leukotriene-b4 and Bronchitis

Exhaled breath condensate (EBC) is a novel, non-invasive method for obtaining samples from the lung. Use of exhaled condensate as a source of biomarkers is based on the hypothesis that aerosol particles of exhaled breath reflect the composition of airway lining fluid. The technique is simple to perform, effort-independent, rapid, may be repeated frequently, and can be easily perform even in young children, adults, or patients with severe disease. EBC contains large number of various mediators including isoprostanes, cysteinyl-leukotrienes, adenosine, hydrogen peroxide, peptides, cytokines. Concentrations of these biomarkers are influenced by inflammation, oxidative stress and modulated by therapeutic interventions. EBC can be used to assess airway inflammation and oxidative stress in the respiratory tract, in differential diagnosis of airway disease and in the treatment monitoring.

Topics: Adult; Ammonia; Asthma; Biomarkers; Breath Tests; Bronchitis; Carbon Monoxide; Child; Diagnosis, Differential; Exhalation; Humans; Hydrogen Peroxide; Inflammation Mediators; Isoprostanes; Leukotriene B4; Nitric Oxide; Oxidative Stress; Respiratory System

Topics: Anaphylaxis; Arachidonic Acids; Asthma; Bronchitis; Histamine; Humans; Leukotriene B4; Lipid Metabolism; Platelet Activating Factor; SRS-A

Topics: Animals; Asthma; Bronchi; Bronchitis; Humans; Leukotriene B4; Neutrophils; Ozone; Prostaglandin-Endoperoxide Synthases

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Aspirin; Asthma; Bronchitis; Dinoprost; Dinoprostone; Epoprostenol; Humans; Leukotriene B4; Lung; Lung Diseases; Prostaglandin D2; Prostaglandin Endoperoxides, Synthetic; Prostaglandin H2; Prostaglandins D; Prostaglandins E; Prostaglandins F; Prostaglandins G; Prostaglandins H; Pulmonary Circulation; Pulmonary Ventilation; SRS-A

alpha1-Antitrypsin (AAT) deficiency predisposes to bronchitis and emphysema associated with neutrophilic airway inflammation. The efficacy of augmentation therapy has not been proven clinically or by demonstrating an effect on airway inflammation. We treated 12 patients with four infusions of Prolastin (60 mg/kg) at weekly intervals and monitored both the serum and secretion concentrations of AAT as well as markers of neutrophilic inflammation, including myeloperoxidase, elastase, and the neutrophil chemoattractants interleukin-8 and leukotriene B(4). Serum AAT rose and was maintained above the protective threshold. In addition, AAT concentrations in the sputum rose from a mean of 0.17 microM (SEM +/- 0.04) before therapy to concentrations similar to nondeficient subjects (0.43 +/- 0.12) 1 week after the first infusion (p < 0.01). This was associated with a reduction in elastase activity (p < 0.002) and the chemoattractant leukotriene B(4) (p < 0.02), which fell from a median baseline value of 13.46 nM (range, 4.17-55.00) to 8.62 nM (4.23-21.59) the day following the last infusion. Although median values for myeloperoxidase and interleukin-8 also fell, the changes failed to achieve statistical significance. In summary, short-term therapy with AAT increased lung secretion concentrations and was associated with a fall in leukotriene B(4), which is thought to be central to the airway inflammation of AAT deficiency.

Topics: alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Biomarkers; Bronchitis; Dose-Response Relationship, Drug; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infusions, Intravenous; Interleukin-8; Leukotriene B4; Male; Pancreatic Elastase; Peroxidase; Prognosis; Reference Values; Sensitivity and Specificity; Sputum; Treatment Outcome

Viable bacteria are often isolated from airway secretions in clinically stable patients with chronic bronchitis. We hypothesized that the number of organisms and bacterial species might be important modulators of airway inflammation.. We performed quantitative sputum cultures in 160 stable patients [55 with chronic obstructive pulmonary disease (COPD) and normal serum alpha(1)-antitrypsin levels, 62 with COPD and severe alpha(1)-antitrypsin deficiency (PiZ), and 43 with idiopathic bronchiectasis]. The results were related to several indicators of the mechanisms and severity of airway inflammation.. Airway bacterial load correlated with sputum myeloperoxidase level, an indirect measure of neutrophil activation and number (r = 0.50, P<0. 001); sputum neutrophil chemoattractants [interleukin-8 level (r = 0. 68, P<0.001) and leukotriene B4 level (r = 0.53, P<0.001)]; sputum leukocyte elastase activity (r = 0.55, P<0.001); and albumin leakage from serum to sputum (r = 0.26, P<0.01). Markers of inflammation increased at bacterial loads of 10(6) to 10(7) colony-forming units per milliliter, and increased progressively with increasing bacterial load. For example, the median (interquartile range) sputum myeloperoxidase level was 0.3 U/mL (0.1 to 0.5 U/mL) for patients who were not colonized or who had mixed normal oropharyngeal flora alone; 0.5 U/mL (0.2 to 0.7 U/mL) for patients with 10(5) to 10(6) colony-forming units per milliliter (P = 0.07); 0.5 U/mL (0.3 to 1.2 U/mL) for patients with 10(6) to 10(7) colony-forming units per milliliter (P<0.01); 0.7 U/mL (0.3 to 1.2 U/mL) for patients with 10(7) to 10(8) colony-forming units per milliliter (P <0.005); and 2.4 U/mL (0.7 to 4.8 U/mL) for patients with 10(8) or greater colony-forming units per milliliter (P<0.0001). The bacterial species influenced airway inflammation; for example, sputum myeloperoxidase activity was greater (P<0.005) in patients colonized with Pseudomonas aeruginosa [median 32 U/mL (interquartile range, 20 to 65 U/mL)] than those colonized with nontypeable Hemophilus influenzae [4 U/mL (2 to 31 U/mL)], which in turn was greater (P = 0.01) than among those colonized with Moraxella catarrhalis [1.1 U/mL (0.6 to 1.8 U/mL)]. We did not find a relation between bacterial load and lung function.. The bacterial load and species contribute to airway inflammation in patients with stable chronic bronchitis. Further studies are required to determine the consequences of bacterial colonization on patient morbidity and decline in lung function.

Topics: Aged; Bacteria; Biomarkers; Bronchitis; Bronchoalveolar Lavage Fluid; Chi-Square Distribution; Chronic Disease; Colony Count, Microbial; Female; Humans; Inflammation Mediators; Interleukin-8; Leukotriene B4; Lung Diseases, Obstructive; Male; Middle Aged; Peroxidase; Prognosis; Reference Values; Severity of Illness Index; Sputum; Statistics, Nonparametric; Stem Cells

We evaluated the levels of 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE] and the expression of 15-lipoxygenase (15-LO) mRNA in induced sputum obtained from 10 control and 15 chronic bronchitis subjects. 15(S)-HETE was evaluated by reverse phase high-performance liquid chromatography separation followed by specific RIA. 15-LO mRNA expression was determined by primed in situ labeling. The levels of both soluble and cell-associated 15(S)-HETE resulted significantly higher in chronic bronchitis than in control subjects. The percentage of cells expressing 15-LO mRNA was significantly higher in chronic bronchitis than in control subjects (P < 0.01). Double staining for specific cell type markers and 15-LO mRNA showed macrophages and neutrophils positive for 15-LO, whereas similar staining of peripheral blood neutrophils did not show evidence for 15-LO expression, suggesting that expression of 15-LO in neutrophils takes place on migration into the airways. Because 15(S)-HETE inversely correlated with the percentage of neutrophils in sputum of chronic bronchitis subjects, we studied the effect of 15(S)-HETE on leukotriene B(4) (LTB(4)) production in vitro and evaluated the concentration of LTB(4) in induced sputum and the contribution of LTB(4) to the chemotactic activity of induced sputum samples ex vivo. The results obtained indicate that macrophages and neutrophils present within the airways of chronic bronchitis subjects express 15-LO mRNA; increased basal levels of 15(S)-HETE may contribute to modulate, through the inhibition of 5-lipoxygenase metabolites production, neutrophil infiltration and airway inflammation associated with chronic bronchitis.

Topics: Adult; Aged; Arachidonate 15-Lipoxygenase; Bronchitis; Cell Count; Cell Survival; Cells, Cultured; Chemotaxis, Leukocyte; Chronic Disease; Humans; Hydroxyeicosatetraenoic Acids; Immunohistochemistry; In Situ Hybridization; Ionophores; Leukotriene Antagonists; Leukotriene B4; Lung Diseases, Obstructive; Macrophages; Middle Aged; Neutrophils; RNA, Messenger; Sputum

Acute bronchitis (AB) is a common lung condition characterized by inflammation of the large bronchi in response to infection. Bronchipret(®) syrup (BRO), a fixed combination of thyme and ivy extracts has been effectively used for the treatment of AB. Combining in vivo and mechanistic in vitro studies we aimed to provide a better understanding of the therapeutic potential of BRO on key aspects of AB and to identify potential mechanisms of action.. Bronchoalveolitis in rats was induced by intratracheal LPS instillation. BRO was administered p.o. once daily at 1- to 10-fold equivalents of the human daily dose. Animals were sacrificed 24-72 h post LPS challenge to analyze leukocyte numbers in lung tissue, bronchoalveolar lavage fluid (BALF) and blood as well as goblet cells in bronchial epithelium. Inhibitory effects of BRO analogue on leukotriene (LT) production were determined in human neutrophils and monocytes as well as on isolated 5-lipoxygenase (5-LO).. BRO significantly reversed the LPS-induced increase in leukocyte numbers in lung tissue, BALF and blood as well as goblet cell numbers in bronchial epithelium. In vitro, BRO analogue suppressed cellular release of LTB4 (IC50 = 36 µg⋅ml(-1)) and cysLT (IC50 = 10 µg⋅ml(-1)) and inhibited the activity of isolated 5-LO (IC50 = 19 µg⋅ml(-1)).. BRO exerts significant anti-inflammatory effects and attenuates goblet cell metaplasia in LPS-induced bronchoalveolitis in vivo potentially via interference with 5-LO/LT signaling. These effects may contribute to its observed clinical efficacy in AB.

Topics: Animals; Bronchitis; Bronchoalveolar Lavage Fluid; Cells, Cultured; Disease Models, Animal; Goblet Cells; Humans; Hyperplasia; Inflammation; Leukotriene B4; Lipoxygenase Inhibitors; Lung; Male; Monocytes; Neutrophils; Plant Extracts; Rats; Rats, Wistar; Thymol; Thymus Plant

Measurements of pulmonary biomarkers can be used to monitor airway inflammation in chronic obstructive pulmonary disease (COPD), but the variability of sampled biomarkers and their inter-relationships are poorly understood. A study was undertaken to examine the intra- and inter-patient variability in spontaneous sputum samples from patients in the stable state and to describe the relationship between biomarkers, cell counts and markers of disease.. Sputum interleukin-1beta, tumour necrosis factor alpha, interleukin 8, myeloperoxidase, leucotriene B4, growth-related oncogene alpha and differential cell counts were measured in patients with moderate to severe stable COPD (n = 14) on 11 occasions over a 1-month period.. There was significant variability in all inflammatory indices (median intra-patient coefficient of variation (CV) 35% (IQR 22-69), median inter-patient CV 102% (IQR 61-145)). Variability could be reduced by using a rolling mean of individual patient data points. Sample size calculations were undertaken to determine the number of patients required to detect a 50% reduction in neutrophil count. Using a crossover design of a putative effective treatment, the number needed using one data point per patient was 72, reducing to 23 when a mean of three data points was used. Significant correlations were demonstrated both between the inflammatory biomarkers themselves and between inflammatory biomarkers and markers of disease. Some relationships were not apparent when results from a single sample were used. The reliability of inter-relationships improved as more data points were used for each patient.. Clear relationships exist between inflammatory biomarkers in patients with stable COPD. Sequential sampling reduced the variability of individual mediators and the potential number of patients needed to power proof of concept interventional studies.

Topics: Aged; Biomarkers; Bronchitis; Chemokine CXCL1; Cross-Over Studies; Cytokines; Female; Humans; Leukotriene B4; Male; Middle Aged; Neutrophils; Peroxidase; Pulmonary Disease, Chronic Obstructive; Sputum

Severe alpha-1-antitrypsin deficiency (AATD), due to homozygosity for the protease inhibitor (Pi) Z allele, is a genetic risk factor for chronic obstructive pulmonary disease (COPD). In a previous study the sputum of severe AATD subjects with airflow obstruction showed a pattern of cellular inflammation similar to COPD patients. It is uncertain whether heterozygotes for the Z allele or intermediate deficiency (PiMZ) have an increased risk of developing COPD.. Sputum cell counts and the supernatant level of the neutrophil chemoattractant interleukin (IL)-8 were investigated by sputum induction in 10 non-smoker asymptomatic PiMZ subjects with normal pulmonary function, 10 patients with stable COPD, and 10 age matched normal subjects. Data are expressed as mean (SD).. The mean (SD) number of neutrophils was significantly higher (p<0.01) in the sputum of PiMZ subjects (84.5 (22.2) x10(4)/ml) and patients with COPD (126.9 (18.8) x10(4)/ml) than in matched normal subjects (55.0 (8.7) x10(4)/ml). IL-8 levels were increased in PiMZ subjects (828.5 (490.6) ng/ml; median 1003.0 ng/ml; range 1260-100 ng/ml) and in COPD patients (882.5 (524.3) ng/ml; median 934.9 ng/ml; range 1506-258 mg/ml) compared with normal subjects (3.5 (0.5) ng/ml; median 3.5 ng/ml; range 4.5-2.5 ng/ml). There was a significant positive correlation between IL-8 supernatant concentration and neutrophil count in PiMZ subjects (p = 0.036; r = 0.66). An inverse correlation was observed between the percentage of neutrophils and forced expiratory volume in 1 second (% predicted) in patients with COPD (p = 0.04; r = -0.43).. These findings indicate that PiMZ subjects without airflow obstruction may have an IL-8 related neutrophilic inflammation in the airways, similar to stable COPD patients, suggesting an increased risk of developing pulmonary changes.

Topics: Aged; alpha 1-Antitrypsin Deficiency; Bronchitis; Carbon Monoxide; Case-Control Studies; Female; Forced Expiratory Volume; Humans; Interleukin-8; Leukotriene B4; Male; Middle Aged; Neutrophils; Sputum; Vital Capacity

Recent studies have repeatedly shown weak correlations among lung function parameters, atopy, exhaled nitric oxide level (Feno), and airway inflammatory markers, suggesting that they are non-overlapping characteristics of asthma in adults. A study was undertaken to determine, using factor analysis, whether the above features represent separate dimensions of childhood asthma.. Clinically stable asthmatic patients aged 7-18 years underwent spirometric testing, methacholine bronchial challenge, blood sampling for atopy markers and chemokine levels (macrophage derived chemokine (MDC), thymus and activation regulated chemokine (TARC), and eotaxin), Feno, and chemokines (MDC and eotaxin) and leukotriene B(4) measurements in exhaled breath condensate (EBC).. The mean (SD) forced expiratory volume in 1 second (FEV1) and Feno of 92 patients were 92.1 (15.9)% predicted and 87.3 (65.7) ppb, respectively. 59% of patients received inhaled corticosteroids. Factor analysis selected four different factors, explaining 55.5% of total variance. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.587. Plasma total and specific IgE levels, peripheral blood eosinophil percentage, and Feno loaded on factor 1; plasma TARC and MDC concentrations on factor 2; MDC, eotaxin and leukotriene B4 concentrations in EBC on factor 3; and plasma eotaxin concentration together with clinical indices including body mass index and disease severity score loaded on factor 4. Post hoc factor analyses revealed similar results when outliers were excluded.. The results suggest that atopy related indices and airway inflammation are separate dimensions in the assessment of childhood asthma, and inflammatory markers in peripheral blood and EBC are non-overlapping factors of asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Asthma; Biomarkers; Bronchitis; Chemokines; Child; Chronic Disease; Factor Analysis, Statistical; Forced Expiratory Volume; Humans; Hypersensitivity, Immediate; Leukotriene B4; Nitric Oxide; Vital Capacity

Airway inflammation, with recruitment of neutrophils to the airway lumen, results in purulent secretions and a variety of potential adverse consequences for patients with chronic bronchitis and bronchiectasis. We hypothesised that gradations of sputum colour would correlate directly with the myeloperoxidase content of sputum and with various other indicators of the activity and consequences of bronchial diseases.. To test this hypothesis, we quantified sputum colour by reference to a sensitive nine point colour chart and correlated this assessment with indices of a number of inflammatory mediators in sputum.. The results indicate that standardised visual measurements of sputum colour correlated strongly with myeloperoxidase, interleukin 8, leucocyte elastase (both activity and total quantity), sputum volume, protein leak, and secretory leucocyte proteinase inhibitor (p<0.001 for all). In addition, there was a strong direct correlation between leucocyte elastase and both myeloperoxidase (p<0.003) and sputum volume (p<0.001), but a strong negative correlation with secretory leucocyte proteinase inhibitor (p<0.001).. These results indicate that sputum colour graded visually relates to the activity of the underlying markers of bronchial inflammation. The results of this simple visual analysis of sputum provides guidance concerning underlying inflammation and its damaging potential. It also provides a useful scientific tool for improving the monitoring of chronic airways diseases and response to treatment.

Topics: alpha 1-Antitrypsin; Biomarkers; Bronchiectasis; Bronchitis; Cathepsin B; Color; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Leukocyte Elastase; Leukotriene B4; Male; Middle Aged; Neutrophils; Pancreatic Elastase; Peroxidase; Proteinase Inhibitory Proteins, Secretory; Proteins; Sputum

There are little data describing noncellular changes in bronchial inflammation during exacerbations of chronic bronchitis. The relationship between sputum colour and airway inflammation at presentation has been assessed during an exacerbation in patients with chronic bronchitis and a primary care diagnosis of chronic obstructive pulmonary disease. Sputum myeloperoxidase, neutrophil elastase, leukotriene B4 (LTB4), interleukin-8 (IL-8), sol:serum albumin ratio and serum C-reactive protein were measured in patients presenting with an exacerbation and mucoid (n = 27) or purulent sputum (n = 42). Mucoid exacerbations were associated with little bronchial or systemic inflammation at presentation, and sputum bacteriology was similar to that obtained in the stable state. Purulent exacerbations were associated with marked bronchial and systemic inflammation (p < 0.025 for all features) and positive sputum cultures (90%). Resolution was related to a significant reduction in LTB4 (p < 0.01), but no change in IL-8, suggesting that LTB4 may be more important in neutrophil recruitment in these mild, purulent exacerbations. In the stable state, IL-8 remained higher in patients who had experienced a purulent exacerbation (2p < 0.02). The presented results indicate that exacerbations of chronic bronchitis, defined by sputum colour, differ in the degree of bronchial and systemic inflammation. Purulent exacerbations are related to bacterial infection, and are associated with increased neutrophilic inflammation and increased leukotriene B4 concentrations.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Bacterial Infections; Bronchitis; Female; Humans; Inflammation Mediators; Leukotriene B4; Male; Middle Aged; Neutrophils; Primary Health Care; Pulmonary Disease, Chronic Obstructive; Sputum

Neutrophils recruited to the airways in chronic obstructive pulmonary disease (COPD) are thought to mediate tissue destruction. Neutrophil recruitment is increased during bacterial exacerbations. The inflammatory process was studied in patients with an acute exacerbation of COPD in order to ascertain the role of leukotriene B4 (LTB4). The sputum of eight subjects with a bacterial exacerbation of COPD was analysed for neutrophil products (myeloperoxidase, elastase) and chemoattractants (interleukin-8 (IL-8) and LTB4). The contribution of LTB4 to the chemotactic activity of the sputum sol phase was determined using the LTB4 receptor antagonist LY293111. The concentrations of the serum acute phase proteins alpha1-proteinase inhibitor, alpha1-antichymotrypsin and C-reactive protein were measured. All patients received appropriate broad-spectrum antibiotic treatment for 7-14 days. Initially, the sputum myeloperoxidase activity was high, indicating neutrophil influx; this was associated with high levels of IL-8 and LTB4. All these concentrations fell with treatment (p<0.01). The chemotactic activity of the sputum was raised on presentation and fell with treatment (p<0.01). LTB4 contributed approximately 30% of the total chemotactic activity on presentation; this diminished with therapy. All acute phase proteins were raised on presentation and fell with therapy (p<0.01). These findings suggest that leukotriene B4 contributes to neutrophil influx into the airway in chronic obstructive pulmonary disease and may influence disease progression.

Topics: Acute-Phase Proteins; Aged; Bacterial Infections; Bronchitis; Case-Control Studies; Female; Humans; Leukotriene B4; Male; Middle Aged; Neutrophil Infiltration; Neutrophils; Sputum

Neutrophil elastase is capable of generating many of the features of chronic bronchial disease. In patients with COPD, airways inflammation with neutrophil recruitment and elastase release is positively correlated with colonizing bacterial load in the stable clinical state (p < 0.0005). In addition, alpha(1)-antitrypsin deficiency is associated with a greater neutrophil load, higher elastase activity, leukotriene-B(4) concentration, and serum protein leak than matched patients without deficiency (p < 0.005). These data confirm an effect of bronchial colonization on airways inflammation in COPD and indicate the role of alpha(1)-antitrypsin in its modulation.

Topics: alpha 1-Antitrypsin Deficiency; Bacteria; Bacterial Infections; Biomarkers; Bronchi; Bronchitis; Humans; Leukocyte Elastase; Leukotriene B4; Peroxidase; Sputum

Many of the features of bronchial disease are believed to be caused by damage to the airways by elastase released by recruited neutrophils. There have been few studies of the mechanisms involved and the interrelationships between components of the inflammatory process. We studied secretions from patients with chronic bronchitis in the stable state. We assessed the presence of neutrophils by measuring myeloperoxidase (MPO) activity and active neutrophil elastase (NE). These results were compared with the chemoattractants interleukin-8 (IL-8) and leukotriene B(4) (LTB(4)), the bronchial inhibitor secretory leukoprotease inhibitor (SLPI), and protein leak (sputum/serum albumin ratio). MPO correlated with NE activity (r = 0.68, p < 0.001) and both IL-8 (r = 0.52, p < 0.001) and LTB(4) (r = 0.41, p < 0.001) indicating an association with the chemoattractants. Elastase activity correlated with IL-8 (r = 0.55, p < 0.001) and LTB(4) (r = 0.41, p < 0.001) but negatively with SLPI (r = -0.49, p < 0.001). NE also correlated positively with protein leak (r = 0.36, p < 0.001), suggesting a cause and effect. MPO and protein leak correlated negatively with FEV(1) (percentage of predicted) only in patients with chronic obstructive pulmonary disease (COPD) without alpha(1)-antitrypsin deficiency (r = -0.37, p < 0.001; r = -0.42, p < 0.01, respectively). These complex interactions provide a template for future studies with specific inhibitors or agonists which will clarify the role of individual factors.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Bronchitis; Enzyme-Linked Immunosorbent Assay; Female; Forced Expiratory Volume; Humans; Interleukin-8; Leukocyte Elastase; Leukotriene B4; Male; Middle Aged; Neutrophil Activation; Neutrophils; Proteinase Inhibitory Proteins, Secretory; Proteins; Secretory Leukocyte Peptidase Inhibitor; Serine Proteinase Inhibitors; Serum Albumin; Sputum; Statistics, Nonparametric

Persistent polymorphonuclear neutrophil (PMN) recruitment to airway is thought to be an important component of continuing inflammation and progression of chronic destructive lung diseases. Although chemoattractants are required for the PMN to migrate, the nature of the chemoattractants in the airways has not yet been clarified. We therefore investigated the contribution of interleukin-8 (IL-8) and leukotriene-B4 (LTB4) to the chemotactic activity of lung secretions by inhibiting their activity using a monoclonal antibody to IL-8 and an LTB4 receptor antagonist (LY293111 sodium). Fifty-nine sputum samples obtained from 19 patients with bronchiectasis were studied. In preliminary studies the chemotactic responses to IL-8 and LTB4 were found to be additive, and we were able to remove their contribution independently with the appropriate antibody and antagonist. The chemotactic activity of the secretions was related to the macroscopic appearance (mucoid, mucopurulent, and purulent), and this appeared to be related to an increase in IL-8 contribution. Chemotactic activity was reduced by antibiotic therapy and again that seemed to relate to a reduction in the IL-8 contribution. The contributions of LTB4 were similar among the three types of sputum in varying clinical states. These data suggest that LTB4 and IL-8 are important chemotactic factors in lung secretions from such patients, although IL-8 appears to play a more important role during acute exacerbations. These results may be useful in determining therapeutic strategies for chronic destructive lung diseases in the future.

Topics: Acute Disease; Anti-Bacterial Agents; Antibodies, Monoclonal; Benzoates; Bronchiectasis; Bronchitis; Cell Movement; Chemotactic Factors; Chemotaxis, Leukocyte; Chronic Disease; Disease Progression; Female; Humans; Interleukin-8; Leukotriene B4; Male; Middle Aged; Mucus; Neutrophils; Receptors, Leukotriene B4; Reproducibility of Results; Sputum; Suppuration

The present study focused on two questions: What effects do cigarette smoking and chronic bronchitis have on the function of the precursors of alveolar macrophages, the blood monocytes? Can seasonal variations affect the function of these cells? Phagocytic activity (the proportion of yeast-ingesting cells and the mean number of yeast particles per ingesting cell) and metabolism of arachidonic acid [secretion of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in zymosan-stimulated cultures] were studied as markers of monocyte function during three seasons: spring (May-June), autumn (November-December), and winter (February). Smokers with chronic bronchitis (SCBs) and asymptomatic smokers (ASs) had a lower proportion (p < 0.05) of ingesting monocytes than healthy nonsmokers (HNSs) during spring, but not during the other two seasons. The secretion of PGE2 was highest during autumn and lowest during spring in the monocytes of all three groups. In autumn, LTB4 secretion was increased in the monocytes of HNSs (p < 0.05) but not in those of ASs and SCBs. LTB4 secretion was similar in all groups during the other two seasons. Cigarette smoking and chronic bronchitis seem to impair the function of monocytes and may thereby affect the systemic host defense activity. Cells collected during autumn were generally more active than those sampled in spring, indicating marked seasonal variation in the function of monocytes from all three groups.

Topics: Arachidonic Acid; Bronchitis; Chronic Disease; Dinoprostone; Female; Humans; In Vitro Techniques; Leukotriene B4; Male; Middle Aged; Monocytes; Phagocytosis; Reference Values; Seasons; Smoking

A study was made of the effect of ketotifen on the concentration of leukotriene B4, prostacyclin and thromboxane A2 in the liquid of bronchoalveolar lavage and on external respiration and cellular immunity during 4 weeks of the treatment of patients with infection-dependent bronchial asthma and chronic obstructive bronchitis. Inclusion of ketotifen into the treatment of patients with bronchial obstruction exerts a stimulating action on the suppressor component of T-cell immunity, leads to a decrease of the content of leukotriene B4 and thromboxane A2 in the lavage liquid, which is accompanied by positive shifts in the clinical course of the broncho-obstructive syndrome. Ketotifen turned out most effective in patients with an initially low content of the subpopulation of T suppressors and with high concentrations of leukotriene B4 and thromboxane A2 in the liquid of bronchoalveolar lavage.

Topics: Adult; Asthma; Bronchi; Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Eicosanoids; Epoprostenol; Female; Humans; Ketotifen; Leukotriene B4; Male; Middle Aged; Thromboxane A2

High-pressure liquid chromatography was used to measure the blood content of lipoxygenase metabolites (LM) of arachidonic acid: leukotriene B4 (LTB4) and hydroxyeicosatetraene acids (5 HETE, 12 HETE, 15 HETE) in 65 patients with acute pneumonia (AP) of mild gravity (group 1) and of medium gravity (group 2), in 23 patients with acute bronchitis (AB), and in 15 normal male persons aged 18 to 20 years. In all the examined, the zonal pulmonary blood flow was measured by regional rheopulmonography. External respiratory function (ERF) was also determined together with the recording of the flow-volume loop. At the height of AP and AB, all the patients demonstrated an increase of LM in the blood, with the maximum LM content being recorded in group 2. During convalescence, AB and AP patients of group 1 manifested normalization of the majority of the parameters. In group 2, they significantly exceeded the control level. 5 and 15 HETE had the closest correlations with the blood flow parameters, whereas LTB4 and 12 HETE had less intensive correlations. The influences of LM such as 5 and 15 HETE on the pulmonary blood flow were associated with deterioration of the blood content of the lungs and venous return, the action of LTB4 was coupled with venous congestion formation, that of 12 HETE with the rise of vascular resistance. Close negative correlations of LTB4 and 5 HETE with the majority of ERF parameters indicate that they are important factors in the pathogenesis of restrictive and obstructive ventilatory disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adolescent; Adult; Arachidonic Acid; Arachidonic Acids; Bronchitis; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Lipoxygenase; Male; Pneumonia; Pulmonary Circulation; Respiratory Mechanics

The addition of ketanserin (a blocker of serotonin S2-receptors) to treatment of bronchial obstruction is shown to lower plasma and platelet concentrations of serotonin, leukotriene B4 level in the lavage fluid, to shift prostacyclin-thromboxane balance to the side of prostacyclin. In 40 patients with chronic obstructive bronchitis treated, the above changes were associated with persistent clinical response, a decrease of bronchial obstruction, being the most profound in a group of patients with chronic catarrhal bronchitis.

Topics: Adult; Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Epoprostenol; Female; Humans; Ketanserin; Leukotriene B4; Male; Middle Aged; Receptors, Serotonin; Respiratory Function Tests; Serotonin; Serotonin Antagonists; Thromboxane A2

A study was made of the content of leukotriene B4, prostacycline and thromboxane A2 in the fluid of bronchoalveolar lavage in 62 patients with chronic bronchitis (CB) in the stage of exacerbation and remission. The time course of changes in the concentration of the eukosanoids was compared with the status of pulmonary local defense factors and cellular immunity. In catarrhal obstructive bronchitis, an important mechanism of a steady maintenance of bronchial obstruction involved a rise of the content of leukotriene B4 whereas in purulent obstructive bronchitis, it was an excess level of thromboxane A2. It is assumed that immunologically dependent activation of the leukotriene B4 and thromboxane synthetase capacity of alveolar macrophages may stipulate the clinical course of CB, modulating the bronchoconstrictor or inflammatory component of the disease. To correct phlogogenous function of alveolar macrophages, the use of immunomodulating therapy with a selective action on the suppressor component of immunity is desirable.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Chronic Disease; Epoprostenol; Humans; Immunity, Cellular; Leukotriene B4; Middle Aged; Thromboxane A2; Thromboxane B2

Leukotrienes (LTs) and prostanoids (Ps) were detected in sputum of patients with chronic bronchitis and/or bronchiectasis (CB/B) using selective superfusion bioassay and radioimmunoassay (RIA) techniques. Analysis of sputum extracts showed a 4-fold increase in the level of LTB4 compared to the cysteinyl-containing LTs (LTC4/LTD4). The measurement of cyclo-oxygenase products (COPs) indicated relatively greater amounts of the vasodilator prostaglandin E2 (PGE2) and prostacyclin (PGI2) compared to the vasoconstrictor prostaglandin F2 alpha (PGF2 alpha) and thromboxane A2 (TxA2) agents (70:30% of total COPs respectively). The presence of eicosanoids (LTs and Ps) in sputum of patients with CB/B suggest that these biologically active substances may act as mediators of bronchoconstriction and inflammation in these diseases.

Topics: Adult; Aged; Animals; Arachidonate 5-Lipoxygenase; Arachidonate Lipoxygenases; Bronchiectasis; Bronchitis; Female; Guinea Pigs; Humans; In Vitro Techniques; Leukotriene B4; Lung; Male; Middle Aged; Muscle, Smooth; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Radioimmunoassay; Sputum; SRS-A

The role of lipoxygenase products was studied in children suffering from chronic diseases of the lung. Leukotrienes C4, D4, E4 and B4 were measured by high performance liquid chromatography (HPLC) and a specific radioimmunoassay (RIA) for C4. Elevated levels (up to 40 ng/ml), especially for leukotriene E4, were found in plasma of asthmatic and bronchitic patients (leukotriene C4 concentrations varied between 0.05 and 40 ng/ml, mean 4.9 +/- 7.8 ng/ml). In healthy donors the concentrations were below the detection limits of HPLC, leukotriene C4 ranging between 5 +/- 4 ng/ml (RIA data). The conversion of leukotriene C4 to D4 and E4 was observed by incubating the samples with synthetic leukotriene C4. The half-life of leukotriene C4 in plasma varied greatly, ranging from less than 12 min to 72 min (mean 39 +/- 16 min). Bronchial lavages yielded leukotriene C4 concentrations of 0.2 to 7 ng. Leukotriene E4 was detected in 10 of 41 cases. Conversion of leukotriene C4 did not occur in 50% of all cases, but was regularly observed in putrid lavages. These data suggest that leukotrienes play an important role in allergic and infectious lung diseases.

Topics: Adolescent; Asthma; Bronchitis; Child; Child, Preschool; Chromatography, High Pressure Liquid; Chronic Disease; Humans; Infant; Leukotriene B4; Leukotriene E4; Radioimmunoassay; Respiratory Tract Diseases; SRS-A

Sputum samples from patients with bronchial asthma, chronic bronchitis and cystic fibrosis were examined for the presence of leukotrienes B4, C4 and D4. Following ethanol extraction and purification on Amberlite XAD-8, leukotrienes were identified by high pressure liquid chromatography (HPLC) using the appropriate markers. Fractions from HLPC were also tested for biological activity using both the Boyden chemotaxis assay and FPL 55712 inhibitable contraction of the isolated guinea-pig ileum. LTB4 was detected in the HPLC fractionated sputa from bronchial asthma (seven of seven), chronic bronchitis (four of four) and cystic fibrosis (four of four). In contrast, bioassay on the guinea-pig ileum failed to detect LTC4 or LTD4 in 17 asthmatic sputa, although they were detected in one of five bronchitics and 16 of 25 patients with cystic fibrosis. The activity in eight of these cystic fibrosis sputa was further characterized by HPLC and shown to be LTC4 and/or LTD4. Sputum from 11 of 17 asthmatics, four of 25 patients with cystic fibrosis and two of five bronchitics contained an anaphylatoxin like substance. The majority of sputum samples containing LTB4 also possessed an activity with physical and biological characteristics of the 5(S), 12(S), 6-trans LTB4 isomer. These studies indicate that lipoxygenase products of arachidonic acid metabolism are present in the sputum in various forms of obstructive airways disease. The failure to detect the 'SRS-A' leukotrienes in sputum from bronchial asthma may be attributable to either losses during extraction, the insensitivity of the assay procedure or to more rapid catabolism of LTC4 and LTD4 by bronchial secretions in asthma than in cystic fibrosis.

Topics: Asthma; Biological Assay; Bronchitis; Chemotaxis, Leukocyte; Chromatography, High Pressure Liquid; Cystic Fibrosis; Humans; Leukotriene B4; Lung Diseases, Obstructive; Muscle Contraction; Neutrophils; Sputum; SRS-A