Objective To study the efect of montelukast for improving bronchial hyperresponsiveness (BHR) in treatment of bronchiolitis. Methods Four hundreds infants, 3 to 24 months old, hospitalized with acute bronchiolitis in three Hospitals (Urumqi Children’s Hospital, Pediatrics Department of First Ailiated Hospital of Xinjiang Medical University, and Pediatrics Department of Army General Hospital) from January, 2007 to January, 2008, were randomly assigned into four groups: placebo group (n=92), budesonide group (n=91), montelukast short-course group (7 days, n=88), and montelukast long-course group (28 days, n=90). Main outcome measure was BHR ater treatment, including recurrent bronchiolitis wheezing and asthma incidence rate. Secondary measures were changes in serum T-IgE level and eosinophilic cationic protein (ECP) level. Results All four groups were comparable at baseline. No signiicant diferences were observed between placebo group and budesonide group in changes of serum T-IgE (F=6.17, P=0.00), ECP (F=8.13, P=0.00), recurrent post-bronchiolitis-wheezing (χ2=49.46, P=0.00) and asthma incidence rate (χ2=27.21, P=0.00). Ater treatment with montelukast, there was statistical signiicance in T-IgE and ECP level, times of recurrent bronchiolitis wheezing and asthma incidence rate, as follows, montelukast short-course group versus placebo group (F=12.56, P=0.00), montelukast short-course group versus budesonide group (F=7.22, P=0.00), montelukast long-course group versus placebo group (F=20.48, P=0.00), montelukast long-course group versus budesonide group (F=13.56, P=0.00), montelukast short-course group versus montelukast long-course group (F=1.04, P=0.00). Conclusions Budesonide treatment for 7 days can not improve bronchial hyperresponsiveness induced by bronchiolitis, while montelukast does, that is, montelukast can decrease both the times of bronchiolitis wheezing and asthma incidence rate. Long-course treatment of montelukast is superior to that of short-course.
ObjectiveTo explore the influence of norepinephrine on the prediction of fluid responsiveness by passive leg raising (PLR) during septic shock.
MethodsForty-six septic shock patients in intensive care unit of Nanjing Drum Tower Hospital were prospectively observed from September to November 2012. Among which 36 septic shock patients were enrolled with a positive PLR test (defined by an increase in stroke volume index ≥10%). A PLR test was performed at baseline (PLR1). A second PLR test (PLR2) was performed at returning to supine position for 10 min and the dose of norepinephrine was increased to maintain MAP ≥65 mmHg for 20 min. The changes of heart rate(HR),mean arterial pressure(MAP),central venous pressure(CVP),cardiac index(CI),stroke volume index(SVI),index of systemic vascular resistance(SVRI),global end-diastolic volume index(GEDVI),and cardiac function index(CFI) were monitored by transpulmonary thermodilution technique (PiCCO).
ResultsPLR1 significantly increased SVI by (20.54±9.63)%,CI by (20.57±9.89)%,MAP by (7.64±5.77)%,and CVP by (25.83±23.39)%. As the dose of norepinephrine increased,SVI was increased by (16.97±9.06)%,CI by (16.78±8.39)%,GEDVI by (9.08±4.47)%,MAP by (28.07±12.48)%,and CVP by (7.86±8.52)%. PLR2 increased SVI by (13.74±8.79)%,CI by (13.79±9.08)%,MAP by (2.93±5.06)%,and CVP by (13.36±14.74)%. The PLR2 and the dose increase of norepinephrine augmented SVI to a significantly lesser extent than the PLR1 performed at baseline (both P<0.05). However,SVI increased by <10% in 6 patients while the baseline PLR was positive in these patients.
ConclusionIn septic patients with a positive PLR at baseline,norepinephrine increases cardiac preload and cardiac output and influences the fluid responsiveness.
Objective To investigate the changes of small airway function and diffusing capacity in patients with mild asthma before and after bronchial provocation test (BPT).Methods BPT was performed in suspected asthma patients with chief complaints of paroxysmal wheeze,chest tightness and cough，but with normal chest X-ray and baseline pulmonary function.BPT positive group was regarded as asthma group，while BPT negative group as control group.Lung volume，ventilatory function and diffusing capacity were measured before and after BPT and compared between the asthma and control groups.Results （A）No statistical differences were found in FEV1%，FEV1/FVC，FVC%，VC%，TLC%，FRC%，RV%，RV/TLC between the asthma and control groups before BPT.FEV1/FVC and FVC% were significantly decreased (all Plt;0.01)，while FRC% (Plt;0.05)，RV% (Plt;0.01) and RV/TLC (Plt;0.01) increased significantly in the asthma group after BPT compared with the control group.The decline rate of FEV1/FVC and FVC% and the increase rate of TLC%，RV%，RV/TLC were significantly higher in the asthma group than those in the control group (all Plt;0.01).（B）Compared with the control group，FEF25%-75% (Plt;0.05)，Vmax75% (Plt;0.01) and Vmax50% (Plt;0.05) were significantly lowered before BPT，while the above parameters and Vmax25% were significantly decreased after BPT in the asthma group (all Plt;0.01).The decline rate of FEF25%-75%，Vmax75%，Vmax50% and Vmax25% was significantly higher in the asthma group than those in the control group (all Plt;0.01).（C）There was no statistical difference in DLCO in both groups before and after BPT.Conclusions Patients with mild asthma had small airways impairment before BCT which further declined after BPT.However,no impairment of diffusion capacity was found before or after BPT.
ObjectiveTo explore the effects of Aspergillus fumigatus (A. fumigatus) on airway inflammation, airway responsiveness and total serum IgE in asthmatic rats.
MethodsEighteen male Wistar rats were divided into three groups randomly, ie. a normal control group, an asthmatic model group, and an A. fumigatus group. The rats in the model group and the A.fumigatus group were sensititized and challenged with ovalbumin to establish asthmatic model. After establishment of asthmatic model, the rats in the A. fumigatus group were treated with chronic A. fumigatus spores inhalation. Subsequently, airway responsiveness/sensitivity to methacholine(Ach), levels of serum IgE and airway inflammation were assessed and compared among three groups.
ResultsCompared with the asthmatic rats, the rats treated with A. fumigatus showed higher airway responsiveness (Penh/baselin value was significantly increased at the Mch concentration of 12.5, 25 and 50 mg/mL), increased inflammatory cells infiltration in pulmonary tissue slices and increased serum IgE level (P < 0.05). Most importantly, serum IgE level was detected in close relationship with PC100 which was defined as the dose of Mch causing 100% increase of enhance pause (Penh) value without Mch challenge (r=-0.873, P < 0.01). Serum IgE level was also closely related to the percentage of eosinophils in bronchoalveolar lavage fluid (r=0.937, P < 0.01).
ConclusionsChronic A. fumigatus inhalation aggravates airway inflammation, bronchial hyperresponsiveness and serum IgE level in asthma. IgE may play an important role in facilitating the development of bronchial responsiveness and eosinophilic inflammation.
To diminish the specific lymphocytes that responsive to the rejection of allograft. Anti-rat CD4,CD8 monoclonal antibodies and trichosnthin (TCS) was conjugated to immunotoxin by heterobifunctional reagent SPDP, 2-IT. The free TCS was removed from conjugates mixture by a column of Sephacryl S-200. The SDS-PAGE and cytotoxic assay was used to measure the biological activity of immunotoxin. SDS-PAGE showed the immunotoxin, free McAb and TCS were in the mixture of conjugation, and the free TCS can be separated by Sephacryl S-200. In Vitro, the lymphocytes of rat can be killed by antiCD4,antiCD8 immunotoxin. The kill capability was relay to the amount of immunotoxin. The authors consider that the immunology unresponsiveness can be induced by antiCD4,antiCD8 immunotoxin. That was useful in induced transplantation tolerance.
Objective To study the mechanism of immune hyporesponsiveness of allograft rejection induced by transfusion nonpufsed allopeptide syngeneic immature dendritic cell (imDC) generated from recipient bone marrow progenitors and to explore a possible strategy for liver allograft protection in clinic. Methods Forty experimental rats were randomly divided into 4 group: control group, cyclosporine A (CsA) group, mature DC (mDC) group and imDC group. In control group, Wistar rats only received liver transplantation. In CsA group, Wistar rats underwent liver transplantation plus CsA treatment 〔10 mg/（kg·d)〕. In mDC group, recipient-derived mDC 1×106 were infused intravenously through the penile vein to Wistar rats. In imDC group, ImDC with the dose of 1×106 were injected into Wistar rats via the dorsum vein of penile. In each group, five recipients were killed on the 10th day after transplantation, the other five recipients were left to observe survival time. The levels of ALT, AST, TBIL, IL-2, IFN-γ, IL-4 and IL-10 were detected. The acute rejection and the expression of FasL/Fas in the grafts were detected by HE and immunohistochemical staining. Western blot was used to detect Scurfin protein expression of CD4+ CD25+ T cells. Results The median survival time of the liver allografts in CsA group and imDC group were significantly longer than that in control group and mDC group ( P ＜ 0.05). The levels of ALT and TBIL in control group and mDC group were significantly higher than those in CsA group and imDC group ( P ＜ 0.05). Compared with CsA group and imDC group, the levels of IL-2 and IFN-γ were higher but the levels of IL-4 and IL-10 were lower in control group and mDC group ( P ＜ 0.01). Slightly or no rejection reaction was found in CsA group and imDC group ( P ＜ 0.05). The Scurfin protein expressions of CD4+ CD25+ T cells of imDC group were significantly higher than those of other three groups. Conclusion Application of nonpufsed allopeptide syngeneic recipient-derived imDC is an effective way to induce immune hyporesponsiveness by blocking indirect recognition in rat liver transplantation model. Survival span is significantly prolonged by its protective effect. The mechanism of immune hyporesponsiveness induced by imDC transfusion might be involved in some aspects: T cell apoptosis, immune deviation of Thl/Th2 cytokine net and inhibition of T lymphocytes responsiveness by regulatory T cells.
ObjectiveTo evaluate the value of stroke volume variation (SVV) and intrathoracic blood volume index (ITBVI) to predict fluid responsiveness in mechanically ventilated septic shock patients with spontaneous breathing.
MethodsA prospective observational study was conducted in the Department of Critical Care Medicine of the First Affiliated Hospital of Guangzhou Medical University. Fluid resuscitation data was collected in septic shock patients who received PiCCO monitoring from June 2013 to June 2014. Transpulmonary thermodilution data were collected before and after fluid resuscitation, including cardiac index (CI), SVV, ITBVI, and central venous pressure (CVP). Seventeen patients were defined as responders by an observed increase of≥15% in the cardiac index (CI) after fluid resuscitation, 12 patients were defined as non-responders. Pearson correlation between changes of CI (ΔCI) and SVV, ITBVI, CVP was established. Area under the receiver operating characteristic (ROC) curve of SVV, ITBVI and CVP was calculated for predicting fluid responsiveness.
ResultsBaseline CI and ITBVI were significantly lower in the responders (P < 0.05).There was no significant difference in baseline SVV between the responders and the non-responders (P > 0.05). A significant correlation was found between baseline ITBVI andΔCI (r=-0.593, P < 0.001), but no significant correlation between SVV andΔCI (r=0.037, P=0.847) or CVP andΔCI (r=0.198, P=0.302). The area under ROC curve of SVV, ITBVI and SVV for predicting fluid responsiveness was 0.640 (P=0.207), 0.865 (P=0.001), and 0.463 (P=0.565), respectively. The cut-off value of ITBVI for predicting fluid responsiveness was 784 mL/m2 with a sensitivity of 100.0% and a specificity of 70.6%.
ConclusionIn mechanically ventilated septic shock patients with spontaneous breathing, ITBVI may be a valuable indicator in predicting fluid responsiveness compared with SVV.
Objective
To investigate the value of central venous-to-arterial carbon dioxide difference/arterial-to-venous oxygen difference ratio [P(cv-a)CO2/C(a-cv)O2] in predicting oxygen metabolism after fluid resuscitation in patients with septic shock.
Methods
A prospective observational study was carried out on septic shock patients admitted in the intensive care unit of Nanjng Drum Tower Hospital from November 2013 to April 2014. All patients underwent fluid challenge (300 ml saline for 20 min, rapid intravenous infusion). The patients were divided into a fluid responded group (ΔCI≥10%) and a fluid unresponded group (ΔCI＜10%), according to the change of cardiac output index (ΔCI) after fluid challenge. Then the patients were divided into two subgroups in the fluid responded group, namely a ΔVO2≥10% group and a ΔVO2＜10% group, according to the change of VO2 (ΔVO2). Cardiac output index (CI) were determined by pulse indicator continuous cardiac output (PICCO). Hemoglobin, arterial carbon dioxide (PaCO2), arterial oxygen (PaO2), arterial oxygen saturation (SaO2), arterial blood lactate, central venous carbon dioxide (PcvCO2), central venous oxygen (PcvO2) and central venous oxygen saturation (ScvO2) were measured by blood gas analysis. P(cv-a)CO2/C(a-cv)O2 and oxygen consumption (VO2) were calculated. P(cv-a)CO2/C(a-cv)O2 before and after fluid challenge was compared between two subgroups.
Results
Fluid challenges were performed in 23 instances in 18 patients, among which 17 instances were defined as the fluid responded group. Compared with the fluid unresponded group, P(cv-a)CO2/C(a-cv)O2, arterial lactate and ScvO2 had no significant difference [P(cv-a)CO2/C(a-cv)O2](mm Hg/ml): 2.05±0.75vs. 1.58±0.67; arterial lactate (mmol/l): 3.78±2.50vs. 3.26±2.42; ScvO2(%): 73.71±9.64vs. 70.30±12.01,P＞0.05] in the fluid responded group before resuscitation. In the fluid responded group, there were 10 instances in the ΔVO2≥10% group and 7 instances in the ΔVO2＜10% group. P(cv-a)CO2/C(a-cv)O2 (mm Hg/ml) was significantly higher in the ΔVO2≥10% group before resuscitation compared with the ΔVO2＜10% group (2.43±0.73vs. 1.51±0.37,P＜0.01). Lactate (mmol/l) was also higher in the ΔVO2≥10% group before resuscitation (4.53±2.52vs. 1.46±0.82,P＜0.01). ScvO2 (%) had no significant difference between two groups (70.79±9.15vs. 72.13±13.42,P＞0.05). The areas under ROC curve (AUCs) of P(cv-a)CO2/C(a-cv)O2, lactate and ScvO2 for predicting ΔVO2≥10% were 0.843, 0.921, and 0.529, respectively. The sensitivity and specificity of P(cv-a)CO2/C(a-cv)O2≥1.885 mm Hg/ml for predicting ΔVO2≥10% after fluid resuscitation were 70% and 86%, respectively.
Conclusion
For septic shock patients with fluid responsiveness, P(cv-a)CO2/C(a-cv)O2 can predict oxygen metabolism after fluid resuscitation and can be used as a reliable parameter to guide fluid resuscitation.
Objective To investigate the role of endogenous Hydrogen Sulfide ( H2S) in airway inflammation and responsiveness in a rat model of chronic passive-smoking. Methods Male SD rats were randomly divided into a control group ( breathing fresh air) and a passive smoking group [ cigarette smoking( CS) passively] , with 18 rats in each group. Six rats in each group were randomly intraperitoneally injected with normal saline, sodium hydrosulfide ( NaHS) or propargylglycine ( PPG, an irreversible inhibitor of cystathionine- γ-lyase) . The animals were divided into six subgroups, ie. Con group, NaHS group, and PPG group, CS group, CS+ NaHS group, and CS + PPG group. After 4 months, lung histological change and airway tension were measured. The H2S levels of plasma and lung tissue were analyzed by the sensitive sulphur electrode assay. The expression of cystathionine-γ-lyase ( CSE) was measured by western blot. Results Compared with the Con group, CSE protein expression in lung tissues was increased in CS group( P lt;0. 05) ; the H2 S levels of plasma were significantly higher in CS group, NaHS group and CS + NaHS group, and much lower in PPG group ( P lt; 0. 05, respectively) . Compared with CS group, the H2S levels of plasma were significantly higher in CS + NaHS group, and much lower in CS + PPG group( P lt; 0. 05, respectively) . The H2S level of lung tissue in each group had no significant difference ( P gt; 0. 05) . Compared with Con group,score of lung pathology was significant elevated, and the responsiveness of airway smooth muscles to ACh and KCl was significant augmented in CS group. Compared with CS group, the score of lung pathology was decreased, and the responsiveness of airway smooth muscles was decreased in CS +NaHS group( P lt;0. 05) , and vise versa in CS + PPG group( P lt; 0. 01) . Conclusion H2S can alleviate airway inflammation and hyperresponsiveness induced by CS, and administration of H2S might be of clinical benefit in airwayinflammation and airway responsiveness.
Objective To study the responsiveness change of neutrophils when experiencing the second insult after the initial temperature activation in cardiopulmonary bypass (CPB) by using an in vitro model. Methods The neutrophils were isolated from blood which was drawn from each of 60 health volunteers. The samples were divided into 5 groups including normothermia, tepid temperature, moderate hypothermia, deep hypothermia, and rewarming hyperthermia by random digital table with 12 in each group according to the change of temperature during CPB. An in vitro model for studying neutrophil responsiveness was established by using a polymerase chain reaction thermocycler. Five time points were set for each group, including T0: starting CPB, T1: starting rewarming, T2: 0.5 h after rewarming, T3: 1 h after rewarming, and T4: 1.5 h after rewarming. Platelet activating factor (PAF) was added into each group at T2, T3, and T4, and then the value of membranebound elastase (MBE) activity was measured as responsiveness of neutrophils. Analysis of covariance was applied by using SPSS 13.0 for statistic analysis. If the [CM(159mm]covariance had significant difference between main effects, Bonferroni method would be applied for pairwise comparison. Results The main effect difference of neutrophil responsiveness among different groups was statistically different (F=4.372,P=0.002). MBE value had no statistical difference between the normothermia and tepid temperature groups (81.9±4.5 ng/10.6 cells vs. 76.5±3.6 ng/106 cells, P=0.134). while the MBE values in these two groups were higher than those in the other three groups (P=0.001). MBE value in the rewarming hyperthermia group was higher than that in the deep hypothermia group (61.2±2.7 ng/106 cells vs. 50.9±3.7 ng/106 cells, P=0.005). There was no statistical difference between the moderate hypothermia group (56.4±3.2 ng/106 cells) and the rewarming hyperthermia group (P=0.167), so was it between the moderate hypothermia group and the deep hypothermia group (P=0.107). The main effects of neutrophil responsiveness at different time points was statistically different (F=3.566, P=0.03) when PAF was added. MBE value at T4 was higher thanthat at T2 (70.9±2.5 ng/106 cells vs. 59.9±2.3 ng/106 cells, P=0.027). There was no statistical difference among T3 (65.5±1.8 ng/106 cells), T2 (P=0.168), and T4 (P=0.292) in MBE value. Conclusion Normothermia， tepid temperature， and rewarming hyperthermia during CPB can enhance neutrophil responsiveness and MBE release when neutrophils suffer the second insult. There is a time window for neutrophils to be easily activated during rewarming period.
