High expression of high-mobility group box 1 in the blood and lungs is associated with the development of chronic obstructive pulmonary disease in smokers.

BACKGROUND AND OBJECTIVE: High-mobility group box 1 (HMGB1) is an important mediator in multiple pathological conditions, but the expression of HMGB1 in chronic obstructive pulmonary disease (COPD) has not yet been completely investigated. We aimed to analyze the relationship between HMGB1 expression in blood and lung tissue and the development of COPD. METHODS: Twenty-eight patients admitted for single pulmonary surgical intervention were enrolled. The expression of HMGB1 in blood and lung tissue was evaluated by enzyme-linked immunosorbent assay analysis and immunohistochemistry stain, respectively. The study patients were divided into smokers with COPD (n = 11), smokers without COPD (n = 8) and non-smoker healthy controls (n = 9). RESULTS: Smokers with COPD compared with smokers without COPD and healthy controls were older in age, with lower post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) ratio (63.1 ± 5.5 vs 77.6 ± 3.6 and 84.5 ± 5.8, P < 0.001 and P < 0.001, respectively) and higher levels of plasma HMGB1 (93.2 ± 139.9 vs 7.3 ± 4.8 and 17.0 ± 19.6 ng/mL, P = 0.016 and P = 0.021, respectively). In smokers with COPD, the numbers and portion of HMGB1-expressing cells in epithelium and submucosal areas were significantly increased. Notably, plasma HMGB1 levels negatively correlated with post-bronchodilator FEV1 /FVC ratio (r = -0.585, P = 0.008) in smokers, but not in non-smokers. CONCLUSIONS: In smokers, high expression of HMGB1 in the blood and lungs is related to the lung function impairment and appears to be associated with the development of COPD.

Assessment of myocardial injury in the emergency department independently predicts the short-term poor outcome in patients with severe carbon monoxide poisoning receiving mechanical ventilation and hyperbaric oxygen therapy.

OBJECTIVES: Patients with severe carbon monoxide (CO) poisoning are often prone to unconsciousness and respiratory distress and as a result will receive mechanical ventilation and hyperbaric oxygen (MV-HBO) therapy. Factors associated with poor outcome at discharge are less defined in this patient population. This study was conducted to identify the prognostic predictors of short-term poor outcome in severely CO-poisoned patients receiving MV-HBO therapy. METHODS: The departmental database and the medical records of 81 patients treated with MV-HBO therapy were reviewed. Demographic and clinical data were extracted for analysis. HBO therapy with 2.5 or 2.8 atmosphere absolute (ATA) was administered to these patients. Short-term poor outcome was defined as an in-hospital death or neurologic sequelae at discharge. All patients were divided into two groups: those with a poor outcome and those without a poor outcome. RESULTS: Nine patients died while in the hospital, 32 patients had neurologic sequelae at discharge, and the incidence of poor outcome was 50.6%. Parameters that were assessed in the emergency department (ED) and highly associated with patients with a poor outcome included myocardial injury, typical findings on brain computed tomography related to CO poisoning, and higher serum levels of alanine transaminase, aspartate aminotransferase, blood urea nitrogen, creatinine, creatine kinase, creatine kinase-myocardial band, troponin-I, and C-reactive protein. These poor outcomes were also correlated with prolonged lag times from the end of CO exposure to ED arrival and from ED arrival to HBO therapy. In a multivariate analysis, myocardial injury was the only independent predictor of poor outcome (odds ratio, 8.2; 95% confidence interval, 1.012-67.610; p=0.049). CONCLUSIONS: The results of this study indicate that myocardial injury assessed at ED arrival independently predicts the short-term poor outcome in severely CO-poisoned patients who receive MV-HBO therapy. Emergency physicians could use this objective marker to identify patients with an increased risk of poor outcome at discharge and refine the treatment protocol by shortening the time of patient transport and administering HBO therapy as soon as possible.

Prevalence of psychiatric morbidity and psychological adaptation of the nurses in a structured SARS caring unit during outbreak: a prospective and periodic assessment study in Taiwan.

To assess the rapidly changing psychological status of nurses during the acute phase of the 2003 SARS outbreak, we conducted a prospective and periodic evaluation of psychiatric morbidity and psychological adaptation among nurses in SARS units and non-SARS units. Nurse participants were from two SARS units (regular SARS [N=44] and SARS ICU [N=26]) and two non-SARS units (Neurology [N=15] and CCU [N=17]). Participants periodically self-evaluated their depression, anxiety, post-traumatic stress symptoms, sleep disturbance, attitude towards SARS and family support. Results showed that depression (38.5% vs. 3.1%) and insomnia (37% vs. 9.7%) were, respectively, greater in the SARS unit nurses than the non-SARS unit nurses. No difference between these two groups was found in the prevalence of post-traumatic stress symptoms (33% vs. 18.7%), yet, three unit subjects (SARS ICU, SARS regular and Neurology) had significantly higher rate than those in CCU (29.7% vs. 11.8%, respectively) (p<0.05). For the SARS unit nurses, significant reduction in mood ratings, insomnia rate and perceived negative feelings as well as increasing knowledge and understanding of SARS at the end of the study (all p<0.001) indicated that a gradual psychological adaptation had occurred. The adjustment of nurses in the more structured SARS ICU environment, where nurses care for even more severely ill patients, may have been as good or better than that of nurses in the regular SARS unit. Occurrence of psychiatric symptoms was linked to direct exposure to SARS patient care, previous mood disorder history, younger age and perceived negative feelings. Positive coping attitude and strong social and family support may have protected against acute stress. In conclusion, the psychological impact on the caring staffs facing future bio-disaster will be minimized with lowered risk factors and a safer and more structured work environment.

Reduced enhancement of high-frequency component in the cross spectrum of ECG and nostril airflow signals in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a chronic airway disease with increased airway resistance. This study investigated the common characteristics of electrocardiographic (ECG) and nostril airflow signals in COPD patients using cross-spectral analysis. Heart rate variability (HRV) measures and cross-spectral (cs) measures of ECG and nostril airflow were compared in COPD patients and normal subjects, and correlated with their clinical characteristics. We found that cross-spectral analysis can lead to a significant increase in normalized high-frequency power (nHFPcs) and a significant decrease in normalized very low-frequency power (nVLFPcs), normalized low-frequency power (nLFPcs), and low-/high-frequency power ratio (LHRcs) in both normal subjects and COPD patients, as compared with their corresponding HRV measures. Further analysis showed that the percentage increase in nHFP (%nHFP) and the percentage decrease in LHR (%LHR) due to cross-spectral analysis in COPD patients were significantly smaller than those of normal subjects. All cross-spectral measures of ECG and nostril airflow in COPD patients did not significantly correlate with their pulmonary function characteristics. However, the nHFPcs correlated significantly and negatively with body mass index (BMI) in both normal subjects and COPD patients, and the %nHFP correlated significantly and negatively with BMI in COPD patients. We conclude that cross-spectral analysis of ECG and nostril airflow signals could lead to reduced enhancement in the high-frequency component in the cross spectrum of COPD patients. The magnitude of reduced enhancement in the high-frequency component in the cross-spectrum was related to the BMI of the patients. Cross-spectral analysis of ECG and nostril airflow might be used to assess the cardiovascular-related functions of COPD patients.

Pneumothorax and mortality in the mechanically ventilated SARS patients: a prospective clinical study.

INTRODUCTION: Pneumothorax often complicates the management of mechanically ventilated severe acute respiratory syndrome (SARS) patients in the isolation intensive care unit (ICU). We sought to determine whether pneumothoraces are induced by high ventilatory pressure or volume and if they are associated with mortality in mechanically ventilated SARS patients. METHODS: We conducted a prospective, clinical study. Forty-one mechanically ventilated SARS patients were included in our study. All SARS patients were sedated and received mechanical ventilation in the isolation ICU. RESULTS: The mechanically ventilated SARS patients were divided into two groups either with or without pneumothorax. Their demographic data, clinical characteristics, ventilatory variables such as positive end-expiratory pressure, peak inspiratory pressure, mean airway pressure, tidal volume, tidal volume per kilogram, respiratory rate and minute ventilation and the accumulated mortality rate at 30 days after mechanical ventilation were analyzed. There were no statistically significant differences in the pressures and volumes between the two groups, and the mortality was also similar between the groups. However, patients developing pneumothorax during mechanical ventilation frequently expressed higher respiratory rates on admission, and a lower PaO2/FiO2 ratio and higher PaCO2 level during hospitalization compared with those without pneumothorax. CONCLUSION: In our study, the SARS patients who suffered pneumothorax presented as more tachypnic on admission, and more pronounced hypoxemic and hypercapnic during hospitalization. These variables signaled a deterioration in respiratory function and could be indicators of developing pneumothorax during mechanical ventilation in the SARS patients. Meanwhile, meticulous respiratory therapy and monitoring were mandatory in these patients.

Synergistic impact of low serum albumin on intensive care unit admission and high blood urea nitrogen during intensive care unit stay on post-intensive care unit mortality in critically ill elderly patients requiring mechanical ventilation.

AIMS: To identify intensive care unit (ICU) risk factors for post-ICU 6-month (PI6M) mortality in critically ill elderly patients requiring mechanical ventilation (MV). METHODS: The present study was a retrospective observational study carried out in a respiratory ICU from December 2008 to December 2009. Medical records of patients aged ≥70 years and receiving MV were reviewed. Risk factors of PI6M mortality were assessed by multivariate Cox regression. RESULTS: Of 120 patients enrolled, 46 (38%) died in the PI6M period. As compared with survivors, non-survivors had lower serum albumin levels on ICU admission, lower estimated glomerular filtration rate, higher peak blood urea nitrogen (BUN) levels during ICU stay (ICU-peak BUN), a higher ratio of prolonged steroid use and longer MV length in ICU. Independent risk factors of PI6M mortality were low albumin on admission (hazard ratio [HR] 3.53 per g/dL decrease, 95% CI [1.97-6.33], P<0.001) and high ICU-peak BUN (HR 1.11 per 10-mg/dL increase, [1.04-1.18], P=0.001). The HR for PI6M mortality was 7.88 [2.97-20.91] for patients with both risk factors (albumin ≤2.8 g/dL and ICU-peak BUN >72 mg/dL) as compared with those without. For patients with high ICU-peak BUN (>72 mg/dL), PI6M survival was better for those with a reduction in BUN level to ≤72 mg/dL at ICU discharge than those without. CONCLUSIONS: Low serum albumin level on ICU admission and high BUN level during ICU stay are two independent risk factors, especially their combination, of PI6M mortality in critically ill elderly patients requiring MV. Furthermore, patients with a reduction in high BUN have a better PI6M survival.

Intensive care unit-acquired bacteremia in mechanically ventilated patients: clinical features and outcomes.

Intensive care unit (ICU)-acquired bacteremia (IAB) is associated with high medical expenditure and mortality. Mechanically ventilated patients represent one third of all patients admitted to ICU, but the clinical features and outcomes in mechanically ventilated patients who develop IAB remain unknown. We conducted a 3-year retrospective observational cohort study, and 1,453 patients who received mechanical ventilation on ICU admission were enrolled. Among patients enrolled, 126 patients who had developed IAB ≧48 hours after ICU admission were identified. The study patients were divided into IAB and no IAB groups, and clinical characteristics of IAB based on specific bacterial species were further analyzed. The multivariate Cox regression analysis showed that ventilator support for chronic obstructive pulmonary disease and congestive heart failure, and patients admitted from nursing home were the independent risk factors for developing IAB. Patients with IAB were significantly associated with longer length of ICU stay, prolonged ventilator use, lower rate of successful weaning, and higher rate of ventilator dependence and ICU mortality as compared to those without IAB. IAB was the independent risk factor for ICU mortality (HR, 1.510, 95% CI 1.054-1.123; p = 0.010). The clinical characteristics of IAB related to specific bacterial species included IAB due to Pseudomonas aeruginosa being likely polymicrobial, lung source and prior antibiotic use; Escherichia coli developing earlier and from urinary tract source; methicillin-resistant Staphylococcus aureus related to central venous catheter and multiple sets of positive hemoculture; and Elizabethkingia meningoseptica significantly associated with delayed/inappropriate antibiotic treatment. In summary, IAB was significantly associated with poor patient outcomes in mechanically ventilated ICU patients. The clinical features related to IAB and clinical characteristics of IAB based on specific bacterial species identified in our study may be utilized to refine the management of IAB.

Impact and predictors of prolonged chest tube duration in mechanically ventilated patients with acquired pneumothorax.

BACKGROUND: Prolonged chest tube duration is less well studied in patients who are supported by mechanical ventilation and have acquired pneumothorax. We investigated the impact of prolonged chest tube duration on patient outcomes and the risk factors associated with prolonged chest tube duration. METHODS: This retrospective observational study included 106 ventilated subjects who had been treated with thoracostomy for pneumothorax between May 2004 and December 2011. We analyzed 61 subjects and 63 events. The subjects were divided into a prolonged chest tube duration group (> 18 d) and a non-prolonged group (≤ 18 d). RESULTS: Subjects with prolonged chest tube duration had significantly higher ICU mortality (P = .006), longer ICU stay (P = .001), longer hospitalization (P = .004), longer mechanical ventilation after development of pneumothorax (P = .003), higher maximum peak inspiratory pressure (P = .03), and a higher rate of surgical emphysema (P = .009). High peak inspiratory pressure and surgical emphysema remained independent predictors of prolonged chest tube duration after multivariate logistic regression analysis. The probability of chest tube removal within 28 days was significantly lower in subjects with both high peak inspiratory pressure and surgical emphysema, compared to subjects without any risk factors (log rank P = .001). CONCLUSIONS: High peak inspiratory pressure and surgical emphysema are independent predictors of prolonged chest tube duration and negatively impact clinical outcomes in this patient group. These findings may provide information for better chest tube management.

Acute kidney injury on ventilator initiation day independently predicts prolonged mechanical ventilation in intensive care unit patients.

PURPOSE: The purpose of this study is to identify the predictors for prolonged mechanical ventilation (PMV) of more than 21 days among intensive care unit (ICU) patients. MATERIAL AND METHODS: A retrospective observational study was conducted in a respiratory ICU from December 2008 to November 2009. The outcome measurement was the occurrence of PMV. Acute kidney injury (AKI) was identified and defined as an increase in the serum creatinine level of 50% or greater from baseline. RESULTS: Of 154 patients enrolled, 41 patients (26.6%) had PMV. Patients with PMV showed higher Acute Physiology and Chronic Health Evaluation II scores, lower serum albumin levels, and more AKI on mechanical ventilation (MV) initiation day compared with the non-PMV patients. Patients with PMV were significantly associated with longer MV duration before the day of readiness for weaning (DRW) and a higher rapid shallow breathing index on DRW. In a multivariate regression analysis, the independent risk factors for PMV were AKI on MV initiation day (odds ratio [OR], 5.630; 95% confidence interval [CI], 1.378-22.994; P = .016), longer MV duration before DRW (OR, 1.289; 95% CI, 1.158-1.435; P < .001), and higher rapid shallow breathing index on DRW (OR, 1.012; 95% CI, 1.003-1.021; P = .010). CONCLUSIONS: Acute kidney injury on MV initiation day is an independent risk factor for PMV of more than 21 days, which may be helpful for clinicians to refine their management of these ICU patients early.

Hyperbaric oxygen therapy as an adjunctive treatment for sternal infection and osteomyelitis after sternotomy and cardiothoracic surgery.

PURPOSE: A retrospective study to evaluate the effect of hyperbaric oxygen (HBO2) therapy on sternal infection and osteomyelitis following median sternotomy. MATERIALS AND METHODS: A retrospective analysis of patients who received sternotomy and cardiothoracic surgery which developed sternal infection and osteomyelitis between 2002 and 2009. Twelve patients who received debridement and antibiotic treatment were selected, and six of them received additional HBO2 therapy. Demographic, clinical characteristics and outcome were compared between patients with and without HBO2 therapy. RESULTS: HBO2 therapy did not cause any treatment-related complication in patients receiving this additional treatment. Comparisons of the data between two study groups revealed that the length of stay in ICU (8.7 ± 2.7 days vs. 48.8 ± 10.5 days, p < 0.05), duration of invasive (4 ± 1.5 days vs. 34.8 ± 8.3 days, p < 0.05) and non-invasive (4 ± 1.9 days vs. 22.3 ± 6.2 days, p < 0.05) positive pressure ventilation were all significantly lower in patients with additional HBO2 therapy, as compared to patients without HBO2 therapy. Hospital mortality was also significantly lower in patients who received HBO2 therapy (0 case vs. 3 cases, p < 0.05), as compared to patients without the HBO2 therapy. CONCLUSIONS: In addition to primary treatment with debridement and antibiotic use, HBO2 therapy may be used as an adjunctive and safe treatment to improve clinical outcomes in patients with sternal infection and osteomyelitis after sternotomy and cardiothoracic surgery.

Characteristic features and outcomes of severe acute respiratory syndrome found in severe acute respiratory syndrome intensive care unit patients.

PURPOSE: The aim of the study was to identify characteristic clinical features and outcomes of critically ill patients with confirmed severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: This retrospective study enrolled all patients admitted to a 12-bed SARS intensive care unit (ICU) in a tertiary care medical center in Taipei between May 15 and July 17, 2003. Patients with positive results of either reverse transcriptase-polymerase chain reaction or antibody to SARS coronavirus were defined as SARS cases and others with negative results as control cases. RESULTS: Of the 50 patients, 14 had confirmed SARS. Demographics were similar between the 2 groups. The highest leukocyte and neutrophil counts, lactate dehydrogenase, and creatine kinase; positive end-expiratory pressure; and use of corticosteroids, ribavirin, and intravenous immunoglobulin were higher in the SARS group. In contrast, the lowest lymphocyte count and the ratio of Pao(2) to the fraction of inspired oxygen were lower in the SARS group. Of the 15 deaths in the control group, 12 (80%) occurred during the first 2 weeks after ICU admission. However, in the confirmed SARS group, 5 (55.6%) of the 9 deaths occurred within the third or fourth week. This difference in timing between these 2 groups was significant (P = .004). CONCLUSIONS: In a SARS ICU, patients with a confirmed diagnosis of SARS had significantly different clinical features and timing of mortality from those of the control group.

Open reading frame 8a of the human severe acute respiratory syndrome coronavirus not only promotes viral replication but also induces apoptosis.

BACKGROUND: A unique genomic difference between human and civet severe acute respiratory syndrome coronaviruses (SARS-CoVs) is that the former has a deletion of 29 nucleotides from open reading frame (orf) 8a' that results in the generation of orf8a and orf8b. The objectives of the present study were to analyze antibody reactivity to ORF8a in patients with SARS and to elucidate the function of ORF8a. METHODS: Western-blot and immunofluorescent antibody assays were used to detect anti-ORF8a antibody. SARS-CoV HKU39849 was used to infect stable clones expressing ORF8a and cells transfected with small interfering RNA (siRNA). The virus loads (VLs) and cytopathic effects (CPEs) were recorded. Confocal microscopy and several mitochondria-related tests were used to study the function of ORF8a. RESULTS: Two (5.4%) of 37 patients with SARS had anti-ORF8a antibodies. The VLs in the stable clones expressing ORF8a were significantly higher than those in control subjects 5 days after infection. siRNA against orf8a significantly reduced VLs and interrupted the CPE. ORF8a was found to be localized in mitochondria, and overexpression resulted in increases in mitochondrial transmembrane potential, reactive oxygen species production, caspase 3 activity, and cellular apoptosis. CONCLUSIONS: ORF8a not only enhances viral replication but also induces apoptosis through a mitochondria-dependent pathway.