TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells.

BACKGROUND: Macrophages promote angiogenesis, metastasis, and drug resistance in several cancers. Similarly, TonEBP/NFAT5 induces metastasis in renal carcinoma and colon cancer cells. However, the role of this transcription factor and that of macrophages in lung cancer cells remains unclear. Therefore, this study investigated the effects of macrophages and TonEBP/NFAT5 expression on cisplatin resistance and migration in A549 lung adenocarcinoma cells. RESULTS: A549 cells were cultured alone or indirectly co-cultured with THP-1-derived macrophages using a transwell culture chamber. Cisplatin-induced cell death was markedly decreased and migration increased in co-cultured A549 cells. Macrophage-conditioned media (CM) showed a similar effect on drug resistance and migration. Cisplatin-induced apoptosis, DNA fragmentation, and cleaved apoptotic proteins PARP and caspase-3 were markedly reduced in macrophage CM-induced A549 cells. Here, ERK, p38, JNK, and NF-κB activities were increased by macrophage CM. Furthermore, the proteins involved in cisplatin resistance and cancer cell migration were identified using specific inhibitors of each protein. ERK and NF-κB inhibition considerably reduced cisplatin resistance. The increase in macrophage CM-induced migration was partially reduced by treatment with ERK, JNK, and NF-κB inhibitors. TonEBP/NFAT5 expression was increased by macrophages, resulting in increased cisplatin resistance, cell migration, and invasion. Moreover, RNAi-mediated knockdown of TonEBP/NFAT5 reduced cisplatin resistance, migration, and invasion in macrophage CM-induced A549 cells. CONCLUSIONS: These findings demonstrate that paracrine factors secreted from macrophages can change A549 cells, resulting in the induction of drug resistance against cisplatin and migration. In addition, the TonEBP/NFAT5 ratio, increased by macrophages, is an important regulator of the malignant transformation of cells.

Chest computed tomography scan utilization and diagnostic outcomes in chronic cough patients with normal chest X-rays: analysis of routinely collected data of a tertiary academic hospital.

Background: The role of chest computed tomography (CT) scan is controversial in the management of chronic cough patients with normal chest X-rays. We investigated the utilization pattern and diagnostic outcomes of chest CT scans using institutional routinely collected data (RCD) in South Korea. Methods: This is a retrospective analysis of adults with chronic cough (>8 weeks in duration) identified from routinely collected electronic health records (EHRs). Structured data were retrieved, including demographics, medical history, symptoms, and diagnostic test results (including chest X-rays and CT scans). Chest CT scan outcomes were classified into major abnormal findings (malignancy, infectious diseases, or other critical conditions that warrant immediate treatment decisions), minor abnormal findings (other abnormal findings), or normal CT. Results: A total of 5,038 chronic cough patients with normal chest X-rays were analyzed. Chest CT scans were performed in 1,006 patients. Prescription of CT scans was significantly associated with older age, male sex, smoking history, and physician-diagnosed history of lung disease. Only 8 of 1,006 (0.8%) patients had major abnormal findings (4 pneumonia, 2 pulmonary tuberculosis, and 2 lung cancer), while 367 (36.5%) had minor findings, and 631 (62.7%) had normal CT scans. However, no baseline parameters were significantly associated with major CT findings. Conclusions: Chest CT scans were frequently prescribed for chronic cough patients with normal chest X-rays, and abnormal findings were frequently found (37.3%). However, the diagnostic yield for malignancy or infectious disease were low (<1%). Given the potential radiation harm, a routine chest CT scan may not be warranted in chronic cough patients with normal chest X-rays.

TonEBP expression is essential in the IL-1ß-induced migration and invasion of human A549 lung cancer cells.

Lung cancer has the highest mortality rate among all cancers, in part because it readily metastasizes. The tumor microenvironment, comprising blood vessels, fibroblasts, immune cells, and macrophages [including tumor-associated macrophages (TAMs)], is closely related to cancer cell growth, migration, and invasion. TAMs secrete several cytokines, including interleukin (IL)-1ß, which participate in cancer migration and invasion. p21-activated kinase 1 (PAK1), an important signaling molecule, induces cell migration and invasion in several carcinomas. Tonicity-responsive enhancer-binding protein (TonEBP) is also known to participate in cancer cell growth, migration, and invasion. However, the mechanisms by which it increases lung cancer migration remain unclear. Therefore, in this study, we aimed to elucidate the mechanisms by which IL-1ß and TonEBP affect lung cancer cell migration and invasion. We found that A549 cocultured-MΦ-secreted IL-1ß induced A549 cell migration and invasion via the PAK1 pathway. TonEBP deficiency reduced A549 cell migration and invasion and increased responsiveness to IL-1ß-induced migration and invasion. PAK1 phosphorylation, which was promoted by IL-1ß, was reduced when TonEBP was depleted. These results suggest that TonEBP plays an important role in IL-1ß induction and invasiveness of A549 cells via the PAK1 pathway. These findings could be valuable in identifying potential targets for lung cancer treatment.

Impact of Previous Occupational Exposure on Outcomes of Chronic Obstructive Pulmonary Disease.

Occupational exposures have been regarded as a risk factor for the development of chronic obstructive pulmonary disease (COPD). However, there is little knowledge regarding the effect of occupational exposure on the treatment outcomes of COPD. Therefore, the aim of this study was to evaluate the question of whether occupational exposure can have a potential impact on COPD outcomes. Methods: Information regarding self-reported occupational exposure for 312 patients with COPD from the Korean Obstructive Lung Disease (KOLD) Cohort were included. A comparison of the rate of acute exacerbation, annual lung function change, and quality of life according to the presence or absence of occupational exposure was performed. Results: Seventy-six patients (24.4%) had experienced occupational exposure; chemical materials were most common. At enrollment, a higher COPD-specific version of the St. George Respiratory Questionnaire total score (39.7 ± 18.8 vs. 33.1 ± 17.6, p = 0.005) and a higher exacerbation history in the past year (30.3% vs. 17.5%, p = 0.017) were observed for patients with occupational exposure compared to those without occupational exposure. Furthermore, in the follow-up period, after adjusting for potential confounders, a higher frequency of acute exacerbation (odd ratio, 1.418; 95% confidence interval, 1.027-1.956; p = 0.033) and a more rapid decline in forced expiratory volume in 1 s (p = 0.009) was observed for COPD patients with occupational exposure compared to those without occupational exposure. Conclusions: In the KOLD cohort, worse outcomes in terms of exacerbation rate and change in lung function were observed for COPD patients with occupational exposure compared to those without occupational exposure. These findings suggest that occupational exposure not only is a risk factor for COPD but also might have a prognostic impact on COPD.

Phenotyping COPD Patients with Emphysema Distribution Using Quantitative CT Measurement; More Severe Airway Involvement in Lower Dominant Emphysema.

Purpose: We explored the differences in clinical manifestations of COPD patients regarding emphysema distribution along with evidence of airway involvement in chest computed tomography (CT) scans. Patients and Methods: The patients were divided into three groups according to the emphysema distribution: the upper dominant (UD), lower dominant (LD), and homogeneous (HD) groups. Airway wall thickness was quantitatively measured and the presence of bronchiectasis and/or bronchial wall thickening (BE/BWT) was visually assessed. Baseline characteristics including the evidence of airway involvement and long-term outcomes were compared among the three groups. Non-severe patients of each group were first treated with 3 months of ICS/LABA combination after 2 weeks of wash-out period and lung functions before and after the treatment were compared. Results: Of the 425 patients, 141 were in the UD, 107 in LD, and 177 in HD. The LD had more severe airway obstruction with lower emphysema index (EI) than the UD (LD vs UD; FEV1, 49.5-14.9 vs 54.6-16.5; EI, 21.0 [IQR: 14.0-33.1] vs 26.3 [IQR: 15.8-39.0]). The LD showed thicker airways (higher WA% and Pi10) and more severe air trapping (higher RV and RV/TLC) than UD. A larger proportion of patients in LD had BE/BWT (35.5% in LD vs 11.3% in UD). In LD, more patients experienced acute exacerbations and the time to first exacerbation was shorter than UD. Non-severe patients in LD treated with 3 months of ICS/LABA combined inhalers showed a notable reduction of RV than UD (LD vs UD; -531.1-936.5 vs -86.5-623.5). Conclusion: The LD showed a more prominent airway involvement than UD, which may cause more frequent exacerbations and a marked reduction of RV after the ICS/LABA combination treatment in LD. Phenotyping of the COPD patients using quantitatively measured emphysema distribution would be useful for predicting treatment response and exacerbation.

Comparison of Predicted Exercise Capacity Equations in Adult Korean Subjects.

BACKGROUND: Maximal oxygen uptake (VO2 max) is a useful index to assess exercise capacity. However, there is no reference value for Koreans. This study aimed to compare actual VO2 max and predicted VO2 max using exercise capacity equations in Korean subjects. METHODS: This retrospective study enrolled 383 patients who underwent cardiopulmonary exercise test (CPET) with incremental maximal cycle ergometer test at Asan Medical Center from January 2020 to May 2021. Stage 1 and 2 lung cancer patients with normal lung function and healthy persons of 50 subjects who had maximal CPET were analyzed. RESULTS: The subjects were aged 65 ± 13 years and predominantly male (74%). CPET results were as follows: absolute VO2 max, 1.2 ± 0.3 L/min; body weight referenced VO2 max, 20 ± 3.9 mL/kg/min; peak work rate, 94 ± 24 watts; peak heart rate, 142 ± 21 bpm; peak O2 pulse, 10 ± 3 mL/beat; minute ventilation, 59 ± 14 L/min; peak respiratory rate, 34 ± 6 breaths per minute; and peak breathing reserve, 41 ± 18%. There was significant discordance between the measured and predicted absolute VO2 max using the Jones, Hansen, and Wasserman prediction equations developed for Caucasian population (P < 0.001). Agreement using Bland-Altman test between true and predicted absolute VO2 max was the best in Chinese equation (-0.03, 2SD = 0.55) compared to Jones (0.42, 2SD = 1.07), Hansen (0.44, 2SD = 0.86), and Wasserman (0.42, 2SD = 0.86) equations. CONCLUSION: The reference value and prediction equation from studies including primarily Caucasians may not be appropriate for Koreans. Since the mean difference is the lowest in Chinese equation, the Chinese equation might be used for the Korean adult population.

Clinical Impact of the Bronchiectasis with Chronic Bronchitis Symptoms in COPD: Analysis of a Longitudinal Cohort.

PURPOSE: Bronchiectasis (BE) is a poor prognostic factor in COPD. However, it is not clear whether the poor prognosis is a result of BE alone or accompanying chronic bronchitis symptoms. Therefore, we investigated the effect of chronic bronchitis symptoms on clinical outcomes in COPD patients with BE. PATIENTS AND METHODS: We analyzed data of COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort. The presence of BE was verified by chest computed tomography. Chronic bronchitis symptoms were determined using items in the symptomatic domain of the SGRQ, which is also used as an alternative definition of chronic bronchitis (CB). Patients were divided into four groups according to the presence of BE and CB symptoms: BE/CB, BE-only, CB-only, and no BE/CB. Demographic features and clinical outcomes were compared among these groups. RESULTS: In total, 389 COPD patients were included in the analysis. BE was present in 148 (38%) patients and CB symptoms were found in 123 patients (33.2%). The patients were divided according to BE and CB symptoms, and the numbers and percentages of each group were as follows: BE/CB, 52 (13.4%); BE-only, 96 (24.7%); CB-only, 77 (19.8%); no BE/CB, 164 (42.2%). No significant differences were observed in baseline characteristics of lung function, radiological findings, and inflammatory markers among the four groups. The proportion of annual exacerbators was higher in the BE/CB and CB-only groups than the other two groups. After adjusting other parameters, the BE/CB group was significantly associated with acute exacerbation of COPD (AE-COPD) (OR = 2.110, p = 0.045). CONCLUSION: BE accompanying CB symptoms is associated with AE-COPD, while BE alone was not significantly associated. This finding suggests that it is more important to examine chronic bronchitis symptoms of BE to predict acute exacerbation than simply to identify BE in COPD patients.

Survey of the management of patients with bronchiectasis: a pilot investigation in Asian populations.

BACKGROUND/AIMS: Although international guidelines for bronchiectasis management have been published in Western countries, there is a lack of data about their application in Asian populations including patients with different phenotypes. We aimed to investigate the current status of bronchiectasis management in Asian populations. METHODS: A nationwide questionnaire survey was performed of Asian respiratory specialists from South Korea, Japan, Taiwan, Singapore, Vietnam, and Sri Lanka. Participants were invited by e-mail to answer a questionnaire comprising 25 questions based on international guidelines for the management of bronchiectasis. RESULTS: A total of 221 physicians participated in the survey. About half of them were Korean (50.2%), with the next most common nationalities being Japanese (23.1%), Taiwanese (13.6%), and Singaporean (7.7%). Only 18 (8.1%) responders had local guidelines for bronchiectasis. While 85 (38.5%) responders checked sputum acid-fast bacillus smear/culture about 1 to 3 times per year, only a small proportion of responders routinely performed a serum immunoglobulin test (36/221, 16.3%) or evaluated for allergic bronchopulmonary aspergillosis (41/221, 18.6%). Less than half (43.4%) of responders performed eradication treatment in patients with drug-sensitive Pseudomonas aeruginosa infection, mainly due to the limited availability of inhaled antibiotics (34.8%). In addition, 58.6% of responders considered physiotherapy such as airway clearance and pulmonary rehabilitation. CONCLUSION: Discrepancies might exist between guideline recommendations and practice for bronchiectasis management in Asian populations, partly due to the limited availability of treatment in each country. The development of local guidelines that consider the phenotypes and situation will help to standardize and improve the management of bronchiectasis.

Safety of early orthopedic surgery in patients with intermediate/low- or low-risk pulmonary embolism.

BACKGROUND: Preoperative pulmonary embolism (PE) is one of the comorbidities in patients with hip fracture. However, previous studies have not identified the optimal timing of surgery in these patients, who might require early surgery. This study aimed to investigate the safety and clinical feasibility of early surgery in patients with hip fracture and acute PE. METHODS: The medical records of 156 patients with hip fracture, who were suspected to have PE and underwent pulmonary computed tomography angiography at Asan Medical Center from January 2008 to December 2017, were retrospectively reviewed. After excluding patients who were diagnosed with PE during the postoperative period, the baseline characteristics and clinical course were compared between patients preoperatively diagnosed with PE (PE group) and patients without PE during the hospital stay (non-PE group). Adverse outcomes were evaluated during 3 months postoperatively. RESULTS: The baseline characteristics were not different between the PE group (n=90) and the non-PE group (n=50). All patients in the PE group were classified as having an intermediate/low or low risk according to the European Society of Cardiology guidelines and underwent surgery within 30 days after the PE diagnosis (median duration: 2 days). None of the patients in both groups developed symptomatic venous thromboembolism (VTE) during the follow-up. Moreover, there were no statistically significant differences in major bleeding, clinically relevant nonmajor (CRNM) bleeding, transfusion amount, bleeding site, and length of hospital stay between the PE and non-PE groups. CONCLUSIONS: Our results suggest that early surgery might be a reasonable treatment option in patients with hip fracture and acute PE.

Clinical Utility of Quantitative CT Analysis for Fissure Completeness in Bronchoscopic Lung Volume Reduction: Comparison between CT and Chartis™.

OBJECTIVE: The absence of collateral ventilation (CV) is crucial for effective bronchoscopic lung volume reduction (BLVR) with an endobronchial valve. Here, we assessed whether CT can predict the Chartis™ results. MATERIALS AND METHODS: This study included 69 patients (mean age: 70.9 ± 6.6 years; 66 [95.7%] males) who had undergone CT to assess BLVR eligibility. The Chartis™ system (Pulmonox Inc.) was used to check CV. Experienced thoracic radiologists independently determined the completeness of fissures on volumetric CT images. RESULTS: The comparison between the visual and quantitative analyses revealed that 5% defect criterion showed good agreement. The Chartis™ assessment was performed for 129 lobes; 11 (19.6%) of 56 lobes with complete fissures on CT showed positive CV, while this rate was significantly higher (40 of 49 lobes, i.e., 81.6%) for lobes with incomplete fissures. The size of the fissure defect did not affect the rate of CV. Of the patients who underwent BLVR, 22 of 24 patients (91.7%) with complete fissures and three of four patients with incomplete fissures (75%) achieved target lobe volume reduction (TLVR). CONCLUSION: The quantitative analysis of fissure shows that incomplete fissures increased the probability of CV on Chartis™, while the defect size did not affect the overall rates. TLVR could be achieved even in some patients with relatively large fissure defect, if they showed negative CV on Chartis™.

Clinical Phenotypes, Comorbidities, and Exacerbations according to Serum 25-OH Vitamin D and Plasma Fibrinogen Levels in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Although vitamin D deficiency is prevalent in patients with chronic obstructive pulmonary disease (COPD), the influence of vitamin D deficiency on COPD has not been fully established. Moreover, the inflammation process is associated with vitamin D deficiency in the general population. Therefore, this study aimed to determine whether clinical phenotypes, comorbidities, and exacerbation rates are affected by the level of plasma fibrinogen, well studied by an inflammatory marker in COPD patients, and 25-hydroxy (25-OH) vitamin D. METHODS: This retrospective study analyzed patients with COPD whose inflammatory marker levels, especially plasma fibrinogen and 25-OH vitamin D levels, had been examined. A correlation analysis was conducted for inflammatory markers and 25-OH vitamin D. Clinical characteristics, comorbidities and exacerbation rates were compared among four groups based on plasma fibrinogen concentrations (threshold, 350 mg/dL) and 25-OH vitamin D levels (threshold, 20 ng/mL). RESULTS: Among 611 patients with COPD, 236 were included in the study. The levels of inflammatory markers had no statistical correlation with the serum 25-OH vitamin D levels. The four groups showed no statistically significant differences in age, sex, smoking history, inhaler use, and severity of comorbidities. Patients with high plasma fibrinogen concentrations and low 25-OH vitamin D levels had lower lung function, higher severity index, and higher annual rate of severe exacerbations 12 months before (0.23/year) and after (0.41/year) the measurement of 25-OH vitamin D levels than did the other patients. CONCLUSION: Our findings suggested an interaction between vitamin D deficiency and COPD. The measurement of plasma fibrinogen concentrations could help identify a severe phenotypic group among patients with vitamin D deficiency.

A Retrospective Study on Efficacy and Safety of Rivaroxaban and Dalteparin for Long-Term Treatment of Venous Thromboembolism in Patients with Lung Cancer.

BACKGROUND: Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear. OBJECTIVES: We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer. METHODS: A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality. RESULTS: The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595-2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624-1.196, p = 0.337). CONCLUSIONS: There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.

Rivaroxaban versus Low-Molecular-Weight Heparin for Venous Thromboembolism in Gastrointestinal and Pancreatobiliary Cancer.

BACKGROUND: Low-molecular-weight heparin (LMWH) is the standard treatment for venous thromboembolism (VTE) in patients with active cancer. However, use of factor Xa inhibitors, such as rivaroxaban, is increasing on the basis of limited clinical evidence. The present single-center study compared the incidence of bleeding and other treatment outcomes in gastrointestinal and pancreatobiliary cancer (GI tract cancer) patients administered rivaroxaban or LMWH for the treatment of VTE. METHODS: Retrospective data from 281 GI tract cancer patients who were treated for VTE with rivaroxaban (n = 78) or LMWH (n = 203) between 1 January 2012 and 31 December 2016, were analyzed. Primary end-point was the incidence of major and clinically relevant bleeding. Secondary outcomes included the incidence of recurrent VTE and mortality. RESULTS: Clinically relevant bleeding occurred in 19 patients (24.4%) in the rivaroxaban group and 31 (15.3%) in the LMWH group (P = 0.074). No inter-group difference was observed for rate of VTE recurrence (3.8% with rivaroxaban vs. 3.9% with LMWH; P > 0.999) or incidence of major bleeding (5.1% with rivaroxaban vs. 8.9% with LMWH; P = 0.296). Multivariate Cox proportional hazards analysis for age, cancer type, metastasis, history of chemotherapy or recent surgery, and Eastern Cooperative Oncology Group performance status revealed a 1.904-fold higher risk of bleeding with rivaroxaban than LMWH (1.031-3.516; P = 0.040). No significant inter-group difference was found in terms of hazard ratio for all-cause mortality. CONCLUSION: Compared to LMWH, rivaroxaban was associated with a higher incidence of clinically relevant bleeding in GI tract cancer patients presenting with VTE.

The natural history of non-cavitary nodular bronchiectatic Mycobacterium avium complex lung disease.

PURPOSE: We aimed to investigate the natural history of non-cavitary nodular bronchiectatic (NC-NB) Mycobacterium avium complex (MAC) lung disease (LD). METHODS: Among all patients diagnosed with NC-NB MAC LD between March 2000 and December 2013, 551 patients who were followed until December 2017 were enrolled at a tertiary referral center in South Korea. Patients were subdivided into progressive and stationary groups, depending on whether treatment was initiated within 3 years after diagnosis. We investigated the proportion of patients not receiving anti-MAC treatment within 3 years after the diagnosis. The rate for spontaneous sputum conversion in the untreated group was also calculated. RESULTS: The mean age of 551 patients was 61.1 years. During the median 5.8 years of follow-up, 323 (58.6%) patients received treatment within 3 years (progressive group), whereas the remaining 228 (41.4%) patients did not (stationary group). Multivariate analysis revealed that age ≤ 60 years, a positive sputum smear, the presence of systemic symptoms, body mass index >18.5 kg/m2, and the involvement of ≥ 4 lobes were predictors of receiving treatment. Additionally, during the median of 5.0 years follow-up, spontaneous sputum conversion occurred in 52.2% of patients who did not receive treatment. CONCLUSIONS: Among patients diagnosed with NC-NB MAC LD, approximately 40% did not receive antibiotic treatment within 3 years of diagnosis. Moreover, about 50% of untreated patients experienced spontaneous sputum conversion.

Bronchial Thermoplasty in Patients with Severe Uncontrolled Asthma: First Korean Cases.

Bronchial thermoplasty is a nonpharmacological treatment for severe asthma that delivers thermal energy to the bronchial walls and reduces hypertrophied smooth muscle mass. Previous studies have shown its efficacy and safety, resulting in approval from the Food and Drug Administration in 2010. In Korea, the first bronchial thermoplasty was carried out in 2014; 4 patients have undergone the procedure so far. This case series presents the medical history and treatment outcomes of these 4 patients. All patients presented with uncontrolled asthma despite optimal medical treatment. Bronchial thermoplasty was performed at the right lower lobe, left lower lobe, and both upper lobes in order at 3-week intervals. All procedures were performed under general anesthesia. Two patients had significant decreases in exacerbations and required a lower dose of inhaled corticosteroids after the procedure. One patient had slightly fewer exacerbations but failed to reduce the use of systemic corticosteroids. One patient had no change in symptoms. One limitation of bronchial thermoplasty is the difficulty of predicting clinical responders. However, since more therapeutic options are needed in the management of severe asthma, especially T2-low asthma, discussion with experts about the feasibility and necessity of bronchial thermoplasty will ensure the best possible care.

Serial blood eosinophils and clinical outcome in patients with chronic obstructive pulmonary disease.

BACKGROUND: Blood eosinophils have been suggested as a potential biomarker in chronic obstructive pulmonary disease (COPD), and their stability over time has been investigated in a few studies. However, the association between the stability of blood eosinophils and long-term clinical outcomes in COPD patients has yet to be fully elucidated. This study aimed to evaluate the stability of blood eosinophils and its association with clinical outcomes in COPD patients. METHODS: In total, 299 COPD patients from the Korean Obstructive Lung Disease cohort with at least two blood eosinophil measurements were included. Patients were stratified according to a cut-off of 300 cells/µL, and the association between eosinophil changes and all-cause mortality was analysed. The annual decline in forced expiratory volume in 1 s (FEV1), serial changes in St George's Respiratory Questionnaire score (SGRQ), and exacerbations during follow-up were compared among eosinophil groups. RESULTS: Patients were stratified into three groups according to the blood eosinophil cut-off: persistently < 300 cells/µL (PL; n = 175), variable (V; n = 68), and persistently ≥300 cells/µL (PH; n = 56). There were no significant differences in baseline characteristics (age, sex, smoking, body mass index, use of inhaled corticosteroids, exacerbations in the previous year, FEV1 (L or % predicted), or emphysema score) among the groups. During a median follow-up of 6.0 years, the PH group had a better survival rate than the PL group (adjusted mortality rate ratio, 0.29; 95% confidence interval, 0.09-0.97; P = 0.045). The PH group also showed improved symptoms and impact domains of SGRQ score compared to the PL group. No difference was found in annual FEV1 decline or exacerbations during follow-up among the groups. CONCLUSIONS: Patients with persistently high blood eosinophils had a better survival rate than those with persistently low blood eosinophils. Serial follow-up of blood eosinophils could help to predict outcomes in COPD patients.

Alternative definitions of chronic bronchitis and their correlation with CT parameters.

Introduction: Phenotyping of chronic bronchitis (CB) using COPD assessment tool (CAT) scores and St George's Respiratory Questionnaire (SGRQ) has rarely been attempted. The present study defined CB using CAT 1 and 2 scores and the questions on the severity of cough and sputum from the SGRQ. Furthermore, the predictability of CT parameters was also assessed for each CB definition. Materials and methods: Patients enrolled in the Korean Obstructive Lung Disease study from June 2005 to October 2015 were evaluated for this study. The patients were spirometrically diagnosed with COPD and had a smoking history of >10 pack-years. Volumetric CT scans were performed for each patient upon enrollment in the cohort. Two definitions of CB using CAT 1/2 scores and SGRQ questions were used to phenotype CB among the study patients. Receiver operating characteristic curve analysis was performed to estimate the predictability of CT parameters for the CB phenotypes. Results: Using CAT 1/2 scores, 57 of 279 (20.4%) patients had CB, and 178 of 573 (31.1%) had CB when the SGRQ questions were used to phenotype it. Total CAT and SGRQ scores were significantly higher in the CB group than those in the non-CB group for both definitions of CB. Forced expiratory volume in 1 second was lower for both CAT-defined and SGRQ-defined CB than that in the non-CB group. Mean wall thickness was significantly higher for both CB groups than in the non-CB group. Expiratory lung volume was higher and mean lung density was significantly lower for the SGRQ-defined CB group than non-CB group. Conclusion: The 2 CB definitions using CAT scores and the SGRQ questions correlated with associated CT airway parameters. SGRQ-defined CB better reflected the accompaniment of small airway obstruction when compared with CAT-defined CB.

Effect of post-filter anticoagulation on mortality in patients with cancer-associated pulmonary embolism.

BACKGROUND: Malignancy is associated with an increased risk of venous thromboembolism. Inferior vena cava filters are a viable alternative when anticoagulation is infeasible because of the risk of bleeding. Although the current guidelines recommend that all patients with a vena cava filter be treated with anticoagulation treatment when the risk of bleeding is reduced, studies concerning the role of concomitant anticoagulation after vena cava filter insertion in high-risk patients are scarce. Since many cancer patients suffer from a high risk of hemorrhagic complications, we aimed to determine the effect of post-filter anticoagulation on mortality in patients with a malignant solid tumor. METHODS: A retrospective cohort study of patients with pulmonary embolism was performed between January 2010 and May 2016. Patients with a solid tumor and vena cava filter inserted because of pulmonary embolism were included. Using Cox proportional hazards model, the prognostic effect of clinical variables was analyzed. RESULTS: A total of 180 patients were analyzed, with 143 patients receiving and 37 patients not receiving post-filter anticoagulation treatment. Mortality was not significantly different between the two groups. The presence of metastatic cancer and that of pancreatobiliary cancer were significant risk factors for mortality. However, post-filter anticoagulation did not show significant effect on mortality regardless of the stage of cancer. CONCLUSION: In patients with cancer-associated pulmonary embolism, the effect of post-filter anticoagulation on mortality may not be critical, especially in patients with a short life expectancy.

Prognostic significance of nuclear factor of activated T-cells 5 expression in non-small cell lung cancer patients who underwent surgical resection.

BACKGROUND: Nuclear factor of activated T-cells 5 (NFAT5) is known to be correlated with migration or invasion of tumor cells based on previous in vitro studies. The aim of this study was to analyze the relationship between NFAT5 expression and clinical prognosis in non-small cell lung cancer (NSCLC) patients who underwent surgical resection. MATERIALS AND METHODS: A total of 92 NSCLC patients who underwent surgical resection were enrolled. The tissue microarray core was obtained from surgically resected tumor specimens. NFAT5 expression was evaluated by immunohistochemistry. Relationships of NFAT5 expression with disease recurrence, overall survival, and disease-free survival (DFS) were analyzed. RESULTS: The mean age of 92 patients was 63.7 y. The median follow-up duration was 63.3 mo. Fifty-one (55%) patients exhibited positive expression of NFAT5. Disease recurrence in the NFAT5-positive group was significantly (P = 0.022) higher than that in the NFAT5-negative group. NFAT5-positive expression (odds ratio: 2.632, 95% confidence interval: 1.071-6.465, P = 0.035) and pathologic N stage (N1-2 versus N0; odds ratio: 3.174, 95% confidence interval: 1.241-8.123, P = 0.016) were independent and significant risk factors for disease recurrence. DFS of the NFAT5-positive group was significantly worse than that of the NFAT5-negative group (89.7 versus 48.7 mo, P = 0.011). A multivariate analysis identified NFAT5 expression (P < 0.029) as a significant independent risk factor for DFS of patients with postoperative pathologic T and N stages (P < 0.001 and P = 0.017, respectively). CONCLUSIONS: NFAT5 expression is a useful prognostic biomarker for NSCLC patients who underwent surgical resection.

Favorable longitudinal change of lung function in patients with asthma-COPD overlap from a COPD cohort.

BACKGROUND: The recognition of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct phenotype of COPD or asthma has increased. Although ACO has worse clinical features than non-ACO COPD, limited information is available on long-term outcomes of lung function decline for ACO and non-ACO COPD. METHODS: COPD patients with at least 3 years of follow-up were selected from the Korean Obstructive Lung Disease cohort. ACO was defined based on 3 major criteria: 1) airflow limitation in individuals 40 years of age and older, 2) ≥10 pack-years of smoking history, and 3) a history of asthma or bronchodilator response of > 400 mL in forced expiratory volume in 1 s (FEV1) at baseline; and at least 1 minor criterion: 1) history of atopy or allergic rhinitis, 2) two separated bronchodilator responses of ≥12% and 200 mL in FEV1, or 3) peripheral blood eosinophils ≥300 cells/µL. Lung function decline was compared using a linear mixed effects model for longitudinal data with random intercept and random slope. RESULTS: Among 239 patients, 47 were diagnosed with ACO (19.7%). During the follow-up period, change in smoking status, use of inhaled corticosteroids (ICS) and long-acting ß2-agonists or ICS and at least 2 exacerbations per year were similar between patients with non-ACO COPD and ACO. Over a median follow-up duration of 5.8 years, patients with non-ACO COPD experienced a faster annual decline in pre-bronchodilator FEV1 than patients with ACO (- 29.3 ml/year vs. -13.9 ml/year, P = 0.042), which was persistent after adjustment for confounders affecting lung function decline. CONCLUSION: Patients with ACO showed favorable longitudinal changes in lung function compared to COPD patients over a median follow-up of 5.8 years.