treatment outcomes in patients with rifabutin-sensitive MDR-TB. Keywords: Multidrug-resistant tuberculosis, Extensively drug-resistant tuberculosis, Rifabutin, Treatment outcome

Objectives The relationship between transthoracic needle biopsy (TTNB) and pleural recurrence of cancer after curative lung resection remains unclear. We aimed to assess whether TTNB increases the ipsilateral pleural recurrence (IPR) rate and identify other potential risk factors for pleural recurrence after surgery. Materials and methods This retrospective study included 392 patients with p-stage I non-small cell lung cancer with solid or part-solid nodules after curative lung resection in 2009–2010. Imbalances among the characteristics were adjusted using an inverse probability-weighted method based on propensity scoring. Multivariate Cox’s regression analysis and the Kaplan-Meier method were used to determine independent risk factors for IPR. Results A total of 243 (62%) patients received TTNB, while 149 (38%) underwent an alternate, or no, diagnostic technique. IPR was significantly more frequent in the TTNB group (p = 0.004), while total recurrence was similar between the groups (p = 0.098). After applying the weighted model, diagnostic TTNB (hazard ratio [HR], 5.27; 95% confidence interval [CI], 1.49–18.69; p = 0.010), microscopic visceral pleural invasion (HR, 2.76; 95% CI, 1.08–7.01; p = 0.033) and microscopic lymphatic invasion (HR, 3.25; 95% CI, 1.30–8.10; p = 0.012) were associated with an increased frequency of IPR. Among patients who received TTNB, microscopic lymphatic invasion was a risk factor for IPR (HR, 2.74; 95% CI, 1.10–6.79; p = 0.030). Conclusions The diagnostic TTNB procedure is associated with pleural recurrence but may be unrelated to overall recurrence-free survival in early lung cancer. Moreover, microscopic lymphatic invasion could be a risk factor for pleural recurrence. TTNB should be carefully considered before lung resection and close follow-up to detect if pleural recurrence is needed.

To evaluate clinical presentations, treatment modalities, and outcomes of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma by stage strata.We retrospectively reviewed 51 patients diagnosed with pulmonary MALT lymphoma between January 2003 and December 2015. To compare treatment modalities and outcomes, we stratified the patients into low-stage (IE/IIE) and high-stage (IIIE/IVE) groups using modified Ann Arbor staging. Progression-free survival was estimated using Kaplan-Meier curves, and differences were compared using the log-rank test. A hazard ratio of progression by stage strata, adjusted for other clinical variables, was determined using a Cox adjusted proportional hazards model.The majority of patients had stage IE disease (76.5%; 39 of 51). With advancing stage, patients were more likely to have respiratory and B symptoms and higher International Prognostic Index scores. The most common treatment modality was surgical resection in low-stage patients (33 of 43) and chemotherapy in high-stage patients (7 of 8). At a median follow-up of 40.7 months, progression-free survival was longer for low-stage patients (median, 40.7 months vs 24.9 months; P .001), and high-stage patients were 9.2 times more likely to progress (hazard ratio, 9.24; 95% confidence interval, 1.93-44.36). Among 30 patients with surgically resected stage IE disease, 8 with central lesions were treated via lobectomy and 22 with peripheral lesions were treated via lobectomy (n = 8) or limited resection (n = 14). One of these patients, with a central lesion, experienced disease recurrence.Our findings suggest that the clinical course of low-stage pulmonary MALT lymphoma, for which the mainstay of treatment is surgical resection, might be indolent.

Mycobacterium avium complex (MAC) was originally composed of 2 species, M. avium and M. intracellulare. However, several new species closely related to M. intracellulare have recently been identified. In addition, M. avium has been further subdivided into 4 subspecies. The aim of this study was to determine the proportion of different MAC species recovered from respiratory specimens and to elucidate the clinical relevance of these species. Clinical isolates, from 219 patients, that had been initially identified as M. avium or M. intracellulare by non-sequencing methods were reidentified using multilocus sequence typing, and the clinical significance of the identified species was then investigated. Of 91 isolates originally identified as M. intracellulare, 75 (82%) were confirmed to be M. intracellulare, 8 (9%) isolates were identified as M. chimaera, and 4 (4%) isolates each were identified as "M. indicus pranii" and M. yongonense. The 128 isolates originally designated as M. avium were determined to be M. avium subsp. hominissuis. Of the 219 patients, 146 (67%) met the diagnostic criteria for MAC lung disease, and for each MAC species, the proportion of patients meeting these criteria was as follows: M. intracellulare (54/75, 72%), M. chimaera (3/8, 38%), "M. indicus pranii" (3/4, 75%), M. yongonense (2/4, 50%), and M. avium subsp. hominissuis (84/128, 66%). In summary, multilocus sequence typing of respiratory isolates initially identified as MAC revealed that, although most isolates were M. avium subsp. hominissuis or M. intracellulare, approximately 7% were newer MAC members, with clinical evidence supporting their potential pathogenicity for humans.

Vitamins are known to be associated with immunity and nutrition. Moreover, vitamin deficiency can affect host immunity to various infectious diseases, including tuberculosis. Although patients with tuberculosis often have vitamin D deficiency, little is known about the levels of other vitamins. Here, we aimed to investigate the status of vitamins A, BWe performed a case-control study to investigate the serum vitamin concentrations in 152 patients with tuberculosis and 137 control subjects. The concentrations of vitamin A, vitamin D, vitamin E, homocysteine, and methylmalonic acid were measured using high-performance liquid chromatography (HPLC) or HPLC-tandem mass spectrometry. Patient demographic data and other biochemical parameters were also analyzed.The serum concentrations of vitamins A, D, and E were significantly lower in patients with tuberculosis than in control subjects (1.4 vs. 2.0 μmol/L, P 0.001; 10.6 vs. 19.3 ng/mL, P 0.001; and 22.8 vs. 30.6 μmol/L, P 0.001, respectively). In contrast, the methylmalonic acid levels were higher in patients with tuberculosis (134.9 vs. 110.8 nmol/L, P 0.001). The prevalences of vitamin deficiencies were significantly higher in patients with tuberculosis. Moreover, multiple vitamin deficiencies were only observed in patients with tuberculosis (22.4% of all patients with tuberculosis vs. 0% of all control subjects). Positive correlations among vitamin A, D, and E concentrations were observed (vitamins A and D, r = 0.395; vitamins D and E, r = 0.342; and vitamins A and E, r = 0.427, P 0.001). Body mass index, total cholesterol, low-density lipoprotein, iron, and total iron-binding capacity all showed positive correlations with vitamin A, D, and E concentrations.Vitamin deficiencies are common in patients with tuberculosis. Further research investigating the clinical importance of vitamin and nutritional status in patients with tuberculosis is needed.

Objectives Recent practice guidelines recommend endosonography for patients with radiological N0 non-small cell lung cancer (NSCLC) when the primary tumors are >3 cm in diameter or centrally located. However, any role for endosonography remains debatable. We evaluated the utility of endosonography in patients with radiological N0 NSCLC based on tumor centrality, diameter and histology. Materials and methods Patients who underwent staging endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with or without transesophageal bronchoscopic ultrasound-guided fine needle aspiration (EUS-B-FNA) for radiological N0 NSCLC were retrospectively investigated using prospectively collected endosonography data. The radiological N0 stage was defined by node diameter as evident on computed tomography images and 18F-FDG uptake using integrated positron emission tomography-computed tomography. Results In total of 168 patients, the median size of the primary tumor was 39 mm, and 41 % of tumors were centrally located. The prevalence of occult mediastinal metastases was 11.3 % (19/168). The sensitivity of endosonography in terms of diagnosing occult mediastinal metastases was only 47 % (9/19); 6 of 10 patients with false-negative endosonography data exhibited metastases in accessible nodes. The diagnostic performance of endosonography did not differ by tumor centrality or diameter. Patients with adenocarcinoma histology showed higher prevalence of occult mediastinal metastases and higher false-negative results in endosonography compared with those with non-adenocarcinoma histology. Conclusion Not all patients with radiological N0 NSCLC benefit from endosonography, given the low prevalence of occult mediastinal metastases and the poor sensitivity of endosonography in this population. The strategy of invasive mediastinal staging needs to be tailored considering the histology of the tumor in this population.

Background Lung cancer is a common comorbidity of idiopathic pulmonary fibrosis (IPF) and has poor outcomes. The incidence and clinical factors related to development of lung cancer in idiopathic pulmonary fibrosis (IPF) are unclear. The aim of this study was to elucidate the cumulative incidence, risk factors, and clinical characteristics of lung cancer in IPF. Methods In this retrospective study, we analyzed clinical data for 938 patients who were diagnosed with IPF without lung cancer between 1998 and 2013. Demographic, physiologic, radiographic, and histologic characteristics were reviewed. Cumulative incidence of lung cancer and survival were estimated by the Kaplan-Meier method. Risk factors of lung cancer development were determined by Cox proportional hazard analysis. Results Among 938 IPF patients without lung cancer at initial diagnosis, lung cancer developed in 135 (14.5%) during the follow-up period. The cumulative incidences of lung cancer were 1.1% at 1 year, 8.7% at 3, 15.9% at 5, and 31.1% at 10 years. Risk factors of lung cancer were male gender, current smoking at IPF diagnosis, and rapid annual decline of 10% or more in forced vital capacity (FVC). Patients who developed lung cancer were mostly elderly men with smoking history. Squamous cell carcinoma followed by adenocarcinoma was the most common histologic type. Lung cancer was frequently located in areas abutting or within fibrosis. Survival was significantly worse in patients with lung cancer compared to patients with IPF alone. Conclusion Lung cancer frequently developed in patients with IPF and was common in current-smoking men with rapid decline of FVC. Electronic supplementary material The online version of this article (10.1186/s12890-019-0905-8) contains supplementary material, which is available to authorized users.

There has been limited evidence for the association between chronic obstructive pulmonary disease (COPD) and the incidence of lung cancer among never smokers. We aimed to estimate the risk of lung cancer incidence in never smokers with COPD, and to compare it with the risk associated with smoking. This cohort study involved 338 548 subjects, 40 to 84 years of age with no history of lung cancer at baseline, enrolled in the National Health Insurance Service National Sample Cohort. During 2 355 005 person-years of follow-up (median follow-up 7.0 years), 1834 participants developed lung cancer. Compared with never smokers without COPD, the fully-adjusted hazard ratios (95% CI) for lung cancer in never smokers with COPD, ever smokers without COPD, and ever smokers with COPD were 2.67 (2.09 to 3.40), 1.97 (1.75 to 2.21), and 6.19 (5.04 to 7.61), respectively. In this large national cohort study, COPD was also a strong independent risk factor for lung cancer incidence in never smokers, implying that COPD patients are at high risk of lung cancer, irrespective of smoking status.

Limited data are available regarding the prognostic factors for patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the prognostic factors associated with long-term mortality in NTM-PD patients after adjusting for individual confounders, including aetiological organism and radiological form.A total of 1445 patients with treatment-naïve NTM-PD who were newly diagnosed between July 1997 and December 2013 were included. The aetiological organisms were as follows:Mycobacterium avium(n=655),M. intracellulare(n=487),M. abscessus(n=129) andM. massiliense(n=174). The factors associated with mortality in NTM-PD patients were analysed using a multivariable Cox model after adjusting for demographic, radiological and aetiological data.The overall 5-, 10- and 15-year cumulative mortality rates for the NTM-PD patients were 12.4%, 24.0% and 36.4%, respectively. On multivariable analysis, the following factors were significantly associated with mortality in NTM-PD patients: old age, male sex, low body mass index, chronic pulmonary aspergillosis, pulmonary or extrapulmonary malignancy, chronic heart or liver disease and erythrocyte sedimentation rate. The aetiological organism was also significantly associated with mortality:M. intracellularehad an adjusted hazard ratio (aHR) of 1.40, 95% CI 1.03–1.91;M. abscessushad an aHR of 2.19, 95% CI 1.36–3.51; andM. massiliensehad an aHR of 0.99, 95% CI 0.61–1.64, compared toM. avium. Mortality was also significantly associated with the radiological form of NTM-PD for the cavitary nodular bronchiectatic form (aHR 1.70, 95% CI 1.12–2.59) and the fibrocavitary form (aHR 2.12, 95% CI 1.57–3.08), compared to the non-cavitary nodular bronchiectatic form.Long-term mortality in patients with NTM-PD was significantly associated with the aetiological NTM organism, cavitary disease and certain demographic characteristics.

Although Mycobacterium massiliense lung disease is increasing in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis, optimal treatment regimens remain largely unknown. This study aimed to evaluate the efficacy of oral macrolide therapy after an initial 2-week course of combination antibiotics for the treatment of M massiliense lung disease.Seventy-one patients received oral macrolides, along with an initial 4-week (n = 28) or 2-week (n = 43) IV amikacin and cefoxitin (or imipenem) treatment. These patients were treated for 24 months (4-week IV group) or for at least 12 months after negative sputum culture conversion (2-week IV group).Total treatment duration was longer in the 4-week IV group (median, 23.9 months) than in the 2-week IV group (15.2 months; P .001). The response rates after 12 months of treatment were 89% for symptoms, 79% for CT scanning, and 100% for negative sputum culture results in the 4-week IV group. In the 2-week IV group, these values were 100% (P = .057), 91% (P = .177), and 91% (P = .147), respectively. Acquired macrolide resistance developed in two patients in the 2-week IV group. Genotyping analyses of isolates from patients who did not achieve negative sputum culture conversion during treatment and from those with positive culture results after successful treatment completion revealed that most episodes were due to reinfection with different genotypes of M massiliense.Oral macrolide therapy after an initial 2-week course of combination antibiotics might be effective in most patients with M massiliense lung disease.ClinicalTrials.gov; No.: NCT00970801; URL: www.clinicaltrials.gov.

// Jung Min Bae 1, * , Ji Yun Jeong 2, * , Ho Yun Lee 1 , Insuk Sohn 3 , Hye Seung Kim 3 , Ji Ye Son 1 , O Jung Kwon 4 , Joon Young Choi 5 , Kyung Soo Lee 1 , Young Mog Shim 6 1 Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea 2 Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu 702-210, Korea 3 Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea 4 Division of Respiratory and Critical Medicine of the Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea 5 Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea 6 Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Korea * These authors contributed equally to this work Correspondence to: Ho Yun Lee, email: hoyunlee96@gmail.com Young Mog Shim, email: youngmog.shim@samsung.com Keywords: lung adenocarcinoma, heterogeneity, radiomics, texture analysis, dual energy CT Received: June 29, 2016 Accepted: November 14, 2016 Published: November 21, 2016 ABSTRACT Purpose: To evaluate the usefulness of surrogate biomarkers as predictors of histopathologic tumor grade and aggressiveness using radiomics data from dual-energy computed tomography (DECT), with the ultimate goal of accomplishing stratification of early-stage lung adenocarcinoma for optimal treatment. Results: Pathologic grade was divided into grades 1, 2, and 3. Multinomial logistic regression analysis revealed i -uniformity and 97.5th percentile CT attenuation value as independent significant factors to stratify grade 2 or 3 from grade 1. The AUC value calculated from leave-one-out cross-validation procedure for discriminating grades 1, 2, and 3 was 0.9307 (95% CI: 0.8514–1), 0.8610 (95% CI: 0.7547–0.9672), and 0.8394 (95% CI: 0.7045–0.9743), respectively. Materials and Methods: A total of 80 patients with 91 clinically and radiologically suspected stage I or II lung adenocarcinoma were prospectively enrolled. All patients underwent DECT and F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, followed by surgery. Quantitative CT and PET imaging characteristics were evaluated using a radiomics approach. Significant features for a tumor aggressiveness prediction model were extracted and used to calculate diagnostic performance for predicting all pathologic grades. Conclusions: Quantitative radiomics values from DECT imaging metrics can help predict pathologic aggressiveness of lung adenocarcinoma.

The aim of this study was to evaluate serum cytokines and natural antimicrobial peptide profiles in pulmonary tuberculosis, and compare them with levels in controls without tuberculosis, to explore the associations between these biomarkers and response to antituberculosis treatment. Serum levels of 10 biomarkers were measured using a Luminex bead array platform. Tuberculosis biosignatures were identified from the discovery cohort (n=148) and were validated in the independent cohort (n=148). Association between biosignatures and clinical outcome was investigated with negative conversion in follow-up sputum culture after 2months of treatment. Serum concentrations of eotaxin, MIP-1α, sIL-2Rα, and lipocalin 2 were significantly different between pulmonary tuberculosis patients and controls (P0.05). Serum concentrations of eotaxin and sIL-2Rα were higher in pulmonary tuberculosis patients than in controls, while those of MIP-1α and lipocalin 2 were lower (P0.05). Eotaxin concentrations were significantly higher in good responders to treatment (P0.05), indicating this immunomolecule may serve as a positive predictor for therapy response in pulmonary tuberculosis. The magnitude serum eotaxin, MIP-1α, sIL-2Rα, and lipocalin 2 are important indicators for pulmonary tuberculosis. These biomarkers alone or combinatorial detections have potential applicability in monitoring tuberculosis patients during antituberculosis treatment.Cytokines and endogenous antimicrobial peptides represent an important part of immune system and the identification of a pattern of differentially expressed those biomarkers (a "biosignature") could help to differentiate tuberculosis infection from the non-infected state which might eventually assist case identification and accelerate access to treatment. In this direction, cytokine analysis including multiple serum biomarkers to evaluate biosignatures of pulmonary tuberculosis would provide basic knowledge to aid understanding of the pathophysiology of tuberculosis infection and for the development of future diagnostic methods, treatments, and monitoring for pulmonary tuberculosis.

Current National Comprehensive Cancer Network guidelines recommend routine brain magnetic resonance imaging (MRI) screening in patients with stage II to IV non-small cell carcinoma, regardless of histological subtype. This recommendation might not be universally applicable, however, because brain metastasis (BM) is seen less frequently in patients with lung squamous cell carcinoma (SCC) than in those with a histological diagnosis of nonsquamous cell carcinoma.The cases of 564 patients with lung SCC in our institution between January 2012 and December 2013 were reviewed prospectively for comprehensive staging. All subjects' lung SCC, but not their BM, was staged on the basis of the seventh edition of the guidelines of the American Joint Committee on Cancer. We evaluated the incidence of BM across the stages and clinical factors associated with BM.Of the 564 patients, 28 (5.0%) had BM. BM did not occur in patients with stage Ia or Ib disease; however, it increased significantly as the disease progressed from stage IIa to IV (p0.001, trend test). Multivariate analysis showed that tumor involvement in N3 lymph nodes and distant metastasis other than BM (M1b) was independently associated with the development of BM.Routine brain MRI screening in patients with lung SCC in stage II to IV can help to evaluate asymptomatic BM. By contrast, we did not find any evidence supporting routine brain MRI screening in patients with stage I disease.

We sought to determine whether quantitative analysis of lung adenocarcinoma manifesting as a ground-glass opacity (GGO) nodule (GGN) on initial CT scans can predict further CT scanning change or rate of growth.This retrospective study included patients with lung adenocarcinoma manifesting as pure GGN on initial CT scans who were followed up with interval CT scanning until resection. All pure GGNs were classified based on CT scanning interval change in three subgroups as follows: group A (development of solid component), group B (growth of GGO component), and group C (no change in size). Nodule size, volume, density, mass, and CT scanning attenuation values were assessed from initial CT data sets.Fifty-four pure GGNs were enrolled and classified into group A (n = 9), group B (n = 25), and group C (n = 20). Nodule size, volume, mass, and density of the GGNs in each subgroup were not significantly different. The 97.5th percentile CT scanning attenuation value and slope of CT scanning attenuation values from the 2.5th to the 97.5th percentile were significantly different among the three subgroups (P = .02, P .00). Three of nine (33%) pure GGNs showing a new solid component developed a solid component within 6 months.The 97.5th percentile CT scanning attenuation value and slope of CT scanning attenuation values from the 2.5th to the 97.5th percentile could be helpful in predicting future CT scanning change and growth rate of pure GGNs. Pure GGNs showing higher 97.5th percentile CT scanning attenuation values and steeper slopes of CT scanning attenuation values may require more frequent follow-up than the usual interval of 6 months.

IntroductionThe maximum standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) may be of prognostic significance for patients with malignant pleural mesothelioma (MPM). This retrospective study aimed to investigate the prognostic value of the SUVmax in patients with MPM.Materials and methodsMedical records were retrospectively reviewed for the patients who were diagnosed with histopathologically proven MPM between 2009 and 2018 at Samsung Medical Center. For each patient, SUVmax was calculated for the primary lesion on PET/CT. To determine optimal cutoff values for predicting mortality, receiver operating characteristic curves were used.ResultsAmong the 54 study patients, 34 (63.0%) had epithelioid subtype, 13 (24.1%) had sarcomatoid or biphasic subtype, and 7 (13.0%) had mesothelioma, not otherwise specified (NOS). The median overall survival (OS) was 8.7 months, and the median SUVmax was 9.9. The median values of SUVmax were 5.5 in patients with epithelioid subtype, 11.7 in those with sarcomatoid/biphasic subtype, and 13.3 in those with NOS subtype (P = 0.003). The optimal cutoff values of SUVmax to predict mortality were 10.1 in all patients, and 8.5 in patients with epithelioid subtype. In multivariate analysis, SUVmax was significantly associated with overall survival in all patients (P = 0.003) and in patients with epithelioid subtype (P = 0.012), but not in those with non-epithelioid subtype.ConclusionsSUVmax in PET/CT is an independent prognostic factor in patients with MPM, especially those with epithelioid subtype. The histologic subtype of MPM should be considered when evaluating the prognostic significance of SUVmax.

Purpose The diagnosis of pulmonary fungal infections is challenging due to the difficulty of obtaining sufficient specimens. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) needle rinse fluid has become an emerging diagnostic material. This study evaluated the role of routine fungal culture from EBUS-TBNA needle rinse fluid, in addition to histopathologic examination and fungal culture of EBUS-TBNA core tissue, in the diagnosis of pulmonary fungal infections. Materials and methods Among patients who underwent EBUS-TBNA, those with results for at least one of three tests (histopathologic examination, fungal culture of EBUS-TBNA core tissue or needle rinse fluid) were included. Patients with a positive test were divided into two groups (clinical fungal infection and suspected fungal contamination) according to their clinical assessment and therapeutic response to antifungal. Results Of 6072 patients, 41 (0.7%) had positive fungal tests and 9 (22%) were diagnosed as clinical fungal infection. Of the 5222 patients who were evaluated using a fungal culture from EBUS-TBNA needle rinse fluid, 35 (0.7%) had positive results. However, only 4 out of 35 (11.4%) were classified as clinical fungal infection. Positive results were determined in 4 of the 68 (5.9%) evaluated by a fungal culture of EBUS-TBNA core tissue, and all were diagnosed as clinical fungal infection. Conclusion Routine fungal culture of EBUS-TBNA needle rinse fluid is not useful due to the low incidence of fungal infection and high rate of contamination. However, fungal culture of EBUS-TBNA core tissue and needle rinse fluid should be considered in patients with clinically suspected fungal infection.

In-depth molecular pathogenesis of ground-glass nodular lung adenocarcinoma has not been well understood. The objectives of this study were to identify genomic alterations in ground-glass nodular lung adenocarcinomas and to investigate whether viral transcripts were detected in these tumors. Nine patients with pure (n = 4) and part-solid (n = 5) ground-glass nodular adenocarcinomas were included. Six were females with a median age of 58 years. We performed targeted exon sequencing and RNA sequencing. EGFR (n = 10), IDH2 (n = 2), TP53 (n = 1), PTEN (n = 1), EPHB4 (n = 1), and BRAF (n = 1) were identified as driver mutations by targeted exon sequencing. Vasculogenesis-associated genes including NOTCH4 and TGFBR3 expression were significantly downregulated in adenocarcinoma tissue versus normal tissue (adjusted P values

Intermittent, three-times-weekly oral antibiotic therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic (NB) Mycobacterium avium complex (MAC) lung disease. However, intermittent therapy is not recommended for patients who have been previously treated. We evaluated 53 patients with recurrent noncavitary NB MAC lung disease who underwent antibiotic treatment for ≥12 months with daily therapy ( n = 26) or intermittent therapy ( n = 27) between January 2008 and December 2015. Baseline characteristics were comparable between daily therapy and intermittent therapy groups. Sputum culture conversion rates did not differ between daily therapy (21/26, 81%) and intermittent therapy (22/27, 82%) groups. Compared to the etiologic organism at the time of previous treatment, recurrent MAC lung disease was caused by the same MAC species in 38 patients (72%) and by a different MAC species in 15 patients (28%). Genotype analysis in patients with sequenced paired isolates revealed that 86% (12/14) of cases with same species recurrence were due to reinfection with a new MAC genotype. In conclusion, most recurrent noncavitary NB MAC lung disease cases were caused by reinfection rather than relapse. Intermittent antibiotic therapy is a reasonable treatment strategy for recurrent noncavitary NB MAC lung disease.

Recent data conflict on the clinical efficacy of later-generation fluoroquinolones, such as moxifloxacin or levofloxacin, for the treatment of multidrug-resistant tuberculosis (MDR-TB) that is resistant to ofloxacin but susceptible to moxifloxacin. The purpose of the present study was to evaluate whether later-generation fluoroquinolones can improve treatment outcomes in patients with ofloxacin-resistant, moxifloxacin-susceptible MDR-TB. A retrospective cohort study was performed on 208 patients with moxifloxacin-susceptible MDR-TB who were treated between 2006 and 2011. Later-generation fluoroquinolones were used for all patients. Overall, 171 patients (82%) had ofloxacin-susceptible, moxifloxacin-susceptible MDR-TB (ofloxacin-susceptible group), and 37 (18%) had ofloxacin-resistant, moxifloxacin-susceptible MDR-TB (ofloxacin-resistant group). Compared to the ofloxacin-susceptible group, the ofloxacin-resistant group was more likely to have a history of MDR-TB treatment ( P < 0.001) and cavitary lesions on chest radiography ( P < 0.001). In addition, the ofloxacin-resistant group was more likely than the ofloxacin-susceptible group to have resistance to the drugs pyrazinamide ( P = 0.003), streptomycin ( P = 0.015), prothionamide ( P < 0.001), and para-aminosalicylic acid ( P < 0.001). Favorable outcomes were more frequently achieved for the ofloxacin-susceptible group than for the ofloxacin-resistant group (91% [156/171] versus 57% [21/37], respectively [ P < 0.001]). In multivariable regression logistic analysis, the ofloxacin-susceptible group was about 5.36 (95% confidence interval, 1.55 to 18.53) times more likely than the ofloxacin-resistant group ( P < 0.001) to have favorable outcomes. Despite in vitro moxifloxacin susceptibility, the frequency of favorable treatment outcomes for ofloxacin-resistant MDR-TB was significantly lower than that for ofloxacin-susceptible MDR-TB, even when later-generation fluoroquinolones were used, indicating that more-aggressive therapies may be needed for ofloxacin-resistant MDR-TB.

Although guidelines recommend amikacin (AMK) inhalation therapy for difficult-to-treat nontuberculous mycobacterial lung disease (NTM-LD), data are limited regarding the safety and clinical efficacy of this salvage therapy. We retrospectively evaluated the treatment outcomes of 77 patients with refractory NTM-LD caused by Mycobacterium abscessus complex (MABC) or M. avium complex (MAC) who initiated AMK inhalation therapy between February 2015 and June 2016. MABC was the most common etiology ( n = 48, 62%), followed by MAC ( n = 20, 26%) and mixed infections ( n = 9, 12%). Isolates with macrolide resistance and baseline AMK resistance were identified in 63 (82%) patients and 5 (6%) patients, respectively. At 12 months after AMK inhalation therapy, 49% of patients had symptomatic improvement, whereas 42% had radiological improvement. Conversion to a negative sputum culture occurred in 14 (18%) patients, and the culture conversion rate was higher in patients infected with macrolide-susceptible isolates (7/14, 50%) than in those infected with macrolide-resistant isolates (7/63, 11%) ( P = 0.003). Significant decreases in sputum semiquantitative culture positivity occurred after AMK inhalation therapy ( P < 0.001). On multivariate analysis, conversion to a negative sputum culture was associated with mixed infections ( P = 0.009), a forced expiratory volume in 1 s of greater than 60% ( P = 0.008), and the absence of macrolide resistance ( P = 0.003). Thirty-eight percent of patients experienced adverse effects, with ototoxicity ( n = 15) being the most common. AMK inhalation salvage therapy may improve the treatment responses in some patients with refractory NTM-LD. However, considering the common adverse effects, further evaluation of the optimal dosage and intervals for AMK inhalation therapy is needed.

This study investigated the changes in the major etiologic organisms and clinical phenotypes of nontuberculous mycobacterial lung disease (NTM-LD) over a recent 15-year period in Korea. The increase of number of patients with NTM-LD was primarily due to an increase of Mycobacterium avium complex (MAC) lung disease (LD). Among MAC cases, the proportion of M. avium increased compared with M. intracellulare, whereas the incidence of M. abscessus complex and M. kansasii LD remained relatively stable. The proportion of cases of the nodular bronchiectatic form increased compared with the fibrocavitary form of NTM-LD., Graphical Abstract

OBJECTIVES Fluoroquinolones (FQs) are the most important second-line drugs for MDR-TB treatment. Therapeutic options for FQ-resistant (FQ-R) MDR/XDR-TB are very limited. The purpose of the present study was to determine treatment outcomes and risk factors associated with unfavourable outcomes of MDR/XDR-TB, focusing on the impacts of FQ-R status and linezolid treatment. METHODS This was a retrospective cohort study of 337 MDR-TB patients, including 144 (42.7%) FQ-R MDR/XDR-TB cases. Treatment outcomes were evaluated according to WHO 2013 recommendations. RESULTS Later-generation FQs such as levofloxacin or moxifloxacin were given to 331 (98.2%) patients. Overall, favourable outcomes were achieved in 272 (80.7%) patients. FQ-R second-line injectable drug-susceptible MDR [adjusted OR (aOR) 4.299, 95% CI 1.239-14.916, P = 0.015] and XDR status (aOR 6.294, 95% CI 1.204-32.909, P = 0.024) were independently associated with unfavourable outcomes. However, FQ-susceptible (FQ-S) second-line injectable drug-resistant MDR status was not associated with unfavourable outcomes (aOR 1.814, 95% CI 0.314-10.485, P = 0.999). Favourable treatment outcomes were more frequent in FQ-R MDR/XDR-TB patients who received linezolid (82.8%) compared with those who did not receive linezolid (58.1%, P = 0.002). When FQ-R MDR/XDR-TB treatment without linezolid was used as a reference, the addition of linezolid was associated with favourable outcomes (aOR 4.081, 95% CI 1.237-13.460, P = 0.017), comparable to those for FQ-S MDR-TB (aOR 4.341, 95% CI 1.470-12.822, P = 0.005). CONCLUSIONS Later-generation FQs could improve treatment outcomes of patients with MDR-TB. Linezolid should be considered for inclusion in FQ-R MDR/XDR-TB treatment regimens.

Deficiencies in essential trace elements are associated with impaired immunity in tuberculosis infection. However, the trace element concentrations in the serum of Korean patients with tuberculosis have not yet been investigated. This study aimed to compare the serum trace element concentrations of Korean adult patients with tuberculosis with noninfected controls and to assess the impact of serum trace element concentration on clinical outcome after antituberculosis treatment. The serum concentrations of four trace elements in 141 consecutively recruited patients with tuberculosis and 79 controls were analyzed by inductively coupled plasma-mass spectrometry. Demographic characteristics were also analyzed. Serum cobalt and copper concentrations were significantly higher in patients with tuberculosis compared with controls, while zinc and selenium concentrations were significantly lower (p &lt, 0.01). Moreover, serum selenium and zinc concentrations were positively correlated (ρ = 0.41, p &lt, 0.05). A high serum copper concentration was associated with a worse clinical outcome, as assessed after one month of antituberculosis therapy. Specifically, culture-positive patients had higher serum copper concentrations than culture-negative patients (p &lt, 0.05). Patients with tuberculosis had altered serum trace element concentrations. Further research is needed to elucidate the roles of individual trace elements and to determine their clinical impact on patients with tuberculosis.

Mycobacterium abscessus lung disease is difficult to treat due to inducible resistance to macrolides. However, 15%-20% of isolates are macrolide susceptible. In 14 patients with macrolide-susceptible M. abscessus lung disease, all isolates had nonfunctional erm(41) gene, and sputum culture conversion rate was achieved in 93% (13/14) following antibiotic therapy.

Purpose The outcomes and predictors of mortality from Pneumocystis pneumonia (PCP) in HIV-negative patients requiring mechanical ventilation (MV) for respiratory failure were evaluated. Materials and Methods This retrospective observational study enrolled 48 patients with PCP requiring MV in the medical intensive care unit (ICU). Multiple logistic regression analysis was used to identify independent predictors of in-hospital mortality. Results The main conditions underlying the PCP were malignancies (60%) or post solid organ transplant (35%). Excluding four patients whose initial treatment was changed due to adverse reactions, 21 (44%) of 44 patients did not respond to the initial treatment. During the ICU stay, additional complications developed: shock in 22 (46%), ventilator-associated pneumonia in 16 (33%), and acute kidney injury in 15 (31%). Ultimately, 31 (65%) patients died while hospitalised. In multivariate analysis, hospital mortality was independently associated with severity of illness on ICU admission, failure of initial antimicrobial treatment for PCP, and newly developed shock during ICU stay. Conclusions PCP in HIV-negative patients requiring MV for respiratory failure remains a serious illness with high mortality. Failure of the initial antimicrobial treatment for PCP as well as severity of illness was independent predictors of poor outcomes.

Summary Background A serum galactomannan (GM) antigen test has been widely used to diagnose invasive pulmonary aspergillosis. However, there are limited data on the use of the serum GM antigen test for the serologic diagnosis of chronic pulmonary aspergillosis (CPA). Methods Data were collected from all consecutive patients with a clinical suspicion of CPA who underwent a serum GM antigen test. Results In total, 334 patients who were suspected to have CPA were eligible for this study and 168 (50%) patients were finally diagnosed with CPA. The serum GM antigen test was positive in 38 (23%) patients with CPA and in 25 (15%) patients without CPA. The sensitivity of the serum GM antigen test was 23% (95% confidence interval [CI], 17–30%), and its specificity was 85% (95% CI, 79–90%), with positive and negative predictive values of 60% (95% CI, 47–72%) and 52% (95% CI, 46–58%), respectively. The accuracy of the test was 54%. The area under the receiver operating characteristic curve was 0.538 (95% CI, 0.496–0.580). Conclusion The serum GM antigen test could not be used for the serologic diagnosis of CPA.

Background: The concept of healthcare-associated pneumonia (HCAP) exists to identify patients infected with highly resistant pathogens who are exposed to the healthcare environment. However, many studies have included immunosuppressed patients who were excluded from the original concept. Objectives: The risk factors of potentially drug-resistant (PDR) pathogens in patients with pneumonia developed outside the hospital were reevaluated after excluding the patients who had immunosuppression. Methods: This was a retrospective study of prospectively collected data from all consecutive patients with pneumonia who were admitted to hospital via the emergency department between January 2008 and December 2011. Results: Pathogens were isolated in a total of 315 patients with pneumonia from our cohort; 33% with PDR pathogens did not meet the criteria for HCAP, but 44% without PDR pathogens did meet the criteria. Variables independently associated with PDR included nursing home residency, hospitalization in the preceding 90 days, antibiotics in the 30 days prior to pneumonia, poor function status and chronic lung disease. The new predictive scoring system based on the logistic regression model had a higher predictive power for the risk of PDR pathogens than the presence of the risk factors or the HCAP criteria. Conclusions: Functional status, pulmonary comorbidity and previous exposure to the healthcare environment were significantly associated with acquiring PDR pathogens in immunocompetent patients with pneumonia that developed out of hospital. However, a risk stratification model was more accurate than the presence of the risk factors or the HCAP criteria for assessing the probability of PDR pathogens.

Background Initial complete resection is a powerful prognostic indicator of survival in thymic epithelial tumors (TETs), but is obviously related to tumor stage. Here, we report the results of a prospective study of neoadjuvant docetaxel/cisplatin in locally advanced TETs. Methods Patients with histologically proven, Masaoka stage III/IV TETs at presentation were enrolled in this open-label, phase II, nonrandomized study. Patients received docetaxel 75 mg/m 2 I.V, followed by cisplatin 75 mg/m 2 I.V on day 1 of every 3-week cycle. After three cycles, surgical resection was performed if the tumor was considered resectable. Results From March 2007 to July 2011, 27 patients were enrolled in the trial. Masaoka stage at presentation was III ( n = 8; 29.6%), IVA ( n = 17; 63.0%), and IVB ( n = 2; 7.4%). Histologic types were nine thymomas (33.3%) and 18 thymic carcinomas (66.7%). After completion of neoadjuvant chemotherapy, 17 patients (63.0%) achieved partial response and 10 (37.0%) had stable disease. Nineteen patients (70.4%) underwent surgery and eight did not because of surgeons' decision ( n = 5), patient refusal ( n = 2), or decision to undergo radiation therapy instead ( n = 1). Fifteen among the 19 patients achieved complete resection (78.9%), which yields 55.6% of complete resection rate with intent-to-treat analysis. The most common side effects of severity greater than grade 3 were neutropenia and diarrhea. With a median follow-up of 42.6 months, 4-year overall survival, and progression-free survival in all patients was 79.4 and 40.6%, respectively. Conclusion Neoadjuvant docetaxel/cisplatin is both feasible and well tolerated, and potentially improves surgical resectability in patients with advanced TETs.

The two-stage system of limited and extensive disease has been widely employed for small cell lung cancer (SCLC). However, the International Association for the Study of Lung Cancer has proposed that the TNM classification should be incorporated into clinical practice. The purpose of this study was to evaluate the applicability of the Union for International Cancer Control (UICC) 7th TNM staging system to SCLC. We retrospectively reviewed the medical records of consecutive patients with newly diagnosed histologically proven SCLC between March 2005 and January 2010. Patients who had other concurrent malignancies or had combined-type SCLC were excluded. We assessed overall survival (OS) according to the T descriptor, N descriptor, M descriptor, and TNM stage grouping. In total, 320 SCLC patients were included. Median age was 65 years and 286 patients (89.4%) were male. Median OS was 12.7 months. There were no significant differences in OS according to the T descriptor (P = 0.880). However, there were significant differences in OS according to the N (P < 0.001) and M (P < 0.001) descriptors and TNM stage grouping (P < 0.001). Hazard ratios for OS, adjusted for known prognostic factors, differed significantly according to the N and M descriptor, and TNM stage grouping, but not according to the T descriptors. The UICC 7th TNM staging system may contribute to a more precise prognosis in SCLC patients. Further studies are required to evaluate the applicability of the TNM staging system to SCLC.

Moxifloxacin (MXF) has in vitro and in vivo activity against Mycobacterium avium complex (MAC) in experimental models. However, no data are available concerning its treatment effect in patients with MAC lung disease. The aim of this study was to evaluate the clinical efficacy of an MXF-containing regimen for the treatment of refractory MAC lung disease. Patients with MAC lung disease who were diagnosed between January 2002 and December 2011 were identified from our hospital database. We identified 41 patients who received MXF for ≥4 weeks for the treatment of refractory MAC lung disease. A total of 41 patients were treated with an MXF-containing regimen because of a persistent positive culture after at least 6 months of clarithromycin-based standardized antibiotic therapy. The median duration of antibiotic therapy before MXF administration was 410 days (interquartile range [IQR], 324 to 683 days). All patients had culture-positive sputum when MXF treatment was initiated. The median duration of MXF administration was 332 days (IQR, 146 to 547 days). The overall treatment success rate was 29% (12/41), and the median time to sputum conversion was 91 days (IQR, 45 to 190 days). A positive sputum acid-fast-bacillus smear at the start of treatment with MXF-containing regimens was an independent predictor of an unfavorable microbiological response. Our results indicate that MXF may improve treatment outcomes in about one-third of patients with persistently culture-positive MAC lung disease who fail to respond to clarithromycin-based standardized antibiotic treatment. Prospective studies are required to assess the clinical efficacy of MXF treatment for refractory MAC lung disease.

The effect of the clinical phenotype of

Ho Jung Jeong,1,* Hyun Lee,1,* Keumhee C Carriere,2,3 Jung Hoon Kim,1 Jin-Hyung Han,1 Beomsu Shin,1 Byeong-Ho Jeong,1 Won-Jung Koh,1 O Jung Kwon,1 Hye Yun Park1 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University of Medicine, Seoul, South Korea; 2Department of Mathematical and Statistical Sciences, University of Alberta, Edmonton, AB, Canada; 3Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, South Korea *These authors contributed equally tothis work Purpose: The association between positive bronchodilator response (BDR) at baseline and the effect of long-term bronchodilator therapy has not been well elucidated in patients with bronchiectasis. The aims of our study were to explore the association between positive BDR at baseline and lung-function improvement following long-term (3–12 months) bronchodilator therapy in bronchiectasis patients with airflow limitation. Materials and methods: The medical records of 166 patients with clinically stable bronchiectasis who underwent baseline pre- and postbronchodilator spirometry and repeated spirometry after 3–12 months of bronchodilator therapy were retrospectively reviewed. For analysis, patients were divided into two groups, responders and poor responders, based on achievement of at least 12% and 200 mL in forced expiratory volume in 1 second (FEV1) following bronchodilator therapy from baseline FEV1. Results: A total of 57 patients (34.3%) were responders. These patients were more likely to have positive BDR at baseline than poor responders (38.6% [22 of 57] vs 18.3% [20 of 109], P=0.004). This association persisted after adjustment for other confounding factors (adjusted odds ratio 2.298, P=0.034). However, we found FEV1 improved significantly following long-term bronchodilator therapy, even in patients without positive BDR at baseline (change in FEV1 130 mL, interquartile range -10 to 250 mL; P

Objective A mutational analysis of tumor tissue samples is an important part of advanced lung cancer treatment strategies. This study evaluated the efficacy of a triple gene analysis using samples obtained via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Methods Either metastatic lymph nodes or primary lung mass samples obtained by EBUS-TBNA were collected between May 2011 and May 2013. We consecutively analyzed epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), and anaplastic lymphoma kinase (ALK) fusion genes using remnant tissue samples. Results A total of 109 patients were diagnosed with non-small cell lung cancer (NSCLC). Of these, 70% were adenocarcinoma, 27% squamous cell carcinoma with NSCLC, and 3% were related to other types of lung cancer. EGFR mutations were detected in 23 cases (21.1%), KRAS mutations in 13 cases (11.9%), and ALK fusion genes in 5 cases (4.9%). The ALK fusion genes could not be analyzed in four cases because of insufficient tissue samples remaining after routine histochemistry and an EGFR/KRAS mutation analysis. We found that small biopsy samples from EBUS-TBNA were adequate for performing a triple gene analysis in 97 patients (96%). ALK fusion protein immunohistochemistry (IHC) was 100% consistent with fluorescence in situ hybridization (FISH). Conclusion Small samples obtained by EBUS-TBNA were found to be sufficient for performing a triple gene analysis following routine histology and IHC. ALK IHC showed a very good concordance with FISH for detecting ALK fusion genes.

Background Treatment outcomes of patients with Mycobacterium abscessus subspecies abscessus lung disease are poor, and the microbial characteristics associated with treatment outcomes have not been studied systematically. The purpose of this study was to identify associations between microbial characteristics and treatment outcomes in patients with M. abscessus lung disease. Methods Sixty-seven consecutive patients with M. abscessus lung disease undergoing antibiotic treatment for ≥12 months between January 2002 and December 2012 were included. Morphotypic and genetic analyses were performed on isolates from 44 patients. Results Final sputum conversion to culture negative occurred in 34 (51%) patients. Compared to isolates from 24 patients with persistently positive cultures, pretreatment isolates from 20 patients with final negative conversion were more likely to exhibit smooth colonies (9/20, 45% vs 2/24, 8%; P = .020), susceptibility to clarithromycin (7/20, 35% vs 1/24, 4%; P = .015), and be of the C28 sequevar with regard to the erm(41) gene (6/20, 30% vs 1/24, 4%; P = .035). Mycobacterium abscessus lung disease recurred in 5 (15%) patients after successful completion of antibiotic therapy. Genotypic analysis revealed that most episodes (22/24, 92%) of persistently positive cultures during antibiotic treatment and all cases of microbiologic recurrence after treatment completion were caused by different M. abscessus genotypes within a patient. Conclusions Precise identification to the subspecies level and analysis of mycobacterial characteristics could help predict treatment outcomes in patients with M. abscessus lung disease. Treatment failures and recurrences are frequently associated with multiple genotypes, suggesting reinfection. Clinical Trials Registration NCT00970801.

This study aims to evaluate the joint effect of severity of airflow limitation and emphysema on postoperative pulmonary complications (PPCs) and overall survival after complete resection in patients with early-stage nonsmall cell lung cancer (NSCLC).We retrospectively studied 413 male patients with pathologic stage I or II NSCLC between 2007 and 2009. Severity of airflow limitation was defined based on forced expiratory volume in 1 s. Emphysema was defined by ≥5% low attenuation area at −950 HU.In multivariable-adjusted analyses, the adjusted odds ratio (aOR) for any PPC, comparing patients with moderate-to-severe airflow limitation to those without airflow limitation, was 2.23, and the aOR comparing patients with emphysema to those without emphysema was 1.77. However, the joint effect of airflow limitation and emphysema was much higher than expected from the independent effects of both factors (aOR 8.90). Moreover, patients with coexisting moderate-to-severe airflow limitation and emphysema had significantly poorer overall survival than any other group.Patients with moderate-to-severe airflow limitation and emphysema had almost nine times the risk of PPCs and poorer survival than patients with neither of these conditions. Integrated assessment of airflow limitation severity and emphysema is necessary for the optimal selection of candidates for lung resection surgery of early-stage NSCLC.

Objective Most small-cell lung cancers (SCLCs) are located within the central aspect of the chest and manifest as a mediastinal or hilar lymphadenopathy. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) makes it possible to perform mediastinal and hilar nodal examinations. The purpose of this study was to evaluate the performance of EBUS-TBNA in the diagnosis of SCLC. Methods The diagnostic performances of EBUS-TBNA and/or transesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-FNA-B/E) were calculated using the standard definitions. Patients The study consisted of a retrospective review of the medical records for all patients with histologically proven SCLC who previously underwent EBUS-TBNA and/or EUS-FNA-B/E from May 2009 to September 2014. Results The analysis was based on 161 patients and 299 aspirated specimens. The patient group included 144 males (89%); the median age was 66 years. EBUS-TBNA and/or EUS-FNA-B/E were performed in 239 mediastinal nodes, 39 hilar/interlobar nodes, and 21 lung parenchymal lesions. The median short diameter of the biopsied lesions was 17 mm. The overall sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of EBUS-TBNA and/or EUS-FNA-B/E on a per-person basis were 97.4%, 100%, 60%, 100%, and 97.5%, respectively. The corresponding values on a per-lesion basis were 91.8%, 100%, 73.0%, 100%, and 93.3%, respectively. There were no serious complications related to EBUS-TBNA. Conclusion In our series of patients with SCLC, EBUS-TBNA had an excellent diagnostic yield in the evaluation of mediastinal, hilar and lung parenchymal lesions. Thus, EBUS-TBNA could be a useful and safe diagnostic method with which to evaluate patients with SCLC.

Background There is controversy regarding palliative chemotherapy for large cell neuroendocrine carcinoma (LCNEC). We evaluated whether advanced LCNEC should be treated similarly to small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). Patients and methods The clinical reports and tumor specimens of 45 consecutive patients who were diagnosed with advanced LCNEC were reviewed. They were divided into SCLC ( n =11) and NSCLC regimen groups ( n =34) according to first-line chemotherapeutic regimens. Results Most patients were male (96%) and smokers (93%) with a median age of 64 years. Neuroendocrine differentiation was established in 42 (93%) tumors by immunohistochemical analyses. Regarding the efficacy of first-line chemotherapy in the SCLC and NSCLC regimen groups, the response rates were 73% and 50% ( P =0.19), and the median progression-free survival times were 6.1 and 4.9 months ( P =0.41), respectively. The difference in overall survival between the two treatment groups was 7.3 months (16.5 vs. 9.2 months, P =0.10). There was also a considerable difference in the type and efficacy of salvage chemotherapeutic regimens between the two groups: salvage regimens with irinotecan, platinum, or taxanes were commonly used with relatively high objective responses in the SCLC regimen group, whereas frequently used agents in the NSCLC regimen group such as pemetrexed, gefitinib, or erlotinib were associated with no objective response. Conclusion Regarding palliative chemotherapy for advanced LCNEC, treatment similar to SCLC is more appropriate than NSCLC.

To determine whether earlier intervention was associated with decreased mortality in critically ill cancer patients admitted to an intensive care unit (ICU). A retrospective observational study was performed of 199 critically ill cancer patients admitted to the ICU from the general ward between January 2010 and December 2010. A logistic regression model was used to adjust for potential confounding factors in the association between time to intervention and in-hospital mortality. In-hospital mortality was 52 %, with a median Simplified Acute Physiology Score 3 (SAPS 3) of 80 [interquartile range (IQR) 67–93], and a median Sequential Organ Failure Assessment (SOFA) score of 8 (IQR 5–11). Median time from physiological derangement to intervention (time to intervention) prior to ICU admission was 1.5 (IQR 0.6–4.3) h. Median time to intervention was significantly shorter in survivors than in non-survivors (0.9 vs. 3.0 h; p