Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia.

Objective: This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients. Methods: This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence. Results: All patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% vs. 42.4%, P = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 - 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg∙d)]. Conclusion: A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.

Influence of the Pre-shock State on the Prognosis of Medical Patients with Sepsis: A Retrospective Cohort Study.

Objective: To investigate the effects of the pre-shock state on the mortality of patients with sepsis. Methods: We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university hospital. These patients were then classified into three groups: sepsis, pre-shock state, and septic shock. The primary outcome was the 28-day mortality rate. The secondary outcomes were the 90-day, 180-day, and 1-year mortality rates. Results: A total of 303 patients (groups: sepsis 135 [44.6%]), pre-shock state (93 [30.7%]), and septic shock (75 [24.8%]) completed the 1-year follow-up. The mortality rates at 28 days, 90 days, and 180 days and 1 year were significantly higher in the pre-shock state group than those of the sepsis group, but significantly lower than those in the septic shock group, especially among older patients. When compared with the pre-shock state group, the sepsis group had significantly lower mortality risks at 28 days, 90 days, and 180 days and 1 year, whereas the sepsis shock group had higher mortality risks at these time points. Conclusion: The mortality rates of patients in the pre-shock state were notably different from those of patients with sepsis or septic shock. The introduction of a modified sepsis severity classification, which includes sepsis, pre-shock state, and septic shock, could offer valuable additional prognostic information.

Pharmacokinetic-pharmacodynamic analysis of ciprofloxacin in elderly Chinese patients with lower respiratory tract infections caused by Gram-negative bacteria.

BACKGROUND: Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad have shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gram-negative bacteria. METHODS: From September 2012 to June 2014, as many as 33 patients were empirically administered beta-lactam and ciprofloxacin combination therapy. Patients were infused with 200 or 400 mg of ciprofloxacin every 12 h, which was determined empirically by the attending physician based on the severity of the LRTI and the patient's renal condition. Ciprofloxacin serum concentrations were determined by high-performance liquid chromatography. Bacterial culture was performed from sputum samples and/or endotracheal aspirates, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. The ratios of the area under the serum concentration-time curve to the MIC (AUC/MIC) and of the maximum serum concentration of the drug to the MIC (Cmax/MIC) were calculated. The baseline data and pharmacokinetic parameters were compared between clinical success group and clinical failure group, bacteriologic success group and bacteriologic failure group. RESULTS: Among the 33 patients enrolled in the study, 17 were infected with Pseudomonas aeruginosa, 14 were infected with Acinetobacter baumannii, and two were infected with Klebsiella pneumoniae. The mean age of the patients was 76.9 ± 6.7 years. Thirty-one patients (93.4%) did not reach the target AUC/MIC value of >125, and 29 patients (87.9%) did not reach the target Cmax/MIC value of >8. The AUC/MIC and Cmax/MIC ratios in the clinical success group were significantly higher than those in the clinical failure group (61.1 [31.7-214.9] vs. 10.4 [3.8-66.1], Z = -4.157; 9.6 [4.2-17.8] vs. 1.3 [0.4-4.7], Z = -4.018; both P < 0.001). The AUC/MIC and Cmax/MIC ratios in the patients for whom the pathogens were eradicated were significantly higher than those in the patients without the pathogens eradicated (75.3 [31.7-214.9] vs. 10.5 [3.8-66.1], Z = -3.938; 11.4 [4.2-17.8] vs. 1.4 [0.4-5.4], Z = -3.793; P < 0.001 for both). Receiver operating characteristic curve analysis showed that the AUC/MIC and Cmax/MIC values were closely associated with clinical and bacteriologic efficacies (P < 0.001 in both). CONCLUSIONS: Ciprofloxacin is inadequately dosed against Gram-negative bacteria, especially for those with relatively high MIC values. Consequently, the target values, AUC/MIC > 125 and Cmax/MIC > 8, cannot be reached.

Meropenem Dosing Based on a Population Pharmacokinetic-Pharmacodynamic Model in Elderly Patients with Infection of the Lower Respiratory Tract.

BACKGROUND: Meropenem is used for the treatment of severe lower respiratory tract infections (LRTIs) caused by multidrug-resistant Gram-negative bacilli. OBJECTIVE: We evaluated the clinical benefits of a strategy of meropenem dosing based on a population pharmacokinetics/pharmacodynamics (PK/PD) model in elderly patients with an LRTI. METHODS: In this prospective single-center open-label randomized controlled trial, 79 elderly patients with an LRTI caused by Gram-negative bacilli were randomized to a study group (SG) or a control group (CG). The latter received meropenem according to a regimen decided by the attending physician. The SG received individualized meropenem therapy with a dosing strategy based on software developed from a meropenem population PK/PD model. The primary endpoint was clinical response to meropenem therapy. Secondary endpoints were the amount of antibiotics used and bacteriologic response. RESULTS: Klebsiella pneumoniae was the most common pathogen (32.9%), followed by Pseudomonas aeruginosa (30.4%) and Escherichia coli (17.7%). A total of 63 (79.7%) patients achieved clinical success. Prevalence of clinical success was significantly higher in the SG than in the CG (89.7 vs. 70.0%; p = 0.029). The daily dose of meropenem was significantly lower in the SG than in the CG (1.5 vs. 2.0 g; p = 0.017). A total of 52 (65.8%) patients experienced bacteriologic success, the median duration of meropenem therapy was 9 days, and the median total dose of meropenem was 18.0 g. There were no significant differences between the groups in these parameters. CONCLUSIONS: A strategy for meropenem dosing based on a population PK/PD model can improve clinical response and avoid overtreatment in elderly patients with an LRTI. ClinicalTrials.gov registration number NCT01944319.

Chronic obstructive pulmonary disease assessment test score correlated with dyspnea score in a large sample of Chinese patients.

BACKGROUND: The chronic obstructive pulmonary disease assessment test (CAT) is an easy to use health-related quality of life questionnaire, the modified Medical Research Council (mMRC) dyspnea scale is a classic dyspnea scale which is widely used, while the correlation between them is still not clear. This study investigated the use of the Chinese translation of CAT in chronic obstructive pulmonary disease patients and its correlation with the mMRC dyspnea scale. METHODS: The multicenter cross-sectional study was conducted in 329 hospitals throughout China from March 1 to April 30, 2010. Chronic obstructive pulmonary disease patients completed both the assessment test and the dyspnea scale during a single study visit. RESULTS: Six thousand, four hundred and thirty-seven patients were evaluated; 74.9% were male and the mean age was (64.9 ± 10.0) years. Median test scores in dyspnea grades 0 to 4 were 14, 16, 22, 26 and 32, respectively; these differences were statistically significant. The CAT score was moderately correlated with mMRC dyspnea grade (r = 0.579, P < 0.001). There was no significant difference in mean CAT score between males and females, and patients of high and low socioeconomic status. Primary analysis suggested that CAT scores were higher in older patients (>65 years) than in younger patients (≤ 65 years) and increased with duration of formal education, but these findings were repudiated by further analysis of subgroups according to mMRC dyspnea grade. CONCLUSIONS: There was no obvious confounding factor influencing use of the CAT in Chinese patients. CAT scores were moderately correlated with the mMRC dyspnea scale.

Pharmacokinetics and pharmacodynamics of meropenem in elderly chinese with lower respiratory tract infections: population pharmacokinetics analysis using nonlinear mixed-effects modelling and clinical pharmacodynamics study.

BACKGROUND: Meropenem is a broad-spectrum antibacterial that is usually used in the treatment of serious lower respiratory tract infections (LRTIs). However, there is a lack of published studies exploring the correlation between the population pharmacokinetics of meropenem, the clinical pharmacodynamics of the drug and the response to the drug in Chinese patients with LRTIs, especially in the elderly. OBJECTIVE: The aim of this study was to develop a pharmacokinetic model of meropenem using patient data and use this to explore the clinical pharmacodynamics of meropenem in the treatment of LRTIs in elderly Chinese patients. METHODS: We measured serum meropenem concentrations in patients who had received meropenem 0.5 or 1.0 g infused over 0.5 hours every 8 or 12 hours, respectively. The pharmacokinetic analysis of meropenem was performed using nonlinear mixed-effects modelling (NONMEM®) software. The minimum inhibitory concentration (MIC) of meropenem against Gram-negative bacilli was tested by the E-test method. The pharmacodynamic parameters of percentage of time above MIC (%T>MIC), the ratio of the drug area under the serum concentration-time curve to MIC (AUC/MIC), the ratio of the maximum serum concentration of the drug to MIC (Cmax/MIC) and the ratio of the minimum serum concentration of the drug to MIC (Cmin/MIC) were analysed for their association with clinical and bacteriological outcomes. RESULTS: A total of 284 serum meropenem concentration measurements were obtained from 75 patients (aged 63-95 years). A two-compartment model fitted the concentration data best. The covariates creatinine clearance (CLCR) and Acute Physiology and Chronic Health Evaluation (APACHE) II score had the most significant effects on meropenem pharmacokinetics. Forty-five patients were enrolled in the pharmacodynamic study, including 25 clinical responders and 21 patients with bacteriological eradication. All of the 45 patients had Gram-negative bacilli isolated from tracheal aspirate or sputum. The %T>MIC, AUC/MIC, Cmax/MIC and Cmin/MIC values for the 25 clinical responders were significantly higher than those for the nonresponders (all p<0.05). However, logistic regression analysis showed that only %T>MIC independently influenced clinical outcome (p=0.001, odds ratio [OR]=1.065). The cut-off value for predicting clinical success using %T>MIC was 76%; the sensitivity and specificity of %T>MIC for predicting a successful response were 84% and 85%, respectively. The %T>MIC, AUC/MIC, Cmax/MIC and Cmin/MIC values, and the serum level of albumin, for the 21 patients with bacteriological eradication were significantly higher than those for patients with bacteriological treatment failure (all p<0.05). Logistic regression analysis showed that %T>MIC (p=0.008, OR=1.047) and serum level of albumin (p=0.033, OR=1.434) independently influenced bacteriological eradication. CONCLUSIONS: To our knowledge, this is the first study to investigate the population pharmacokinetics and clinical pharmacodynamics of meropenem in elderly Chinese. CLCR and APACHE II score have significant influences on meropenem pharmacokinetics. In LRTI patients, the cut-off value of 76% for %T>MIC can be applied to optimize their meropenem dose regimen to achieve clinical success.

Intrahospital dissemination of carbapenem-resistant Acinetobacter baumannii and analysis of the infected patients' prognosis.

OBJECTIVE: To assess the genetic relationship of clinical isolates of carbapenem-resistant A. baumannii(resistant to both imipenem and meropenem) from January 2007 to March 2008 in Peking University Third Hospital for measures to decrease the isolates; to investigate the characteristics of patients with carbapenem-resistant A.baumannii colonization or infection and to evaluate antibiotic treatment for health care-associated infections caused by carbapenem-resistant A.baumannii. METHODS: The medical records of patients with carbapenem-resistant A. baumannii colonization or infection were reviewed. Antibiotic susceptibilities of the isolates were determined by the standardized disk-diffusion method and the clonal relationship of the isolates was analyzed by pulsed-field gel electrophoresis. RESULTS: A total of 49 carbapenem-resistant A. baumannii strains were isolated from the 49 patients hospitalized during the study period and pulsed-field gel electrophoresis typing yielded 7 different patterns. A total of 45 (91.8%) genotyped strains showed clonal relationship. The most frequently identified predisposing factors were intensive care unit stay, invasive procedures, and hypoalbuminemia. Chronic obstructive pulmonary disease (12 cases) and cerebrovascular disease (10 cases) were the most common comorbid conditions. The mortality of patients with carbapenem-resistant A. baumannii infection was 38.1% (8 of 21 patients), and the acute physiology and chronic health evaluation II score, initial antibiotic therapy failure rate and the presence of hypoalbuminemia were significantly increased in the death group. Combination therapy regimens had higher success rates than monotherapy regimens(11/13, 84.6% vs. 3/17, 17.6%). CONCLUSION: There has been clonal spread of carbapenem-resistant A. baumannii strains among patients in our hospital since 2007. Intensive care unit stay, invasive procedures, hypoalbuminemia, chronic obstructive pulmonary disease and cerebrovascular disease were common in patients with carbapenem-resistant A. baumannii colonization or infection. Antibiotic combination therapy may be effective for carbapenem-resistant A. baumannii infection.

[Clinical analysis of lymphoma with chest involvement: report of 25 cases].

OBJECTIVE: To study clinical characteristics and diagnostic methods of lymphoma with chest involvement. METHODS: Twenty-five lymphoma patients with chest involvement were retrospectively analysed, they were all diagnosed in Peking University Third Hospital during 2000 to 2007. The data were collected including clinical manifestations, blood examinations, chest X-ray and CT scan, diagnostic methods and pathologic diagnosis. RESULTS: The median age of the 25 patients was 46 years old. Pyrexia (13 cases), weight loss over 10 percent in 6 months (11 cases), cough (10 cases), shortness of breath (9 cases) and painless enlargement of the peripheral lymph nodes (16 cases) were common manifestations. Erythrocyte sedimentation rate and serum lactate dehydrogenase (LDH) level were increased in 72.7% and 81% patients, respectively. The enlargement of mediastinum lymph nodes (16 cases, 64%) was the most common presentation of chest radiography, followed by pulmonary involvement (15 cases, 60%) including infiltration or pulmonary consolidation, mass, multiple nodules, diffuse ground-glass shadow, miliary lesion. There were also presentations of pleural effusion (10 cases, 40%), pericardial effusion (4 cases, 16%), chest wall mass (2 cases, 8%). Eighteen patients (72%) had at least two kinds of these presentations. The appearance of pleural effusion were yellow turbid, bloody or chyliform. Rivalta tests were all positive. The median value of pleural effusion examinations were listed as follows: specific gravity 1.031, total cells 9800 x 10(6)/L, WBC 6.72 x 10(9)/L, lymphocyte 86%, neutrophil 14%, protein 31.4 g/L, LDH 296 U/L, adenosine deaminase (ADA) 67.4 U/L. Most patients (16 cases) were diagnosed by surgical biopsy, especially peripheral lymph nodes biopsy (12 cases). Other patients were diagnosed by ultrasound or CT-guided biopsy (5 cases), video-assisted thoracoscopic pleural biopsy (1 case), video-mediastinoscopic mediastinum lesion biopsy (1 case), bronchial mucosa biopsy through bronchoscope (1 case), bone marrow examination (1 case). All the cases were non-Hodgkin lymphoma except one. CONCLUSIONS: There was no specific clinical manifestation for lymphoma with chest involvement, but in almost half of patients there were enlargement of not only peripheral but also mediastinum lymph nodes. And there were some characteristics in serum, pleural effusion, chest X-ray and CT scan. Surgical biopsy of peripheral lymph nodes was a simple and convenient method for diagnosis. Micro-invasive biopsy had good diagnostic value for lymphoma with chest involvement, including ultrasound- or CT-guided biopsy for superficial mass, pleura, lung, liver, spleen and deep lymph nodes, video-assisted thoracoscopic and video-mediastinoscopic biopsy for pleura, lung and mediastinum lesions. But bronchial mucosa and lung biopsy during bronchoscopy had a low diagnostic rate for lymphoma.

Potential for cost-savings in the care of hospitalized low-risk community-acquired pneumonia patients in China.

BACKGROUND: The cost of treating community-acquired pneumonia (CAP) in China is a heavy economic burden for the society. OBJECTIVE: To investigate the costs of hospitalization of low-risk CAP patients and how hospitalization costs can be reduced through proper usage of hospital resources. METHODS: Two hundred thirty-six patients with low-risk CAP who were hospitalized between January 2000 and December 2005 in a 1161-bed tertiary care teaching hospital were included in a retrospective cohort study. Their hospitalization costs and antibiotic therapy were analyzed. General linear model was utilized to determine correlative variables associated with total hospital costs. RESULTS: The median length of hospital stay was 12 days and the median duration of intravenous (IV) antibiotic therapy was 10 days, they were correlated significantly (P = 0.000, r = 0.81). The median total hospital cost was $556.50 (mean $705.60), of which 48.9% was for drugs, 21.9% for laboratory tests, 8.6% for radiology, 6.5% for medical staff, 6.3% for hospital beds, and 5.3% for examination. General linear model analysis determined that duration of IV antibiotic therapy, Pneumonia Severity Index class, age, and initial empirical antibiotic therapy failure were correlative factors of total hospital costs. Pathogens were identified in 106 patients (44.9%), Mycoplasma pneumoniae was the most common pathogen (19.9%), followed by Streptococcus pneumoniae (8.5%), and Haemophilus influenza (5.5%). The majority of patients accepted initial empirical beta-lactam (37.3%) or fluoroquinolone (30.9%) monotherapy, the empirical treatment failure rates were 20.5% and 5.5%, respectively. CONCLUSIONS: Efforts to reduce duration of IV antibiotic therapy will have the most profound effect on reducing total hospital costs of low-risk CAP. The atypical pathogens should be considered for initial empirical antibiotics in low-risk CAP therapy in China.

[Risk factors and prognosis in 31 patients with extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae bloodstream infection].

OBJECTIVE: To investigate the risk factors, prognosis and resistance to antibiotics in patients with extended-spectrum b-lactamase (ESBLs)-producing Escherichia coli and Klebsiella pneumoniae bloodstream infection. METHODS: A retrospective study was conducted in patients with Escherichia coli and Klebsiella pneumoniae bloodstream infection isolated from Jan. 2004 to Dec. 2005 in Peking University Third Hospital. Those with ESBLs-producing sepsis were case patients, while non-ESBLs-producing sepsis were control patients. The unpaired Student's t-test or non-parametric test and Chi-square test was used for comparison of risk factors, prognosis and resistance to antibiotics between the two groups. RESULTS: A total of 265 (265/748, 35.4%) strains of ESBLs-producing Escherichia coli and 56 (56/266, 21.1%) strains of Klebsiella pneumoniae were isolated between 2004 and 2005, respectively. There were 15 patients with ESBLs-producing sepsis (M/F: 8/7, age 11 - 82 yr) and 16 with non-ESBLs-producing sepsis (M/F: 5/11, age 7 d-84 yr). The frequent origins of infection in the 2 groups were respiratory system, peritoneal cavity and reproductive system. No statistical difference was found between the 2 groups in clinical symptoms such as temperature, fever type, respiratory rate, heart rate, shock, white blood cells. Pitt bacteremia score and APACHE II score (all P > 0.05). No statistical difference was found between the 2 groups in risk factors such as length of hospital stay before pathogen isolation, length of ICU stay, use of mechanical ventilation, duration of mechanical ventilation, use of central venous catheter, glucocorticosteroids or immunosuppressants, histamine-2-receptor agonists, urinary catheter, operation, gastric tube, total parenteral nutrition, previous hospital admission, anemia and hypoalbuminemia (all P > 0.05). However, the number of use of third-generation cephalosporin given 2 weeks before strains isolation was 9 in case patients (9/11) and 3 in control patients (3/10, chi(2) = 5.743, P < 0.05). The antibiotic resistance rate of ESBLs-producing Escherichia coli and Klebsiella pneumoniae increased significantly, including piperacillin (9 vs. 5, chi(2) = 7.013, P < 0.01), cefepime (7, 0, chi(2) = 7.467, P < 0.01), ceftazidime (9, 1, chi(2) = 11.317, P < 0.01), cefoperazone/sulbactam (11, 2, chi(2) = 11.780, P < 0.01), levofloxacin (12, 7, chi(2) = 5.662, P < 0.05). Five in case patients (5/15) and 2 in control patients (2/16) died. CONCLUSIONS: Use of third-generation cephalosporin is an important risk factor for ESBLs-producing Escherichia coli and Klebsiella pneumoniae bloodstream infection. It is of great clinical significance in supervising ESBLs epidemiology and the third-generation cephalosporin usage.

[Epidemiological survey of asthma in a rural area of Yanqing County in Beijing].

OBJECTIVE: To evaluate the epidemiology and risk factors of asthma of people aged more than 40 years living in the rural area of Beijing. METHODS: The data of 1,638 people aged more than 40 years living in 5 villages of Yanqing County in Beijing were collected. Respiratory symptoms, the living conditions, life styles and cooking habits, personal history and family history were collected. Physical examination and lung function tests (ventilation function and bronchodilation tests) were also performed. Asthma was diagnosed based on symptoms, signs, and lung function tests. Univariate analysis and Logistic analysis were employed to evaluate the risk factors for asthma. RESULTS: The prevalence of asthma was 1.89% (31/1 638). For those with asthma, the male to female ratio was 1:4.2, the difference being significant (P<0.05). Common triggering factors for asthma included influenza, cold air, passive smoking and cooking oil smoke. There were statistic differences between asthmatics and non-asthmatics in respiratory disease history in childhood, frequent cough before age 14, and years of exposure to biomass fuel. Cough before age 14 was closely associated with asthma. Only 12.9% of the cases had been diagnosed before this study, indicating that asthma was a underdiagnosed disease in this area. CONCLUSION: The prevalence of asthma is high in this rural area of Beijing. Life style changes and management of respiratory infections before age 14 are indicated for reducing risk factors for asthma. More attention should be paid to early diagnosis of asthma in rural areas.

[The relationship between sputum eosinophils and responses to treatment of inhaled glucocorticoids in patients with persistent asthma].

OBJECTIVE: To evaluate the treatment responses of asthmatics with and without sputum eosinophilia to inhaled glucocorticoids, and therefore to verify whether low sputum eosinophils predict poor response to treatment with inhaled glucocorticoids. METHODS: Forty-two symptomatic asthmatic patients, who had not received glucocorticoid therapy in the 3 months preceding the study, were examined before and 1 month and 3 months after treatment with inhaled glucocorticoids. At each visit, all patients underwent spirometry, symptom scoring and sputum induction. The level of eosinophil cationic protein (ECP) in the sputum supernatants was measured by radioimmunoassay. The patients were divided into 2 groups according to sputum eosinophil (EOS) percentages, an EOS group (EOS > 3%) and a non-EOS group (EOS < 3%). The response to inhaled glucocorticoid therapy (as measured by symptom scores and FEV(1)% pred) and the changes of sputum measurements were compared between the 2 groups. RESULTS: In the EOS group, the baseline EOS [0.080 (0.063 - 0.178)] and ECP level [(324 +/- 149) microg/L] were significantly higher than those of the non-EOS group [0.017 (0.006 - 0.021) and (152 +/- 68) microg/L, respectively, t = 4.40, 3.33, both, all P < 0.01]. Baseline FEV(1), FEV(1)% pred and symptom scores were not different between the 2 groups [EOS group: (1.98 +/- 0.67) L, (65 +/- 20)%, 7.0 (5.0 - 10.0), non-EOS group: (2.07 +/- 1.05) L, (66 +/- 27)%, 5.0 (2.0 - 9.0), t = -0.62, -0.09, 1.32, respectively, all P > 0.05]. After 1 month and 3 months inhaled glucocorticoid therapy, the sputum EOS, ECP, the symptom score, FEV(1) and FEV(1)% pred were [0.019 (0.010 - 0.060), [0.036 (0.006 - 0.070); (173 +/- 153) microg/L, (173 +/- 122) microg/L; 3.0 (1.0 - 6.0), 3.0 (1.0 - 5.0); (2.42 +/- 0.64) L, (2.43 +/- 0.76) L; (77 +/- 13)%, (77 +/- 18)%; respectively in the EOS group, which were significantly different as compared to baseline values (F = 6.73, 6.71, 5.93, 7.38, 5.78, respectively, all P < 0.05). But in the non-EOS group, the sputum EOS, ECP, the symptom score, FEV(1) and FEV(1)% pred were 0.013 (0.000 - 0.025), 0.012 (0.004 - 0.031), (111 +/- 50) microg/L, (117 +/- 50) microg/L; 3.0 (0.0 - 6.0), 3.0 (1.0 - 7.3), (2.22 +/- 0.86) L, (2.21 +/- 0.24) L, (71 +/- 20)%, (65 +/- 21)%; respectively at 1 and 3 months, which showed that the sputum EOS, FEV(1) and FEV(1)% pred did not change (F = 1.98, 0.80, 1.37, respectively, all P > 0.05), but the ECP level and the symptom score improved (F = 3.78, 3.59, respectively, both P < 0.05). Multiple stepwise regression showed that baseline FEV(1), severity degree and sputum EOS correlated significantly with changes in FEV(1) after treatment. Among the baseline indexes examined, sputum EOS had the highest negative predictive value (89.5%) for the response to treatment. CONCLUSIONS: In asthmatics with low sputum EOS, inhaled glucocorticoid therapy for 3 months failed to improve pulmonary function. The result confirmed that low sputum EOS was the best predictor for poor glucocorticoid effect in asthma.

[Characteristics of the airway inflammation and the relationship to interleukin-17 in severe asthma].

OBJECTIVE: To investigate the characteristics of airway inflammation in severe asthma and the association with interleukin-17 (IL-17). METHODS: Sixteen patients with mild persistent asthma, 14 patients with moderate persistent asthma and 18 patients with severe persistent asthma, as well as 15 normal control subjects, were included in this study. At baseline, asthma symptom score was recorded, and lung function was measured. Induced sputum was obtained and processed for cell differential and the supernatant was assayed for the concentrations of IL-17 and IL-8 by sandwich enzyme-linked immunosorbent assay (ELISA), eosinophil cationic protein (ECP) by the immuno-CAP system, and neutrophil myeloperoxidase (MPO) by a colorimetric method, and the values were normalized to the protein content. Then 15 mild to moderate and 15 severe asthmatic patients received inhaled corticosteroid (Pulmicort, Astra-Zeneca) therapy for 4 weeks, and the above measurements were repeated. RESULTS: The percentage of sputum eosinophils and the level of ECP were significantly increased in mild [0.0670 +/- 0.0740, (155 +/- 91) x 10(-6) g/g protein], moderate [0.0830 +/- 0.0440, (180 +/- 83) x 10(-6) g/g protein] and severe [0.1240 +/- 0.1430, (191 +/- 87) x 10(-6) g/g protein] asthmatic patients, as compared to the normal controls [0.0000 +/- 0.0010, (44 +/- 25) x 10(-6) g/g protein, P < 0.01)]; but there was no significant difference among mild, moderate and severe asthma (P > 0.05). On the contrary, the percentage of sputum neutrophils was significantly increased in patients with severe asthma (0.589 +/- 0.203) as compared to patients with mild (0.455 +/- 0.154) and moderate (0.449 +/- 0.194) asthma and normal controls (0.313 +/- 0.134, P < 0.01). The level of MPO was also increased in severe asthma [(31 +/- 10 ) U/g protein] as compared to mild [(12 +/- 4) U/g protein] and moderate [(22 +/- 7) U/g protein] asthma and normal controls [(10 +/- 4) U/g protein, P < 0.01]. The sputum level of IL-17 in severe, moderate asthma [(264 +/- 137) x 10(-9) g/g protein, (172 +/- 65) x 10(-9) g/g protein] was significantly higher than those in mild asthma [(126 +/- 52) x 10(-9) g/g protein] and normal controls [(56 +/- 20) x 10(-9) g/g protein, P < 0.01]. As compared to the normal controls [(83 +/- 36) x 10(-9) g/g protein], the level of IL-8 in severe asthma [(531 +/- 321) x 10(-9) g/g protein] was significantly increased (P < 0.01), and those in mild [(410 +/- 181) x 10(-9) g/g protein] and moderate [(438 +/- 148) x 10(-9) g/g protein] asthma were also increased, although the difference was not statistically significant (P > 0.05). The level of IL-17 was correlated positively with IL-8, neutrophils and MPO (r = 0.525, 0.349, 0.602, all P < 0.01). After steroid therapy, the percentage of eosinophils, the levels of ECP, MPO, IL-17 and IL-8 decreased significantly in all patients combined, but the percentage of neutrophils remained unchanged (P > 0.05) and still significantly higher in severe asthmatic patients (0.642 +/- 0.157) as compared to mild and moderate asthmatic patients (0.394 +/- 0.147, P < 0.01). CONCLUSIONS: Airway neutrophilia is a feature of severe asthma. The IL-17/IL-8 pathway may be involved in the initial neutrophil influx into the airways.