Hidden loss to follow-up among tuberculosis patients managed by public-private mix institutions in South Korea.

In South Korea, public-private mix (PPM) was launched in 2011. This retrospective cohort study sought to determine the rate of loss to follow-up (LTFU) among drug-susceptible tuberculosis (DS-TB) patients in all nationwide PPM institutions, and the risk factors for LTFU. National notification data for DS-TB patients diagnosed between August 2011 and July 2014 in PPM institutions were analysed. Determination of LTFU included detection of instances where patients were transferred out, but when they did not attend at other TB centres in the following two months. Univariable and multivariable competing risk models were used to determine risk factors for LTFU. 73,046 patients with 78,485 records were enrolled. Nominally, 3426 (4.4%) of records were LTFU. However, after linking the multiple records in each patient, the percentage of LTFU was 12.3% (9004/73,046). Risk factors for LTFU were: being foreign-born (3.13 (95% CI 2.77-3.53)), prior LTFU (2.31 (2.06-2.59)) and greater distance between the patient's home and the TB centre (4.27 (4.03-4.53)). 'Transfer-out' was a risk factor in patients managed by treatment centres close to home (1.65 (1.49-1.83)), but protective for those attending centres further (0.77 (0.66-0.89)) or far-away (0.52 (0.46-0.59)) from home. By considering the complete picture of a patient's interactions with healthcare, we identified a much higher level of LTFU than previously documented. This has implications for how outcomes of treatment are reported and argues for a joined-up national approach for the management and surveillance of TB patients, in nations with similar healthcare systems.

Natural History of Contralateral Bullae/Blebs After Ipsilateral Video-Assisted Thoracoscopic Surgery for Primary Spontaneous Pneumothorax: A Retrospective Cohort Study.

BACKGROUND: Contralateral bullae/blebs are frequently found in patients who are scheduled to undergo ipsilateral video-assisted thoracoscopic surgery (VATS) for primary spontaneous pneumothorax (PSP). RESEARCH QUESTION: Should visible contralateral bullae/blebs be simultaneously resected when ipsilateral VATS bullectomy is performed? STUDY DESIGN AND METHODS: In this single-center, retrospective cohort study, we included patients aged ≤ 30 years who underwent ipsilateral VATS for PSP from April 2009 to December 2019. Electronic medical records, radiograph images, and preoperative high-resolution CT images were reviewed. The primary end point was recurrence-free survival (no contralateral pneumothorax) after discharge of ipsilateral VATS for PSP, determined via Kaplan-Meier analysis. Recurrence was compared between the group with and that without contralateral bullae/blebs by using the log-rank test. A multivariable Cox proportional hazards model was constructed to investigate risk factors for contralateral pneumothorax. RESULTS: Among 567 patients, contralateral pneumothorax occurred in 86 of them after ipsilateral VATS (15.2%) during a median follow-up period of 51.3 (interquartile range, 67.2) months. The 1-, 5-, and 10-year recurrence-free survival rates were 92.2%, 83.7%, and 79.9%, respectively. Contralateral recurrence was higher in the group with (82/455, 18.0%) than in that without (4/112, 3.6%) contralateral bullae/blebs (P < .001). Age (hazard ratio [HR], 0.701; 95% CI, 0.629-0.780; P < .001), current smoking (HR, 2.106; 95% CI, 1.158-3.831; P = .015), and the presence of bullae/blebs (increasing with size, HR, 4.818-8.980; all P < .05) were independent risk factors for contralateral pneumothorax. The annual rates of contralateral pneumothorax in the group with (4.0%) and in that without (0.7%) contralateral bullae/blebs declined over time. INTERPRETATION: Although contralateral bullae/blebs were common in patients who underwent ipsilateral VATS for PSP and were statistically significantly associated with future pneumothorax, the annual rate of pneumothorax was 4.0% in such patients, and it decreased over time. Therefore, a conservative approach on unruptured contralateral bullae/blebs is recommended.

Investigating the appropriate adenosine deaminase cutoff value for the diagnosis of tuberculous pleural effusion in a country with decreasing TB burden.

As the burden of tuberculosis (TB) in South Korea decreases while that of malignancy increases with an aging society, the composition of etiology for pleural effusion is changing. The aim of this study was to investigate the diagnostic value of adenosine deaminase (ADA) for diagnosis of tuberculous pleural effusion (TPE) in this circumstance. Medical records of patients who underwent medical thoracoscopy from May 2015 to September 2020 in Incheon St. Mary Hospital, Korea were retrospectively reviewed. TPE was diagnosed if one of the following criteria was met: (1) granuloma in pleura, (2) positive TB polymerase chain reaction or culture in pleural fluid or tissue with non-specific pathologic findings in pleura, or (3) bacteriologically confirmed pulmonary TB with non-specific pathologic findings in pleura. A total of 292 patients, including 156 with malignant pleural effusion (MPE), 52 with TPE, and 84 with other benign effusion, were analyzed. Among 206 patients with lymphocyte dominant pleural effusion, the area under receiver characteristic curve of ADA for diagnosis of TPE was 0.971. The sensitivity and specificity of a current cutoff value of 40 IU/L were 1.00 and 0.61, respectively, whereas those of a raised cutoff value of 70 IU/L were 0.93 and 0.93, respectively. Among 54 patients with ADA levels of 40-70 IU/L, 30 (55.6%) patients were diagnosed as MPE, 21 (38.9%) as other benign effusion, and only 3 (5.6%) as TPE. Caution is needed in clinical diagnosis of TPE with current ADA cutoff value in countries with decreasing TB incidence, due to many false positive cases.

Cross-sectional survey on home mechanical ventilator use: major deficiencies in a home care system in South Korea.

BACKGROUND: Despite the increased use of home mechanical ventilation (HMV), data on home care services for HMV users in Asian countries are scarce. This study investigated the current status of HMV use in the Seoul metropolitan area. METHODS: This cross-sectional study involved three university-affiliated hospitals. Subjects who were receiving HMV at home for >3 months were included, and door-to-door visits were done to collect data (e.g., on devices, caregivers, and healthcare service use) from the subjects or their families. RESULTS: Among the 140 individuals who were initially screened, 38 adults and 26 children were finally enrolled; the duration of HMV use was 14.5 (8.8-37.5) months and 20.5 (7.0-28.0) months, respectively. Tracheostomy ventilation was performed in 36.8% of the adults and 61.5% of the children, and life-support ventilator in 55.3% and 96.2%, respectively. Regarding ancillary devices, 42.1% of the adults and 80.8% of the children had an oxygen monitoring device, while only one member of each group had a cough assist device. Among those with a tracheostomy, 64.3% of adults and 81.3% of children had an AMBU-bag. Reliance on a family member for care was determined in 65.8% of adults and 88.5% of children, but a home visit by a hospital nurse during the previous year occurred in only 26.3% of the adults and 3.8% of the children. Emergency incidents at home occurred in 39.5% of the adults and 50.0% of the children, with dyspnea being the most common cause. Out-of-pocket expenses tended to be higher in the tracheostomy (vs. non-tracheostomy) group and in children (vs. adults). CONCLUSIONS: Our study highlights the challenges faced by adults and children dependent on HMV, and their families. There is an urgent need for nationwide standardization of care for patients receiving HMV at home.

Effect of serum isoniazid level on treatment outcomes among tuberculosis patients with slow response - A retrospective cohort study.

BACKGROUND: In this study, we investigate the effects of low serum TB drug level on treatment outcome among TB patients with slow response in South Korea, where the prevalence of rapid acetylator is relatively high. METHODS: Among the pulmonary TB patients whose treatment outcomes were reported between 2014 and 2018 at Incheon St. Mary hospital, those who underwent TDM because of delayed culture conversion or reversion were included. Primary outcome was microbiological failure defined as (1) positive sputum culture after 120 days of treatment, or (2) culture-confirmed relapse within one year after treatment completion. Patients with culture conversion within 120 days and no relapse were classified as the final conversion group. Clinical characteristics and serum drug concentration at 2 h after administration (C2hr) were compared between those two groups. RESULTS: A total of 55 pulmonary TB patients were included. Prevalence of subtherapeutic range of C2hr for isoniazid and rifampin was 78.2% and 21.8%, respectively. With one year of follow-up, 21 cases were classified as the microbiological failure group, and 34 cases as the final conversion group. In a multivariable logistic regression model for predicting microbiological failure, C2hr of isoniazid was the most significant predictor after adjusting for the effects of age and sex (adjusted odds ratio, 0.29; p = 0.009). In a tree-based classification model, C2hr of isoniazid with cutoff level 2.5 µg/ml was the most important variable for predicting microbiological failure. CONCLUSIONS: Low serum isoniazid level was related to poor treatment outcomes among the TB patients with slow response.

Non-invasive ventilation for acute respiratory failure: pressure support ventilation vs. pressure-controlled ventilation.

BACKGROUND: The best ventilator mode for patients receiving non-invasive ventilation (NIV) has not been clarified. This study compared the effectiveness of two pressure-targeted modes, i.e., pressure support ventilation (PSV) and pressure-controlled ventilation (PCV), in patients receiving NIV. METHODS: This was a prospective multicentre observational study of NIV use for acute respiratory failure (ARF) in adult patients. We compared the two pressure-targeted modes in terms of NIV success and complication rates. RESULTS: Among 176 patients receiving NIV, 88 patients were included in the study (PCV mode, n=29; PSV mode, n=59). The study population had a median age of 73.0 years and median body mass index of 20.8 kg/m2. The applied inspiratory positive airway pressure (IPAP) was higher in patients with PCV than in those with PSV [18.0 cmH2O (15.0-20.5 cmH2O) vs. 15.0 cmH2O (12.0-17.0 cmH2O), respectively, P=0.001]. More patients with PCV received sedatives and experienced dry mouth than those with PSV; however, the incidences of large leaks were low in both groups (n=5 vs. n=2, respectively). With regard to NIV outcomes, 24 (27.2%) patients experienced NIV failure and 13 (14.8%) died in hospital. PSV mode was a significant factor for NIV success [odds ratio (OR), 2.303; 95% confidence interval (CI), 1.216 to 4.360] in multivariate analyses and this association remained significant in a 1:1 matched cohort (n=29 per group). CONCLUSIONS: In contrast to PCV mode, PSV mode was significantly associated with NIV success in the intensive care unit setting, particularly when large leaks were not a major concern. Nevertheless, further well-designed multicenter, protocol-driven randomized controlled trials are warranted.

Effects of long term normobaric hyperoxia exposure on lipopolysaccharide-induced lung injury.

Purpose/Aim of the study: Prolonged exposure to hyperoxia can cause injury to normal lung tissue. However, patients with acute hypoxic respiratory failure are frequently exposed to very high oxygen levels. This study investigated the effects of long term normobaric hyperoxia exposure in a mouse model of acute severe lung injury (SLI).Meterials and Methods: C57BL/6J mice were injected intratracheally with lipopolysaccharide (LPS, 4 mg/kg) to induce acute lung injury. After 2 h, mice were divided into two groups, and then exposed to room air or hyperoxic conditions for 48 h. Animals in the hyperoxia group were placed within their cages in a Plexiglass chamber with an atmosphere of 95% O2 maintained constant using an oxygen analyzer. After exposure to normoxia (N) or hyperoxia (H) for 48 h, the left lungs were collected for tissue paraffin block or oxidative stress assay. One lobe of the right lung was collected for lung/body weight ratio. The lung injury score and the mean linear intercept were evaluated in hematoxylin and eosin -stained lungs. The biochemical tests were performed by using ELISA assay.Results: Lung injury scoring, lung/body weight, and mean linear intercept were not significantly different between the N + LPS (NLPS) and H + LPS (HLPS) groups. Similar trends were observed in hydroxyproline and transforming growth factor-ß (TGF-ß) levels. Total cell and neutrophil counts in bronchoalveolar lavage fluid showed no significant differences between NLPS and HLPS groups. Histological analyses demonstrated more severe lung injury and fibrosis in the NLPS group than in the HLPS group. In addition, interleukin (IL)-1ß was significantly decreased in the HLPS group compared to the NLPS group. Other inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and IL-6, showed similar trends. The malondialdehyde (MDA) level was significantly lower in the HLPS group than in the NLPS group.Conclusions: Exposure to hyperoxia did not augment lung injury in the LPS-induced lung injury model, and some indicators even showed better outcomes. These results suggest that long-term high-oxygen therapy in patients with SLI has low risk of lung injury.

Factors associated with discrepancy between fresh frozen and permanent biopsy from medical thoracoscopy: single center analysis of 172 medical flexible thoracoscopy cases.

BACKGROUND: Frozen sections prepared during medical thoracoscopy (MT) have precise diagnostic ability in pleural pathology and may assist in decision-making before pleurodesis. The present study evaluated the diagnostic sensitivity of frozen sections from flex-rigid MT, and further evaluated clinical parameters for their association with a discrepancy between frozen sections and permanent paraffin sections. METHODS: This retrospective study evaluated 172 patients who underwent flex-rigid MT between February 2017 and November 2019 at Incheon Saint Mary's Hospital. RESULTS: Of the 172 patients, 85 were pathologically diagnosed with malignancy based on permanent paraffin sections. An accurate diagnosis by fresh frozen section was feasible in 88.2% of the cases compared to the permanent paraffin sections. Among the 85 patients, 75 had malignancies in frozen sections, while 10 patients showed otherwise. In the 85 malignant cases, age, sex, the volume of effusion, thoracoscopic findings, as well as the final pathological diagnosis (lung vs. non-lung origin) were included in univariate analysis for an association with non-malignant frozen section results. High adhesion grade and malignancy other than lung cancer were significant factors associated with frozen section negative cases in a multivariable analysis. CONCLUSIONS: Taking fresh frozen sections during MT using a flex-rigid bronchoscope is a useful diagnostic modality with reliable sensitivity for malignancy. However, if the pre-procedural diagnosis is likely to be a malignancy other than lung cancer, and if severe adhesions are present in the pleural cavity, the final pathological confirmation should be determined based on permanent paraffin sections, not only on fresh frozen sections.

Diagnosis and Prognosis of Sepsis Based on Use of Cytokines, Chemokines, and Growth Factors.

The focus of sepsis has shifted from inflammation to organ dysfunction on the basis of a recent definition based on the sequential organ failure score (SOFA). A diagnostic and prognostic marker is necessary under this definition but is currently unknown. We enrolled 80 sepsis patients consecutively admitted to an intensive care unit through the emergency department and 80 healthy control patients who received routine health check-ups from August 2018 to January 2019. SEPSIS-3 criteria were used for the diagnosis of patients based on SOFA score ≥ 2 from the baseline along with evidence of infection. Concentrations of 28 cytokines, eight chemokines, and nine growth factors were measured on the day of diagnosis. Hierarchical cluster analysis was performed for molecules. The majority of infections were pneumonia (45% of patients) and urinary tract infections (40% of patients). Most of the measured molecules were increased in patients with sepsis. Area under receiver operating characteristic curve (AUROC) values were found to be as follows: hepatic growth factor (HGF), 0.899; interleukin-1 receptor antagonist (IL-1RA), 0.893; C-C motif ligand 5 (CCL5) 5, 0.887; C-X-C motif chemokine 10 (CXCL10), 0.851; CCL2, 0.840; and IL-6, 0.830. IL-1RA, IL-6, IL-8, IL-15, and CCL11 concentrations correlated with SOFA score with statistical significance. Prognosis multivariate analysis revealed an odds ratio of 0.968 for epidermal growth factor (EGF). Three clusters were formed, of which Clusters 2 and 3 were associated with nonsurvivors. Diagnosis of sepsis was performed using cytokines, chemokines, and growth factors. HGF revealed the highest diagnostic capability, and EGF predicted favorable prognosis among the tested molecules.

Correction to: Are there differences among operators in false-negative rates of endosonography with needle aspiration for mediastinal nodal staging of non-small cell lung cancer?

Following publication of the original.

Are there differences among operators in false-negative rates of endosonography with needle aspiration for mediastinal nodal staging of non-small cell lung cancer?

BACKGROUND: Endosonography with needle aspiration (EBUS/EUS-NA) is recommended as the first choice for mediastinal nodal assessment in non-small cell lung cancer (NSCLC). It is important to maintain adequate negative predictive value of the procedure to avoid unnecessary additional surgical staging, but there are few studies on the influence of operator-related factors including competency on false negative results. This study aims to compare the false negative rate of individual operators and whether it changes according to accumulation of experience. METHODS: This is a retrospective study of NSCLC patients who were N0/N1 by EBUS/EUS-NA and confirmed by pathologic staging upon mediastinal lymph node dissection (n = 705). Patients were divided into a false negative group (finally confirmed as pN2/N3) and a true negative group (pN0/N1). False negative rates of six operators and whether these changed according to accumulated experience were analyzed. RESULTS: There were 111 (15.7%) false negative cases. False negative rates among six operators ranged from 8.3 to 21.4%; however, there were no statistical differences before and after adjustment for patient characteristics and procedure-related factors (P = 0.346 and P = 0.494, respectively). In addition, false negative rates did not change as each operator accumulated experience (P for trend = 0.632). CONCLUSIONS: Our data suggest that there would be no difference in false negative rates regardless of which operator performs the procedure assuming that the operators have completed a certain period of observation and have performed procedures under the guidance of an expert.

Normobaric hyperoxia inhibits the progression of lung cancer by inducing apoptosis.

Hypoxia is a critical characteristic of solid tumors with respect to cancer cell survival, angiogenesis, and metastasis. Hyperoxic treatment has been attempted to reverse hypoxia by enhancing the amount of dissolved oxygen in the plasma. In this study, we evaluated the effects of normobaric hyperoxia on the progression of lung cancer to determine whether oxygen toxicity can be used in cancer therapy. Following a tail vein injection of the Lewis lung carcinoma cells, C57BL/6J mice were exposed to a 24-h normobaric hyperoxia/normoxia cycle for two weeks. In addition, A549 lung cancer cells were incubated in a normobaric hyperoxia chamber for a 24-h period. As a result, the size and number of tumors in the lung decreased significantly with exposure to normobaric hyperoxia in the mouse model. Cell viability, colony-forming ability, migration, and invasion all decreased significantly in A549 cells exposed to normobaric hyperoxia and the normal control group exposed to normobaric hyperoxia showed no significant damage. Oxidative stress was more prominent with exposure to normobaric hyperoxia in cancer cells. A549 cells exposed to normobaric hyperoxia showed a significantly higher cell apoptosis ratio compared with A549 cells without normobaric hyperoxia exposure and normal human lung cells (BEAS-2B cells). The Bax/Bcl-2 mRNA expression ratio also increased significantly. Changes in the key regulators of apoptosis were similar between in vivo and in vitro conditions. The p-ERK level decreased, while the p-JNK level increased, after normobaric hyperoxia exposure in A549 cells. This study demonstrated the role of normobaric hyperoxia in inhibiting lung cancer. Normal tissue and cells showed no significant hyperoxic damage in our experimental setting. The anti-tumor effect of normobaric hyperoxia may due to the increased reactive oxygen species activity and apoptosis, which is related to the mitogen-activated protein kinase pathway. Impact statement Normobaric hyperoxia (NBO) is a feasible therapy for cancer with a low complication rate. Although NBO may be beneficial in cancer treatment, very few studies have been conducted; thus, the evidence is thin. This is the first study to clearly demonstrate morphological changes in lung cancer with NBO exposure and to investigate the underlying mechanisms both in vivo and in vitro. This study will arouse interest in NBO treatment and promote further research.

Clinical significance of nuclear factor erythroid 2-related factor 2 in patients with chronic obstructive pulmonary disease.

Background/Aims: Several studies have identified a role for nuclear factor erythroid 2-related factor 2 (Nrf2) in the development of chronic obstructive pulmonary disease (COPD). However, the relationship between the plasma Nrf2 level and the extent of systemic inflammation associated with COPD status remains unclear. METHODS: Patients diagnosed with COPD were recruited from St. Paul's Hospital, The Catholic University of Korea, between July 2009 and May 2012. Patients were classified into two groups according to the severity of their symptoms on initial presentation, a COPD-stable group (n = 25) and a COPD-exacerbation group (n = 30). Seventeen patients were enrolled as a control group (n = 17). The plasma levels of Nrf2 and other systemic inf lammatory biomarkers, including interleukin 6 (IL-6), surfactant protein D (SP-D), and C-reactive protein (CRP), were measured. We collected clinical data including pulmonary function test results, and analyzed the relationships between the biomarker levels and the clinical parameters. RESULTS: Plasma Nrf2 and CRP levels significantly increased in a stepwise manner with an increase in inflammatory status (control vs. COPD-stable vs. COPD-exacerbation) (p = 0.002, p < 0.001). Other biomarkers of systemic inflammation (IL-6, SP-D) exhibited similar tendencies, but significant differences were not apparent. Furthermore, we observed negative correlations between the plasma level of Nrf2 and both the forced expiratory volume in 1 second (FEV1) (r = -0.339, p = 0.015) and the forced expiratory ratio (FEV1/forced vital capacity [FVC]) (r = -0.342, p = 0.014). However, CRP level was not correlated with any measured parameter. Conclusions: Plasma Nrf2 levels gradually increased in line with disease severity and the extent of systemic inflammation in patients with COPD.

Factors Related to the Diagnostic Yield of Flexible Bronchoscopy without Guidance in Bronchoscopically Invisible Peripheral Lung Lesions.

BACKGROUND: We aimed to analyze the factors predicting the diagnostic performance of flexible bronchoscopy without guidance in peripheral lung lesions that are endoscopically invisible. METHODS: This was a retrospective study conducted in St. Paul's Hospital, The Catholic University of Korea, between January 2007 and March 2013. We included all patients who received bronchoscopy during this period. The analyzed variables were age, sex, the etiology of the lesion, lesion size, distance from the pleura, and presence of the bronchus sign. We used multiple logistic regression analysis to identify the significant independent factors associated with diagnostic yield. RESULTS: We included 151 patients in this study. The overall diagnostic yield was 58.3%. The sensitivity was 43.2% for malignant disease and 78.1% for benign disease. The benign lung lesions (p<0.001), lesion size (p=0.015), presence of the exposed type of bronchus sign (p<0.001), and presence of cavitary lung lesions (p=0.005) were factors influencing the yield of flexible bronchoscopy by univariate analysis. In a multivariate logistic regression analysis, the exposed type of bronchus sign and benign lung lesions were independent predicting factors (odds ratio [OR]: 27.95; 95% confidence interval [CI], 7.56-103.32; p<0.001 and OR, 4.91; 95% CI, 1.76-13.72; p=0.002). CONCLUSION: The presence of the exposed type of bronchus sign and benign lung lesions are determining factors of the diagnostic yield in flexible bronchoscopy in evaluating peripheral lesions that are not endoscopically visible.

Demographic Changes in Intensive Care Units in Korea over the Last Decade and Outcomes of Elderly Patients: A Single-Center Retrospective Study.

BACKGROUND: Aging is a significant issue worldwide, and Korea is one of the most rapidly aging countries. Along with the demographic transition, the age structure of intensive care unit (ICU) patients changes as well. METHODS: The aim of this study was to analyze the change in age distribution of the ICU patients over the last 10 years and its effect on clinical outcomes. Single-center, retrospective analysis of all patients aged ≥18 years admitted to either the medical or surgical ICU at St. Paul's Hospital, The Catholic University of Korea, between January 2005 and December 2014 was conducted. For clinical outcome, in-hospital mortality, duration of ICU stay, and hospital stay were analyzed. Cost analysis was performed to show the economic burden of each age strata. RESULTS: A total of 10,366 ICU patients were admitted to the chosen ICUs during the study period. The proportion of elderly patients aged ≥65 years increased from 47.9% in 2005 to 63.7% in 2014, and the proportion of the very elderly patients aged ≥80 years increased from 12.8% to 20.7%. However, this increased proportion of elderly patients did not lead to increased in-hospital mortality. The percent of ICU treatment days attributable to elderly patients increased from 51.1% in year 2005 to 64.0% in 2014. The elderly ICU patients were associated with higher in-hospital mortality compared to younger age groups. CONCLUSIONS: The proportion of elderly patients admitted to ICUs increased over the last decade. However, overall in-hospital mortality has not increased during the same period.

Dyspnea as a Prognostic Factor in Patients with Non-Small Cell Lung Cancer.

PURPOSE: To investigate associations between dyspnea and clinical outcomes in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From 2001 to 2014, we retrospectively reviewed the prospective lung cancer database of St. Paul's Hospital at the Catholic University of Korea. We enrolled patients with NSCLC and evaluated symptoms of dyspnea using modified Medical Research Council (mMRC) scores. Also, we estimated pulmonary functions and analyzed survival data. RESULTS: In total, 457 NSCLC patients were enrolled, and 259 (56.7%) had dyspnea. Among those with dyspnea and whose mMRC scores were available (109 patients had no mMRC score), 85 (56.6%) patients had an mMRC score <2, while 65 (43.3%) had an mMRC score ≥2. Significant decreased pulmonary functions were observed in patients with dyspnea. In multivariate analysis, aging, poor performance status, advanced stage, low forced expiratory volume in 1 second (%), and an mMRC score ≥2 were found to be significant prognostic factors for patient survival. CONCLUSION: Dyspnea could be a significant prognostic factor in patients with NSCLC.

Risk Factor and Clinical Outcome of Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation.

PURPOSE: The development of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) deteriorates patients' quality of life. This study aimed to analyze the prevalence, clinical features, risk factors and prognostic factors of BOS. MATERIALS AND METHODS: This retrospective study included patients who underwent allogeneic HSCT from January 2002 to December 2008 and survived for ≥100 days after transplantation. RESULTS: Of 860 patients who survived for ≥100 days, 36 (4.2%) met the diagnostic criteria. The duration of BOS development after transplantation was 466.00 (284.00-642.75) [median (interquartile range)] days. The risk factor for the development of BOS was peripheral blood as the stem cell source with a hazard ratio (HR) of 2.550 [95% confidence interval (CI): 1.274-5.104, p=0.008]. In multivariate analysis, pretransplant FEV1/FVC (HR: 0.956, 95% CI: 0.921-0.993, p=0.020) and time from HSCT to diagnosis of BOS (HR: 0.997, 95% CI: 0.994-0.999, p=0.009) were independent prognostic factors associated with mortality. CONCLUSION: Peripheral blood as a stem cell source is a risk factor for the development of BOS. A decreased pretransplant FEV1/FVC and shorter duration of time from transplantation to diagnosis of BOS are poor prognostic factors for BOS.

Association between vitamin D receptor polymorphisms and osteoporosis in patients with COPD.

BACKGROUND: Patients with COPD are at an increased risk of osteoporosis. Although many studies have addressed the relationship between the vitamin D receptor (VDR) polymorphisms and bone health, this relationship has not been fully investigated in patients with COPD. In this study, we investigated the association of VDR polymorphisms with bone mineral density (BMD) and other clinical parameters in patients with COPD. PATIENTS AND METHODS: In total, 200 patients with COPD were included in this study. The VDR polymorphisms rs1544410 (A/G-BsmI), rs7975232 (A/C-ApaI), rs731236 (C/T-TaqI), and rs10735810 (C/T-FokI) were determined by Sanger sequencing using blood DNA samples. BMD of the lumbar vertebra and the femoral neck was measured by dual-energy X-ray absorptiometry. Other clinical parameters were also evaluated. Haplotype and multivariate analyses were also performed. RESULTS: Sex, body mass index, steroid use, percentage of forced expiratory volume in 1 second (FEV1), alkaline phosphatase, and 25-hydroxyvitamin D significantly influenced the risk of osteoporosis. Patients with osteoporosis were more likely to carry the rs7975232 C allele compared to normal patients with BMD. Haplotypes GCT and GAT were related to osteoporosis. Patients without the haplotype GAT allele showed a significantly lower T-score at the femoral neck and an increased risk of osteoporosis (odds ratio [OR]= 2.78, 95% confidence interval [CI]= 1.20-6.48, P=0.018) compared with carriers in the dominant model. CONCLUSION: Genetic variations in VDR are significantly associated with osteoporosis among patients with COPD. Further studies are required to confirm the role of the VDR polymorphisms in osteoporosis among patients with COPD.