Jeng-Yuan Hsu

Effects of Prone Position on Inflammatory Markers in Patients with ARDS Due to Community-acquired Pneumonia

BACKGROUND/PURPOSE Acute respiratory distress syndrome (ARDS) is a serious disorder of intensive care unit patients. We evaluated the safety of continuous prone position ventilation (PRONE) and its effects on oxygenation and plasma cytokine concentrations in patients with ARDS caused by severe community-acquired pneumonia (CAP). METHODS This was a prospective observational clinical study conducted in a respiratory intensive care unit of a 1200-bed medical center in central Taiwan. Twenty-two patients with severe CAP and ARDS were included. They were treated by traditional supine ventilation (SUPINE, n = 11) or PRONE (n = 11) if they met the criteria for ARDS. Patients in the PRONE group were ventilated in prone position continuously for at least 72 hours. Plasma cytokines were collected and analyzed at baseline, 24 hours and 72 hours after enrolment. Serial PaO2/FiO2 and complications were evaluated. RESULTS Complications associated with PRONE were minor and self-limited. PRONE had higher PaO2/FiO2 ratio than SUPINE did at 48 hours after enrolment. The levels of plasma IL-6 concentration declined significantly with time in the PRONE group (p = 0.011). The levels of plasma IL-6 concentration at enrolment, 24 hours and 72 hours after enrolment also predicted the 14th day mortality of all patients. CONCLUSION PRONE was a safe and effective maneuver for improving oxygenation in patients with severe CAP and ARDS. PRONE also influenced IL-6 expression in patients with severe CAP.

Activity of gefitinib in advanced non-small-cell lung cancer with very poor performance status

Advanced non-small-cell lung cancer (NSCLC) patients with poor performance status (PS) are less likely to respond to chemotherapy, or to have an improvement in survival, but more likely to experience toxicity. We retrospectively evaluated the efficacy and tolerability of gefitinib in patients with advanced NSCLC and very poor PS in Taiwan. Patients with stage IIIB, IV NSCLC with an Eastern Cooperative Oncology Group (ECOG) PS of 3–4 received oral gefitinib 250 mg once daily. Totally, 52 patients were included (25 men, 27 women). Forty-three patients (82.7%) were in a PS of 3. Tumor response rate was 25.0% (13/52). Tumor response rate to gefitinib was highest in chemonaive patients 38.1% (8/21) vs. failed 1 chemotherapy regimen 13.3% (2/15) vs. failed 2 or more chemotherapy regimens 18.8% (3/16), p = 0.015. The median overall survival was 2.5 months (response group 9.1 months, stable disease 3.1 months, and progressive group 0.8 month, p < 0.001). Adverse events, mainly skin reactions and diarrhea, were generally mild (grade 1 or 2) except paronychia and acne. Thus, gefitinib has clinically antitumor activity and good tolerability in {Taiwan} patients with advanced NSCLC and very poor performance status, with a higher response rate than that seen Europe or in European heritage Americans. Chemonaive patients responded better than patients with prior chemotherapy. Formal clinical trials are warranted to evaluate the role of gefitinib in this situation.

Predictive Factors of Gefitinib Antitumor Activity in East Asian Advanced Non-small Cell Lung Cancer Patients

Background: Gender, smoking history, adenocarcinoma histology, performance status, and East Asian ethnicity were predictive factors of gefitinib response in previous analysis. However, these factors tend to be correlated with each other; it is not clear whether gender, smoking history, and adenocarcinoma histology were all independent predictors for response in East Asian populations. Methods: Tumor response, survival and predictive factors of gefitinib response of advanced non-small cell lung cancer patients treated between May of 2002 and November of 2004 were collected retrospectively from three medical centers in Taiwan. Univariate and multivariate logistic regression models were used to test potential predictive factors associated with response to gefitinib. Overall survivals between groups with different predictive factors were compared by log-rank tests. Multivariate analyses were performed to identify factors that independently predict for survival. Results: A total of 428 patients were analyzed. The median follow-up duration for living patients was 19.5 months (range, 10.2–39.9). Objective tumor response was observed in 114 patients (26.6%, 95% confidence interval [CI]: 22.4%–30.8%) and disease stabilization in 129 patients (30.2%). Response rate was statistically significant higher in adenocarcinoma, good performance status, and chemonaive patients in multivariate analysis. The median survival was 7.4 months (95% CI: 5.8–9.0) and 1-year survival was 34.3% (95% CI: 29.0%–38.0%). Significant independent predictive factors associated with longer survival in multivariate analysis were good performance status (p < 0.001) and responsiveness to gefitinib (p < 0.001). In 286 chemotherapy-treated patients, the response rate was 22.7%. Median and 1-year survival was 7.9 months and 36.7%, respectively. Good performance status was predictive of tumor response (p < 0.001) and better survival (p < 0.001) in multivariate analysis. Response to gefitinib was predictive of better survival (p < 0.001). Conclusions: Gender and smoking status were not, but good performance status (PS), no previous chemotherapy, and adenocarcinoma histology were independent predictive factors in multivariate analysis for gefitinib response in Taiwanese advanced non-small cell lung cancer population. In patients previously treated with chemotherapy, only good PS was an independent predictor for tumor response in multivariate analysis.

Procalcitonin is a valuable prognostic marker in ARDS caused by community-acquired pneumonia

Background and objective:  ARDS is life‐threatening acute respiratory failure, and pneumonia is one of the most common causes of direct ARDS. Procalcitonin (PCT) has been evaluated for its utility in determining the aetiology of community‐acquired pneumonia (CAP), choice of antibiotics and prediction of outcome. This study evaluated the role of PCT in predicting the outcome of patients with ARDS caused by severe CAP.

Evaluation of a new inflammatory molecule (triggering receptor expressed on myeloid cells-1) in the diagnosis of pleural effusion

Background and objective:  The triggering receptor expressed on myeloid cell‐1 (TREM‐1) is a newly discovered molecule that is associated with the inflammatory response to microorganisms. We investigated the role of surface and soluble TREM‐1 in differentiating different disease entities in pleural effusion formation.

Etiology and cytokine expression in patients requiring mechanical ventilation due to severe community-acquired pneumonia.

BACKGROUND The relationship between bacterial etiology and serum cytokine levels in patients with severe community-acquired pneumonia (CAP) without response to initial empiric treatment remains unclear. This study investigated the bacterial etiology, outcomes, and bronchoalveolar and systemic cytokines (interleukin [IL]-1beta, IL-8, IL-10) in these patients. METHODS This hospital-based study enrolled 47 consecutive patients without response to initial empiric treatment and requiring mechanical ventilation due to severe CAP between July 1, 2000 and October 31, 2001, in a respiratory intensive care unit of a 1200-bed teaching hospital in central Taiwan. Bronchoalveolar lavage (BAL) was performed within 3 days after hospitalization. BAL fluid was processed for quantitative bacterial cultures. Blood samples were taken just before BAL, and the levels of both BAL and serum cytokines were measured. RESULTS The most common pathogens isolated were Pseudomonas aeruginosa (22.5%) and Klebsiella pneumoniae (25%). Patients with a K. pneumoniae isolate (n = 10) had significantly higher levels of IL-1beta in BAL fluid and significantly higher levels of IL-10 in serum and BAL fluid than patients with other etiologies. Non-survivors had higher levels of serum IL-8 (p = 0.001), serum IL-10 (p < 0.001) and BAL IL-10 (p = 0.039) than survivors. Marked increases in local and systemic cytokine expression (IL-8 and IL-10) were noted in rapidly fatal cases. CONCLUSION P. aeruginosa and K. pneumoniae are the most common causes of CAP requiring mechanical ventilation in Taiwan. Cytokine patterns in the BAL fluid and serum of patients with severe CAP due to K. pneumoniae showed significant elevations compared to other pathogens. Bronchoalveolar and systemic cytokine levels (especially IL-10) predicted mortality. These findings suggest the need for a clinical trial to determine how immunomodulating therapy might affect cytokine profiles and clinical outcome.

Key Process Indicators of Mortality in the Implementation of Protocol-driven Therapy for Severe Sepsis

BACKGROUND/PURPOSE Severe sepsis and septic shock are life-threatening disorders. Integrating treatments into a bundle strategy has been proposed to facilitate timely resuscitation, but is difficult to implement. We implemented protocol-driven therapy for severe sepsis, and analyzed retrospectively the key process indicators of mortality in managing sepsis. METHODS Continuous quality improvement was begun to implement a tailored protocol-driven therapy for sepsis in a 24-bed respiratory intensive care unit (RICU) of Taichung Veterans General Hospital from January 2007 to February 2008. Patients, who were admitted to the RICU directly, or within 24 hours, were enrolled if they met the criteria for severe sepsis and septic shock. Disease severity [Acute Physiology and Chronic Health Evaluation (APACHE) II and lactate level], causes of sepsis, comorbidity and site of sepsis onset were recorded. Process-of-care indicators included resuscitation time (Tr-s), RICU bed availability (Ti-s) and the ratio of completing the elements of the protocol at 1, 2, 4 and 6 hours. The structure and process-of-care indicators reflated to mortality at 7 days after RICU admission and at RICU discharge were identified retrospectively. RESULTS Eighty-six patients (mean age, 71 +/- 14 years, 72 men, 14 women, APACHE II, 25.0 +/- 7.0) were enrolled. APACHE II scores and lactate levels were higher for mortality than survival at 7 days after RICU admission (p < 0.01). For the process-of-care indicators, Ti-s (562.2 +/- 483.3 vs.1017.3 +/- 557.8 minutes, p = 0.03) and Tr-s (60.7 +/- 207.8 vs. 248.5 +/- 453.1 minutes, p = 0.07) were shorter for survival than mortality at 7 days after RICU admission. The logistic regression study showed that Tr-s was an important indicator. The ratio of completing the elements of protocols at 1, 2, 4 and 6 hours ranged from 70% to 90% and was not related to mortality. CONCLUSION Protocol-driven therapy for sepsis was put into clinical practice. Early resuscitation and ICU bed availability were key process indicators in managing sepsis, to reduce mortality.

Predictive value of serial measurements of sTREM-1 in the treatment response of patients with community-acquired pneumonia.

BACKGROUND/PURPOSE To evaluate the roles of plasma sTREM-1 (soluble triggering receptor expressed on myeloid cells-1) and C-reactive protein (CRP) in predicting treatment response in patients with community-acquired pneumonia (CAP). METHODS Patients with CAP were enrolled prospectively at a medical center in central Taiwan from September 1, 2004 to July 31, 2005. They were treated according to the guidelines proposed by the American Thoracic Society. Patients were noted as nonresponsive to initial treatment if they had one of the following: persistent fever for more than 3 days, progression on chest radiograph, switching to other antibiotics, or need of mechanical ventilation and/or chest tube drainage. RESULTS Fifty-eight patients (43 males/15 females; mean age, 67 +/- 21 years) with CAP were enrolled. Twelve (12/58, 21%) were nonresponsive. In the response group, CRP was reduced up to 58% from day 1 to day 3 (from 18.8 to 7.8 mg/dL), whereas sTREM-1 was reduced by only 15% (from 32.8 to 28.1 pg/mL). In the nonresponse group, CRP still declined 20% (from 22.2 to 17.7 mg/dL), whereas sTREM-1 was persistently high (from 61.7 to 63.7 pg/mL). Using multivariate logistic regression analysis, both CRP (p = 0.006) and sTREM-1 (p = 0.046) on day 3 predicted treatment response significantly, but CRP on day 3 had stronger statistic power. CONCLUSION Both CRP and sTREM-1 on day 3 could be useful in predicting nonresponsive CAP patients. Differential trends between sTREM-1 and CRP in nonresponsive CAP suggest that sTREM-1 could be an adjuvant biomarker to CRP in predicting CAP patients without response to empiric treatment.

Differences in IL-8 in serum and exhaled breath condensate from patients with exacerbated COPD or asthma attacks

BACKGROUND/PURPOSE The collection of exhaled breath condensate (EBC) is a noninvasive method that can be used to monitor the inflammatory status of patients with chronic airway diseases. We aimed to study differences in cytokine expression between patients with exacerbations of chronic obstructive pulmonary disease (COPD) and patients with asthma attacks. METHODS Using a custom-made device and methods based on American Thoracic Society (ATS)/European Respiratory Society (ERS) recommendations, EBC samples were collected from nine COPD patients, 12 asthma patients and 10 healthy individuals. Cytokine concentrations in serum and EBC were measured via commercial ELISA kits. RESULTS Of four cytokines measured in EBC [interleukin-8 (IL-8), IL-17, IL-4 and tumor necrosis factor-α (TNF-α)], only IL-8 was significantly higher in COPD than in asthma patients (5.27 ± 0.18 vs. 4.36 ± 0.34 pg/mL, p = 0.001). Moreover, COPD patients had higher serum IL-8 than asthma patients (10.57 ± 0.55 vs. 5.15 ± 0.24 pg/mL, p < 0.001). No significant correlation between serum and EBC cytokine concentrations was observed in each subgroup of patients. CONCLUSION Compared with patients with asthma attacks, patients with exacerbated COPD had increased IL-8 expression in both serum and EBC. These results suggest that IL-8 may be more important in airway and systemic inflammation in COPD exacerbations than in asthma attacks.

Wheezing, a significant clinical phenotype of COPD: experience from the Taiwan Obstructive Lung Disease Study.

Background COPD is an important public health challenge with significant heterogeneity of clinical presentation and disease progression. Clinicians have been trying to find phenotypes that may be linked to distinct prognoses and different therapeutic choices. Not all patients with COPD present with wheezing, a possible clinical phenotype that can help differentiate patient subgroups. Methods The Taiwan Obstructive Lung Disease study was a retrospective, multicenter research study to investigate the treatment patterns of COPD after the implementation of the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines. Between November 2012 and August 2013, medical records were retrieved from patients with COPD aged ≥40 years; patients diagnosed with asthma were excluded. Demographic data, lung function, symptom scores, and acute exacerbation were recorded and analyzed, and the differences between patients with and without wheezing were evaluated. Results Of the 1,096 patients with COPD, 424 (38.7%) had the wheezing phenotype. The wheezing group had significantly higher COPD Assessment Test scores (12.4±7.8 versus 10.5±6.7, P<0.001), higher modified Medical Research Council grade (2.0±1.0 versus 1.7±0.9, P<0.001), and more acute exacerbations within the past year (0.9±1.3 versus 0.4±0.9, P<0.001) than the nonwheezing group. The postbronchodilator forced expiratory volume in 1 second was lower in wheezing patients (1.2±0.5 L versus 1.5±0.6 L, P<0.001). Even in patients with maintenance treatment fitting the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines, the wheezing group still had worse symptom scores and more exacerbations. Conclusion Wheezing is an important phenotype in patients with COPD. Patients with COPD having the wheezing phenotype are associated with worse symptoms, more exacerbations, and worse lung function.