Design and Study of a Portable High-frequency Ventilator for Clinical Applications.

Treatment costs for ventilator-dependent patients are a substantial burden not only for their family but also for medical systems in general. Recently, using high-frequency ventilators have been shown to reduce the risk of lung injury through low-volume airflow. However, the machines used today remain bulky, costly, and only for use in hospital settings. To provide intermediate therapy for patients between hospitalization and complete discharge, a portable, light-weight high-frequency ventilator is an urgent need. This work presents the design of a portable high-frequency ventilator and a study of its practicality for further clinical medical applications. Through the integration of advanced electronics and mechanical instruments, we develop a portable high-frequency ventilator with reconfigurable oxygen flow rate, applied pressure, and air volume for the needs of individual patients. A miniaturized portable high-frequency ventilator with digital controller and feedback system for stabilization and precision control is implemented. The efficiency of CO2 washout using the proposed ventilator has been demonstrated in animal trials.

Triggering receptor expressed on myeloid cells-1 in pleural effusions: a marker of inflammatory disease.

BACKGROUND: Triggering receptor expressed on myeloid cells (TREM)-1 is a recently described molecule that plays an important role in myeloid cell-activated inflammatory responses. The aim of this study was to investigate the expression of TREM-1 in pleural effusions of various causes. METHODS: For this cross-sectional, observational study conducted between February and August 2005 in Taiwan, 74 patients with pleural effusions of varying etiology were investigated. Soluble TREM-1 (sTREM-1) was measured in pleural fluid samples, and cells in the fluid were assessed for surface expression of TREM-1. RESULTS: Concentrations of sTREM-1 were significantly higher in infectious and neoplastic pleural effusions (189.1+/-36.7 and 69.9+/-22.8ng/ml, mean+/-sem) than in transudates (10.1+/-5.3ng/ml; P<0.001). Among infectious effusions, the sTREM-1 levels were significantly higher in parapneumonic than in tuberculous effusions (301.8+/-49.8 vs. 38.9+/-17.3ng/ml; P<0.001). TREM-1 was expressed on a portion of the myeloid (CD11b positive) cells in each type of effusion, without significant differences among them (transudative, 34.7%; neoplastic, 36.0%; parapneumonic, 27.7%; tuberculous, 21.2%; P=0.861). Non-myeloid cells expressed very little TREM-1 (transudative, 6.3%; neoplastic, 0.5%; parapneumonic, 1.0%; tuberculous, 0.7%; P=0.192). CONCLUSIONS: sTREM-1 expression in pleural fluids is highest in parapneumonic and neoplastic effusions but low in transudates. In infectious effusions, a high concentration of sTREM-1 may exclude tuberculous pleurisy.

Early evolution of arterial oxygenation in severe community-acquired pneumonia: a prospective observational study.

PURPOSE: Acute respiratory failure requiring mechanical ventilation in severe community-acquired pneumonia has been shown to be a significant negative prognostic factor. We analyzed the early evolution of the Pao(2)/Fio(2) ratio and evaluated its clinical value as an outcome predictor. MATERIALS AND METHODS: This is a prospective study conducted in a tertiary referral hospital. In 62 adult patients requiring early mechanical ventilation due to severe community-acquired pneumonia, we measured serial changes in Pao(2)/Fio(2) ratio and other clinical variables within the first 48 hours of mechanical ventilation and compared the difference between survivors and nonsurvivors. RESULTS: The initial Pao(2)/Fio(2) ratio was lower in nonsurvivors (n = 27) than in survivors (n = 35) (158.0 +/- 55.8 vs 117.9 +/- 50.6, P = .025). Over the next 48 hours, the ratio increased significantly in survivors but not in nonsurvivors (analysis of variance, P < .001). An increase in Pao(2)/Fio(2) ratio greater than 56 mm Hg had a sensitivity of 75% and a specificity of 81% of survival. A definite causative pathogen was identified in 36 patients (58%) and the 3 most commonly isolated pathogens were Streptococcus pneumoniae, Staphylococcus aureus, and Klebsiella pneumoniae. Ten patients received inadequate initial empirical antimicrobial therapy, in which the Pao(2)/Fio(2) ratio change was significantly less than those who were adequately treated (analysis of variance, P < .001). Mortality was much higher (86% [6/7]) in patients who received inadequate antibiotics and where Pao(2)/Fio(2) ratio change was less than 56 mm Hg. On multivariate analysis, trend changes in Pao(2)/Fio(2) ratio over 48 hours, shock, and Acute Physiology and Chronic Health Evaluation II score were documented to be independent predictors of mortality. CONCLUSIONS: A progressive improvement of Pao(2)/Fio(2) ratio during the first 48 hours of mechanical ventilation indicates favorable outcome. Serial measurement of this ratio should be considered in decision making for therapeutic strategy.

Lack of prognostic value of EGFR mutations in primary resected non-small cell lung cancer.

PURPOSE: To investigate the prognostic value of epidermal growth factor receptor (EGFR) mutations in a series of Taiwanese patients with primary resected lung adenocarcinomas never treated with epidermal growth factor receptor tyrosine kinase (TK) inhibitor. PATIENTS AND METHODS: A total of 27 of 35 patients whose EGFR mutational status in exons 18, 19, and 21 of the TK domain had been previously determined using nested polymerase chain reaction (PCR) were included in this retrospective study. All 27 patients underwent potentially curative pulmonary resection. Clinicopathological information was obtained from patient records and pathology reports. Disease-free survival (DFS) and overall survival (OS) of patients were estimated with the Kaplan-Meier method, and Cox regression model was used for multivariate analysis. RESULTS: Heterozygous EGFR mutations were detected in 15 of 27 patients (55.5%). There was no significant difference in DFS between patients with wild-type EGFR (median, 16.87 months) and mutant EGFR (median, 18.13 months; P = 0.83). No significant difference in OS was also noted between the wild-type and mutant groups (P = 0.45, median follow-up 22.6 months). Cox regression model and multivariate analysis of survival difference by age, stage, histology, and adjuvant treatment did not reach statistical significance. CONCLUSION: EGFR mutations do not have significant prognostic value in primary resected non-small cell lung cancer (NSCLC), and further well-designed large prospective studies are warranted to determine the prognostic value of EGFR mutations in NSCLC.

Experience with a step-down respiratory care center at a tertiary referral medical center in Taiwan.

OBJECTIVE: The aim of the study was to describe the outcome of patients after 1 year's implementation of an integrated delivery system for respiratory care mandated by the National Health Insurance Bureau in Taiwan. DESIGN: A retrospective observational study was conducted in a step-down respiratory care center (RCC). PATIENTS: Patients included adults receiving prolonged mechanical ventilation (> or =21 days). MEASUREMENTS AND MAIN RESULTS: A total of 224 cases were available for review; 108 (48.2%) patients were successfully weaned. Those who failed weaning had a longer stay in the intensive care unit and RCC (25.1 vs 20.9 and 31.4 vs 18.6 days, P < .05), but there were no differences in the patients' ages (74.3 vs 70.4 years, P = .17) or the Simplified Acute Physiology Score II (52 vs 46.9, P = .18) before admission to the RCC. After discharge from the RCC, only 4.9% of the patients still on a ventilator were weaned within 1 year. Patients who failed weaning in the RCC had a shorter overall survival (5.2 vs 10.4 months, P < .05) and a lower 1-year survival (23.6% vs 44.6%, P < .05). CONCLUSION: Patients admitted to the RCC were still critically ill. Patients who failed weaning in the RCC had had a longer intensive care unit and RCC stay and a worse outcome after leaving the RCC.

Effect of a hospital-based case management approach on treatment outcome of patients with tuberculosis.

BACKGROUND/PURPOSE: Tuberculosis (TB) continues to pose a heavy public health burden in Taiwan. This prospective study analyzed the factors influencing treatment outcome in patients with TB treated with and without a hospital-based case management (HBCM) approach in a referral center in Taipei. METHODS: A register-based cohort study design was used to enroll all new cases of pulmonary or extrapulmonary TB from February 2003 to January 2004. The case manager served as the coordinator among patients, physicians and public health nurses, to facilitate compliance with anti-TB treatment. Treatment outcomes were assessed according to the consensus recommendations of the World Health Organization and the International Union Against Tuberculosis and Lung Disease. RESULTS: Suspected or confirmed pulmonary or extrapulmonary TB was diagnosed in 524 patients in our hospital from February 2003 to January 2004. Fifty-two of these patients were excluded due to duplicate reporting, previous treatment or death before enrollment. Out of 472 patients enrolled, 103 whose original diagnosis was revised were further excluded, leaving 369 cases eligible for analysis. Patients with case management had a significantly higher rate of successful treatment (cured plus completed treatment) compared to patients without case management, (240/277, 86.6% vs. 67/92, 72.8%; p = 0.002). The overall successful treatment rate including both case and non-case management was 83.2% (307/369), which was higher than the nationwide surveillance data of 78.3% in 2002 and 69.4% in 2003. CONCLUSION: Treatment of TB patients by a HBCM approach provides improved treatment outcomes compared to those without case management.

Female sex and bronchioloalveolar pathologic subtype predict EGFR mutations in non-small cell lung cancer.

STUDY OBJECTIVES: The prevalence of epidermal growth factor receptor (EGFR) mutations in gefitinib-naive lung cancer patients is higher in adenocarcinomas, in women, and in Japanese. To further investigate the prevalence of EGFR mutations in relation to ethnic and geographic factors, we evaluated EGFR mutations in a series of Taiwanese patients with primary lung adenocarcinomas who had never been treated with gefitinib. DESIGN AND METHODS: We retrospectively studied 35 primary lung adenocarcinoma samples for mutations in the tyrosine kinase domain of EGFR; exons 18, 19, and 21 were analyzed by nested polymerase chain reaction and automated sequencing. Clinicopathologic information was obtained from patient records and pathology reports. Correlation between EGFR mutations and patient characteristics, including sex, smoking history, and pathologic subtypes, were evaluated by using the chi(2) test and logistic regression analysis. RESULTS: Heterozygous EGFR mutations were detected in 17 of 35 patients (48%). Missense mutations in exon 21 (13 of 17 patients, 76%) were the most frequent mutations detected. EGFR mutations were more frequent in women (13 of 18 patients [72%]) than in men (4 of 17 patients [23%]; p = 0.004), more frequent in nonsmokers (14 of 21 patients [66%]) than in current smokers (3 of 14 patients [21%]; p = 0.009), and when any degree of bronchioloalveolar carcinoma (BAC) was present (14 of 21 patients [66%]) compared with pure adenocarcinoma (3 of 14 patients [21%]; p = 0.009). Logistic regression analysis demonstrated that female gender (odds ratio [OR], 10.913; 95% confidence interval [CI], 1.778 to 66.97; p = 0.01) and BAC, including adenocarcinomas with any bronchioloalveolar features (OR, 9.708; 95% CI, 1.464 to 64.393; p = 0.019), were significantly associated with EGFR mutations. CONCLUSIONS: In our series, female sex and bronchioloalveolar pathologic subtype predicted the presence of EGFR mutations in lung adenocarcinomas, and the high frequency of EGFR mutations supports the hypothesis that genetic backgrounds and/or environmental factors may affect the pathogenesis of certain lung cancers.

Azygos vein varix mimicking mediastinal mass in a patient with liver cirrhosis: a case report.

A giant venous varix of the azygos arch is a very rare cause of a mediastinal mass. The usual diagnosis of a mediastinal mass by mediastinoscopy or percutaneous fine-needle aspiration or biopsy is very hazardous if there is a venous varix. Noninvasive thoracic CT scanning is a safe and better choice for diagnosis. We describe the case of a woman with a posterior mediastinal mass caused by a giant azygos vein varix. Thoracic CT documented the diagnosis. The etiology of the azygos varix was portal hypertension secondary to liver cirrhosis.

Adverse effects of ribavirin and outcome in severe acute respiratory syndrome: experience in two medical centers.

STUDY OBJECTIVES: To assess the effect of ribavirin-induced anemia on the outcome of severe acute respiratory syndrome (SARS). DESIGN: A retrospective observational study. SETTING: Two medical centers in Taiwan. PATIENTS: Forty-four patients with SARS who received ribavirin and 7 patients with SARS who did not receive ribavirin. MEASUREMENTS AND RESULTS: The mean peak C-reactive protein and lactate dehydrogenase levels were higher in SARS patients who were receiving ribavirin therapy than in SARS patients who were not receiving ribavirin therapy. The mortality was also higher, but the difference was not statistically significant. On multivariate analysis, hemoglobin level was an independent prognostic correlate of hypoxemia or mortality (odds ratio, 2.0; 95% confidence interval, 1.1 to 3.8; p = 0.03). The hemoglobin began decreasing in two thirds of SARS patients (32 of 44 patients; 73%) who were receiving ribavirin 3 days after therapy with the antiviral drug was started. Patients with a drop in hemoglobin level of > 2 g/dL had a significantly higher mortality rate than the other patients. Hypoxemia developed in one third of SARS patients (17 of 44 patients; 39%) who were receiving ribavirin, all of whom were anemic. Of the 17 hypoxemic patients, 11 (65%) had a drop in hemoglobin of > 2 g/dL, and 4 patients (24%) required a blood transfusion. The mean slope of the hemoglobin decrease was significantly steeper (p = 0.001) in hypoxemic patients with SARS who were receiving ribavirin than in the nonhypoxemic patients with SARS who were receiving ribavirin. Only one of seven SARS patients (14%) who was not receiving ribavirin became anemic, but this individual was not hypoxemic. Eventually, 5 of 17 hypoxemic and anemic SARS patients (29%) who were receiving ribavirin died. The combination of hypoxia with anemia was thus significantly associated with a higher mortality (p < 0.001). CONCLUSIONS: Hypoxia combined with anemia increased the risk for death in SARS patients. Unless ribavirin can be shown to be effective against SARS-coronavirus, the risk of anemia posed by this drug argues against its use in SARS patients.

Comparative study of patients with and without SARS who fulfilled the WHO SARS case definition.

To differentiate severe acute respiratory syndrome (SARS) from non-SARS illness, we retrospectively compared 53 patients with probable SARS and 31 patients with non-SARS who were admitted to Mackay Memorial Hospital from April 27 to June 16, 2003. Fever (> 38 degrees C) was the earliest symptom (50/53 SARS vs. 5/31 non-SARS, p < 0.0001), preceding cough by a mean of 4.5 days. The initial chest X-ray study was normal in 22/53 SARS cases versus 5/31 non-SARS cases. SARS patients with an initially normal chest X-ray study developed infiltrates at a mean of 5 +/- 3.44 days after onset of fever (21/22 SARS vs. 0/5 non-SARS). Rapid radiographic progression of unifocal involvement to multifocal infiltrates was seen in 22 of 24 SARS vs. 0 of 26 non-SARS patients (p < 0.0001). Pleural effusion was not present in any SARS patients but was seen in 6 of 26 non-SARS cases (p < 0.0001). Initial lymphopenia, thrombocytopenia, and elevated lactate dehydrogenase were all more common in SARS than non-SARS (p < 0.0001). They may help differentiate SARS from non-SARS if a reliable and rapid diagnostic test is not available.

Quantitative culture of endotracheal aspirates in the diagnosis of ventilator-associated pneumonia in patients with treatment failure.

STUDY OBJECTIVE: To study the correlation of bacteriology between quantitative cultures of protected specimen brush (PSB), BAL, and quantitative endotracheal aspirate (QEA) in ventilator-associated pneumonia (VAP) patients with treatment failure. DESIGN: Prospective observational clinical study. SETTING: A 15-bed medical ICU of tertiary medical center. PATIENTS: Forty-eight patients receiving mechanical ventilation with clinical suspected VAP who had been treated with antibiotics for at least 72 h without improvement. INTERVENTION: QEA, PSB, and BAL were performed with patients receiving antibiotics. The diagnostic thresholds for QEA, PSB, and BAL were 10(5), 10(3), and 10(4) cfu/mL, respectively. MEASUREMENTS AND RESULTS: Microbial culture findings were positive in 24 BAL samples (50%), in 23 PSB samples (48%), and in 28 QEA samples (58%). The correlations between of QEA vs PSB and QEA vs BAL were significant (rho = 0.567 and rho = 0.620, p < 0.01, respectively). The most commonly isolated microorganisms were Acinetobacter baumannii (27%), Staphylococcus aureus (24%), Stenotrophomonas maltophilia (15%), and Pseudomonas aeruginosa (10%). Using the predetermined criteria, bacterial pneumonia was diagnosed in 28 of 48 suspected VAP episodes based on PSB and/or BAL results. The diagnostic efficiency of QEA at threshold of 10(5) cfu/mL had a sensitivity of 92.8% and a specificity of 80%. CONCLUSIONS: QEA correlated with PSB and BAL in patients with suspected VAP who responded poorly to the existent antibiotic treatment. QEA missed only two cases of bacterial pneumonia diagnosed by invasive PSB and/or BAL with acceptable sensitivity and specificity. More importantly, QEA is noninvasive and easily repeatable. Early use of QEA is helpful to clinical physicians in decision making with regard to antibiotics use.

Clinical and laboratory features of severe acute respiratory syndrome vis-a-vis onset of fever.

STUDY OBJECTIVES: Severe acute respiratory syndrome (SARS) is a rapidly progressive disease caused by a novel coronavirus (CoV) infection. However, the disease presentation is nonspecific. The aim of this study was to define clearly the presentation, clinical progression, and laboratory data in a group of patients who had SARS. DESIGN: Retrospective observational study. SETTING: A tertiary care medical center with 51 negative-pressure isolation rooms in Taipei, Taiwan. PATIENTS: Fifty-three patients with SARS seen between April 27 and June 16, 2003. RESULTS: Fever (ie, temperature > 38 degrees C) was the most common symptom (98%) and the earliest. When admitted to the isolation unit of the hospital for observation, most patients reported nonspecific symptoms associated with their fever. Only two patients with preexisting illnesses had cough on the same day the fever began. Eventually, 39 patients (74%) developed cough, beginning at a mean (+/- SD) time of 4.5 +/- 1.9 days after fever onset, and 35 patients (66%) had diarrhea beginning at a mean time of 6.0 +/- 3.3 days after fever onset. Thirty-one patients (59%) had abnormal findings on chest radiographs on hospital admission, and all but 1 patient (98%) eventually developed lung infiltrates that were consistent with pneumonia. The majority of patients (63%) first developed unifocal infiltrates at a mean time of 4.5 +/- 2.1 days after fever onset, while in 37% of patients the initial infiltrates were multifocal, appearing at a mean time of 5.8 +/- 1.3 days after fever onset. Common laboratory findings included lymphopenia (on hospital admission, 70%; during hospitalization, 95%), thrombocytopenia (on hospital admission, 28%; during hospitalization, 40%), elevated lactate dehydrogenase (on hospital admission, 58%; during hospitalization, 88%), creatine kinase (on hospital admission, 18%; during hospitalization, 32%), and aspartate aminotransferase or alanine aminotransferase levels (on hospital admission, 27%; during hospitalization, 62%). Throat or nasopharyngeal swab for SARS-CoV by reverse transcriptase polymerase chain reaction (PCR) and real-time PCR was positive in 40 of the 47 patients (85%) in whom the test was performed. CONCLUSIONS: None of the presenting symptoms or laboratory findings are pathognomonic for SARS. Even though cough developed in a majority of patients, it did not occur until later in the disease course, suggesting that a cough preceding or concurrent with the onset of fever is less likely to indicate SARS. While PCR for SARS-CoV appears to be the best early diagnostic test currently available, it is clear that better methods are needed to differentiate between SARS and non-SARS illness on initial presentation.

Pseudomembranous tracheobronchitis caused by Aspergillus in immunocompromised patients.

We report 2 cases of Aspergillus pseudomembranous tracheobronchitis in patients with diabetes. The first patient succumbed to progressive obstructive respiratory failure despite mechanical ventilation and antifungal therapy. However, the second patient survived. Aspergillus tracheobronchitis should be considered in immuno-compromised patients presenting with cough, chest pain, fever, dyspnea and upper airway obstruction. Early bronchoscopy and histologic examination should be performed. Early, appropriate treatment may be life saving.