Echogenic swirling pattern, carcinoembryonic antigen, and lactate dehydrogenase in the diagnosis of malignant pleural effusion.

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.

Risk factor analysis of nosocomial lower respiratory tract infection in influenza-related acute respiratory distress syndrome.

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.

Using a machine learning approach to predict mortality in critically ill influenza patients: a cross-sectional retrospective multicentre study in Taiwan.

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.

Impact of corticosteroid treatment on clinical outcomes of influenza-associated ARDS: a nationwide multicenter study.

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.

Pre-Treatment with Ten-Minute Carbon Dioxide Inhalation Prevents Lipopolysaccharide-Induced Lung Injury in Mice via Down-Regulation of Toll-Like Receptor 4 Expression.

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.

Bidirectional association between tuberculosis and sarcoidosis.

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.

Integrated safety summary of phase II and III studies comparing oral nemonoxacin and levofloxacin in community-acquired pneumonia.

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.

First tidal volume greater than 8 mL/kg is associated with increased mortality in complicated influenza infection with acute respiratory distress syndrome.

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 (VT) in the first three days after intubation was greater than 8 mL/kg of predicted body weight (PBW). Patients whose first measured VT 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 VT 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 VT may be important in reducing mortality.

Predictors of survival in patients with influenza pneumonia-related severe acute respiratory distress syndrome treated with prone positioning.

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.

Effect of dyspnea on frailty stages and related factors in Taiwanese men with COPD.

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.

Association of day 4 cumulative fluid balance with mortality in critically ill patients with influenza: A multicenter retrospective cohort study in Taiwan.

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.

Comparative efficacy and tolerability of beclomethasone/formoterol and fluticasone/salmeterol fixed combination in Taiwanese asthmatic patients.

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 (FEV1), 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.

Endobronchial Lesion in Eosinophilic Granulomatosis with Polyangiitis.

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.

CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer.

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.

Panels of tumor-derived RNA markers in peripheral blood of patients with non-small cell lung cancer: their dependence on age, gender and clinical stages.

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.

Gastro-oesophageal reflux disease increases the risk of intensive care unit admittance and mechanical ventilation use among patients with chronic obstructive pulmonary disease: a nationwide population-based cohort study.

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.

Airway obstruction due to tracheomalacia caused by innominate artery compression and a kyphotic cervical spine.

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.

Intravenous immunoglobulin replacement therapy to prevent pulmonary infection in a patient with Good's syndrome.

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.

Differences in COPD patient care by primary family caregivers: an age-based study.

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.

Tartrate-resistant acid phosphatase 5a in sarcoidosis: further evidence for a novel macrophage biomarker in chronic inflammation.

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.