Search

Pei-Ju Chen,1 Kuang-Yao Yang,2,3 Wann-Cherng Perng,4 Kuan-Chia Lin,5,6 Kwua-Yun Wang7 1School of Nursing, National Yang-Ming University, Taipei, Taiwan, Republic of China; 2Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; 3Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; 4Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 5Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan, Republic of China; 6Communty Medicine Research Center, Preventive Medicine Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China; 7Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China Purpose: Chronic obstructive pulmonary disease (COPD) impacts health-related quality of life in men more than in women. In patients with dyspnea, frailty is more likely to develop and aggravate disability. Despite this, few studies have addressed frailty in men with COPD. The present study investigated the effects of dyspnea and its related factors on frailty in men with COPD. Patients and methods: This cross-sectional observational study selected 125 participants by voluntary sampling at the thoracic outpatient clinics of two medical centers in Taiwan. The modified Medical Research Council questionnaire was used as the basis to classify dyspnea. Data were collected using questionnaires and analyzed using IBM SPSS Statistics for Windows, version 24.0 (IBM Corporation., Armonk, NY, USA). Results: There were 85.90% and 26.70% patients with COPD assessed in the unfit stage among the dyspnea and non-dyspnea groups, respectively. Additionally, the number of medication use and the COPD Assessment Test (CAT) scores were correlated with the period from fitness to unfitness among the dyspnea group and non-dyspnea group. Conclusion: COPD with dyspnea was more common in the unfit stages. The total number of medication use and CAT scores were significantly related to frailty. Keywords: chronic obstructive, dyspnea, frail elderly, men, pulmonary disease

The 5-year survival is poor for stage IV non-small cell lung cancer (NSCLC). Recently, cell immunotherapy has emerged as a new treatment strategy. This study aimed to evaluate the efficacy and safety of Immune killer cells (IKC) in patients with stage IV NSCLC after the failure of prior chemotherapy. This study enrolled 26 patients with stage IV NSCLC who failed at least two lines of chemotherapy with or without targeted therapy. The IKC was given alone weekly for 24 weeks. The primary endpoint was progression-free survival (PFS). Secondary outcomes included overall survival (OS), pain intensity, quality of life (QOL), and safety. The median PFS for the intent-to-treat (ITT) population (i.e., all enrolled patients) was 3.8 month. In the per-protocol (PP) population (i.e., patients receiving > 12 IKC infusions), the median PFS was 5.6 months. Moreover, the ITT population showed a 1-year survival rate of 60.0%, while that for the PP population was 85.7%. Only 7 out of 200 AEs (3.5%) were related to the IKC infusion, and they were all rated as grade 1 in severity. The IKC infusion was well tolerated. This novel immunotherapy prolonged the PFS and improved the survival compared with historical data. It might be a potential treatment strategy for stage IV NSCLC patient who failed prior chemotherapy.ClinicalTrials.gov identifier: NCT03499834., (© 2024. The Author(s).)

The echogenic swirling pattern has a role in predicting malignant pleural effusion (MPE). However, its predictive ability is suboptimal, and its clinical utility remains to be defined. The aim of this study was to assess the diagnostic potential of the echogenic swirling pattern combined with pleural carcinoembryonic antigen (CEA) and routine laboratory tests of pleural effusion in MPE. The 80 consecutive patients with underlying malignancy and pleural effusions were recruited. All patients underwent one diagnostic thoracentesis with a cytologic examination of pleural fluid. Our study showed that the sensitivity of echogenic swirling patterns in MPE diagnosis was 67.7%, specificity was 72.2%, positive predictive value (PPV) was 89.4%, and negative predictive value (NPV) was 39.4%. Both CEA and lactate dehydrogenase (LDH) had acceptable sensitivity (71.0% and 60.7%) and specificity (72.2% and 77.8%). Combining the echogenic swirling pattern, pleural CEA, and pleural LDH, the highest sensitivity (95.2%) with a good PPV (86.8) was reached. In this clinical study, we found that combining the echogenic swirling pattern, pleural CEA, and pleural LDH had a higher sensitivity and a high positive predictive value for the diagnosis of MPE. This combination is a potentially suitable method for MPE screening in cancer patients with pleural effusions., (© 2022. The Author(s).)

Background: Corticosteroid treatment has been widely used in the treatment of septic shock, influenza, and ARDS, although some previous studies discourage its use in severe influenza patients. This multicenter retrospective cohort study conducted in the intensive care units (ICUs) of eight medical centers across Taiwan aims to determine the real-world status of corticosteroid treatment in patients with influenza-associated acute respiratory distress syndrome (ARDS) and its impact on clinical outcomes. Between October 2015 and March 2016, consecutive ICU patients with virology-proven influenza infections who fulfilled ARDS and received invasive mechanical ventilation were enrolled. The impact of early corticosteroid treatment (≥ 200 mg hydrocortisone equivalent dose within 3 days after ICU admission, determined by a sensitivity analysis) on hospital mortality (the primary outcome) was assessed by multivariable logistic regression analysis, and further confirmed in a propensity score-matched cohort., Results: Among the 241 patients with influenza-associated ARDS, 85 (35.3%) patients receiving early corticosteroid treatment had similar baseline characteristics, but a significantly higher hospital mortality rate than those without early corticosteroid treatment [43.5% (37/85) vs. 19.2% (30/156), p < 0.001]. Early corticosteroid treatment was independently associated with increased hospital mortality in overall patients [adjusted odds ratio (95% CI) = 5.02 (2.39-10.54), p < 0.001] and in all subgroups. Earlier treatment and higher dosing were associated with higher hospital mortality. Early corticosteroid treatment was associated with a significantly increased odds of subsequent bacteremia [adjusted odds ratio (95% CI) = 2.37 (1.01-5.56)]. The analyses using a propensity score-matched cohort showed consistent results., Conclusions: Early corticosteroid treatment was associated with a significantly increased hospital mortality in adult patients with influenza-associated ARDS. Earlier treatment and higher dosing were associated with higher hospital mortality. Clinicians should be cautious while using corticosteroid treatment in this patient group.

Objectives: Current mortality prediction models used in the intensive care unit (ICU) have a limited role for specific diseases such as influenza, and we aimed to establish an explainable machine learning (ML) model for predicting mortality in critically ill influenza patients using a real-world severe influenza data set., Study Design: A cross-sectional retrospective multicentre study in Taiwan SETTING: Eight medical centres in Taiwan., Participants: A total of 336 patients requiring ICU-admission for virology-proven influenza at eight hospitals during an influenza epidemic between October 2015 and March 2016., Primary and Secondary Outcome Measures: We employed extreme gradient boosting (XGBoost) to establish the prediction model, compared the performance with logistic regression (LR) and random forest (RF), demonstrated the feature importance categorised by clinical domains, and used SHapley Additive exPlanations (SHAP) for visualised interpretation., Results: The data set contained 76 features of the 336 patients with severe influenza. The severity was apparently high, as shown by the high Acute Physiology and Chronic Health Evaluation II score (22, 17 to 29) and pneumonia severity index score (118, 88 to 151). XGBoost model (area under the curve (AUC): 0.842; 95% CI 0.749 to 0.928) outperformed RF (AUC: 0.809; 95% CI 0.629 to 0.891) and LR (AUC: 0.701; 95% CI 0.573 to 0.825) for predicting 30-day mortality. To give clinicians an intuitive understanding of feature exploitation, we stratified features by the clinical domain. The cumulative feature importance in the fluid balance domain, ventilation domain, laboratory data domain, demographic and symptom domain, management domain and severity score domain was 0.253, 0.113, 0.177, 0.140, 0.152 and 0.165, respectively. We further used SHAP plots to illustrate associations between features and 30-day mortality in critically ill influenza patients., Conclusions: We used a real-world data set and applied an ML approach, mainly XGBoost, to establish a practical and explainable mortality prediction model in critically ill influenza patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with severe influenza-related acute respiratory distress syndrome (ARDS) have high morbidity and mortality. Moreover, nosocomial lower respiratory tract infection (NLRTI) complicates their clinical management and possibly worsens their outcomes. This study aimed to explore the clinical features and impact of NLRTI in patients with severe influenza-related ARDS., Methods: This was an institutional review board approved, retrospective, observational study conducted in eight medical centers in Taiwan. From January 1 to March 31 in 2016, subjects were enrolled from intensive care units (ICUs) with virology-proven influenza pneumonia, while all of those patients with ARDS requiring invasive mechanical ventilation and without bacterial community-acquired pneumonia (CAP) were analyzed. Baseline characteristics, critical-illness data and clinical outcomes were recorded., Results: Among the 316 screened patients with severe influenza pneumonia, 250 with acute respiratory failure requiring intubation met the criteria of ARDS, without having bacterial CAP. Among them, 72 patients developed NLRTI. The independent risk factors for NLRTI included immunosuppressant use before influenza infection [odds ratio (OR), 5.669; 95% confidence interval (CI), 1.770-18.154], extracorporeal membrane oxygenation (ECMO) use after ARDS (OR, 2.440; 95% CI, 1.214-4.904) and larger corticosteroid dosage after ARDS (OR, 1.209; 95% CI, 1.038-1.407). Patients with NLRTI had higher in-hospital mortality and longer ICU stay, hospitalization and duration on mechanical ventilation., Conclusion: We found that immunosuppressant use before influenza infection, ECMO use, and larger steroid dosage after ARDS independently predict NLRTI in influenza-related ARDS. Moreover, NLRTI results in poorer outcomes in patients with severe influenza. The reviews of this paper are available via the supplemental material section.

Various animal studies have shown beneficial effects of hypercapnia in lung injury. However, in patients with acute respiratory distress syndrome (ARDS), there is controversial information regarding the effect of hypercapnia on outcomes. The duration of carbon dioxide inhalation may be the key to the protective effect of hypercapnia. We investigated the effect of pre-treatment with inhaled carbon dioxide on lipopolysaccharide (LPS)-induced lung injury in mice. C57BL/6 mice were randomly divided into a control group or an LPS group. Each LPS group received intratracheal LPS (2 mg/kg); the LPS groups were exposed to hypercapnia (5% carbon dioxide) for 10 min or 60 min before LPS. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. LPS significantly increased the ratio of lung weight to body weight; concentrations of BALF protein, tumor necrosis factor-α, and CXCL2; protein carbonyls; neutrophil infiltration; and lung injury score. LPS induced the degradation of the inhibitor of nuclear factor-κB-α (IκB-α) and nuclear translocation of NF-κB. LPS increased the surface protein expression of toll-like receptor 4 (TLR4). Pre-treatment with inhaled carbon dioxide for 10 min, but not for 60 min, inhibited LPS-induced pulmonary edema, inflammation, oxidative stress, lung injury, and TLR4 surface expression, and, accordingly, reduced NF-κB signaling. In summary, our data demonstrated that pre-treatment with 10-min carbon dioxide inhalation can ameliorate LPS-induced lung injury. The protective effect may be associated with down-regulation of the surface expression of TLR4 in the lungs.

Background: Nemonoxacin, a novel nonfluorinated quinolone, has broad-spectrum antibacterial activity, including activity against antibiotic-resistant strains, and was developed for treating community-acquired pneumonia (CAP). This report provides an integrated safety summary of oral nemonoxacin from two phase II and one phase III clinical studies., Methods: Patients with mild CAP were randomized for treatment with nemonoxacin 500 mg (NEMO-500MG), nemonoxacin 750 mg (NEMO-750MG), or levofloxacin 500 mg (LEVO), orally, once daily, for 7-10 days. Hematological, gastrointestinal, and hepatic disorders; electrocardiography abnormalities; and reported quinolone-associated clinical concerns were included in this analysis., Results: A total of 520, 155, and 320 subjects were assigned to receive NEMO-500MG, NEMO-750MG, and LEVO, respectively. The incidence of adverse events (AEs) was the highest (54.8%) in the NEMO-750MG group (NEMO-500MG, 36.9%; NEMO-750MG, 54.8%; LEVO, 39.7%) and that of drug-related AEs was comparable between the three groups (NEMO-500MG, 22.9%; NEMO-750MG, 31.0%; LEVO, 22.5%). The majority (>80%) of the patients showed mild drug-related AEs and the distribution based on severity was similar between the groups. The most commonly reported drug-related AEs included neutropenia (NEMO-500MG, 2.5%; NEMO-750MG, 8.4%; LEVO, 4.4%), nausea (NEMO-500MG, 2.5%; NEMO-750MG, 7.1%; LEVO, 2.5%), leukopenia (NEMO-500MG, 2.3%; NEMO-750MG, 4.5%; LEVO, 3.1%), and increased alanine aminotransferase level (NEMO-500MG, 4.4%; NEMO-750MG, 0%; LEVO, 2.5%)., Conclusion: Nemonoxacin was well tolerated and no clinically significant safety concerns were identified, suggesting that it possesses a desirable safety and tolerability profile similar to that of levofloxacin, and may be a suitable alternative to fluoroquinolones for treating patients with CAP., (Copyright © 2019. Published by Elsevier B.V.)

Background and Objective: Tuberculosis (TB) and sarcoidosis are both granulomatous diseases with potential interassociations. However, much uncertainty remains; thus, the present study aimed to clarify the association between these diseases., Methods: We established two cohorts in this retrospective longitudinal cohort study using data obtained from the Taiwan National Health Insurance Database from 2000 to 2015. One cohort, which comprised 31 221 patients with TB and 62 442 age-, sex- and index year-matched controls, was used to analyse the risk of sarcoidosis; the other cohort comprised 2442 patients with sarcoidosis and 9688 controls and was used to assess the risk of TB. A Cox proportional hazards model adjusted for potential confounders was used in each cohort., Results: Patients with TB showed an 8.09-fold higher risk of developing sarcoidosis than non-TB subjects (95% CI = 3.66-17.90), whereas patients with sarcoidosis showed a 1.85-fold higher risk of developing TB than non-sarcoidosis subjects (95% CI = 1.36-2.50). The TB subtype analysis revealed the highest risk of developing sarcoidosis in patients with extrapulmonary TB, and the highest risk of developing extrapulmonary TB was observed in patients with sarcoidosis compared with non-sarcoidosis subjects. Patients with TB showed a higher risk of developing sarcoidosis throughout the follow-up period, but patients with sarcoidosis only showed a higher risk of developing TB within the first year., Conclusion: TB is a risk factor for developing sarcoidosis. The results of this bidirectional cohort study also highlight the clinical difficulty of diagnosing sarcoidosis and TB., (© 2019 Asian Pacific Society of Respirology.)

Backgrounds: Severe influenza infection causes substantial morbidity and mortality worldwide and remains an important threat to global health. This study addressed factors related to treatment outcomes in subjects of complicated influenza infection with acute respiratory distress syndrome (ARDS) during the Taiwan epidemic in the Spring of 2016., Methods: This is a retrospective study conducted by Taiwan Severe Influenza Research Consortium (TSIRC), including eight tertiary referral medical centers. Patients with virology-proven influenza infection admitted to intensive care unit (ICU) between January and March 2016 were included for analysis., Results: We identified 263 patients with complicated influenza infection who fulfilled ARDS criteria; the mean age was 59.8 ± 14.6 (years), and 66.1% (166/263) were male. Type A influenza (77.9%, 205/263) virus was the main pathogen during this epidemic. The 30-day mortality rate was 23.2% (61/263). The mean tidal volume (V T ) in the first three days after intubation was greater than 8 mL/kg of predicted body weight (PBW). Patients whose first measured V T was >8 mL/kg PBW had an increased 30-day mortality (p = 0.04, log-rank test). In a multivariate Cox proportional hazard regression model, an increase of 1 mL/kg PBW of first V T was associated with 26.1% increase in 30-day mortality (adjusted hazard ratio 1.261, 95% confidence interval [CI] 1.072-1.484, p < 0.01)., Conclusion: First tidal volume, shortly after intubation, greater than 8 mL/kg PBW is an independent risk factor for mortality in complicated influenza infection with ARDS. Timely recognition of ARDS with strict adherence to protective ventilation strategy of lowering V T may be important in reducing mortality., (Copyright © 2018. Published by Elsevier B.V.)

Background: The study was designed to compare the efficacy and tolerability of a fixed combination of extra-fine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol in Taiwanese asthmatic patients., Methods: This was a phase III, multicentre, randomized, two-arm parallel groups, controlled study. Patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 mcg plus formoterol 6 mcg (BDP/F) or fluticasone 125 mcg plus salmeterol 25 mcg (FP/S), both delivered 2 inhalations twice daily. The efficacy and tolerability of these two combinations were compared., Results: Among the 253 randomized subjects, 244 patients were evaluable (119 in the BDP/F group and 125 in the FP/S group). A significant improvement from baseline to the end of treatment period was observed in both BDP/F and FP/S groups in forced expiratory volume in the first second (FEV 1 ), forced vital capacity (FVC), morning and evening peak expiratory flow (PEF), Asthma Control Test (ACT) score and the use of rescue medication. FVC increase from pre-dose was significant after 5 min post inhalation in the BDP/F group only, while statistically significant within group improvement was not achieved until 30 min post inhalation in the FP/S group., Conclusion: The BDP/F combination is comparable in efficacy and tolerability to FP/S combination in Taiwanese asthmatic patients, with the advantage of rapid onset of improvement of FVC, consistent with the faster improvement of pulmonary hyperinflation with BDP/F., (Copyright © 2017. Published by Elsevier B.V.)

Background: Patients with influenza complicated with pneumonia are at high risk of rapid progression to acute respiratory distress syndrome (ARDS). Prone positioning with longer duration and lung-protective strategies might reduce the mortality level in ARDS. The aim of this study is to investigate the survival predictors of prone positioning in patients with ARDS caused by influenza pneumonia., Methods: This retrospective study was conducted by eight tertiary referral centers in Taiwan. From January 1 to March 31 in 2016, all of the patients in intensive care units with virology-proven influenza pneumonia were collected, while all of those patients with ARDS and receiving prone positioning were enrolled. Demographic data, laboratory examinations, management records, ventilator settings and clinical outcomes were collected for analysis., Results: During the study period, 336 patients with severe influenza pneumonia were screened and 263 patients met the diagnosis of ARDS. Totally, 65 patients receiving prone positioning were included for analysis. The 60-day survivors had lower Acute Physiology and Chronic Health Evaluation (APACHE) II score, pneumonia severity index (PSI), creatinine level and lower rate of receiving renal replacement therapy than non-survivors (22.4 ± 8.5 vs. 29.2 ± 7.4, p = 0.003; 106.6 ± 40.9 vs. 135.3 ± 48.6, p = 0.019; 1.2 ± 0.9 mg/dL vs. 3.1 ± 3.6 mg/dL, p = 0.040; and 4% vs. 42%, p < 0.005). Multivariate Cox regression analysis identified PSI (hazard ratio 1.020, 95% confidence interval 1.009-1.032; p < 0.001), renal replacement therapy (hazard ratio 6.248, 95% confidence interval 2.245-17.389; p < 0.001), and increase in dynamic driving pressure (hazard ratio 1.372, 95% confidence interval 1.095-1.718; p = 0.006) which were independent predictors associated with 60-day mortality., Conclusions: In the present study, in evaluating the effect of prone positioning in patients with influenza pneumonia-related ARDS, pneumonia severity index, renal replacement therapy and increase in dynamic driving pressure were associated with 60-day mortality in patients with influenza pneumonia-related ARDS receiving prone positioning.

Background: Fluid balance is a fundamental management of patients with sepsis, and this study aimed to investigate the impact of cumulative fluid balance on critically ill patients with influenza admitted to an intensive care unit (ICU)., Methods: This multicenter retrospective cohort study was conducted by the Taiwan Severe Influenza Research Consortium (TSIRC) which includes eight medical centers. Patients with virology-proven influenza infection admitted to ICUs between October 2015 and March 2016 were included for analysis., Results: A total of 296 patients were enrolled (mean age: 61.4±15.6 years; 62.8% men), and 92.2% (273/296) of them required mechanical ventilation. In the survivors, the daily fluid balance was positive from day 1 to day 3, and then gradually became negative from day 4 to day 7, whereas daily fluid balance was continuously positive in the non-survivors. Using the cumulative fluid balance from day 1-4 as a cut-off point, we found that a negative cumulative day 1-4 fluid balance was associated with a lower 30-day mortality rate (log-rank test, P = 0.003). To evaluate the impact of shock on this association, we divided the patients into shock and non-shock groups. The positive correlation between negative day 1-4 fluid balance and mortality was significant in the non-shock group (log-rank test, P = 0.008), but not in the shock group (log-rank test, P = 0.396). In a multivariate Cox proportional hazard regression model adjusted for age, sex, cerebrovascular disease, and PaO2/FiO2, day 1-4 fluid balance was independently associated with a higher 30-day mortality rate (aHR 1.088, 95% CI: 1.007-1.174)., Conclusions: A negative day 1-4 cumulative fluid balance was associated with a lower mortality rate in critically ill patients with influenza. Our findings indicate the critical role of conservative fluid strategy in the management of patients with complicated influenza.

Eosinophilic granulomatosis with polyangiitis is a systemic vasculitis. It could affect respiratory system, kidney, and central nervous system frequently; however, all body organs could be involved. Asthma and eosinophilic pneumonia are predominant manifestations in respiratory system. Bronchoalveolar lavage or lung biopsy may be used for diagnosis, but endobronchial lesion is not considered as a manifestation of eosinophilic granulomatosis with polyangiitis. Here we present a case of eosinophilic granulomatosis with polyangiitis with unusual endobronchial lesion which was confirmed by endobronchial biopsy.

Background/purpose: Lung cancer is a heterogeneous disease with varied outcomes. Molecular markers are eagerly investigated to predict a patient's treatment response or outcome. Previous studies used frozen biopsy tissues to identify crucial genes as prognostic markers. We explored the prognostic value of peripheral blood (PB) molecular signatures in patients with advanced non-small cell lung cancer (NSCLC)., Methods: Peripheral blood mononuclear cell (PBMC) fractions from patients with advanced NSCLC were applied for RNA extraction, cDNA synthesis, and real-time polymerase chain reaction (PCR) for the expression profiling of eight genes: DUSP6, MMD, CPEB4, RNF4, STAT2, NF1, IRF4, and ZNF264. Proportional hazard (PH) models were constructed to evaluate the association of the eight expressing genes and multiple clinical factors [e.g., sex, smoking status, and Charlson comorbidity index (CCI)] with overall survival., Results: One hundred and forty-one patients with advanced NSCLC were enrolled. They included 109 (77.30%) patients with adenocarcinoma, 12 (8.51%) patients with squamous cell carcinoma, and 20 (14.18%) patients with other pathological lung cancer types. A PH model containing two significant survival-associated genes, CPEB4 and IRF4, could help in predicting the overall survival of patients with advanced stage NSCLC [hazard ratio (HR) = 0.48, p < 0.0001). Adding multiple clinical factors further improved the prediction power of prognosis (HR = 0.33; p < 0.0001)., Conclusion: Molecular signatures in PB can stratify the prognosis in patients with advanced NSCLC. Further prospective, interventional clinical trials should be performed to test if gene profiling also predicts resistance to chemotherapy., (Copyright © 2016. Published by Elsevier B.V.)

Peripheral blood mononuclear cell (PBMC)-derived gene signatures were investigated for their potential use in the early detection of non-small cell lung cancer (NSCLC). In our study, 187 patients with NSCLC and 310 age- and gender-matched controls, and an independent set containing 29 patients for validation were included. Eight significant NSCLC-associated genes were identified, including DUSP6, EIF2S3, GRB2, MDM2, NF1, POLDIP2, RNF4, and WEE1. The logistic model containing these significant markers was able to distinguish subjects with NSCLC from controls with an excellent performance, 80.7% sensitivity, 90.6% specificity, and an area under the receiver operating characteristic curve (AUC) of 0.924. Repeated random sub-sampling for 100 times was used to validate the performance of classification training models with an average AUC of 0.92. Additional cross-validation using the independent set resulted in the sensitivity 75.86%. Furthermore, six age/gender-dependent genes: CPEB4, EIF2S3, GRB2, MCM4, RNF4, and STAT2 were identified using age and gender stratification approach. STAT2 and WEE1 were explored as stage-dependent using stage-stratified subpopulation. We conclude that these logistic models using different signatures for total and stratified samples are potential complementary tools for assessing the risk of NSCLC., Competing Interests: The authors declare that they have no potential conflict of interest relevant to this article reported. HJT reports being an employee of Advpharma. The sponsor did not have any role in designing the research and analyzing or commenting the results.

Good's syndrome is an acquired immunodeficiency state associated with thymoma and characterized by recurrent pulmonary infections. We describe a 67-year-old woman who presented with respiratory symptoms caused by concomitant disseminated cytomegalovirus infection and Pneumocystis jiroveci pneumonia 38 months after thymectomy for a thymoma. Immunologic analysis revealed hypogammaglobulinemia with absent B-cell population as demonstrated by flow cytometry, consistent with Good's syndrome. Following treatment with sulfamethoxazole/trimethoprim and ganciclovir, the patient improved with resolution of her respiratory symptoms. However, the patient subsequently experienced additional infections, necessitating additional subsequent hospital admissions. During the last admission, intravenous immunoglobulin (IVIG) replacement therapy was initiated and continued after discharge. Infection has been prevented for one year after beginning IVIG replacement therapy. This case reveals that in patients with combined humoral and cell-mediated immune deficiency, concomitant infection with different pathogens is not unusual, and immediate specific therapy is important. Periodic IVIG infusion, to maintain adequate Ig levels, is recommended., (Copyright © 2012. Published by Elsevier B.V.)

Introduction: Gastro-oesophageal reflux disease (GORD) is common among chronic obstructive pulmonary disease (COPD) patients and may have a deleterious effect on COPD prognosis. However, few studies have investigated whether GORD increases the risk of severe outcomes such as intensive care unit (ICU) admittance or mechanical ventilator use among COPD patients., Methods: Propensity score matching by age, sex, comorbidities and COPD severity was used to match the 1,210 COPD patients with GORD sourced in this study to 2,420 COPD patients without GORD. The Kaplan-Meier method was used to explore the incidence of ICU admittance and machine ventilation with the log rank test being used to test for differences. Cox regression analysis was used to explore the risk of ICU admittance and mechanical ventilation use for patients with and without GORD., Results: During the 12-month follow-up, GORD patients and non-GORD patients had 5.22 and 3.01 ICU admittances per 1000 person-months, and 4.34 and 2.41 mechanical ventilation uses per 1000 person-month, respectively. The log rank test revealed a difference in the incidence of ICU admittance and machine ventilation between the two cohorts. GORD was found to be an independent predicator of ICU admittance (adjusted hazard ratio (HRadj) 1.75, 95% confidence interval (CI) 1.28-2.38) and mechanical ventilation (HRadj 1.92, 95% CI 1.35-2.72)., Conclusion: This is the first investigation to detect a significantly higher incidence rate and independently increased risk of admission to an ICU and mechanical ventilation use among COPD patients who subsequently developed GORD during the first year following their GORD diagnosis than COPD patients who did not develop GORD.

Tracheomalacia can cause variable degrees of intrathoracic airway obstruction and is an easily overlooked cause of respiratory distress in adults. Here, we report a case of acute respiratory failure in which subglottic stenosis was accidentally identified during endotracheal intubation. Subsequent bronchoscopy and computed tomography of the thorax and neck revealed tracheal compression with tracheomalacia caused by a tortuous innominate artery and a kyphotic cervical spine. The patient underwent rigid bronchoscopy with metal stent implantation, and her symptoms were alleviated. These findings outline the importance of precise diagnosis and interventions for preventing recurrent life-threatening respiratory failure in such cases., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Because Taiwan has the fastest aging rate among developed countries, care for the elderly is becoming more prominent in the country. Primary family caregivers play an important role in patient health and health promotion behavior. Chronic obstructive pulmonary disease (COPD), an age-related disease, is a major public health problem with high morbidity and mortality and can be a long-term burden for family members; however, little attention has been given to the differences in COPD care between elder caregivers and other caregivers. This study aimed to investigate the differences between elder family caregivers and non-elder family caregivers caring for COPD patients in Taiwan, including caring behavior, caregiver response, and caring knowledge., Methods: This cross-sectional study was conducted between March 2007 and January 2008; 406 primary family caregivers of COPD patients from the thoracic outpatient departments of 6 hospitals in north-central Taiwan were recruited to answer questionnaires measuring COPD characteristics, care behavior, caregiver response, and COPD knowledge. All questionnaires, which addressed caregiver knowledge, care behaviors, and care reactions, were shown to have acceptable validity and reliability, and the data were analyzed using univariate and generalized linear model techniques., Results: The elder caregivers group had 79 participants, and the non-elder caregivers comprised 327 participants. The COPD-related knowledge scale results were positively correlated with the family caregiver caring behavior scale, suggesting that better COPD-related knowledge among family caregivers may result in improved caring behavior. After adjusting for all possible confounding factors, the elder caregivers had significantly lower COPD-related knowledge than the non-elder caregivers (P<0.001). However, there were no significant differences in the family caregiver caring behavior scale or the caregiver reaction assessment scale between the two groups., Conclusions: Elder family caregivers require increased education regarding medications and preventive care in COPD patient care.

Aims and Objectives: To explore health literacy status in asthma patients and to examine the causal model linking health literacy to health outcome-related factors via mediator and moderator variables., Background: Understanding how low health literacy may influence health outcomes is important., Design: This is a cross-sectional survey study., Methods: A total of 326 asthma patients aged 20 years and older (average: 51 ± 18·3 years) were recruited by purposive sampling from pulmonary medicine outpatient departments at three medical centres and a regional teaching hospital in northern Taiwan. Data were collected via structured questionnaires, including measures of socio-demographic and disease characteristics; medical decision-making; asthma knowledge, attitudes and self-efficacy; healthcare experience and health outcome-related factors (metered-dose inhaler/dry-powder inhaler usage proficiency, medical use, self-management behaviour). Three hundred patients who met the inclusion criteria and completed the questionnaire survey were analysed., Results: Overall, 217 subjects (72·3%) had adequate functional health literacy, 42 (14%) had inadequate functional health literacy, and 41 (13·7%) had marginal functional health literacy. Subjects' average asthma knowledge, attitudes and self-efficacy scores were 7·23 ± 2·69, 51·46 ± 6·18 and 58·31 ± 8·10, respectively. Health literacy correlated positively with asthma knowledge (r = 0·605), attitudes (r = 0·192) and medical decision-making (r = 0·413)., Conclusions: Health literacy is positively associated with proficiency in metered-dose inhaler usage, asthma knowledge, attitudes and medical decision-making, but is not significantly associated with medical care use and self-management behaviour. Health literacy had an indirect effect on self-management behaviour through the mediation effect of asthma attitudes. No moderator was found for the effect of health literacy on health outcome-related factors., Relevance to Clinical Practice: Results of this study may help to develop adequate intervention strategies to improve the health outcomes of asthma patients., (© 2013 John Wiley & Sons Ltd.)

Stanniocalcin-1 (STC1) is an endogenous glycoprotein whose anti-inflammatory effects occur through induction of uncoupling proteins to reduce oxidative stress. In this study, we tested the hypothesis that exogenous recombinant human STC1 (rhSTC1) protects against lipopolysaccharide (LPS)-induced acute lung injury in mice. Anesthetized C57BL/6 mice underwent intratracheal spraying of LPS (20 µg/10 g body wt), and lung injury was assessed 24h later by analyzing pulmonary edema, bronchoalveolar lavage fluid, and lung histopathology. Lung inflammation, oxidative stress, and expression of STC1 and its downstream uncoupling protein 2 (UCP2) were analyzed at specific time points. Expression of UCP2 was suppressed initially but was subsequently upregulated after STC1 elevation in response to intratracheal administration of LPS. Intratracheal rhSTC1 treatment 1h before or after LPS spraying significantly attenuated pulmonary inflammation, oxidative stress, cell apoptosis, and acute lung injury. Pretreatment with STC1 short interfering RNA 48 h before LPS spraying inhibited the expression of STC1 and UCP2 and significantly increased the extent of lung injury. These findings suggest that STC1 is an endogenous stress protein that may counteract LPS-induced lung injury by inhibiting the inflammatory cascade and inducing antioxidant and antiapoptotic mechanisms. However, the potential clinical application of STC1 and the direct linkage between UCP2 and LPS-induced lung injury remain to be further investigated., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background/purpose: Tartrate-resistant acid phosphatase (TRACP) 5a is expressed strongly in inflammatory macrophages (MΦ). Serum TRACP5a is elevated in rheumatoid arthritis patients with extra-articular manifestations of rheumatoid nodules, in a percentage of patients with end-stage chronic kidney disease, and may be a risk marker for acute myocardial infarction. This proof-of-concept study was undertaken in patients with sarcoidosis to further substantiate our hypothesis that TRACP5a protein is a biomarker for macrophages in other chronic inflammatory diseases., Methods: Immunohistochemical staining for TRACP5a and CD68 was performed in tissues of 19 patients with sarcoidosis. We also measured circulating TRACP5a protein and other inflammation biomarkers including interkeukin-6, angiotensin-converting enzyme, and C-reactive protein in 13 patients. Twenty healthy age-matched nonsmoking individuals were used as the reference group., Results: All sarcoidosis tissues showed strong staining for TRACP5a and CD68 in the non-caseating granulomatous lesions and localized specifically to MΦ, multinucleate giant cells, and epithelioid MΦ. Serum TRACP5a protein was elevated significantly in active sarcoidosis patients compared with the control group, and levels fluctuated with disease activity in one patient studied longitudinally., Conclusion: TRACP5a protein is expressed abundantly in the granulomatous tissues and may be elevated in a significant proportion of sarcoidosis patients. These findings further support our hypothesis that serum TRACP5a is derived from systemic inflammatory MΦ and thereby may be a biomarker of inflammation for sarcoidosis and also reflect its disease activity., (Copyright © 2012. Published by Elsevier B.V.)

Background: Earlier studies have demonstrated an association between N-acetyltransferase 2 (NAT2) catalytic activity and the genotype of a recently published tag single nucleotide polymorphism (SNP), rs1495741. There have been no reports on the relationship between the rs1495741 genotype and antituberculosis drug-induced hepatotoxicity (ATDIH) to date., Objective: The aim of the present study was to determine the frequency of the NAT2 tag SNP (rs1495741) in the Taiwanese and its relation to the incidence of ATDIH., Materials and Methods: A total of 348 tuberculosis patients were enrolled to determine the frequency of NAT2 tag SNP rs1495741 and its relation to the incidence of ATDIH. The conventional NAT2 variants alleles have also been investigated. Furthermore, to evaluate the correlation of NAT2 activity and rs1495741 genotypes, a pharmacokinetic study of isoniazid was also conducted in healthy volunteers., Results: Among the 348 tuberculosis patients, 20 (5.7%) were diagnosed with ATDIH. The frequencies of the three rs1495741 genotypes, viz., AA, AG, and GG, were 24.7, 52.3, and 23.0%, respectively. Signi&filig;cant differences among rs1495741 genotypes and susceptibility to hepatotoxicity were noted (odds ratio=14.068, P<0.05). Moreover, the rs1495741 genotypes showed an association with the isoniazid dosage required for induction of hepatotoxicity. In the pharmacokinetic study, NAT2 activity was strongly associated with genotype categories (P<0.001)., Conclusion: The present study demonstrated that the three genotypes according to rs1495741 were in good accordance with conventional NAT2 alleles-inferred phenotypes and the tag SNP could be used as a proxy to determine the susceptibility to ATDIH.

Background: COPD becomes a long-term burden on family members who serve as day-to-day caregivers, and causes healthcare systems to incur substantial costs. COPD is both preventable and treatable, and one important aspect of COPD treatment is patients' self-management. This study aimed to investigate relationships between self-management and the caregiver burden, and the influence of family caregivers' caring behavior on COPD patients' self-care behavior., Methods: In a cross-sectional study conducted between March 2007 and January 2008, 192 pairs of COPD patients (age > 40 years, normal cognitive function) and their primary family caregivers were recruited to answer questionnaires measuring COPD characteristics and COPD knowledge (patients and caregivers); functional status, health beliefs, self-efficacy, and self-care (patients); and caring behavior and caregiver response (family members). All questionnaires were shown to have acceptable validity and reliability, and the data were analyzed using univariate and multivariate techniques., Results: Patients' ages, scores in health belief, self-efficacy and disease-related knowledge were shown to correlate with patients' self-care behavior. Patients' self-care behavior was negatively correlated with family caregivers' caring behavior (ρ = -0.21, P = .003), but positively with caring duration of family caregiver caring behavior (ρ = 0.15, P = .037). Patients with a spouse as caregiver exhibited higher self-care ability than patients not married to their caregivers (P = .038). However, patients' self-care behavior decreased with higher family caregivers' COPD knowledge (P = .041) and caring behavior (P = .01), and patients regularly taking medication exhibited low self-care scores., Conclusions: Family caregivers' caring behavior had a partial negative effect on COPD patients' self-care behavior.

Objective: To report a case of invasive pulmonary aspergillosis mimicking lung cancer with lung to lung metastases in ectopic adrenocorticotropic hormone syndrome (EAS)., Clinical Presentation and Intervention: A 60-year-old man suffering from hypokalemic alkalosis, hypertension and limbs paralysis was referred to our hospital. EAS caused by malignancy of lung was highly suspected due to multiple pulmonary nodules presenting on chest film and positron emission tomography (PET) images. Video-assisted thoracic surgical biopsy tissue was used to confirm invasive aspergillosis instead of malignancy. Finally, the patient died of opportunistic infection., Conclusion: This case showed that although EAS is usually associated with solid tumors, multiple pulmonary nodules secondary to opportunistic infections such as invasive aspergillosis must be kept in mind., (Copyright © 2012 S. Karger AG, Basel.)

Background: Adaptive support ventilation (ASV) facilitates ventilator liberation in postoperative patients in surgical intensive care units (ICU). Whether ASV has similar benefits in patients with acute respiratory failure is unclear., Methods: We conducted a pilot study in a medical ICU that manages approximately 600 mechanically ventilated patients a year. The ICU has one respiratory therapist who manages ventilators twice during the day shift (8:00 am to 5:00 pm). No on-site respiratory therapist was present at night. We prospectively enrolled 79 patients mechanically ventilated for ≥ 24 hours on pressure support of ≥ 15 cm H(2)O, with or without synchronized intermittent mandatory ventilation, F(IO(2)) ≤ 50%, and PEEP ≤ 8 cm H(2)O. We switched the ventilation mode to ASV starting at a "%MinVol" setting of 80-100%. We defined spontaneous breathing trial (SBT) readiness as a frequency/tidal-volume ratio of < 105 (breaths/min)/L on pressure support of ≤ 8 cm H(2)O and PEEP of ≤ 5 cm H(2)O for at least 2 h, and all spontaneous breaths. The T-piece SBT was considered successful if the frequency/tidal-volume ratio remained below 105 (breaths/min)/L for 30 min, and we extubated after successful SBT. The control group consisted of 70 patients managed with conventional ventilation modes and a ventilator protocol during a 6-month period immediately before the ASV study period., Results: Extubation was attempted in 73% of the patients in the ASV group, and 80% of the patients in the non-ASV group. The re-intubation rates in the ASV and non-ASV groups were 5% and 7%, respectively. In the ASV group, 20% of the patients achieved extubation readiness within 1 day, compared to 4% in the non-ASV group (P = <.001). The median time from the enrollment to extubation readiness was 1 day for the ASV group and 3 days for the non-ASV group (P = .055). Patients switched to ASV were more likely to be liberated from mechanical ventilation at 3 weeks (P = .04). Multiple logistic regression analysis showed that, of the independent factors in the model, only ASV was associated with shorter time to extubation readiness (P = .048 via likelihood ratio test)., Conclusions: Extubation readiness may not be recognized in a timely manner in at least 15% of patients recovering from respiratory failure. ASV helps to identify these patients and may improve their weaning outcomes.

Background: Allergic rhinitis (AR) often coexists with and can significantly worsen bronchial asthma (BA). We evaluated the proportion of patients with BA and concomitant AR (BA+AR) diagnosed and treated in an average clinical practice., Methods: A cross-sectional study methodology was used to determine the prevalence of AR in patients more than 15 years of age with a documented history of asthma who experienced wheezing during the prior 12 months. The International Study of Asthma and Allergies in Childhood standardized written questionnaire was used and therapeutic class choices were recorded., Results: Among 750 surveyed asthma patients, 524 patients (69.9%) experienced AR. Of those with BA and AR, there were 44 patients (8.4%) who were not diagnosed with AR, and the treatment rate for AR was 62.1%. The most frequent severity level of BA and AR were moderate persistent (38.9%) and intermittent mild (52.5%), respectively. There were no significant differences between patients with AR and without AR., Conclusions: The prevalence of AR in patients with asthma was 69.9% in this study. Despite Allergic Rhinitis and its Impact on Asthma guideline recommendations encouraging evaluation and treatment of AR among asthmatics, nearly 8.4% of asthmatics with AR were undiagnosed, and 37.9% of asthmatics with AR were untreated for AR., (Copyright © 2011. Published by Elsevier B.V.)

Background: Limited evidence is available on the use of budesonide inhalation suspension (BIS) for the treatment of mild to severe acute asthma exacerbations (AAE) in adults in an inpatient setting. This study was conducted to evaluate the efficacy of a five-day course of BIS compared with oral prednisolone (OP) in the management of adults with AAE., Methods: A retrospective study examined the response of 28 patients hospitalized with mild to severe acute asthma exacerbation from January 2003 to December 2003. These patients, who were steroid free ≥ 1 yr, were administered a five-day course of BIS (2 × 2 mg bid) or OP (2 × 15 mg bid). PEF, FEV(1) and asthma symptom scores were recorded daily., Results: The BIS (n = 13) and OP (n = 15) treatment groups were comparable at baseline for demographic characteristics and prebronchodilator (fenoterol) FEV(1) of 52.4% predicted normal value and 54.6% predicted normal value, respectively. Mean change of morning PEF was 152 L/min during BIS treatment and 130 L/min for OP treatment; the mean changes of morning forced expiratory volumes in 1 s (FEV(1)) were 1.0 and 0.7 L, respectively. The mean change in daytime symptom scores were -1.6 and -1.3 in the BIS and the OP groups, respectively. Improvements in PEF, FEV(1) and daytime symptom scores were significantly different between baseline and after treatment in each treatment group (p < 0.05). However, improvements in both BIS and OP groups were similar., Conclusion: Budesonide inhalation suspension may be an alternative treatment of acute asthma exacerbation in adults who are at risk for systemic corticosteroids., (Copyright © 2010. Published by Elsevier Ltd.)

Differentiating tuberculosis (TB) from pneumonia remains a challenge. We evaluated the cytokine profiles of whole blood cells from patients with TB (n = 38) or pneumonia (n = 30) and from healthy individuals (n = 30) before and after stimulating cells with ESAT-6 or lipopolysaccharide (LPS). When the percent change in the levels of gamma interferon (IFN-gamma) after stimulation with ESAT-6 was used in receiver operating characteristics (ROC) analysis (a graphic method to determine the diagnostic accuracy of a test) to identify a patient with TB, the area under the curve (AUC) was 90.4%, and a cutoff point of a 3.59% change produced a corresponding sensitivity, specificity, and accuracy of over 80%. When the change in IFN-gamma after stimulation of blood cells with LPS was used to identify a patient with pneumonia, the AUC reached 89.1%, and a cutoff point of 3.59% produced a sensitivity, specificity, and accuracy of approximately 80% each. When the change in interleukin-12 (IL-12) after stimulation of blood cells with LPS was selected to define a patient with pneumonia, the AUC was 85.2%, and a cutoff point of 2.08% gave a sensitivity, specificity, and accuracy of 80.0%, 78.9%, and 79.4%, respectively. We conclude that the percent change in IFN-gamma after stimulation of whole blood cells with ESAT-6 may differentiate patients with TB from patients with pneumonia. The percent change in IFN-gamma and IL-12 after LPS stimulation of whole blood cells could differentiate patients with pneumonia from patients with TB.

Differences in the histological manifestation of synchronous lung cancers are rare. Synchronous multiple primary lung cancers (SMPLC) are associated with long-term tobacco use, which could independently lead to mutations in the p53 and K-ras genes. We present the case of an 82-year-old man who smoked 30 cigarettes daily for the past 60 years. CT of the chest showed a right upper lobe mass. Bronchoscopy revealed an intra-lumen nodular lesion in the right lower lobe bronchus. The diagnoses of small cell lung carcinoma (SCLC) of the right upper lobe and non-small cell lung carcinoma (NSCLC) of the right lower lobe were confirmed by the morphologic features and the detected immunoreactivity. Immunohistochemical analyses showed a strong positive reaction for p53 in samples of the SCLC and NSCLC. The cancers had a different phenotype, but similar genetic abnormalities may have developed due to the carcinogens in the cigarettes.

Background: Removing the artificial airway is the last step in the mechanical ventilation withdrawal process. In order to assess cough effectiveness, a critical component of this process, we evaluated the involuntary cough peak flow (CPFi) to predict the extubation outcome for patients weaned from mechanical ventilation in ICUs., Methods: One hundred fifty patients were weaned from ventilators, passed a spontaneous breathing trial (SBT), and were judged by their physician to be ready for extubation in the Tri-Service General Hospital ICUs from February 2003 to July 2003. CPFi was induced by 2 mL of normal saline solution at the end of inspiration and measured using a hand-held respiratory mechanics monitor. All patients were then extubated., Results: Of 150 enrolled patients for this study, 118 (78.7%) had successful extubation and 32 (21.3%) failed. In the univariate analysis, there were higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (16.0 vs 18.5, P = .018), less negative maximum inspiratory pressure (-45.0 vs -39.0, P = .010), lower cough peak flows (CPFs) (74.0 vs 42.0 L/min, P < .001), longer postextubation hospital stays (15.0 vs 31.5 days, P < .001), and longer postextubation ICU stays (1.0 vs 9.5 days, P < .001) in the extubation failures compared with the extubation successes. In the multivariate analysis, we found that a higher APACHE II score and a lower CPF were related to increasing risk of extubation failure (odds ratio [OR] = 1.13; 95% CI, 1.03-1.25; and OR = 0.95; 95% CI, 0.93-0.98, respectively). The receiver operator characteristic curve cutoff point for CPF was 58.5 L/min, with a sensitivity of 78.8% and specificity of 78.1%., Conclusions: CPFi as an indication of cough reflex has the potential to predict successful extubation in patients who pass an SBT.

Background: Adaptive support ventilation (ASV) is a new mode of mechanical ventilation that seeks an optimal breathing pattern based on the minimum work of breathing (WOB) principle. The operator's manual for the ventilators that provide ASV recommends that the %MinVol setting be started at 100% (the 100%MinVol setting), but it is unclear whether that setting reduces WOB in patients with respiratory failure., Methods: We studied 22 hemodynamically stable patients with respiratory failure who were on pressure-support ventilation. We switched the ventilation mode to ASV and started at the 100%MinVol setting. We then increased the %MinVol setting by 10% every 5 min until 1-3 mandatory breaths per min appeared, and called that setting the ASV target point. We then tested 2 additional %MinVol settings: 20% below the ASV target point (target-point-20%), and 20% above the ASV target point (target-point+20%). We tested each %MinVol setting for 10 min. At the end of each 10-min period we measured respiratory variables, pressure-time product (PTP), and airway occlusion pressure at 0.1 s after the onset of inspiratory flow (P(0.1))., Results: In 18 patients (82%), at the 100%MinVol setting, the actual minute volume (V(E)) was greater than the target V(E). At the ASV target point the mean +/- SD %MinVol setting was 165 +/- 54% and was associated with a 40% decrease in PTP and P(0.1), but V(E) did not change. At target-point+20%, V(E) increased slightly, primarily due to a small increase in tidal volume, and PTP and P(0.1) further decreased. At target-point-20%, PTP and P(0.1) were similar to those at the 100%MinVol setting. At the ASV target point the 6 patients with chronic obstructive pulmonary disease had a lower mean %MinVol setting (125 +/- 23%) than the 16 patients who did not have chronic obstructive pulmonary disease (180 +/- 55%)., Conclusions: The 100%MinVol setting was frequently not associated with lower WOB in patients with respiratory failure. The %MinVol setting that significantly reduced WOB could be detected by increasing the %MinVol setting until a few mandatory breaths began to appear, and was on average 165% of the MinVol setting.

Mycobacterium tuberculosis infection is a major world health issue. The early identification of patients at risk for a poor response to anti-M. tuberculosis therapy would help elucidate the key players in the anti-M. tuberculosis response. The objective of the present study was to correlate the modulation of cytokine expression (interleukin-1 [IL-1], IL-6, IL-8, IL-10, IL-12, gamma interferon [IFN-gamma], interferon-inducible protein [IP-10], and monocyte chemotactic protein 1 [MCP-1]) with the clinical response to 2 months of intensive therapy. From January to December 2007, 40 M. tuberculosis-infected patients and 40 healthy patients were recruited. After exclusion for diabetes, 32 patients and 36 controls were analyzed. The clinical responses of the M. tuberculosis-infected patients on the basis of the findings of chest radiography were compared to their plasma cytokine levels measured before and after 2 months of intensive anti-M. tuberculosis therapy and 6 months of therapy with human cytokine antibody arrays. Chest radiographs of 20 of 32 M. tuberculosis-infected patients showed improvement after 2 months of intensive therapy (early responders), while the M. tuberculosis infections in 12 of 32 of the patients resolved after a further 4 months (late responders). The levels of expression of TNF-alpha, MCP-1, IFN-gamma, and IL-1beta were decreased; and the level of IL-10 increased in early responders. After adjustment for age, gender, and the result of sputum culture for M. tuberculosis, significant differences in the levels of MCP-1 and IP-10 expression were observed between the early and the late responders after 2 months of intensive anti-M. tuberculosis therapy. Due to the interpatient variability in IP-10 levels, intrapatient monitoring of IP-10 levels may provide more insight into the M. tuberculosis responder status than comparison between patients. Plasma MCP-1 levels were normalized in patients who had resolved their M. tuberculosis infections. Further studies to evaluate the association of the modulation in MCP-1 levels with early and late responses are warranted.

1. Glutamine is an amino acid that is used to treat various diseases. Glutamine has been reported to have protective effects in human pulmonary epithelia-like cells exposed to hyperoxia. However, the effects of glutamine in hyperoxia-induced lung injury have not been investigated in vivo. 2. Mice treated with saline or glutamine [(750 mg/kg) intravenously] were randomly exposed to hyperoxia for 48 or 72 h. Control mice treated with saline or glutamine were exposed to room air. Cytokine levels in bronchoalveolar lavage fluid (BALF), heat shock protein (HSP) 70, the wet/dry (W/D) weight ratio, malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and pathoglogical findings in lung tissue were evaluated to determine the effects of glutamine on acute lung injury. In addition, survival was monitored. 3. Lung expression of HSP70 was significantly enhanced in both the control (room air) and 48 and 72 h hyperoxic glutamine-treated mice. The W/D ratio, BALF concentrations of tumour necrosis factor-alpha and interleukin-6, MDA levels, MPO activity, neutrophil infiltration and interstitial oedema in lung tissue were significantly lower at 48 and 72 h of hyperoxia in glutamine-treated mice compared with saline-treated mice. 4. In a separate series of experiments evaluating survival, after 96 h continuous exposure to hyperoxia, all saline-treated mice died. In contrast, all glutamine-treated mice died after 108 h exposure to hyperoxia. 5. The data suggest that glutamine administered to mice during hyperoxia has a protective effect against hyperoxia-induced acute lung injury and improves survival.

No standard protocol exists for the treatment of acute respiratory distress syndrome induced by inhalation of smoke from a smoke bomb. In this case, a 23-year-old man was exposed to smoke from a smoke grenade for approximately 10 to 15 minutes without protective breathing apparatus. Acute respiratory distress syndrome developed subsequently, complicated by bilateral pneumothorax and pneumomediastinum 48 hours after inhalation. Despite mechanical ventilation and bilateral tube thoracostomy, the patient was severely hypoxemic 4 days after hospitalization. His condition improved upon treatment with high-dose corticosteroids, an additional 500-mg dose of methylprednisolone, and the initiation of extracorporeal life support. Arterial oxygenation decreased gradually after abrupt tapering of the corticosteroid dose and discontinuation of the life support. On day 16 of hospitalization, the patient experienced progressive deterioration of arterial oxygenation despite the intensive treatment. The initial treatment regimen (ie, corticosteroids and extracorporeal life support) was resumed, and the patient's arterial oxygenation improved. The patient survived.

Transformation of a poorly differentiated squamous cell carcinoma (SCC) of the esophagus into a âcarcinosarcomaâ of the pleura and lung has never been reported and its histogenetic origin is still debated. A 48-year-old man was admitted due to progressive dysphagia and a weight loss of 5 kilograms within 2 months. Upper gastrointestinal panendoscopic biopsy revealed poorly differentiated SCC of thoracic esophagus, upper third, T4N1M1a, stage IVa. He received concurrent chemoradiotherapy (CCRT). About 9 months later, rapid progression of lung metastases and pleural effusion were found. According to the histopathological and immunohistochemical stain results, carcinosarcoma was diagnosed. Palliative therapy was given and the patient eventually died of the disease 9 months after SCC of the thoracic esophagus was diagnosed and one month after carcinosarcoma of the pleura and lung were confirmed.

Background: Acute respiratory distress syndrome (ARDS) associated with pulmonary lipiodol embolism is a rare complication of transcatheter arterial chemoembolization (TACE). We performed a survey of ARDS associated with pulmonary lipiodol embolism after TACE., Methods: A retrospective analysis of the cases of all patients with hepatic tumors who received transcatheter arterial embolization or TACE between January 2006 and December 2006 was performed. The diagnosis of pulmonary lipiodol embolism was confirmed by chest computed tomography (CT)., Results: The diagnosis of ARDS associated with pulmonary lipiodol embolism was confirmed in 4 patients. All had large (> or =5 cm) and hypervascular tumors. There was no evidence of hepatocellular carcinoma arteriovenous shunting in any of our patients as determined by angiography and multidetector CT. The volumes of lipiodol infused in the 4 patients were 50, 20, 30, and 20 mL. Only 2 patients received injections of carcinostatic agents. The onset of respiratory symptoms occurred between 1 hour and 4 days after TACE. Respiratory symptoms consisted of dyspnea and tachypnea. Chest CT scans revealed linear high-density shadows, suggestive of lipiodol retention in both lungs of all patients., Conclusion: Pulmonary lipiodol embolism after TACE can occur within a short time frame. Whether or not there is intrahepatic arteriovenous shunting detected by multidetector CT and angiography, clinicians should avoid high doses of iodized oil and carcinostatic agents. We suggest that CT should be used for the diagnosis of pulmonary lipiodol embolism.

Background: Small-cell lung cancer accounts for 15-20% of all lung cancers, and it is the cell type most commonly associated with paraneoplastic syndrome. Small-cell lung cancer presenting as ectopic adrenocorticotropic hormone (ACTH) syndrome associated with hypothyroidism and hypogonadotropic hypogonadism is clinically very rare., Case Report: A 43-year-old man who presented with bilateral lower-extremity edema and hypokalemia had a mass lesion in his left hilum base visible on chest radiograph. Biopsy identified the mass as small-cell lung cancer with focal ACTH staining. The endocrine tests disclosed hypercortisolism, hypogonadism and hypothyroidism., Results: Partial remission as evidenced by regression of the tumor mass and return to normal serum cortisol and ACTH levels occurred after the first course of combination chemotherapy using cisplatin and etoposide. An unexpected left-sided spontaneous pneumothorax developed after the first course of chemotherapy and was treated with thoracostomy and a chest tube. The patient developed persistent air leakage and chronic empyema. The patient received surgery of the Eloesser flap and reconstruction with the latissimus dorsalis flap. The treatment of the complicated problems was successful., Conclusion: Combination chemotherapy may prove effective in the treatment of small-cell lung cancer with ectopic ACTH syndrome, hypothyroidism and hypogonadism., (Copyright 2009 S. Karger AG, Basel.)

A 24-year-old female with an anomalous systemic arterial (ASA) supply to normal basal segments of the left lower lobe (LLL) has been suffering from occasional hemoptysis for the last 4.5 years. Our hospital has been following her up for the last 2.5 years. In the first chest radiograph, an unobvious retrocardiac hazy nodule was shown. The following chest computed tomography scan performed indicated clearly this anomaly. According to our analysis of similar reported cases in the English medical literature, the statistics suggest a close relation between Asian population and this anomaly. Therefore, ASA supply to normal basal segments of the LLL should be put into consideration when examining an Asian patient with symptoms of hemoptysis or exertional dyspnea but showing no obvious image findings in chest radiographs.

Hyperglycemia and hypoxia synergistically retard diabetic wound healing. We investigated the direct effect of hyperbaric and normobaric hyperoxia on skin fibroblasts cultured in a high-glucose medium. Detroit 551 human dermal fibroblasts cultured in Dulbecco's modified Eagle's medium containing d-glucose had reduced cell survival compared with cells grown in normal glucose medium; survival was 27.5+/-3.8% lower in 25 mM glucose and 30.6+/-3.7% lower in 50 mM glucose. Cell survival decreased because of inhibition of cell proliferation and enhanced cell death. Daily hyperbaric oxygen therapy at 2.5 atmosphere absolute for 90 minutes on 3 consecutive days reduced cell proliferation and increased cell death in normal cultured fibroblasts. Hyperbaric oxygen therapy and high-glucose medium had a synergistic effect and reduced survival by 37.6+/-4.4% (25 mM glucose) and 39.6+/-5.1% (50 mM glucose). The effects of hyperbaric oxygen and high-glucose medium were associated with overproduction of reactive oxygen species. Our results suggest that direct exposure of skin fibroblasts to hyperbaric oxygen affects cell growth and superimposes the toxic effect of high glucose. This cytotoxicity may be related to the production of reactive oxygen species in the fibroblasts.

Unlabelled: There has been no human epidemiological data regarding the hepatic injuries of hexachloroethane-zinc oxide (HC/ZnO) inhalation. This is the first epidemiological study to investigate whether HC/ZnO inhalation exposure can induce hepatic dysfunction in exposed soldiers. Twenty soldiers, exposed to high concentration of HC/ZnO smoke for 3-10 min in a narrow tunnel (0.6 m in width) during military training, were recruited as exposed group and they were divided into high-exposed group (n=10) and low-exposed group (n=10) by the distance from the explosion locale as a surrogate of exposure condition. Another 64 soldiers, not visiting the explosion areas, were recruited as referents. Venous blood was collected for liver function analyses. After log transformation of alanine aminotransferase (ALT) and adjustment for potential confounders, serum ALT in high-exposed soldiers was statistically significantly higher than those of referents for the 3 weeks following exposure. The serum ALT in low exposed soldiers was statistically significantly higher than those of referents at the 3rd week following exposure. The mean ALT levels also showed decreasing gradients by the distance from exposure locale. In addition, the proportions of abnormality on ALT (>40U/L) were also significantly different among three exposure conditions. Follow-up study showed that the hepatic dysfunction started from 1 to 2 weeks and peaked from 3rd to 5th week after exposure. ALT level was then returned to normal within 6-8 weeks after removing from HC/ZnO smoke exposure. No sequelas in hepatic dysfunction were found until 72 weeks follow-up., Conclusion: We concluded that inhalation of HC/Zn smoke can induce acute, dose-dependent and definite temporal relationship hepatic dysfunction.

The purpose of this study was to investigate an outbreak of tuberculosis (TB) in a bacillus Calmette-Guérin-vaccinated military population and propose an appropriate method of control. We divided 593 subjects into "close contacts" and "non-close contacts" of an index case and examined all subjects by chest X-radiography (CXR). For "close contacts," we performed several tests for patients with abnormal CXRs. "Non-close contacts" had no pulmonary infiltration and no evidence of TB. We administered tuberculin skin tests (TST) to 21 "close contacts" who had pulmonary infiltrations. Seven patients had a TST > or =18 mm, two of whom had active pulmonary TB. We administered antituberculous agents to all seven patients for 6 months. Fourteen subjects with TSTs <18 mm had no evidence of TB during the 18-month follow-up period. Among the other 178 "close contact" subjects with no infiltrations evident on the initial CXR, one patient developed TB pleuritis. We conclude that it is important to use early treatment for "close contacts" of a TB index case by performing the TST and testing for pulmonary infiltration on CXRs.

Background: White smoke inhalation is an uncommon but potentially deadly cause of acute lung injury. No clinical spectrum or treatment protocol have been developed., Methods: Twenty patients accidentally been exposed to white smoke during military training were the subjects of this study. We analyzed clinical manifestations, cytokine changes, and treatment outcomes., Results: All patients initially presented with fever, dry cough, chest tightness, and shortness of breath. Twenty-five percent of these patients had severe acute lung injury requiring artificial ventilation support. Elevation of serum tumor necrosis factor-alpha was observed before treatment with antibiotics and glucocorticoids, but the elevation of transforming growth factor-beta(1) was delayed for 2 to 4 weeks after the accident. All the patients had leukocytosis, which correlated positively to disease severity and negatively to intensive treatments. Ninety-five percent of patients had varying degrees of restrictive ventilation impairment, and 85% of these patients had a significantly reduced diffusion capacity in the lungs. Seventy percent of these patients had transient impairment of liver function, which did not correlate to disease severity. The respiratory sequela of restrictive ventilation impairment developed in the most severely affected patients, whereas other tissue toxicities were mostly transient. Treatment included glucocorticoids, antibiotics, and respiratory therapy. All of the patients survived., Conclusion: A proper ventilation strategy, early pharmacologic therapy including glucocorticoids, and complication prevention may contribute to good treatment outcomes after white smoke inhalation.

Pulmonary bullae are a common late complication in patients with emphysema. Non-communicating emphysematous bullae may expand during air travel when the ambient pressure is reduced, resulting in various forms of barotrauma including pneumothorax and air embolism. We report a 62-yr-old man with emphysema who developed hemoptysis during international commercial air travel. CT scan of the chest obtained after the travel showed air-fluid level in an enlarged bulla. He underwent resection of the bulla and had a full recovery. This is a unique presentation of stretch injury of a bulla as a form of pulmonary barotrauma occurring during commercial air travel. With the most recent ruling by the Federal Aviation Administration to allow patients with advanced chronic obstructive lung disease to travel by air with their own supplemental oxygen devices, physicians need to be aware of this type of pulmonary barotrauma and properly advise such patients who are planning to travel by air.

Study Objectives: In this study, we determined the effects of various body temperatures (BTs) after initiation of lipopolysaccharide (LPS)-induced lung injury., Design and Setting: Forty-nine, adult, male, Sprague-Dawley rats each weighing 300 to 400 g were used, Methods: The treated rats were challenged with intraperitoneal (IP) administration of 5 mg/kg LPS. Control animals received IP saline solution injections. After 16 h, treated and control animals were anesthetized. The animals received direct intratracheal (IT) injection of LPS (1 mg/0.2 mL) or saline solution (control animals). A cooling or heating blanket was then used to control BT. The rats were randomly assigned to three control groups of mild hypothermia (34 degrees C) plus saline solution, normothermia (37 degrees C) plus saline solution, and mild hyperthermia (39 degrees C) plus saline solution, and three LPS groups of mild hypothermia plus LPS, normothermia plus LPS, and mild hyperthermia plus LPS, where each condition was maintained for 5 h. The mean arterial pressure (MAP) and blood gas concentrations were measured. BAL was done in the left lung 5 h after the IT injection of LPS with temperature control. Parts of the right lung were excised for myeloperoxidase (MPO) and malondialdehyde (MDA) measurements, whereas the rest was collected for wet/dry (W/D) ratio determination., Results: Normothermia plus LPS caused significantly increased W/D ratio, LDH activities, protein concentrations, and tumor necrosis factor-alpha concentrations in BAL fluid, and MPO activities and MDA levels in lung tissues when compared to saline solution control group. MAP and Pao(2) were significantly decreased. The pathologic picture also showed increased neutrophil infiltration in lung tissues. In contrast, treatment with mild hypothermia but not hyperthermia significantly attenuated these parameters when compared with the normothermia-plus-LPS group., Conclusions: These experimental data suggest that mild hypothermia applied after initiation of acute lung injury induced by LPS in rats had a protective effect by inhibiting the inflammatory reaction.

Study Objectives: Zinc chloride smoke inhalation injury (ZCSII) is uncommon and has been rarely described in previous studies. We hypothesized that structural changes of the lung might correlate with pulmonary function. To answer this question, we correlated findings from high-resolution CT (HRCT) scan and the results of pulmonary function tests (PFTs) in patients with ZCSII., Design: Retrospective cohort study., Setting: University hospital., Patients: Twenty patients who had been hospitalized with ZCSII-related conditions., Measurements: The study included HRCT scan scores (0 to 100), static and dynamic lung volumes, and diffusing capacity of the lung for carbon monoxide (D(LCO))., Results: HRCT scans and PFTs were performed initially after injury (range, 3 to 21 days) in all patients and during the follow-up period (range, 27 to 66 days) in 10 patients. The predominant CT scan findings were patchy or diffuse ground-glass opacities with or without consolidation. The majority of patients showed a significant reduction of FVC, FEV1, total lung capacity, and D(LCO), but normal FEV1/FVC ratio values. Changes of functional parameters correlated well with HRCT scan scores. Substantial improvements in CT scan abnormalities and pulmonary function were observed at follow-up., Conclusions: The majority of our patients with ZCSII presented with a predominant parenchymal injury of the lung that was consistent with a restrictive type of functional impairment and a reduction in Dlco rather than with obstructive disease. Our results suggest that HRCT scanning and pulmonary function testing may reliably predict the severity of ZCSII.