IL-2 and IL-10 levels in induced sputum and serum samples of asthmatics.

BACKGROUND: There is consisting evidence that asthma is associated with airway inflammation. Originally IL-10 and IL-2 were described as lymphokines produced by T cells in mediating cellular infiltration into the airways and continue to be of interest in evaluating asthma pathogenesis. The aim of this study was to evaluate the serum and sputum levels of IL-2 and IL-10 in asthmatic subjects and healthy controls and to correlate disease activity and other clinical indices with concentrations of IL-2 and IL-10 in serum and sputum samples. METHODS: We evaluated cell profiles and IL-2 and IL-10 levels in induced sputum samples and in serum samples of 6 mild, 5 moderate, 7 severe asthmatic patients and 5 healthy controls by using ELISA. RESULTS: The mean IL-2 in sputum samples of asthmatics and controls were 35.3 +/- 13.2 pg/ml and 35.3 +/- 8.4 pg/ml, respectively. The mean IL-2 in serum samples of asthmatics and controls were 42.7 +/- 21.1 pg/ml and 30.3 +/- 2.4 pg/ml, respectively. Both levels did not result in any statistically significant difference between asthmatics and controls. There was no correlation between serum and sputum IL-2 levels, however sputum IL-2 levels correlated with percentage of sputum lymphocytes (p < 0.03, r = 0.51). The mean IL-10 levels in sputum samples of asthmatics and controls were 4.4 +/- 3.3 pg/ml and 3.9 +/- 5.9 pg/ml, respectively, the mean IL-10 level in serum of asthmatics and controls were 4.1 +/- 3.8 pg/ml and 2.3 +/- 2.5 pg/ml, respectively. We could not find statistically significant difference of serum or sputum IL-10 levels between asthmatics and controls. There was only correlation between serum and sputum IL-10 levels in asthmatics (p < 0.0008, r = 0.73). There was no difference between asthmatic subgroups regarding sputum and serum levels of IL-2 and IL-10. No correlation could be demonstrated between sputum or serum IL-2 and IL-10 levels and clinical severity. CONCLUSIONS: We have demonstrated the presence of detectable concentrations of the IL-2 and IL-10 in serums and induced sputum samples of asthmatics, however, they have no predictive value for asthma since their levels are not increased in asthmatic patients over controls. Moreover, IL-2 level positively correlated with lymphocyte percentage in induced sputum. The results suggest that measurement of IL-2 and IL-10 concentrations in serum and sputum will not be of diagnostic use in asthma and a reflection of the severity of asthmatic airway inflammation.     

Serum concentrations of nitric oxide, tumor necrosis factor (TNF)-alpha and TNF soluble receptors in women with overweight and obesity

The aims of the present study was to examine how overweight and obesity affect serum concentrations nitric oxide (NO) metabolites and to determine whether there is association between serum concentrations tumor necrosis factor (TNF)-alpha and TNF soluble receptors (sTNF-R) in subjects with overweight and obesity. The study groups involved 154 women: 102 obese (81 obese with body mass index [BMI] 30 to 40 kg/m2 and 21 obese with BMI > 40 kg/m2), 24 overweight patients, and 28 lean controls. Serum concentrations of NO metabolites and of TNF-alpha and its soluble receptors (sTNF-R1, sTNFR-2) were measured by enzyme-linked immunosorbent assay (ELISA) kits. Serum concentration of insulin was measured by radioimmunoassay (RIA). Plasma glucose, cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglicerydes were determined by enzymatic procedure. Body composition was determined by impedance analysis using Bodystat (Douglas, British Isles). Serum concentrations of NO in the overweight group (35.1 +/- 12.1 micromol/L) and the obese groups with BMI 30 to 40 kg/m2 (32.8 +/- 9.3 micromol/L) and with BMI greater than 40 kg/m2 (33.3 +/- 8.5 micromol/L) were significantly higher when compared to controls (28.2 +/- 8.1 micromol/L): P < .05; P < .01, and P < .01, respectively. There was no difference in levels of NO between the overweight group and both obese groups. Serum concentration of TNF-alpha was also significantly higher in the group with overweight (6.5 +/- 3.1 pg/mL), in the obese group with BMI 30 to 40 kg/m2 (6.8 +/- 3.1 pg/mL), and in the obese group with BMI greater than 40 kg/m2 (7.4 +/- 2.6 pg/mL) when compared to controls (2.9 +/- 2.2 pg/mL): P < .00005; P < .00005, and P < .0000001, respectively. However, serum concentrations of sTNF-R1 and -R2 did not differ significantly between the overweight group, both obese groups, and controls. In conclusion, we observed increased serum concentrations of TNF-alpha and NO in overweight and obese women. It seems that there is an association between serum concentrations of TNF-alpha and NO; however, this relationship depends on the degree of obesity.     

Elevated circulating plasma adiponectin in underweight patients with COPD

BACKGROUND: Adiponectin is an adipose tissue-derived specific protein that has antiinflammatory as well as anti-atherosclerotic effects. In the United States, many patients with COPD are obese and die of cardiovascular diseases. However, in Japan, patients with COPD are frequently cachexic and die of respiratory failure. This study was designed to investigate the role of adiponectin in these differences in characteristics of COPD. METHODS: We enrolled normal-weight and underweight male patients with COPD (n = 31; age, 71 +/- 1 years; body mass index [BMI], 20.1 +/- 0.6 kg/m(2)) and age-matched, healthy, male, control subjects (n = 12). The adiponectin levels were measured by enzyme-linked immunosorbent assay. Correlation of adiponectin levels with pulmonary function and serum levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin-6) were estimated. RESULTS: Adiponectin levels in patients with COPD were significantly higher than those in control subjects (p<0.01) and inversely correlated with BMI (r = - 0.55, p<0.01). Even in the normal-weight patients with COPD, adiponectin levels were significantly higher than those in control subjects (p<0.01). Adiponectin levels in patients with COPD significantly correlated with percentage of predicted residual volume (r = 0.40, p<0.05). In patients with TNF-alpha levels > 5 pg/mL, there was a significant correlation between plasma adiponectin and serum TNF-alpha levels (r = 0.68, p<0.05). CONCLUSIONS: Plasma adiponectin levels in patients with COPD were elevated and correlated with body weight loss, hyperinflation, and systemic inflammation. Increased adiponectin may reduce cardiovascular events in underweight patients with COPD.     

Endothelin-1 levels in the pathophysiology of chronic obstructive pulmonary disease and bronchial asthma

BACKGROUND: Endothelin-1 (ET-1) has been implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). The ET-1 levels are elevated during exacerbations of asthma and COPD in bronchoalveolar lavage, serum, and sputum and fails with treatment of the exacerbations. Hypoxemia stimulates ET-1 secretion. OBJECTIVE: The aim of this study was to examine the serum ET-1 levels in stable asthmatic and COPD patients. MATERIALS AND METHODS: We examined 48 COPD and 26 asthmatic patients and 34 normal subjects. We collected arterial samples to measure baseline ET-1 levels in all patients and in the control group, during the day. All the patients underwent formal polysomnography (EEG, ECG, airflow, respiratory muscle movement, oximeter) to detect the presence of nocturnal, nonapneic, and oxyhemoglobin desaturation. Twelve of the COPD patients and six of the asthmatic patients were disqualified because of inadequate sleep or sleep apnea syndrome. Nineteen of the COPD patients desaturated below a baseline sleep saturation of 90% for 5 min or more, reaching a nadir saturation of at least 85%. We collected arterial samples to measure ET-1 levels, 5 min after the first period of desaturation in each of the 19 desaturators COPD patients. None of the 20 asthmatic patients exhibited oxyhemoglobin desaturation during sleep. RESULTS: Baseline arterial ET-1 levels during the day were significantly higher in "desaturators" COPD patients (2.08+/-0.28 pg/ml) compared to "non-desaturators" COPD patients (1.38+/-0.16 pg/ml) (P<0.001) and to asthmatics (0.7+/-0.85 pg/ml) (P<0.001). ET-1 Levels in normal subjects were 1.221+/-0.02 pg/ml. In "desaturators" COPD patients ET-1 levels during the night, 5 min after the first oxyhemoglobin desaturation, were significantly higher (4.28+/-1.10 pg/ml) compared to those during the day (2.08+/-0.28 pg/ml) (P<0.001). A significant negative correlation was observed between ET-1 levels and degree of desaturation during the day (P=0.005, r=0.632) and during the night (P<0.001, r=0.930) in "desaturators" COPD patients. CONCLUSION: According to our results: (1) ET-1 levels were significantly higher in "desaturators" COPD patients than in "non-desaturators" COPD and in asthmatics; (2) ET-1 levels were significantly higher during the night than during the day in "desaturators" COPD patients; (3) the degree of desaturation correlated negatively with the ET-1 levels in "desaturators" COPD patients, both during daytime and nighttime. These findings are consistent with the hypothesis that ET-1 is implicated in the pathophysiology of asthma and COPD, especially if nocturnal, nonapneic, oxyhemoglobin desaturation exists.     

Relationship between serum tumor necrosis factor-alpha and insulin resistance in obese men with Type 2 diabetes mellitus

We analyzed serum concentrations of tumor necrosis factor-alpha (TNF-alpha) for their role in insulin resistance in 12 obese men with untreated Type 2 diabetes mellitus and in 6 age-and BMI-matched obese controls. Insulin resistance was expressed using the homeostasis model assessment (HOMA-R). Six of the patients were insulin-resistant (HOMA-R>5.0), while six were not (HOMA-R相似文献   

Comparison of Sputum and Serum Eosinophil Cationic Protein (ECP) Levels in Nonatopic Asthma and Chronic Obstructive Pulmonary Disease

The aim of the present study was to investigate whether sputum eosinophil cationic protein (ECP) concentrations could be a useful marker in the differential diagnosis between intrinsic asthma and chronic obstructive pulmonary disease (COPD). For this purpose total blood eosinophil counts were obtained and concentrations of serum and sputum ECP from 10 nonatopic asthmatics with a mild attack and 9 COPD patients with acute exacerbation were measured by radioimmunoassay. Mean serum ECP concentration was 54.3 ± 23.0 g/L in the asthmatic group and 83.3 ± 79.2 g/L in the COPD group (p: n.s.). In the group of asthmatics mean sputum ECP level was 984.5 ± 1245.5 mg/L/g sputum and in the COPD group it was 417.5 ± 363.5 mg/L/g sputum. There was no significant difference in sputum ECP levels between patients with asthma and COPD. We conclude that neither sputum nor serum ECP levels are useful markers in differential diagnosis of asthma attack and acute exacerbation of COPD.     

Addition of inhaled corticosteroid on combined bronchodilator therapy in patients with COPD

PURPOSE: Bronchodilator therapy is the first step treatment in patients with COPD. The beneficial effects of corticosteroids either in health status or in airway inflammation in COPD have been previously studied. The aim of this study was to evaluate whether adding inhaled corticosteroids to combined bronchodilator therapy has additive clinical and anti-inflammatory effects in COPD patients. SUBJECTS AND METHODS: Thirty patients with COPD were included in the study. All patients were receiving inhaled anticholinergic and long-acting beta-2 agonist. Inhaled corticosteroid (budesonide 800 microg daily) was added to their current medications for 12 weeks. Before and after this treatment period, spirometric values and arterial blood gas parameters were determined, blood was drawn for measurement of serum inflammatory markers and sputum was induced. RESULTS: All patients were male, mean age was 67.7+/-8.7 years and duration of disease was 9.7+/-4.3 years. The induced sputum total cell counts, eosinophil and neutrophil counts decreased with corticosteroid treatment. The induced sputum IL-8 and TNF-alpha levels decreased significantly (IL-8; 835.9+/-217 versus 378.4+/-105 pg/ml, p=0.0001, TNF-alpha; 320.7+/-129 versus 201.3+/-52 pg/ml, p=0.003). Serum inflammatory markers and sputum LTB4 levels did not change with treatment. CONCLUSION: These results suggested that the addition of inhaled corticosteroids to combined bronchodilator therapy might have anti-inflammatory effects in patients with COPD.     

Leukotriene E(4) in urine in patients with asthma and COPD--the effect of smoking habit

Leukotriene E(4) (LTE(4)) is implicated in asthma pathophysiology and possibly in chronic obstructive pulmonary disease (COPD) as one of the causes of persistent bronchoconstriction and mucus hypersecretion. Cigarette smoking stimulates cysteinyl leukotrienes (CysLTs) production. We investigated whether LTE(4) is equally increased in asthma and COPD and whether smoking significantly affects LTE(4) levels. Secondary outcomes involved correlations with inflammatory and functional parameters. We studied 40 patients with COPD [20 smokers], 40 asthmatics [20 smokers] and 30 healthy subjects [15 smokers]. Spirometry (FEV(1)% pred., FEV(1)/FVC) was performed, urine was collected for measurement of LTE(4) and creatinine, induced sputum was collected for differential cell counts and serum for ECP. LTE(4)/creatinine levels (pg/mg) [mean (sd)] were increased in asthmatic patients compared to COPD and controls, [125.6(54.5) vs. 54.5(19) vs. 55.9(18.9)pg/mg, respectively, P<0.0001 for asthma]. Smoking significantly affects LTE(4) levels only in asthmatic patients [164 (48) vs. 87 (26.3), P<0.0001 for smokers]. The only significant correlation was between eosinophils in induced sputum and LTE(4)/creatinine levels in asthmatics. In conclusion, patients with asthma presented higher LTE(4) values compared to normals and patients with COPD. Smoking significantly affects LTE(4) values only in asthmatics indicating a different underlying CysLTs inflammatory process in this condition.     

Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine

BACKGROUND: Interleukin-17 (IL-17) is a novel cytokine secreted by activated human memory CD4+ T cells. In vivo IL-17 recruits neutrophils into the airways via the release of CXC chemokines (interleukin-8) from bronchial epithelial cells. Since neutrophils are implicated in pathogenesis of chronic obstructive pulmonary disease (COPD) chronic bronchitis (CB) and asthma, we hypothesized that there would be increased concentration of IL-17 in the airways of these patients. To test this hypothesis, we measured levels of IL-17 in induced sputum of COPD patients, chronic bronchitis and asthmatics and compared them with healthy controls. METHODS: Levels of IL-17 in induced sputum were measured via ELISA method in 19 COPD, 16 CB, 10 asthma and 11 control subjects. Airway responsiveness to methacholine was performed in people with FEV1 higher than 70% of predicted. RESULTS: There were no significant differences in IL-17 levels between control group and the other groups. However, levels of IL-17 in sputum of COPD patients were significantly lower than in asthma (P=0.004) and in CB (P=0.01) groups. Medians and (ranges) were as follows: asthma--37.6 pg/ml (18.8-55.7 pg/ml), CB 293 pg/ml (18.8-49.7 pg/ml) and COPD 24.6 pg/ml (0-34.1 pg/ml). Comparison of healthy control subjects (PC20 > 8 mg/ml) to a group with bronchial hyperreactivity, which consisted of asthmatics and CB patients, whose PC20 was less than 8 mg/ml, revealed that levels of IL-17 were significantly increased in the second group (P=0.02). Also, levels of IL-17 were significantly increased (P=0.02) in the asthmatic patients with bronchial hyperreactivity compared to healthy subjects. Moreover levels of IL-17 in sputum of all studied subjects correlated negatively with PC20 (r=-0.51, P=0.002). CONCLUSIONS: According to our results IL-17 is probably not involved in pathogenesis of stable COPD, but it may play a role in people with airway hyperresponsiveness.     

Asthma severity, exacerbation risk, and controller treatment burden in underweight and obese children

OBJECTIVE: The relationship between weight status and asthma characteristics in children remains inadequately defined. Very little has been published on the risk of exacerbation, physician perception of severity, and the level controller treatment prescribed to underweight and obese children with asthma in a real-world setting. METHODS: We assessed the diagnostic severity, pulmonary function, exacerbation prevalence, and controller treatment level in 10,559 new asthma patients seen at one of four pediatric asthma subspecialty clinics among three BMI groups. Participants were analyzed by body mass index (BMI)-percentile based on Centers for Disease Control & Prevention classification. Multivariable logistic regression models were used to assess the associations between BMI-percentile cohort group and asthma outcomes. RESULTS. Underweight asthmatics were rare (2.5%) relative to obese asthmatics but appeared to have the greatest impairment in forced vital capacity and had the greatest controller treatment burden. Obese asthmatic children made up 26.2% of our cohort and were more likely to have severe disease (odds ratio (OR) 1.40, 95% confidence interval (CI) 1.06-1.85) and airflow obstruction (OR 1.36, 95% CI 1.16-1.59) compared to normal weight asthmatics. Obese asthmatics were not at greater risk for exacerbation (OR 1.41, 95% CI 0.64-3.11) or high treatment burden (OR 1.03, 95% CI 0.83-1.28). CONCLUSIONS. Obesity is more common than underweight status among children with asthma. Both underweight and obese children with asthma have worse lung function and asthma-related outcomes compared to similar normal weight children, though the phenotypic characteristics of underweight and obese asthmatics differed considerably.     

Determinants of BMI in patients with COPD

OBJECTIVE: COPD is characterized by significant chronic inflammation that is evident not only in the pulmonary compartment but also in the circulation. Peripheral blood features of COPD include markers of oxidative stress and altered circulating levels of inflammatory mediators and acute-phase proteins. The presence of a systemic inflammatory response may influence quality of life by giving rise to weight loss, muscle wasting and tissue depletion. The aim of the present study was to evaluate the determinants of body mass and the value of serum tumour necrosis factor alpha (TNF-alpha) as a marker of weight loss in COPD patients, and to correlate this with the burden of oxidative stress as measured by serum malonyldialdehyde (MDA) levels. METHODOLOGY: Fifty-two male COPD patients (mean age 62.55 +/- 6.81 years) were studied. After anthropometric measurements and standard spirometry, serum TNF-alpha concentration was measured by enzyme-linked immunosorbent assay using an hTNF-alpha kit, and MDA was studied spectrophotometrically using the Yoshioka-Kawada method. RESULTS: The mean BMI was 24.82 +/- 3.46. BMI was lower than normal (< 19) in six patients. Mean serum TNF-alpha concentration was 14.99 +/- 8.98 pg/mL and MDA was 0.93 +/- 0.13 nmol/L. There was no significant correlation between serum MDA and TNF concentrations (P = 0.140). Serum TNF-alpha and MDA concentrations were not correlated with severity of airflow obstruction or degree of hypoxaemia (P > 0.05 for all). BMI was negatively correlated with burden of smoking (pack-years) (r = -0.392, P= 0.004); but not with pulmonary function, degree of hypoxaemia, serum TNF-alpha or MDA levels. BMI was significantly lower in current smokers than ex-smokers (P = 0.041); however, serum MDA and TNF levels were similar in both groups. CONCLUSION: The results of this study indicate that body mass is related to smoking status (both pack-years and continuance of smoking) in COPD; however, serum TNF-alpha concentration does not seem to be a good marker of weight loss in these patients.     

Body mass index and response to emergency department treatment in adults with severe asthma exacerbations: a prospective cohort study

BACKGROUND: In acute asthma (AA), overweight/obesity (body mass index [BMI]>or=25 kg/m2) have been related to poorer outcomes and higher risk of complications. METHODS: We designed a prospective cohort study to determine if overweight/obese adults with severe episodes of AA require longer duration of emergency department (ED) treatment and have higher hospitalization rates compared with underweight/normal asthmatics (BMI<25 kg/m2). All patients received inhaled albuterol (maximum 6 h). Patients were discharged or admitted according to standard accepted criteria. The weight and height of each patient were measured during the ED stay. RESULTS: Four hundred twenty-six patients (mean, 33.4+/-11.5 years [+/-SD]; 63% women) with severe exacerbations (FEV1, 28.2+/-11.9% of predicted) were enrolled. One hundred sixty-three patients (38.3%) were classified as overweight/obese. Patients with BMI>or=25 kg/m2 showed significant increases in length of ED stay (2.3 h vs 1.9 h, p=0.01) and rate of hospitalization (13.7% vs 6.8%, p=0.02), despite adjustments for other confounding variables. They also presented a higher rate of use of inhaled steroids and theophylline within the past 7 days. At the end of treatment, overweight/obese patients displayed more wheezing. Multivariate analysis demonstrated that BMI>or=25 kg/m2 resulted unrelated to final change in peak expiratory flow from baseline. By contrast, BMI>or=25 kg/m2 was related with duration of ED treatment (p=0.002). CONCLUSIONS: Overweight/obese patients were admitted to the hospital more frequently than underweight/normal patients. This may reflect a difference in the perception of dyspnea, or it may reflect an underlying difference in asthma severity between the two groups.     

Sputum cathelicidin, urokinase plasminogen activation system components, and cytokines discriminate cystic fibrosis, COPD, and asthma inflammation

BACKGROUND: Interest in airways inflammatory disease has increasingly focused on innate immunity. We investigated several components of innate immunity in induced sputum of patients with cystic fibrosis (CF), COPD, and asthma, and healthy control subjects. METHODS: Twenty eight patients with mild CF lung disease (age > or = 12 years; FEV1, 74 +/- 3% predicted [mean +/- SE]), 74 adults with COPD (FEV1, 55 +/- 2% of predicted), 34 adults with persistent asthma (FEV1, 66 +/- 2% of predicted), and 44 adult control subjects (FEV1, 85 +/- 1% of predicted) were studied while in stable clinical condition. Levels of sputum interleukin (IL)-8, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, human cationic antimicrobial protein 18 (CAP18), urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 were determined. Cell sources were investigated by flow cytometry and immunohistochemistry. Spirometry was performed prior to sputum induction. RESULTS: CF patient sputum showed greatest increase in IL-8 compared to that of patients with COPD and asthma (which were also greater than control subjects), and elevated levels of TNF-alpha and IL-10 compared to other groups. There were no differences in IFN-gamma. CAP18 levels were elevated in CF and COPD patients compared to control subjects, while asthma patients had reduced CAP18 levels. uPA levels were similar but uPAR was elevated in CF and COPD patients more so than in asthma patients, while PAI-1 levels were elevated in all three disease groups. CAP18 localized to neutrophil secondary granules; neutrophils were also sources of IL-8 and PAI-1. CAP18 and PAI-1 negatively correlated with pulmonary function. CONCLUSION: Induced-sputum innate immune factor levels discriminate inflammatory changes in CF, COPD, and asthma, suggesting potential roles in pathophysiology and as well as providing disease-specific biomarker patterns.     

支气管哮喘和慢性阻塞性肺疾病患者诱导痰中基质金属蛋白酶及其抑制剂与气道炎症及气流受限

目的探讨支气管哮喘（简称哮喘）和慢性阻塞性肺疾病（COPD）患者诱导痰中基质金属蛋白酶9（MMP-9）和基质金属蛋白酶抑制剂1（TIMP-1）的水平及其与炎性细胞数、肺功能的关系。方法分别选择14例缓解期哮喘患者（哮喘组）、12例稳定期COPD患者（COPD组）和10名健康对照者（健康对照组）进行肺功能测定和用诱导痰检查方法对痰炎性细胞进行分类计数，并用酶联免疫吸附试验（ELISA）法测定诱导痰上清液中自细胞介素4（IL-4）、MMP-9和TIMP-1浓度。结果哮喘组患者诱导痰中嗜酸粒细胞、中性粒细胞分别为0．181±0．067、0．30±0．07，健康对照组为0．007±0．005、0．26±0．06，COPD组为0．042±0．017、0．50±0．10，3组细胞间比较差异有统计学意义（F值分别为4．32、4．13，P均〈0．05）。哮喘组、COPD组、健康对照组间诱导痰中IL-4浓度分别为（19±7）×10^-3／L、（14±6）×10^-3g／L、（11±4）×10^-3g／L，3组诱导痰中IL-4浓度比较差异无统计学意义（F=1．56，P均〉0．05），且分别与嗜酸粒细胞、中性粒细胞和第一秒用力呼气容积占预计值百分比（FEV1占预计值％）无相关（r分别为0．33、0．11、0．19、0．25、0．39、0．40、0．21、0．35、0．17，P均〉0．05）。哮喘组和COPD组诱导痰中MMP-9、TIMP-1浓度分别为（15．9±6．0）g／L、（13．4±5．1）g／L、（19．8±8．5）g／L、（16．7±7．6）g／L，健康对照组分别为（1．8±1．1）g／L、（1．3±0．9）g／L，两组MMP-9、TIMP-1浓度比较差异有统计学意义（F值分别为2．99、4．22，P均〈0．05）。哮喘组MMP-9浓度与嗜酸粒细胞呈正相关（r=0．71，P〈0．05）；COPD组MMP-9浓度与中性粒细胞呈正相关（r=0．59，P〈0．05），但与FEV。占预计值％和第一秒用力呼气容秽用力肺活量（FEV1／FVC）无相关（r分别为0．22、0．16、0．25、0．30，P均〉0．05）。哮喘组和COPD组TIMP．1浓度均与嗜酸粒细胞和中性粒细胞无相关（r分别为0．27、0．31、0．20、0．35，P均〉0．05），但与FEV。占预计值％呈负相关（r分别为-0．58、-0．62，P均〈0．05）。哮喘组和COPD组诱导痰中MMP-9／TIMP-1比值分别为0．8±0．7、0．8±0．6，两组比较差异无统计学意义（F=1．78，P〉0．05），但与健康对照组（1．5±0．6）比较差异有统计学意义（F=3．70，P〈0．05），且与FEV1占预计值％呈正相关（r分别为0．56、0．61，P均〈0．05）。结论哮喘组和COPD组患者诱导痰中MMP-9／TIMP-1比值的失衡与气道炎症和气流受限有关，这种失衡在哮喘和COPD细胞外基质的重塑和气流受限的发病机制中发挥重要作用。     

血清瘦素对慢性阻塞性肺疾病患者营养状态影响的初步研究

目的 探讨血清瘦素及肿瘤坏死因子α（ＴＮＦ－α）的慢性阻塞性肺疾病（ＣＯＰＤ）患者营养不良发生中的意义。方法 测定３１例ＣＯＰＤ患者（分为营养不良组１２例,非营养不良组１９例）及１１名正常人的血清瘦素、ＴＮＦ－α浓度、体重指数（ＢＭＩ）、理想体重百分比（ＮＷ％）、三头肌皮皱厚度（ＴＳＦ）、肩胛下皮皱厚度（ＳＳＦ）、上臂中部臂围（ＭＡＣ）,血清白蛋白（ＡＬＢ）、总淋巴细胞计数（ＬＹＭ）等指标。瘦素与     

Asthma Severity,Exacerbation Risk,and Controller Treatment Burden in Underweight and Obese Children

Objective. The relationship between weight status and asthma characteristics in children remains inadequately defined. Very little has been published on the risk of exacerbation, physician perception of severity, and the level controller treatment prescribed to underweight and obese children with asthma in a real-world setting. Methods. We assessed the diagnostic severity, pulmonary function, exacerbation prevalence, and controller treatment level in 10,559 new asthma patients seen at one of four pediatric asthma subspecialty clinics among three BMI groups. Participants were analyzed by body mass index (BMI)-percentile based on Centers for Disease Control & Prevention classification. Multivariable logistic regression models were used to assess the associations between BMI-percentile cohort group and asthma outcomes. Results. Underweight asthmatics were rare (2.5%) relative to obese asthmatics but appeared to have the greatest impairment in forced vital capacity and had the greatest controller treatment burden. Obese asthmatic children made up 26.2% of our cohort and were more likely to have severe disease (odds ratio (OR) 1.40, 95% confidence interval (CI) 1.06–1.85) and airflow obstruction (OR 1.36, 95% CI 1.16–1.59) compared to normal weight asthmatics. Obese asthmatics were not at greater risk for exacerbation (OR 1.41, 95% CI 0.64–3.11) or high treatment burden (OR 1.03, 95% CI 0.83–1.28). Conclusions. Obesity is more common than underweight status among children with asthma. Both underweight and obese children with asthma have worse lung function and asthma-related outcomes compared to similar normal weight children, though the phenotypic characteristics of underweight and obese asthmatics differed considerably.     

Relation of body mass index to outcome in patients with known or suspected coronary artery disease

Increased body mass index (BMI), a parameter of total body fat content, is associated with an increased mortality in the general population. However, recent studies have shown a paradoxic relation between BMI and mortality in specific patient populations. This study investigated the association of BMI with long-term mortality in patients with known or suspected coronary artery disease. In a retrospective cohort study of 5,950 patients (mean age 61 +/- 13 years; 67% men), BMI, cardiovascular risk markers (age, gender, hypertension, diabetes, current smoking, angina pectoris, old myocardial infarction, heart failure, hypercholesterolemia, and previous coronary revascularization), and outcome were noted. The patient population was categorized as underweight, normal, overweight, and obese based on BMI according to the World Health Organization classification. Mean follow-up time was 6 +/- 2.6 years. Incidences of long-term mortality in underweight, normal, overweight, and obese were 39%, 35%, 24%, and 20%, respectively. In a multivariate analysis model, the hazard ratio (HR) for mortality in underweight patients was 2.4 (95% confidence interval [CI] 1.7 to 3.7). Overweight and obese patients had a significantly lower mortality than patients with a normal BMI (HR 0.65, 95% CI 0.6 to 0.7, for overweight; HR 0.61, 95% CI 0.5 to 0.7, for obese patients). In conclusion, BMI is inversely related to long-term mortality in patients with known or suspected coronary artery disease. A lower BMI was an independent predictor of long-term mortality, whereas an improved outcome was observed in overweight and obese patients.     

哮喘患者痰液细胞因子和哮嗜酸细胞阳离子蛋白水平及意义

目的 探讨痰中细胞因子、嗜酸细胞阳离子蛋白（ＥＣＰ）水平与哮喘严重程度的关系。方法 采用酶联免疫法及荧光光免疫法对轻（Ｍ组１０例）中、重度（ＭＳ组１５例）哮喘２痰液白细胞介素（ＩＬ）５、肿瘤坏死因子α（ＴＮＦ－α）、可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）、ＥＣＰ水平进行检测。结果 中、重度哮喘患溶液ＩＬ－５（３５ｎｇ／Ｌ以上）、ＴＮＦ－α（Ｍ组为１４９±５９ｎｇ／Ｌ，ＭＳ组为２６７±１４７ｇ／Ｌ     

Nutritional status and long-term mortality in hospitalised patients with chronic obstructive pulmonary disease (COPD)

Patients with chronic obstructive pulmonary disease (COPD) often have difficulties with keeping their weight. The aim of this investigation was to study nutritional status in hospitalised Nordic COPD patients and to investigate the association between nutritional status and long-term mortality in this patient group. In a multicentre study conducted at four university hospitals (Reykjavik, Uppsala, Tampere and Copenhagen) hospitalised patients with COPD were investigated. Patient height, weight and lung function was recorded. Health status was assessed with St. George's Hospital Respiratory Questionnaire. After 2 years, mortality data was obtained from the national registers in each country. Of the 261 patients in the study 19% where underweight (BMI <20), 41% were of normal weight (BMI 20-25), 26% were overweight (BMI 25-30) and 14% were obese. FEV(1) was lowest in the underweight and highest in the overweight group (p=0.001) whereas the prevalence of diabetes and cardio-vascular co-morbidity went the opposite direction. Of the 261 patients 49 (19%) had died within 2 years. The lowest mortality was found among the overweight patients, whereas underweight was related to increased overall mortality. The association between underweight in COPD-patients, and mortality remained significant after adjusting for possible confounders such as FEV(1) (hazard risk ratio (95% CI) 2.6 (1.3-5.2)). We conclude that COPD patients that are underweight at admission to hospital have a higher risk of dying within the next 2 years. Further studies are needed in order to show whether identifying and treating weight loss and depletion of fat-free mass (FFM) is a way forward in improving the prognosis for hospitalised COPD patients.     

Possible effects of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease

PURPOSE: Expression of vascular endothelial growth factor (VEGF) is reduced in the lungs of patients with emphysema. We examined whether VEGF levels in sputum differed in patients with emphysema, bronchitis, or asthma, as compared with controls. METHODS: Fifty-nine patients with chronic obstructive pulmonary disease (COPD) (25 with emphysema, 19 with chronic bronchitis, and 15 with a mixed type), 20 patients with bronchial asthma, and 11 normal controls were included in the study. The concentration of VEGF in induced sputum and the correlations between VEGF levels and pulmonary function were examined. RESULTS: The mean (+/- SD) concentration of VEGF in induced sputum was significantly higher in patients with asthma (6440 +/- 1820 pg/mL, P <0.0001) or bronchitis (4120 +/- 1100 pg/mL, P <0.0001) than in normal controls (1860 +/- 1220 pg/mL), but significantly lower in patients with emphysema (500 +/- 300 pg/mL, P =0.03). The concentration of VEGF in sputum from patients with bronchitis correlated inversely with forced expiratory volume in 1 second (r = -0.87; P =0.0002); in contrast, there was a positive correlation between these two measurements in patients with emphysema (r = 0.82; P <0.0001). In addition, sputum VEGF concentrations correlated with the diffusing capacity of carbon monoxide in patients with emphysema (r = 0.87; P <0.0001), but not in those with bronchitis (r = -0.22; P =0.36). CONCLUSION: In patients with bronchitis, increased levels of VEGF in induced sputum were associated with airflow limitation. In contrast, decreased levels of VEGF were associated with airflow limitation and alveolar destruction in patients with emphysema. Thus, our findings suggest that VEGF may affect the pathogenesis of these two common types of COPD.