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1.
The fatty acid pattern of the phospholipids in the bronchial secretion of patients with cystic fibrosis (CF) showed an increase of the mole fraction of arachidonic acid (AA) in most phospholipid classes compared to normals. Increase of AA in some classes was also found in patients with chronic bronchitis and in patients chronically colonized with Pseudomonas aeruginosa but in the diphosphatidylglycerol, lysophosphatidylethanolamine and sphingomyelin phospholipids, high fractions of AA was found exclusively in CF patients. Arachidonic acid was found to attain the highest ratios in CF in seven of the nine major bronchial phospholipids compared to the controls. There was no difference in the ratio saturated/unsaturated fatty acids between the CF patients and the control groups. A tendency towards unsaturation of the fatty acids in the bronchial secretion seems to be characteristic of infection and inflammation but AA appears to be more markedly increased in CF. Thus, the recorded changes may be characteristic for CF and not secondary to infection and/or inflammation in general, nor to P. aeruginosa colonization.  相似文献   

2.
BACKGROUND: Bronchoalveolar lavage (BAL) is an established technique for measuring antibiotic concentrations in the epithelial lining fluid (ELF) of the bronchiolar and alveolar regions; however, the results may not reflect concentrations in bronchial regions. Bronchoscopic microsampling (BMS) is a technique that makes it possible to obtain multiple samples from bronchial ELF. OBJECTIVE: BMS and BAL were used to analyze the pharmacokinetics of gatifloxacin in bronchial ELF from healthy young adult subjects and adult patients with chronic bronchitis. METHODS: Bronchial ELF samples were obtained by BMS at 1, 2, 3, 4, 6, 10, and 24 hours after administration of a single oral dose of gatifloxacin 200 mg in healthy young adult (aged 20-25 years) subjects, and at 1, 2, 4, and 10 hours after a single dose in patients with chronic bronchitis (aged > or =20 years). At least 1 month after the initial BMS, alveolar (BAL) and bronchial (BMS) ELF samples were obtained from another group of healthy subjects 2 hours after administration of a single oral dose of gatifloxacin 200 mg for comparison of gatifloxacin concentrations in samples obtained by the 2 techniques. RESULTS: Bronchial ELF samples were obtained from 8 healthy subjects and 5 patients with chronic bronchitis; alveolar ELF samples were obtained from a separate group of 5 healthy subjects. For the healthy subjects, the mean (SD) AUC(0-24) in serum and bronchial ELF, corrected for mg/kg doses, was 4.6 (1.1) and 7.6 (3.5) mg x h/L, respectively. In the patients with chronic bronchitis, the AUC(0-10) in serum and bronchial ELF, corrected for mg/kg doses, was 3.9 (0.8) and 4.1 (1.5) mg x h/L. The C(max) in serum and bronchial ELF, corrected for mg/kg doses, was 0.6 (0.2) and 1.4 (0.8) mg/L in healthy subjects and 0.7 (0.2) and 0.7 (0.2) mg/L in patients with chronic bronchitis. In healthy subjects, the C(max) and AUC(0-24) were significantly higher in bronchial ELF than in serum (both, P < 0.05). Gatifloxacin concentrations were significantly lower in bronchial ELF obtained by BMS than in alveolar ELF obtained by BAL (P < 0.05). CONCLUSIONS: Based on the findings of this study in small numbers of healthy young adult volunteers and patients with chronic bronchitis, BMS appears to be a promising method for measuring drug concentrations and determining the pharmacokinetic profile of gatifloxacin in bronchial ELF. Additional studies are needed to correlate measured concentrations obtained by BMS with clinical and/or microbiologic outcomes in larger populations.  相似文献   

3.
Simultaneous bronchial biopsy and serum samples were obtained from 14 patients after a single oral dose of 200 mg ofloxacin and from ten patients during the course of multiple dose oral treatment, (200 mg ofloxacin bd) for acute exacerbations of chronic bronchitis. Duplicate bronchial samples from different parts of the lung were obtained from five patients. Concentrations in bronchial mucosa were equal to or higher than serum concentrations. There were no statistically significant differences in concentrations after single or multiple doses but there appeared to be a trend towards higher concentrations after multiple doses. After a single dose bronchial and serum concentrations ranged from 1.3 to 15.5 mg/kg and from 0.1 to 5.0 mg/l, respectively, between 1 and 6 h after dosing. After multiple dosing of patients with acute exacerbations of chronic bronchitis bronchial and serum concentrations ranged from 1.7 to 21.0 mg/kg and 1.0 to 6.1 mg/l, respectively between 1 and 12 h. The percentage difference in ofloxacin concentrations in five duplicate bronchial samples from different parts of the lung was -4%, (95% confidence intervals +22% to -30%). Thus, the model of bronchial sampling after single dosing of patients before diagnostic bronchoscopy gave results that were similar to those obtained after multiple dosing of patients with acute exacerbations of chronic bronchitis. After multiple dosing ofloxacin concentrations were greater than 1 mg/l or greater than 1 mg/kg in serum and bronchial mucosa throughout the dosing interval, which is above the MIC for most respiratory pathogens.  相似文献   

4.
The morbidity and mortality due to asthma and chronic bronchitis are still rising in several countries. The aim of this study was to investigate whether early detection of patients with fast progressive asthma or chronic bronchitis in general practice was possible from a cross-sectional assessment of symptoms, smoking behaviour, quality of life, physical signs of the chest, allergy, and lung function. Data of 162 patients who had participated in a long-term randomized controlled intervention study in general practice were analysed. Fifty-six out of the 162 patients showed fast progressive disease (FPD, a rapid annual decline in FEV1 in combination with a high exacerbation rate). Measurements at the start of the study were used in a logistic regression analysis in order to detect the patients at risk (with FPD). A lower maximal expiratory flow at 50% of expired volume (MEF50) was related to an increased risk of FPD in both asthma and chronic bronchitis (relative risks of 16.8 and 8.0 respectively, p less than 0.05). Most lung function indices, but also quality of life and pack years, were significant predictors of FPD in chronic bronchitis (p less than 0.05). However, it was not possible to detect FPD reliably with these predictors separately or even with the combination of several relevant clinical variables; 18% of the patients with chronic bronchitis and 22% of the patients with asthma were still misclassified. It was concluded from this study that more than one measurement over time (monitoring) is necessary to detect the patients at risk. Monitoring should include assessments of objective ventilatory function indices (PEFR, FEV1 or MEF50).  相似文献   

5.
In the disease cystic fibrosis (CF), pulmonary infection with Pseudomonas aeruginosa is a common clinical complication that determines most morbidity and almost all excess mortality. We postulated that in this disease a defect in Pseudomonas-reactive IgG antibodies may contribute to chronic Pseudomonas infections. Bronchoalveolar lavages were performed upon 13 patients with CF, 7 patients with chronic bronchitis characterized by recurrent Pseudomonas infections, and 4 normal volunteers. The levels of various proteins important to host defenses and proteases were determined; enzyme inhibition studies were performed. CF respiratory immunoglobulin levels were significantly elevated when compared with both normals and patients with chronic bronchitis (P less than 0.05). Albumin and transferrin levels were decreased in the CF lung fluids. CF elastolytic activity was strikingly elevated (means = 6.02 micrograms/mg total protein) and the inhibitory profile suggested such activity resembled a serine-proteinase. Alpha-1-antitrypsin antigenic levels were not altered in CF respiratory fluids. There was a tendency for the lavage IgG to fall as elastase levels rose (r = -0.29). IgG opsonins for two Pseudomonas immunotypes were isolated with affinity chromatography for functional and immunochemical studies. Bacterial phagocytic rates in the presence of these Pseudomonas-reactive IgG opsonins derived from CF lavage fluid were depressed (0.3% uptake/unit time) when compared with similarly titered positive controls (uptake = 1.3%/unit time, P less than 0.001). Additionally, normal pulmonary macrophage intracellular killing of Pseudomonas was severely altered in the presence of opsonins derived from CF respiratory fluids. At some time points, less than 30% of the bacteria were killed. CF IgG opsonins contain a cleavage fragment (100,000 D, 5S sedimentation coefficient) with antigenic determinants similar to the Fab portion of IgG. The presence of such a fragment was inversely correlated with phagocytic functional activity. Intact IgG comprised as little as 18% of the CF lavage fluid specimens. Aliquots of intact human IgG, when mixed with the CF opsonins, augmented Pseudomonas uptake and improved intracellular killing. Conversely, peptide fragments of IgG opsonins, which are proteolytically derived in vitro, duplicated in our system the defect observed with opsonins derived from CF lung fluids; bacterial uptake was inversely related to the concentration of F(ab')2 and to a greater degree, to Fc present in the opsonic mixture. We concluded that IgG respiratory opsonins are fragmented, inhibiting phagocytosis and serving a permissive role in the chronic Pseudomonas pulmonary infection in the disease CF.  相似文献   

6.
Lactoferrin and lysozyme are proteins found in high concentrations on mucosal surfaces, and they have activities potentially important for the modulation of inflammation. To investigate whether these proteins might contribute to the modulation of the intraluminal airway inflammation associated with chronic bronchitis, lactoferrin and lysozyme were measured in bronchoalveolar lavage (BAL) fluid from 22 subjects with chronic bronchitis and, for comparison, with 10 symptom-free smokers and 16 normal subjects. As a further control, transferrin, a protein structurally homologous to lactoferrin but not known to arise in airway epithelial cells, was also measured. BAL was performed by sequentially instilling and retrieving five 20 ml aliquots of normal saline solution into each of three sites. Analyzing the first aliquots separately from the later four provided fluid that was enriched for airway contents. The concentration of lactoferrin (11.83 +/- 2.86 micrograms/ml vs 0.68 +/- 0.18 micrograms/ml, p less than 0.00001), and lysozyme (6.75 +/- 1.51 micrograms/ml vs 0.52 +/- 0.09 microgram/ml, p less than 0.00001), but not transferrin (3.22 +/- 0.38 microgram/ml vs 2.68 +/- 0.24 micrograms/ml, p = 0.55) was higher in the bronchial sample lavage fluid, suggesting an airway origin for lactoferrin and lysozyme. In subjects with chronic bronchitis, bronchial sample lactoferrin (23.1 +/- 0.5 micrograms/ml) and lysozyme (12.6 +/- 3.5 micrograms/ml) were elevated compared with the normal subjects' lactoferrin (1.9 +/- 0.5 micrograms/ml, p less than 0.0001) and lysozyme (0.77 +/- 0.22 microgram/ml, p less than 0.0001) and the symptom-free smokers' lactoferrin (4.1 +/- 0.8 micrograms/ml, p = 0.005) and lysozyme (4.9 +/- 1.3 micrograms/ml, p = 0.02). Transferrin concentrations did not demonstrate the same relationships. Finally, when the content of bronchial sample lactoferrin and lysozyme were compared with the content of bronchial sample neutrophils, poor correlations were found, which may imply an airway epithelial origin for the two proteins. Thus lactoferrin and lysozyme appear to arise in the lower respiratory tract within the airways and their levels are elevated in association with chronic bronchitis. This suggests that lactoferrin and lysozyme may contribute to the modulation of airway inflammation in chronic bronchitis.  相似文献   

7.
The level of the derivatives of protein and lipid metabolism increases in the blood of patients with bronchial asthma (BA) and chronic asthmatic bronchitis (CAB), in particular that of peroxide radicals, the products of lipid peroxidation (LPO), the fraction of acid soluble metabolites--average mass molecules (AMM). The blood acquires unusual toxicity. The content of AMM in the blood of BA and CAB patients shows correlation with LPO and is in direct relation to severity of clinical symptoms. The removal of toxic products from the body by hemosorption promotes clinical remission and a decrease in AMM and LPO levels.  相似文献   

8.
A study was made of the tissue and humoral immunity in 276 persons with prenosological and nosological signs of chronic bronchitis among the indigenous population as well as in newcomers living under the conditions of ultracontinental climate. Seasonal fluctuations of indices of the cellular and humoral immunity were more noticeable in the former than in the latter. Persons with prenosological signs of bronchitis were characterized by less pronounced tension of the cellular immunity in autumn than healthy people whereas considerable inhibition of the cellular immunity and change in the rhythm of its seasonal fluctuations were noted in patients with chronic bronchitis.  相似文献   

9.
A study was made of the lung surfactant (LS) according to the results of an analysis of neutral lipid fractions, examination of total phospholipids (PL) and surface tension (ST) in expirates (EX) of 127 patients with acute pneumonia (AP), 30 patients with acute bronchitis (AB) and in 77 healthy persons. As compared to the control and AB patients, AP patients demonstrated a significant increase in EX of the level of cholesterol (CS), esters of cholesterol (ECS), free fatty acids (FFA), PL, ST and a decrease of the content of tri- and diglycerides (TG, DG). Linear negative correlations were established between external respiration and CS, ECS, FFA, ST and positive ones between external respiration and TG and DG. Relations between ventilation and PL were of nonlinear character. Parameters that characterize the pulmonary volumes and capacities correlated most closely with some lipid fractions whereas parameters of bronchial patency had relations of medium and low intensity. It is concluded that destructive processes in the LS are likely to be coupled. The given processes are reflected in the rise of lipid fractions in EX, with ventilation function of the lungs being deranged in AP.  相似文献   

10.
Histamine and serotonin levels were measured in expired air humidity condensate (EAHC), bronchoalveolar lavage fluid and sputum of 9 patients with chronic nonobstructive bronchitis and 25 healthy controls. It was found that concentration of biogenic amines depended on the form of chronic bronchitis, activity of bronchial inflammation, characteristics of bronchial obstruction, degree of respiratory insufficiency. EAHC furnished most complete information.  相似文献   

11.
Heightened systemic oxidative stress is increasingly recognized as a feature of cystic fibrosis (CF). The consequences of long-term exposure to free radical attack include a predisposition to diseases such as cancer and atherosclerosis. An increased incidence of malignancy among adult patients with CF has been reported, but the absence of atherosclerotic disease is well described. The aim of the present study was to assess endothelial function in vivo and relate this to the potential of serum from patients with CF to induce oxidative-mediated damage in cultured human endothelial cells. A group of 11 CF patients was matched with a group of healthy volunteers with regard to age and sex. Endothelial function was assessed as endothelium-dependent and -independent vasodilation by measuring forearm blood flow in response to infused acetylcholine and sodium nitroprusside respectively. Confluent monolayers of cultured human endothelial cells were exposed to serum from CF patients and control subjects. Following exposure, cell death was assessed by lactate dehydrogenase release, and the degree of lipid peroxidation in the membrane was assessed by measuring the content of lipid hydroperoxides, malondialdehyde and 4-hydroxynonenal. Endothelial monolayers exposed to serum from CF patients released significantly less lactate dehydrogenase following exposure than those exposed to serum from healthy controls (1.8% and 3.0% respectively; mean difference -1.2%; 95% confidence intervals -1.9% to -0.1%; P<0.05) and contained significantly less 4-hydroxynonenal (0.75 and 3.41 micromol/g of protein respectively; mean difference -2.66 micromol/g; 95% confidence intervals -5.10 to -0.22 micromol/g; P<0.05). There was no significant difference between patients and controls in the extent of serum-induced membrane peroxidation, as assessed by malondialdehyde or lipid hydroperoxides, or in endothelial function, as assessed by forearm blood flow. In conclusion, despite evidence for heightened systemic oxidative stress in CF, patients displayed no impairment of endothelial function, and their serum caused significantly less damage to human endothelial cells than that from matched controls.  相似文献   

12.
In order to assess the specificity of transferrin molecular changes, we compared concentrations of subfractions and total transferrin in cirrhotic patients, in patients having non-alcoholic hepatitis, in patients with liver cancer, and in controls. The study was carried out in 79 patients divided into four groups: 20 patients with biopsy-proven cirrhosis of alcoholic origin, 20 patients with non-alcoholic hepatitis, 19 patients with liver cancer and 20 controls. Subfractions of serum transferrin were separated by isoelectric focusing followed by direct immunofixation. Fractions pI 5.7 percentages (expressed as percentages of one fraction over total transferrin) were significantly higher in the cirrhotic group than in the control group (p less than 0.01). Fraction pI 5.9 percentages were significantly higher in the cirrhotic group than in the hepatitis or control groups (p less than 0.05), or liver cancer group (p less than 0.01). A quantitative increase of fraction pI 5.7 was found in the cirrhotic patients. However, in this study, this parameter did not discriminate between patients with parenchymal liver diseases of alcoholic or other origin. Therefore, the value of determining fraction pI 5.7 as a marker of chronic alcohol consumption seems questionable. The elevation of fraction pI 5.9 constantly found in the cirrhotic patients could not be explained and needs further investigations.  相似文献   

13.
Endoscopic examination of the bronchial tree and investigation of pulmonary mucociliary transport by aerosol scintigraphy of the lungs were carried out in 40 patients and 10 controls. All the patients had exacerbation of chronic obstructive bronchitis. 20 of these were smokers and 20 nonsmokers. Healthy controls without lung pathology have never smoked. The findings indicate that in chronic sufferers with bronchitis and long history of smoking the rate of mucociliary clearance is reduced to 44% of the normal value and to 65% of the value for nonsmoking patients. This evidence is confirmed by the data obtained on the involvement of bronchial mucosa epithelium and at histologic examination of biopsy specimens.  相似文献   

14.
The lipid composition and rheological properties of expectorated airway secretions have been analyzed in 16 patients with cystic fibrosis (CF), separated into two groups according to whether their secretions were superinfected or not. The total lipid content was higher in the superinfected CF secretions. The content in cholesterol and GL1, GL3 and GL4 glycosphingolipid fractions were significantly higher in the superinfected in comparison to the non-superinfected group. The viscosity was two-fold higher in the CF superinfected group. A significant correlation (r = 0.72, p less than 0.01) was observed between the apparent viscosity and the total lipid content of CF secretions. Cholesterol, glycosphingolipids and sphingomyelin were the lipid components which were the most closely and positively correlated to the viscosity. On the opposite, phosphoglycerol was negatively correlated (r = -0.72, p less than 0.05) to the viscoelastic properties of CF airway secretions.  相似文献   

15.
Iron, by catalyzing the generation of the hydroxyl radical via the Haber-Weiss reaction, may participate in oxidant tissue injury. To determine whether iron might contribute to cigarette smoke-induced lung injury, we estimated the iron content of the lower respiratory tract by measuring intracellular iron content of pulmonary macrophages and extracellular iron content of bronchoalveolar lavage fluid from cigarette smokers and nonsmokers. Bronchoalveolar lavage was performed by using methods that allow for recovery of samples enriched for bronchial and alveolar contents. The intracellular iron content of the alveolar macrophages was determined by staining cytocentrifuged, air-dried pulmonary macrophages with a modified Prussian blue stain and assigning a score of 0 to 3 (0 = no stain, 3 = dense staining throughout the cytoplasm) to 100 macrophages. The extracellular iron level of bronchoalveolar lavage fluid was determined by using modifications of the Ferrozine method of Carter. Macrophage intracellular iron content was measured in a group of cigarette smokers with chronic bronchitis (n = 17), in smokers without chronic bronchitis (n = 15), and in normal volunteers (n = 15). Extracellular iron concentration was determined in a subset of the subjects with chronic bronchitis (n = 12) and in a separate group of normal volunteers (n = 5). The intracellular iron score was elevated in the bronchial sample lavage fluid in both the smokers with chronic bronchitis (45.3 +/- 13.9) and the asymptomatic smokers (26.6 +/- 8.0) compared with the normal individuals (8.1 +/- 1.7, p less than 0.03, both comparisons), but did not differ between the two groups of cigarette-smoking subjects (p = 0.68).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

16.
The authors have presented an analysis of the results of a study of patients with chronic asthmatic bronchitis and bronchial asthma to detect possible qualitative differences in changes of indices that characterize the intensity of free radical oxidation and antioxidant activity. With this aim in view the level of lipid peroxidation (LPO), alpha-tocopherol content and SOD activity were determined. In patients with bronchial asthma a raised LPO level was noted in parallel with a decrease in alpha-tocopherol content and SOD activity up to the values below the normal ones. A degree of deviation of the indices from those in health depended on the gravity of a course of bronchial asthma. In patients with asthmatic bronchitis in exacerbation and remission with a raised LPO level alpha-tocopherol content and SOD activity remained within normal. These differences can be used for differential diagnosis.  相似文献   

17.
A combined study of some indices of external respiratory function (vital capacity, air flow peak rate and derivative values), physical exercise tolerance, ECG signs of hypertrophy of the right ventricle and pulmonary hypertension, microcirculation of the bulbar conjunctiva was performed in 125 patients with chronic bronchitis prior to and after submaximum bicycle ergometric testing. All indices in nonobstructive chronic bronchitis slightly changed as compared to controls. Most of the patients with bronchial obstruction at the peak of exercise demonstrated distinct signs of respiratory insufficiency, an increase in bronchial obstruction, pulmonary hypertension and right ventricular hypertrophy. A conclusion was made of the necessity of a wide use of bicycle ergometry in early diagnosis of cor pulmonale. In genesis of the latter the leading role was played by bronchial permeability disorder.  相似文献   

18.
A total of 140 patients with chronic bronchitis were examined and distributed into 4 groups depending on the presence and degree of instrumentally recordable bronchial obstruction: chronic non-obstructive bronchitis (CNB), obstruction of the proximal bronchi, obstruction of the distal bronchi, generalized obstruction. In the presence of unmarked exacerbation, the laboratory data in all the groups pointed to a moderate degree of the inflammatory process and tension of the immunity system. The groups of patients with distal and generalized obstruction manifested dysfunction in the production of blood serum immunoglobulins with an isolated increase in the IgM content. Analysis of histological alterations in bronchial biopsies withdrawn from the large bronchi confirmed the immune type of inflammation in CB exacerbation whatever the presence and degree of bronchial obstruction. Based on the character of alterations in the blood serum content of immunoglobulins and morphological evidence for the immune type of inflammation the authors lay emphasis on the originality of the immune response in cases of CB exacerbation with obstruction of the distal bronchi. Describe the time-course of the cellular immunity in the groups of patients with CNB and in those with distal obstruction treated with a drug having a thymomimetic action.  相似文献   

19.
The paper is concerned with the results of clinical observation of 161 patients with chronic bronchitis aged 20 to 65 and 120 healthy controls. Serum glycoproteins (haptoglobin and ceruloplasmin) were determined over time in the patients with chronic bronchitis using the colorimetric method. Activation of bronchial inflammation was shown to be attended by a sharp rise of blood haptoglobin and ceruloplasmin imbalance. Changes revealed in concentrations of blood glycoproteins did not return to normal in many of the patients for long. The above parameters should be used for differential-diagnostic purposes.  相似文献   

20.
目的 :探讨老年慢性支气管炎患者血清及痰液白细胞介素水平变化及其意义。方法 :以放射免疫法测定 42例老年慢性支气管炎急性发作患者 ,3 7例老年慢性支气管炎缓解期患者以及 3 1例健康对照者血清及痰液中IL 2、IL 4、IL 6、IL 8水平 ,并对以上三组上述细胞因子水平进行统计学分析。结果 :急性组与缓解组血清与痰液中IL 4、IL 6、IL 8水平均高于正常对照组 (P <0 0 5 ) ,其中 ,急性组血清与痰液中上述细胞因子水平较对照组更高(P <0 0 5 )。但是 ,急性组与缓解组IL 2水平低于正常对照组 (P <0 0 5 ) ,其中 ,急性组较缓解组更低 (P <0 0 5 )。同时 ,直接相关分析表明 ,急性组血清IL 6与IL 8、IL 6与IL 4呈正相关关系 (P <0 0 5 ) ;痰液中IL 4、IL 6、IL 8相互间呈正相关关系 (P <0 0 5 )。结论 :IL 2、IL 4、IL 6、IL 8均参与老年慢性支气管炎的发病机制 ,在慢性气道炎症病理过程及急性发作中起着重要作用。这些指标的测定对于老年慢性支气管炎的诊断及炎症反应评估有一定的临床价值。  相似文献   

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