Performance and Clinical Utility of Various Chronic Obstructive Pulmonary Disease Case-Finding Tools.

BACKGROUND AND AIM: Chronic obstructive pulmonary disease (COPD) is frequently underdiagnosed because of the unavailability of spirometers, especially in resource-limited outpatient settings. This study provides real-world evidence to identify optimal approaches for COPD case finding in outpatient settings. METHODS: This retrospective study enrolled individuals who were at risk of COPD (age ≥40 years, ≥10 pack-years, and ≥1 respiratory symptom). Eligible participants were examined using various COPD case-finding tools, namely the COPD Population Screener (COPD-PS) questionnaire, a COPD prediction (PCOPD) model, and a microspirometer, Spirobank Smart; subsequently, the participants underwent confirmatory spirometry. The definition and confirmation of COPD were based on conventional spirometry. Receiver operating characteristic curve (ROC), area under the curve (AUC), and decision curve analyses were conducted, and a clinical impact curve was constructed. RESULTS: In total, 385 participants took part in the study [284 without COPD (73.77%) and 101 with COPD (26.23%)]. The microspirometer exhibited a higher AUC value than did the COPD-PS questionnaire and the PCOPD model. The AUC for microspirometry was 0.908 (95% confidence interval [CI] = 0.87-0.95), that for the PCOPD model was 0.788 (95% CI = 0.74-0.84), and that for the COPD-PS questionnaire was 0.726 (95% CI = 0.67-0.78). Decision and clinical impact curve analyses revealed that a microspirometry-derived FEV1/FVC ratio of <74% had superior clinical utility to the other measurement tools. CONCLUSION: The PCOPD model and COPD-PS questionnaire were useful for identifying symptomatic patients likely to have COPD, but microspirometry was more accurate and had higher clinical utility. This study provides real-world evidence to identify optimal practices for COPD case finding; such practices ensure that physicians have convenient access to up-to-date evidence when they encounter a symptomatic patient likely to have COPD.

Novel App-Based Portable Spirometer for the Early Detection of COPD.

Chronic obstructive pulmonary disease (COPD) is preventable and treatable. However, many patients remain undiagnosed and untreated due to the underutilization or unavailability of spirometers. Accordingly, we used Spirobank Smart, an app-based spirometer, for facilitating the early detection of COPD in outpatient clinics. This prospective study recruited individuals who were at risk of COPD (i.e., with age of ≥40 years, ≥10 pack-years of smoking, and at least one respiratory symptoms) but had no previous COPD diagnosis. Eligible participants were examined with Spirobank Smart and then underwent confirmatory spirometry (performed using a diagnostic spirometer), regardless of their Spirobank Smart test results. COPD was defined and confirmed using the postbronchodilator forced expiratory volume in 1 s/forced vital capacity values of <0.70 as measured by confirmatory spirometry. A total of 767 participants were enrolled and examined using Spirobank Smart; 370 participants (94.3% men, mean age of 60.9 years and mean 42.6 pack-years of smoking) underwent confirmatory spirometry. Confirmatory spirometry identified COPD in 103 participants (27.8%). At the optimal cutoff point of 0.74 that was determined using Spirobank Smart for COPD diagnosis, the area under the receiver operating characteristic was 0.903 (95% confidence interval (CI) = 0.860-0.947). Multivariate logistic regression revealed that participants who have an FEV1/FVC ratio of <74% that was determined using Spirobank Smart (odds ratio (OR) = 58.58, 95% CI = 27.29-125.75) and old age (OR = 3.23, 95% CI = 1.04-10.07 for 60 ≤ age < 65; OR = 5.82, 95% CI = 2.22-15.27 for age ≥ 65) had a higher risk of COPD. The Spirobank Smart is a simple and adequate tool for early COPD detection in outpatient clinics. Early diagnosis and appropriate therapy based on GOLD guidelines can positively influence respiratory symptoms and quality of life.

Allogeneic human umbilical cord-derived mesenchymal stem cells reduce lipopolysaccharide-induced inflammation and acute lung injury.

Acute lung injury (ALI) is the clinical disorder of acute hypoxemic respiratory deficiency and it is associated with a high mortality rate. Increased lung permeability, infiltration of inflammatory cells, secretion of inflammatory cytokines, and pulmonary edema are hallmarks of ALI. Currently, there is no effective pharmacological agent approved for ALI, and the treatment regimens available are mostly supportive. Mesenchymal stem cells (MSCs) are multipotent stromal cells with immunomodulating potential, which therefore hold great promise for the treatment of ALI. We established an LPS-induced ALI mouse model by intratracheal injection of lipopolysaccharide (LPS). Human umbilical cord-derived MSCs (hUC-MSCs) were delivered through the tail vein to assess the effects of MSCs on relieving LPS-induced ALI. Intratracheal injection of LPS increased the infiltration of neutrophils and enhanced the expression of pro-inflammatory cytokines, such as IL-6, IL-1ß and TNF-α. Administration of hUC-MSCs decreased pathological signs of inflammation, as well as reduced ALI scores. The levels of IL-6, IL-1ß and TNF-α were also dose-dependently inhibited in the bronchoalveolar lavage fluids from damaged lung tissues. Moreover, MPO and BAX levels were decreased by the hUC-MSC treatment, suggesting hUC-MSCs may play the role in inhibiting ROS production and apoptotic death in ALI repair. These results highlight the potential of hUC-MSCs to alleviate bacterial endotoxin-induced inflammation, and may represent an effective modality for the treatment of ALI in clinical settings.

Beauvericin-induced cell apoptosis through the mitogen-activated protein kinase pathway in human nonsmall cell lung cancer A549 cells.

Beauvericin (BEA) is a cyclic hexadepsipeptide that derives from Codyceps cicadae. Our previous study results indicated that the cytotoxic effects of BEA on human A549 lung cancer cells BEA occur through an apoptotic pathway, which involves the up-regulation of cytochrome c release from mitochondria, upregulation of caspase 3 activity, and cellular and morphological changes. In this study, we identified that the mitogen-activated protein kinase (MAPK) inhibitor U0126 inhibits the cytotoxic effects of BEA on A549 cells. After exposing human A549 cells to 10 µM BEA, we observed a significant and dose-dependent increase in the percentage of hypoploid (sub-G1) phase cells in the A549 population. Following the pretreatment of the A549 cells with 25 µM U0126, the distribution of A549 cells in the sub-G1 phase decreased significantly. The BEA treatment resulted in a significant increase apoptosis in A549 cells by in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Moreover, the MEK1/2 (mitogen-activated protein kinase kinase)-ERK42/44 (extracellular signal-regulated kinases)-90RSK (ribosomal s6 kinase) signaling pathway was activated in BEA-induced apoptotic A549 cells. Furthermore, treatment with MEK1/2 inhibitor U0126 was capable to attenuate the BEA induced typical apoptotic morphological change, apoptotic cells, and MEK1/2-ERK42/44-90RSK signaling pathway. These results suggested that MEK1/2-ERK42/44-90RSK signaling pathway may play a important role in BEA-induced apoptosis in human NSCLC A549 cancer cells.

ß-Elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion.

ß-elemonic acid, a known triterpene, exhibits anti-inflammatory effects, yet research on the pharmacological effects of ß-elemonic acid is rare. We investigated the anticancer effects and the related molecular mechanisms of ß-elemonic acid on human non-small cell lung cancer (NSCLC) A549 cells. The effects of ß-elemonic acid on the growth of A549 cells were studied using a 3-(4,5)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using Annexin V staining. The effect of ß-elemonic acid on the cell cycle of A549 cells was assessed using the propidium iodide method. The change in reactive oxygen species (ROS) was detected using a dichlorodihydrofluorescein diacetate (DCFH-DA) assay with microscopic examination. The expression levels of Bcl-2 family proteins, mitogen-activated protein kinase (MAPK) family proteins and cyclooxygenase 2 (COX-2) were detected using western blot analysis. Our data revealed that ß-elemonic acid strongly induced human A549 lung cancer cell death in a dose- and time-dependent manner as determined by the MTT assay. ß-elemonic acid-induced cell death was considered to be apoptotic when the phosphatidylserine exposure was observed using Annexin V staining. The death of human A549 lung cancer cells was caused by apoptosis induced by activation of ROS activity, increase in the sub-G1 proportion, downregulation of Bcl-2 expression, upregulation of Bax expression and inhibition of the MAPK signaling pathways. These results clearly demonstrated that ß-elemonic acid inhibits proliferation by inducing hypoploid cells and cell apoptosis. Moreover, the anticancer effects of ß-elemonic acid were related to the MAPK signaling pathway, ROS activation and glutathione depletion in human A549 lung cancer cells.

TD-19, an erlotinib derivative, induces epidermal growth factor receptor wild-type nonsmall-cell lung cancer apoptosis through CIP2A-mediated pathway.

Some patients with nonsmall-cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) mutations still respond to gefitinib and erlotinib, suggesting that there may be a mechanism(s) other than the EGFR pathway that mediates the tumoricidal effects. In the current study, we tested the efficacy of TD-19, a novel compound chemically modified from erlotinib, which has more potent apoptotic effects than erlotinib in EGFR wild-type NSCLC cell lines. TD-19 induced significant cell death and apoptosis in H358, H441, H460, and A549 cells, as evidenced by increased caspase-3 activity and cleavage of procaspase-9 and poly (ADP-ribose) polymerase. The apoptotic effect of TD-19 in H460 cells, which were resistant to erlotinib, was associated with downregulation of cancerous inhibitor of protein phosphatase 2A (CIP2A), increased protein phosphatase 2A (PP2A) activity, and decreased AKT phosphorylation, but minimal effects on EGFR phosphorylation. Overexpression of CIP2A partially protected the H460 cells from TD-19-induced apoptosis. Okadaic acid, a known PP2A inhibitor, significantly reduced TD-19-induced apoptosis, while forskolin, which increased PP2A activity, increased the apoptotic effect of TD-19. TD-19 inhibited the growth of H460 xenograft tumors by ∼80%. We conclude that TD-19 exerted tumoricidal effects on NSCLC cells. TD-19 provides proof that the CIP2A pathway may be a novel target for the treatment of EGFR wild-type NSCLC.

CIP2A mediates erlotinib-induced apoptosis in non-small cell lung cancer cells without EGFR mutation.

BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors show favorable clinical response in some patients with non-small cell lung cancer (NSCLC) who have no EGFR mutation, indicating alternative mechanisms for their tumoricidal effects. We previously showed erlotinib, a selective EGFR antagonist, inhibited the growth of sensitive hepatocellular carcinoma cells by inhibiting the cancerous inhibitor of protein phosphatase 2A (CIP2A) pathway. The aim of this study was to determine if erlotinib can also inhibit the growth of NSCLC cells by inactivating the CIP2A-dependent signaling pathway. METHODS: Four NSCLC cell lines (H358 H441 H460 and A549) were treated with erlotinib to determine their sensitivity to erlotinib-induced cell death and apoptosis. Expression of CIP2A and the downstream AKT were analyzed. The effects of CIP2A on erlotinib-induced apoptosis were confirmed by overexpression of CIP2A and knockdown of CIP2A gene expression in the sensitive cells and resistant cells, respectively. In vivo efficacy of erlotinib against H358 xenograft tumor was also determined in nude mice. RESULTS: Erlotinib induced significant cell death and apoptosis in H358 and H441 cells, as evidenced by increased caspase 3 activity and cleavage of pro-caspase 9 and PARP, but not in H460 or A549 cells. The apoptotic effect of erlotinib in the sensitive H358 cells was associated with downregulation of CIP2A, increase in PP2A activity and decrease in AKT phosphorylation. Overexpression of CIP2A and AKT protected the sensitive H358 cells from erlotinib-induced apoptosis. Knockdown of CIP2A gene expression by siRNA enhanced the erlotinib-induced apoptotic in the resistant H460 cells that resembled the sensitive H358 cells. Erlotinib also inhibited the growth of H358 tumors in nude mice. CONCLUSIONS: The CIP2A-dependent pathway mediates the tumoricidal effects of erlotinib on NSCLC cells without EGFR mutations in vitro and in vivo. CIP2A may be a novel molecular target against NSCLC for future drug development.

Risk of colorectal cancer in type 2 diabetic patients: a population-based cohort study.

OBJECTIVE: Most of the existing findings on the association between diabetes mellitus and colorectal cancer were generated from studies in Western societies. However, significant differences in cancer incidence and cancer-prone lifestyles are apparent between Asian and Western countries. This study aims to estimate the risks of colorectal cancer in the diabetic population in Taiwan by conducting a large-scale, controlled cohort study. METHODS: From Taiwan's Longitudinal Health Insurance Database 2005 (LHID2005), a total of 37 001 diabetic patients were identified. We also obtained data for four controls per patient, matched for sex, age and year of first entry into the LHID2005. All patients were followed up from the date of entry into the LHID2005 until they developed colorectal cancer or to the end of 2006, whichever was earlier. We used Cox's regression models to assess the risk of developing colorectal cancer, with adjustment for sex, age, comorbid disorders, and socioeconomic characteristics. RESULTS: We identified 37 001 diabetic patients and 148 004 controls. The adjusted hazard ratio for colorectal cancer in diabetes mellitus patients was 2.1 (95% confidence interval, 1.82-2.42) compared with controls. The risk was significant to both men and women. The adjusted hazard ratios for colorectal cancer were 2.03 (95% confidence interval, 1.68-2.47) in male diabetes mellitus patients and 2.17 (95% confidence interval, 1.77-2.67) in female diabetes mellitus patients. CONCLUSIONS: Our findings based on a large population-based cohort study provide evidence that diabetes mellitus may increase the risk of colorectal cancer in Asians.

Idiopathic pulmonary fibrosis in Taiwan - a population-based study.

BACKGROUND: This study took advantage of a large population-based database of the Taiwan National Health Insurance (NHI) to investigate the epidemiology of idiopathic pulmonary fibrosis (IPF) in Taiwan. METHODS: This is a retrospective cohort study based on secondary analysis of prospectively collected data in the NHI system and governmental data on death registry in Taiwan during 1997-2007. By using the broad and narrow definitions for IPF, we estimated incidence and prevalence rates of IPF, and its associated clinical outcomes. RESULTS: The estimates of annual IPF incidence rates became more stable after 2000, ranging between 0.9 and 1.6 cases per 100,000 persons. The prevalence rates became more than twofold from 2000 to 2007 (from 2.8 to 6.4 cases per 100,000 persons for the broad definition, and from 2.0 to 4.9 cases per 100,000 persons for the narrow definition). Men of age older than 75 years had markedly higher incidence and prevalence rates than other groups. Around 40% of all incidences and about 30% of prevalent cases occurred in this population group. The median survival time after IPF diagnosis was 0.9 year (interquartile range (IQR), 0.2-2.5 years) and 0.7 year (IQR, 0.1-2.3 years) for the broad and narrow definitions, respectively. Progression of IPF was the leading cause of death, followed by cancer. CONCLUSIONS: In Taiwan, elderly men were the major group suffering from IPF. Survival time was short after IPF diagnosis, and the poor survival was largely attributable to quick IPF progression after diagnosis.

Preventive use of noninvasive ventilation after extubation: a prospective, multicenter randomized controlled trial.

BACKGROUND: The effectiveness of noninvasive ventilation (NIV) after extubation in preventing post-extubation respiratory failure is still controversial. METHODS: We conducted a prospective, multicenter randomized controlled study involving patients on mechanical ventilation for > 48 hours who tolerated a 2-hour spontaneous breathing trial and were subsequently extubated. The patients were randomized to NIV or standard medical therapy. Re-intubation rate within 72 hours was the primary outcome measure. Multivariable logistic regression analysis was used to determine predictors for extubation failure. RESULTS: We randomized 406 patients to either NIV (no. = 202) or standard medical therapy (no. = 204). The 2 groups had similar baseline clinical characteristics. There were no differences in extubation failure (13.2% in control and 14.9% in NIV), intensive care unit or hospital mortality. Cardiac failure was a more common cause of extubation failure in control than in NIV. There was no difference in rapid shallow breathing index (RSBI) in extubation failure patients between control (80) and NIV (73). When using data from all patients, we found Acute Physiology and Chronic Health Evaluation (APACHE II) scores (odds ratio [OR] 1.13, 95% CI 1.07-1.20, P < .001), maximal inspiratory pressure (OR 1.04, 95% CI 1.00-1.08, P = .03), and RSBI (OR 1.03, 95% CI 1.02-1.05, P < .001) to be predictors of extubation failure. Abundant secretions were the most common reason (35.1%) for extubation failure identified by attending physicians. CONCLUSIONS: Preventive use of NIV after extubation in patients who passed spontaneous breathing trial did not show benefits in decreasing extubation failure rate or the mortality rate.

Diagnostic value of an enzyme-linked immunospot assay for interferon-γ in genitourinary tuberculosis.

The aim of this study was to evaluate the diagnostic performance of an enzyme-linked immunospot (ELISPOT) assay for interferon-γ in patients with suspected genitourinary tuberculosis (TB). A total of 30 patients with suspected genitourinary TB at the National Taiwan University Hospital, Taipei, Taiwan, were prospectively enrolled from January 2007 to December 2009, and 12 of whom had positive urine culture for Mycobacterium tuberculosis. Frequency and dysuria were the most common symptoms noted in 6 (50.0%) and 4 (33.3%) patients, respectively. Pyuria was the most common finding of urinalysis noted in 11 (91.7%) patients. Six (50.0%) patients had positive acid-fast stain in urine. Among the 30 patients, 13 patients had positive ELISPOT assay. Eleven patients with positive ELISPOT assay had culture-confirmed TB, and the remaining 2 patients without evidence of active TB had positive ELISPOT assay. The overall sensitivity, specificity, positive predictive value, and negative predictive value for genitourinary TB diagnosis by the ELISPOT assay were 91.7% (95% confidence interval [CI], 59.8-99.6%), 88.9% (95% CI, 63.9-98.1%), 84.6% (95% CI, 53.7-97.3%), and 94.1% (95% CI, 69.2-96.7%), respectively. In conclusion, ELISPOT assay can provide useful support in diagnosing genitourinary TB.

Diagnostic usefulness of enzyme-linked immunospot assay for interferon-gamma for tuberculosis in cancer patients.

The interferon-γ enzyme-linked immunospot assay (ELISPOT) has been demonstrated to be useful in the diagnosis of active tuberculosis (TB). In this study we aimed to evaluate the diagnostic performance of the ELISPOT assay in cancer patients with suspected pulmonary TB. Eighty-one cancer patients with suspected pulmonary TB were prospectively enrolled from April 2007 to December 2008, to investigate the diagnostic sensitivity and specificity of the ELISPOT assay. Of the 38 patients with TB, 33 (86.8%) had positive ELISPOT results. Of the 43 patients without TB, the results of the ELISPOT assay were negative in 35 (81.3%) patients. The overall sensitivity was 86.8%, specificity 81.3%, positive predictive value 80.5% and negative predictive value 87.5%. No significant difference was noted for the diagnostic performance of the ELISPOT assay for diagnosing TB between solid cancer and haematological cancer patients. In addition, a quantitative study did not show that TB patients with solid cancers have a better response than haematological cancer patients as measured by spot-forming cells per 10(6) peripheral blood mononuclear cells after exposure to early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10). In conclusion, the ELISPOT assay could be a useful supplementary tool for the diagnosis of pulmonary TB among cancer patients, irrespective of cancer type.

Bacteremia caused by non-faecalis and non-faecium enterococcus species at a Medical center in Taiwan, 2000 to 2008.

SUMMARY OBJECTIVES: Human infections due to non-faecalis and non-faecium Enterococcus species are emerging but data on the characteristics of these infections are limited. METHODS: We retrospectively reviewed the computerized database of the bacteriology laboratory at National Taiwan University Hospital from January 2000 through December 2008 to identify patients with non-faecalis and non-faecium enterococcal bacteremia. RESULTS: Enterococcal bacteremia was diagnosed in 1887 patients during the study period and was caused by non-faecalis and non-faecium enterococci in 182 (9.6%) of these patients. The causative organisms included Enterococcus casseliflavus (n = 59, 3.1%), Enterococcus gallinarum (n = 58, 3.0%), Enterococcus avium (n = 45, 2.4%), Enterococcus hirae (n = 9, 0.5%), Enterococcus raffinosus (n = 9, 0.5%), Enterococcus durans (n = 2, 0.1%), Enterococcus cecorum (n = 2, 0.1%), and Enterococcus canintestini (n = 1, 0.5%). A commercially-available phenotypic identification system misidentified six isolates based upon sequence analysis of 16S and groESL genes. Among the 182 patients, 74 (40.7%) had catheter-associated bloodstream infection and 69 (37.9%) presented with biliary tract infection. Healthcare-associated enterococcal bacteremia comprised 99 (54.4%) episodes and a polymicrobial etiology was found in 106 (58.2%) episodes. The clinical manifestations varied between the infecting Enterococcus species. Multivariate logistic regression showed that immunocompromised status is the only risk factor for the all cause mortality. CONCLUSIONS: Non-faecalis and non-faecium Enterococcus species can cause protean manifestations which vary with the infecting Enterococcus species. Misidentification of unusual enterococcal species might occur by the commercial identification methods and accurate identification with molecular methods is required.

The role of mild hypothermia in air embolism-induced acute lung injury.

BACKGROUND: Mild hypothermia has become an important treatment for ischemic brain injury. However, the role of mild hypothermia in air embolism-induced lung injury has not been explored. In this study, we investigated whether treatment with mild hypothermia before and synchronous with air infusion can attenuate acute lung injury induced by air embolism. METHODS: In this rat model study (Sprague-Dawley rats), pulmonary air embolism was induced by venous infusion of air at a rate of 25 microL/min for 40 minutes. Control animals received no air infusion. The rats were randomly assigned to 2 control groups of normothermia (37 degrees C) and mild hypothermia (34 degrees C) and 3 air embolism groups of mild hypothermia induced before air infusion, normothermia with air infusion, and mild hypothermia induced synchronous with air infusion. At the end of the experiment, the variables of lung injury were assessed. RESULTS: Air infusion elicited a significant increase in lung wet/dry weight ratio and protein, lactate dehydrogenase, and tumor necrosis factor-alpha concentration of the bronchoalveolar lavage fluid. Myeloperoxidase activity, neutrophil infiltration, and interstitial edema in lung tissue were also significantly increased. In addition, nuclear factor-kappaB activity was significantly increased in the lungs. Treatment with mild hypothermia before air infusion reduced increases in these variables, whereas mild hypothermia synchronous with air infusion had no significant effect on them. CONCLUSIONS: Our study suggests that mild hypothermia before air infusion decreases air embolism-induced acute lung injury. The protective mechanism seems to be the inhibition of inflammation.

Correlation between the %MinVol setting and work of breathing during adaptive support ventilation in patients with respiratory failure.

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.

Diagnostic value of procalcitonin for bacterial infection in elderly patients in the emergency department.

OBJECTIVES: To evaluate the diagnostic performance of procalcitonin (PCT) in elderly patients with bacterial infection in the emergency department (ED). DESIGN: Prospective. SETTING: ED of a tertiary care hospital. PARTICIPANTS: Elderly patients with systemic inflammatory response syndrome (SIRS) enrolled from September 2004 through August 2005. MEASUREMENTS: A serum sample for the measurement of PCT, two sets of blood cultures, and other cultures of relevant specimens from infection sites were collected in the ED. Two independent experts blinded to the PCT results classified the patients into bacterial infection and nonbacterial infection groups. RESULTS: Of the 262 patients with SIRS enrolled, 204 were classified as having bacterial infection and 48 as having bacteremia. PCT levels were significantly higher in patients with bacteremia than in those without. The area under the receiver operating characteristic curve for identification of bacteremia according to PCT was 0.817 for the old-old group (>or=75), significantly higher than 0.639 for the young-old group (65-74); P=.02). The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of PCT for bacteremia in patients aged 75 and older were 96.0%, 68.3%, 33.8%, and 98.8%, respectively, with a PCT cutoff value of 0.38 ng/mL. CONCLUSION: PCT is sensitive for diagnosing bacteremia in elderly patients with SIRS at ED admission but is helpful in excluding bacteremia only in those aged 75 and older. PCT is not an independent predictor of local infections in these patients.

Enhancement effects of hypercapnia on the acute lung injury caused by acid aspiration.

Acid aspiration or intrapulmonary instillation of gastric particles causes lung inflammation leading to acute lung injury (ALI). Hypercapnia exerts different effects on ALI caused by various insults. The effects of hypercapnia on lung inflammation and injury due to acid aspiration are yet to be determined. The present study was designed to investigate the involvement of inducible nitric oxide synthase (iNOS) and other mediators in acid-aspiration-induced ALI. We also sought to evaluate the effects of hypercapnia on the lung and associated changes induced by acid aspiration. We used Spague-Dawley rats anesthetized with intraperitioneal pentobarbital (40 mg/kg). Gastric acid particles were prepared from the stomach contents of rats at necropsy. The rats were randomly assigned to receive intratracheal instillation of physiological saline solution (PSS) at pH 7.24 (Control group), PSS at pH 1.25 (Low pH, LPH group), gastric particles (GP group), and GP with low pH PSS (GPLPH group). There were 10 rats in each group. The animals were observed for 6 hrs. To evaluate the effects of hypercapnia, we carried out two series of experiments: one under normocapnia and the other under hypercapnia with alteration of CO2 fraction in inspired air. Arterial pressure (AP) was monitored from the femoral arterial catheter. Heart rate was obtained from AP traicing. We determined the blood gases and acid-base status. Lung weight to body weight (LW/BW) ratio, LW gain (LWG), protein concentration in bronchoalveolar lavage (PCBAL) and leakage of Evans blue dye tracer were measured. Plasma nitrate/nitrite, methyl guanidine (MG), myeloperoxidase (MPO), phospholipase A2 (PLA2), proinflammatory cytokines were assessed. Histopathological examination of the lung tissue was performed. We employed reverse-transcriptase polymerase chain reaction to detect the expression of iNOS mRNA. GP and GPLPH caused hypotension, decreases in PaO2, pH and SaO2, and an increase in PaCO2. The insults also elevated LW/BW, LWG, PCBAL and dye leakage, plasma nitrate/nitrite, MG, MPO, PLA2, tumor necrosis factor(alpha), interleukin-beta and interleukin-6. The lung pathology was characterized by alveolar edema and hemorrhage with inflammatory cells infiltration. Assessment of lung injury score revealed that GP and GPLPH caused ALI. Furthermore, hypercapnia significantly enhanced ALI and associated changes following LPH, GP and GPLPH. Intratracheal instillation of GP in normal or low pH PSS causes ALI accompanied with biochemical changes. The release of nitric oxide via iNOS isoform is detrimental to the lung. Hypercapnia tended to enhance ALI and associated changes induced by gastric acid instillation.