Tzuen Ren Hsiue

Prediction of Arterial Blood Gas Values from Venous Blood Gas Values in Patients with Acute Respiratory Failure Receiving Mechanical Ventilation

BACKGROUND AND PURPOSE Arterial blood gas (ABG) analysis is useful in evaluation of the clinical condition of critically ill patients; however, arterial puncture or insertion of an arterial catheter may cause many complications. This study evaluated whether pH, partial pressure of carbon dioxide (PCO2) and bicarbonate (HCO3-) values of venous blood gas (VBG) could accurately predict their ABG analogs for patients with acute respiratory failure treated by mechanical ventilation in an intensive care unit (ICU). METHODS Forty six patients who were admitted to the ICU due to acute respiratory failure and treated by mechanical ventilation were included in this study. Blood for VBG analysis was sampled from the cubital or dorsal palmar veins, while ABG was sampled simultaneously from the radial or brachial arteries via an arterial catheter at the other upper extremity. Regression equations and mean percentage-difference equations were derived to predict arterial pH, PCO2, and HCO3- values from their VBG analogs. The equations were validated by evaluating VBG and ABG samples from a separate group of 11 patients. RESULTS A total of 46 paired samples from 46 patients were evaluated. The mean percentage differences between the venous and arterial values divided by venous values for pH, PCO2, and HCO3- were (mean +/- SD): deltapH (%), 0.50 +/- 0.45; deltaPCO2 (%), 17.09 +/- 9.60; and deltaHCO3- (%), 9.72 +/- 7.73; respectively. Regression equations for prediction of pH, PCO2 and HCO3- values were: arterial pH (pHa) = 0.45 + 0.94 x venous pH (pHv) [r = 0.83, p < 0.0001]; partial pressure of arterial CO2 (PaCO2) = 3.06 + 0.76 x partial pressure of venous CO2 (PvCO2) [r = 0.86, p < 0.0001]; and arterial HCO3- (HCO3-a) = 2.34 + 0.82 x venous HCO3- (HCO3-v) [r = 0.91, p < 0.0001]. The predicted ABG values from the mean percentage-difference equations were derived as follows: pHa = pHv x 1.005; PaCO2 = PvCO2 x 0.83; and HCO3-a = HCO3-v x 0.90. Validation of the regression equations and mean percentage-difference equations revealed only a small (clinically insignificant) variation between the actual and predicted ABG values. CONCLUSIONS Venous blood gas can accurately predict the ABG values of pH, PCO2 and HCO3- for patients with acute respiratory failure being treated with mechanical ventilation.

Combined intrapleural and intravenous chemotherapy, and pulmonary irradiation, for treatment of patients with lung cancer presenting with malignant pleural effusion. A pilot study.

Objectives: Patients with non-small-cell lung cancer (NSCLC) and malignant pleural effusion (MPE) are difficult to manage clinically and have a short life expectancy. In this pilot study, we designed a protocol of combined intrapleural (i.p.) and intravenous (i.v.) chemotherapy and pulmonary irradiation to enhance local as well as systemic control of the disease. Methods: From April 1998 to April 2000, 27 patients with NSCLC and symptomatic MPE were eligible for the study. Patients received pre-radiation chemotherapy (cisplatin 60 mg/m2 i.p. on day 1; gemcitabine 1,000 mg/m2 i.v. on days 1, 8, and 15, q4week × 3) after surgical implantation of i.p. and i.v. port-A, followed by radiotherapy (7,020 cGy/39fr), and, finally, post-radiation chemotherapy (docetaxel 60 mg/m2 q3week × 3–6 i.v.). Results: Grade 1/2 nausea/vomiting and impaired renal function were more common from pre-radiation than post-radiation chemotherapy; however, grade 3/4 toxicities from pre-radiation chemotherapy were minimal. Conversely, grade 3/4 leukopenia and grade 1/2 alopecia, diarrhea, elevation of SGOT/SGPT, and sensory impairment were more common following post-radiation chemotherapy. Only two patients experienced recurrence of pleural effusion. The overall response rate was 55% with 7% complete remission, 48% partial remission, 22% stable disease, and 22% progressive disease. The median failure-free and overall survival was 8 and 16 months, respectively. The one-year survival rate was 63% (95% confidence interval, 45–80%). Conclusions: We conclude that the combination of i.p. and i.v. chemotherapy and pulmonary irradiation is feasible and should be tested in a larger clinical trial to determine whether survival can be improved for this cohort of patients.

Antimicrobial resistance of bacterial isolates from respiratory care wards in Taiwan: a horizontal surveillance study

A horizontal surveillance study was conducted to identify common bacteria and mycobacteria from 611 respiratory aspirates and 165 urinary samples from 611 patients hospitalised at 17 respiratory care wards (RCWs) in Taiwan. Some major resistance phenotypes, including methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis, and multidrug-resistant Pseudomonas aeruginosa (MDR-PA) and Acinetobacter baumannii (MDR-AB), were identified. Pulsotypes of ESBL-producing P. mirabilis isolates were determined by pulsed-field gel electrophoresis. The prevalences of MRSA, ESBL-producing E. coli (K. pneumoniae and P. mirabilis), carbapenem-resistant (resistant to imipenem and meropenem) P. aeruginosa, MDR-PA, carbapenem-resistant A. baumannii and MDR-AB were, respectively, 86.7%, 20.0% (50.7% and 24.1%), 18.4%, 1.2%, 32.1% and 8.9% for respiratory aspirates and 100%, 25.4% (27.3% and 25.0%), 48.3%, 10.3%, 50.0% and 21.4% for catheterised urinary samples. Among the 44 respiratory isolates of P. mirabilis with an ESBL phenotype, 22 different pulsotypes (>80% identity) were identified. Among 103 isolates of mycobacteria, 90 (87.4%) belonged to rapidly growing mycobacteria and 4 (4%) were Mycobacterium tuberculosis. Among the 404 patients with available clinical information, true infections were found in 28.0%, the most prevalent of which were urinary tract infection (20.5%) and ventilator-associated pneumonia (10.9%). High prevalences of various multidrug-resistant bacteria among the respiratory and urinary tracts of patients present a clinical difficulty in choosing empirical antibiotic treatment in RCWs.

Comparative effects of l-NOARG and l-NAME on basal blood flow and ACh-induced vasodilatation in rat diaphragmatic microcirculation

The effects of Nω‐nitro‐l‐arginine (l‐NOARG) and Nω‐nitro‐l‐arginine methyl ester (l‐NAME) on diaphragmatic microcirculation in male Sprague‐Dawley rats were assessed under basal conditions and after acetylcholine (ACh) stimulation. In addition, l‐arginine (l‐arg) was used with the aim of preventing l‐NOARG and l‐NAME from inhibiting ACh‐induced vasodilatation, in order to explore the possibility that l‐NOARG is not only a nitric oxide (NO) synthase inhibitor but also a muscarinic receptor antagonist. Male Sprague‐Dawley rats were anaesthetized with urethane and mechanically ventilated. The left hemi‐diaphragm of each rat was prepared and microvascular blood flow was recorded during continuous superfusion with bicarbonate‐buffered prewarmed Ringer solution by using laser‐Doppler flowmetry. The drugs were topically applied to the surface of the hemi‐diaphragm. Baseline microvascular blood flow was unaffected after 15 min superfusion with any one of the following agents: l‐NOARG (0.1 mm), l‐NAME (0.1 mm), l‐arg (10 mm). ACh (0.03 mm, 0.1 mm and 0.3 mm) elicited a significant increase of microvascular blood flow (171±16%, 214±55%, and 323±68% of baseline values, respectively), via interaction with the muscarinic receptor, for the vasodilator response was severely inhibited by 15 min superfusion with atropine (0.3 mm). Following 15 min superfusion with either of the l‐arg analogues (0.1 mm), the ACh‐induced vasodilator response was significantly inhibited. Pretreatment with l‐arg (10 mm) for 5 min, followed by co‐administration of l‐arg (10 mm) and l‐NOARG (0.1 mm) for another 15 min significantly prevented the inhibitory effect of l‐NOARG on ACh‐induced vasodilatation. However, a similar pretreatment schedule with l‐arg failed to prevent l‐NAME from exerting its inhibitory effect. Neither of the l‐arg analogues potentiated sodium nitroprusside (10 μm and 30 μm)‐induced vasodilatation. However, adenosine (0.1 mm)‐induced vasodilatation was slightly but significantly attenuated by either l‐NOARG (0.1 mm) or l‐NAME (0.1 mm), an effect which was prevented by l‐arg (10 mm). In conclusion, an increase in endothelium‐dependent blood flow stimulated by ACh may occur in diaphragmatic microcirculation of anaesthetized rats independently of low baseline NO activity. The results also suggest that l‐NAME has muscarinic receptor antagonist action in addition to its ability to inhibit NO synthase. Thus, we suggest that l‐NAME should not be used as a specific NO synthase inhibitor in the rat diaphragm in situations in which there is potential for muscarinic receptors to be stimulated.

Dermatophagoides-farinae-Induced Pulmonary Eosinophilic Inflammation in Mice

Dermatophagoides farinae (Der f) is one of the most common species of dust mites that induce asthma and allergic rhinitis. We have reported that Der f challenge on sensitized mice elicited a distinct type of hypersensitivity, called early-type hypersensitivity (ETH), in subcutaneous tissues and in airways. The airway ETH was accompanied by a series of inflammatory and immunological events including cytokine production, adhesion molecule expression, inflammatory cell infiltration, eosinophilia, and airway hyperreactivity. In the present study, we further defined the course of the Der-f-induced eosinophilia and examined the local cytokine gene expression and the roles of cytokines, mast-cell-derived vasoactive amines, and corticosteroids in the development of pulmonary eosinophilia. BALB/c mice were sensitized with crude extract of Der f in complete Freunds adjuvant and were intranasally challenged with Der f on day 14 after sensitization. The number of blood eosinophils, total and differential leukocyte counts in bronchoalveolar lavage (BAL) fluids, and the expression of cytokine genes in BAL cells were assessed at various time points after challenge for up to 12 days. The total number of leukocytes in the BAL fluids was increased 6 h after challenge (AC) and peaked at 72 h. The early cellular response in the BAL fluids was dominated by neutrophils which were subsequently replaced by a marked infiltration of eosinophils. The number of eosinophils in BAL fluids increased at 24 h and peaked at 72 h, making up 43% of all cells recovered by BAL. BAL eosinophils declined gradually to normal background levels around day 12. Concurrently, there was a significant reduction in the number of eosinophils in blood 24 h AC. The number of blood eosinophils increased thereafter, reached a peak at 72 h, and remained above baseline level for up to 10 days. Saline challenge did not induce eosinophilia in BAL fluids and blood of sensitized mice. Histopathological examination revealed a mixed granulocytic, monocytic pulmonary inflammation with a large number of eosinophils accumulating within the submucosa of the airways and blood vessels of sensitized mice after challenge. Der f challenge induced a sequential expression pattern of eight cytokine genes in BAL cells. The mRNA of interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha strongly expressed throughout the course of the experiment. The IL-6 mRNA expression peaked at 0.5-72 h, IL-10 at 1-6 and 48-72 h, IL-4 at 6-72 h, IL-2 at 6-96 h, IL-5 at 24-72 h, and interferon-gamma at 24-96 h. Intraperitoneal injection of sensitized mice with monoclonal antibody (mAb) to murine IL-5 (TRFK5, 300 micrograms/mouse) 1 h before challenge caused 62% suppression of eosinophils in the BAL fluids. The concomitant accumulation of neutrophils and mononuclear cells, however, was not affected by this treatment. On the other hand, intranasal administration of mAb to murine TNF-alpha (MP6-XT3, 20 micrograms/ mouse), but not IL-5, 1 h before challenge and 24 h AC significantly reduced the numbers of eosinophils, neutrophils, and lymphocytes in the BAL fluids. The intraperitoneal injection of dexamethasone (50 mg/kg) for a total of four times resulted in total inhibition of the Der-f-induced cellular responses, whereas vasoactive amine antagonists (diphenhydramine, ketanserin and cyprohepatidine) did not show any effect.

Mite-Induced Allergic Airway Inflammation in Guinea Pigs

BACKGROUND Mites are the most common aeroallergen in human allergic asthma. However, no animal model of mite-induced allergic airway inflammation has been reported before. In this study, an animal model of mite-induced allergic airway inflammation in guinea pigs was developed. METHODS Firstly, we found that two intraperitoneal injections of 100 micrograms crude mite extract (CME), but not multiple aerosol inhalations of 10 mg/ml CME, can cause sensitization in guinea pigs. The sensitization to mites was confirmed by the measurement of serum antimite antibody titer and the detection of anaphylactic bronchoconstriction after intravenous injection of CME solution. Then, single or multiple aerosol challenges with different concentrations (8, 4 or 1 mg/ml) of CME in these sensitized animals were performed. The total white cell and differential counts in the bronchoalveolar lavage (BAL) fluids were studied at different time intervals after challenge in different animals, and tracheal pathology was performed to detect the allergic airway inflammation. For comparison with the study in animals treated with CME, a BAL study in animals treated with ovalbumin was also performed. RESULTS The inhalation challenge of CME aerosol in sensitized animals caused prolonged eosinophilia in BAL fluid which persisted for at least 7 days after single challenge. Neither inhalation challenge at higher concentrations of CME aerosol nor repeated inhalation challenges increased the degree of eosinophilia in BAL fluid compared to a single challenge. Using the same procedures, we also found that the mite model caused more eosinophilia in BAL fluid than did ovalbumin. CONCLUSION This is the first report of an animal model of mite-induced allergic airway inflammation in guinea pigs which can provide us with a useful model to study airway inflammation of mite-induced asthma in humans.

Genetic variants of pulmonary SP‐D predict disease outcome of COPD in a Chinese population

Although surfactant protein‐D (SP‐D) has been suggested as a biomarker for chronic obstructive pulmonary disease (COPD), the relationship between genetic variants of SP‐D and disease outcome of COPD remains unknown. We hypothesized that genetic polymorphisms of SP‐D are associated with COPD‐related phenotypes and disease prognosis.

Using Post-bronchodilator FEV1 is Better Than Pre-bronchodilator FEV1 in Evaluation of COPD Severity

Abstract Background: The current standards for the diagnosis and treatment of patients with COPD clearly rely on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria based on post-bronchodilator spirometric values. However, clinical evidence for using the post-bronchodilator FEV1 in the severity classification has not been fully investigated. Methods: Patients with COPD were enrolled and followed up prospectively between October 2006 and January 2011. We compared the observed 3-year risk of all causes and respiratory mortality with the risk predicted by the pre- and post-bronchodilator percent predicted FEV1. Other important phenotypes including BMI, MMRC dyspnea scale, ECOG performance status and severe AECOPD (acute exacerbation) were also compared between the two groups. The different severity classifications of COPD, measured according the GOLD guidelines by post- and pre-bronchodilator percent predicted FEV1 were compared for prediction of mortality. Results: There were 35 deaths among the 300 COPD patients (11.7%). Multivariate analysis showed that the post-bronchodilator percent predicted FEV1 was a significant independent predictor of mortality but pre-bronchodilator percent predicted FEV1 was not (p = 0.008 vs 0.126) and it was more strongly correlated with all studied predictors of outcome than the pre-bronchodilator percent predicted FEV1. Kaplan-Meier analysis showed that the discrimination ability to predict mortality from the GOLD criteria using post bronchodilator percent predicted FEV1 (p = 0.009) was better than using pre-bronchodilator percent predicted FEV1 (p = 0.131). Conclusions: The post-bronchodilator percent predicted FEV1 is better than the pre-bronchodilator percent predicted FEV1 in the evaluation of the severity of disease in COPD patients and is more accurate in predicting the risk of death by the GOLD classification.

Comparison of global initiative for chronic obstructive pulmonary disease 2013 classification and body mass index, airflow obstruction, dyspnea, and exacerbations index in predicting mortality and exacerbations in elderly adults with chronic obstructive pulmonary disease.

To examine whether the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) 2013 revision offers greater predictive ability than the body mass index, airflow obstruction, dyspnea, and exacerbations (BODEx) index in elderly adults with chronic obstructive pulmonary disease (COPD).

Asthma incidence, remission, relapse and persistence: a population-based study in southern Taiwan.

BackgroundIn western countries, late-onset asthmatics are more severe than early-onset asthmatics in clinic-based studies. However, whether asthma occurrence rates were higher in late ages than in younger ages was inconclusive. This information is essentially lacking in Asian population.MethodsThe participants were schoolchildrens parents recruited from 94 elementary and middle schools in 2004. A cross-sectional self-administered questionnaire was sent through the children to their parents to survey their respiratory health. We investigated typical asthma symptoms occurring at different ages and subsequent remission or relapse after the first asthma event. Person-years of the participants from birth to the time of survey were used as the denominator.ResultsAmong the 25,377 participants consisting of 949,807 total person-years, 860 reported ever having asthma. Highest incidences occurred at ages 0-12 and 36-40 years. The incidence of asthma was higher in males before puberty, and higher in females after puberty, with overall incidences 1.00 and 0.77 per 1000 person-years for females and males, respectively. Participants with late-onset asthma (onset age >12 years) comprised a large portion of adult current asthmatics. More than 52% of persistence or relapse was observed in early-onset asthma (onset age >12 years). The younger birth cohort had a more prominent later peak of asthma incidence than the older one.ConclusionsIn Asian population, asthma occurrence showed a U-shape age distribution with a prominent second peak in the thirties. A high proportion of early-onset asthma relapsed and most of late-onset asthma persisted or relapsed in adulthood.