leukotriene-b4 and Lung-Diseases--Obstructive

The likelihood that the leukotriene products derived from the 5-lipoxygenase pathway mediate aspects of obstructive airways diseases is strongly suggested by their documented capacities to effect airway spasmogenicity, airway hyperreactivity, tissue edema formation, mucus secretion, and tissue infiltration by leukocytes. That the various leukotriene components of SRS-A have unique receptors on responding tissues and are recoverable from airway surfaces in several inflammatory lung diseases and that several resident and infiltrating cell types have significant potential for leukotriene biosynthesis lend further support to their postulated pathobiologic roles. To fulfill Koch's postulates for proof of leukotrienes' etiologic role, it remains to be shown that inhibition of their biosynthesis or specific antagonism at their end-organ receptors can greatly ameliorate these disease states.

Topics: Animals; Arachidonate Lipoxygenases; Bronchial Spasm; Dose-Response Relationship, Drug; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Leukotriene B4; Lipoxygenase; Lung; Lung Diseases, Obstructive; Macrophages; Mast Cells; Monocytes; Pulmonary Alveoli; Pulmonary Ventilation; Receptors, Leukotriene; Receptors, Prostaglandin; SRS-A; Vital Capacity

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

To determine the ex vivo leukotriene (LT) biosynthesis in peripheral blood neutrophils (PBNs) and inflammatory cells in bronchoalveolar lavage fluid (BALF) obtained from horses affected with recurrent airway obstruction (RAO).. 6 RAO-affected and 6 control horses.. Before and 6, 24, and 48 hours after stabling, disease severity was determined subjectively by clinical and mucus scores and measurement of the maximal change in pleural pressure (deltaPpl(max)); PBNs were isolated and BALF samples were examined cytologically. The PBN and BALF cells were activated with a calcium ionophore in the presence of arachidonic acid, and production of LTC4 and LTB4 was measured per 10(6) cells.. Clinical and mucus scores and deltaPpl(max) increased during stabling in RAO-affected horses, but not in control horses. In neutrophils and BALF cells from both groups, production of LTB4 exceeded that of LTC4. At all times, LTB4 production by PBNs was less in RAO-affected horses than it was in control horses. Before stabling, LTB4 production by cells in BALF was low in RAO-affected horses, but increased considerably after 6 hours of stabling. This increase coincided with the migration of neutrophils into the airways. In control horses, production of LTB4 did not change during stabling.. Results suggested increased production of LTB4 in airways of RAO-affected horses, compared with control horses, that may contribute to the infiltration of neutrophils into the lungs and the sustained inflammation associated with RAO.

Topics: Analysis of Variance; Animals; Arachidonic Acid; Bronchoalveolar Lavage Fluid; Calcium-Binding Proteins; Horse Diseases; Horses; Leukotriene B4; Leukotriene C4; Lung Diseases, Obstructive; Neutrophils; Pressure; Time Factors

In previous studies it had been shown that leukotriene-B4 [LTB4] concentrations in the exhaled breath mirror the inflammatory activity of the airways if the respiratory tract has been exposed to occupational hazards. In diving the respiratory tract is exposed to cold and dry air and the nasopharynx, as the site of breathing-gas warming and humidification, is bypassed. The aim of the present study was to obtain LTB4-concentrations in the exhaled breath and spirometric data of 17 healthy subjects before and after thirty minutes of technically dried air breathing at normobar ambient pressure. The exhaled breath was collected non-invasively, via a permanently cooled expiration tube. The condensate was measured by a standard enzyme immunoassay for LTB4. Lung function values (FVC, FEV1, MEF 25, MEF 50) were simultaneously obtained by spirometry. The measured pre- and post-exposure LTB4- concentrations as well as the lung function values were in the normal range. The present data gave no evidence for any inflammatory activity in the subjects' airways after thirty minutes breathing technically dried air.

Topics: Air; Breath Tests; Diving; Enzyme-Linked Immunosorbent Assay; Humans; Humidity; Inflammation; Leukotriene B4; Lung Diseases, Obstructive; Male; Occupational Diseases; Reference Values; Respiratory Function Tests; Spirometry

Neutrophilic airway inflammation may underlie the pathogenesis of COPD. We examined repeated measurements of the fractional concentration of exhaled nitric oxide (FENO) and the correlation with cells and mediators in induced sputum (IS) from patients with COPD.. Eleven COPD subjects (9 men and 2 women, aged 46 to 69 years) with predicted FEV(1) of 45 to 70%.. A hospital research laboratory.. Single-cohort, prospective study with four visits at two weekly intervals.. FENO and spirometry were assessed at all visits, and IS for differential cell count, leukotriene-B(4) (LTB(4)) and interleukin (IL)-8, nitrite, and nitrate at visit 1, visit 3, and visit 4.. During the study, there were significant declines in mean percent predicted FEV(1), from 55.2 to 51.6% (p = 0.029), and mean FEV(1)/FVC ratio, from 50.4 to 45.4% (p = 0.001), accompanied by a significant increase in FENO geometric mean (95% confidence limits), from 15.2 (10.9 to 21.2) to 23.6 (17.1 to 32.4) parts per billion (p = 0.037), and sputum LTB(4), from 1.79 (1.03 to 3.11) to 3.57 (1.95 to 6.53) ng/mL (p = 0.033), but no significant change in other sputum parameters. From visits 1 to 4, the change in percent neutrophils correlated with the changes in FENO and IL-8 (r = 0.648, p = 0.028; r = 0.60, p = 0.05, respectively). Hypertonic saline solution induction of sputum caused a fall in FEV(1), from 1.83 +/- 0.44 to 1.46 +/- 0.44 L (p = 0.049).. The worsening spirometry results were accompanied by significant increases in FENO and sputum LTB(4). FENO may be related to neutrophilic inflammation driven by the chemoattractant IL-8. FENO and IS may be useful markers of airway inflammation in COPD patients. Sputum induction with hypertonic saline solution causes a significant fall in FEV(1) requiring appropriate caution.

Topics: Aged; Breath Tests; Cell Count; Female; Forced Expiratory Volume; Humans; Interleukin-8; Leukotriene B4; Lung Diseases, Obstructive; Male; Middle Aged; Neutrophils; Nitric Oxide; Prospective Studies; Saline Solution, Hypertonic; Spirometry; Sputum; Vital Capacity

Patients with homozygous (PiZ) alpha(1)-antitrypsin (AAT) deficiency have not only low baseline serum AAT levels (approximately 10 to 15% normal) but also an attenuated acute phase response. They are susceptible to the development of premature emphysema but may also be particularly susceptible to lung damage during bacterial exacerbations when there will be a significant neutrophil influx. The purposes of the present study were to assess the inflammatory nature of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) in subjects with AAT deficiency, to compare this with COPD patients without deficiency, and to monitor the inflammatory process and its resolution following appropriate antibacterial therapy. At the start of the exacerbation, patients with AAT deficiency had lower sputum AAT (p < 0.001) and secretory leukoprotease inhibitor (SLPI; p = 0.02) with higher elastase activity (p = 0.02) compared with COPD patients without deficiency. Both groups had a comparable acute phase response as assessed by C-reactive protein (CRP) but the AAT-deficient patients had a minimal rise in serum AAT (to < 6 microM). After treatment with antibiotics, in patients with AAT deficiency, there were significant changes in many sputum proteins including a rise in SLPI levels, and a reduction in myeloperoxidase (MPO) and elastase activity (p < 0. 005 for all measures); the sputum chemoattractants interleukin-8 (IL-8) and leukotriene B(4) (LTB(4)) fell (p < 0.01), and protein leak (sputum/serum albumin ratio) became lower (p < 0.01). The changes were rapid and within 3 d of the commencement of antibiotic therapy the biochemical markers had decreased significantly, but took a variable time thereafter to return to baseline values. In conclusion, patients with AAT deficiency had evidence of increased elastase activity at the start of the exacerbation when compared with nondeficient COPD patients which probably reflects a deficient antiproteinase screen (lower sputum AAT and SLPI). The increased bronchial inflammation at presentation resolved rapidly with 14 d of antibiotic therapy.

Topics: Acute Disease; Acute-Phase Reaction; Aged; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Bacterial Infections; Bronchi; C-Reactive Protein; Female; Humans; Inflammation Mediators; Interleukin-8; Leukotriene B4; Lung Diseases, Obstructive; Male; Middle Aged; Pancreatic Elastase; Peroxidase; Phenotype; Proteinase Inhibitory Proteins, Secretory; Proteins; Respiratory Tract Infections; Secretory Leukocyte Peptidase Inhibitor; Serine Proteinase Inhibitors; Serum Albumin; Sputum

Persistent neutrophilia is a feature of chronic obstructive pulmonary disease (COPD). Leukotriene synthesis inhibitors and cysteinyl leukotriene receptor antagonists have shown efficacy in the treatment of asthma. Antagonism of leukotriene (LT)B(4) receptors is being considered as a mode of treating COPD. We examined the capacity for inhibition of leukotriene synthesis and LTB(4) receptor antagonism to reduce survival of neutrophils from patients with COPD and those from normal subjects. The basal apoptosis level of these cells was 55.4 +/- 2.4% (mean +/- SEM) of total cells. Separate exposure to lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), dexamethasone (DEX), and LTB(4) increased neutrophil survival (p < 0. 001). The LTB(4) receptor antagonist SB201146 abolished LPS-induced survival in a concentration-dependent manner (10 pmol to 0.1 microM), with an IC(50) of 1.9 nM. Combined exposure to SB201146 and to the cysteinyl leukotriene antagonist SKF104353 did not have a greater effect on survival than did exposure to SB201146 alone. Inhibition of 5-lipoxygenase (5-LO) with BWA4C and of 5-LO-activating protein (FLAP) with MK886 abolished GM-CSF- and DEX-induced neutrophil survival. BWA4C and MK886 abolished GM-CSF- induced neotrophil survival in a concentration-dependent manner (1 nM to 10 microM), with IC(50) values of 182.0 nM and 63.1 nM, respectively. These findings demonstrate reversal of LPS-, GM-CSF-, and DEX-induced neutrophil survival by LTB(4) receptor antagonism and inhibitors of 5-LO and FLAP. They also suggest a potential additional antiinflammatory mode of action of these compounds through reduction of cell survival.

Topics: 5-Lipoxygenase-Activating Proteins; Acrylates; Adult; Apoptosis; Arachidonate 5-Lipoxygenase; Benzeneacetamides; Carrier Proteins; Cell Survival; Dexamethasone; Dicarboxylic Acids; Dose-Response Relationship, Drug; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hydroxamic Acids; In Vitro Techniques; Indoles; Leukotriene Antagonists; Leukotriene B4; Lipopolysaccharides; Lipoxygenase Inhibitors; Lung Diseases, Obstructive; Membrane Proteins; Neutrophils; Pyridines; Receptors, Leukotriene B4

The effect of the phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX), salbutamol and sodium nitroprusside was evaluated regarding PGE2 and LTB4 release and cAMP and cGMP level in human alveolar macrophages obtained from controls and COPD patients. Basal levels per five million control- respectively COPD alveolar macrophages: cAMP 1.2 and 1.0 pmole; cGMP 8.4 and 9.1 fmole; PGE2 120 and 63 pg and LTB4 19.2 and 14.8 pg. In both populations IBMX increased cAMP level by 55-93% and salbutamol+IBMX by 285-252%. Except for the 61% rise in LTB4 release by salbutamol+IBMX the drugs hardly affected PGE2 and LTB4 release from control macrophages. In COPD alveolar macrophages, however, IBMX and IBMX+salbutamol largely reduced PGE2 release (63 vs 11 pg per 10(6) cells) but less efficiently increased LTB4. In both macrophage populations sodium nitroprusside (SNP) substantially increased (3-4 fold) cGMP level but did not affect eicosanoid production. Present results indicate that drugs which enhance cAMP level decrease PGE2 release from COPD macrophages and stimulate the release of LTB4 a chemotactic mediator involved in bronchial inflammatory reactions.

Topics: 1-Methyl-3-isobutylxanthine; Adult; Albuterol; Bronchoalveolar Lavage Fluid; Cyclic AMP; Cyclic GMP; Dinoprostone; Female; Humans; Leukotriene B4; Lung; Lung Diseases, Obstructive; Macrophages, Alveolar; Male; Middle Aged; Nitroprusside; Smoking

Gc-globulin has been found in bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease (COPD) and adult respiratory distress syndrome (ARDS) and has been shown to enhance neutrophil chemotaxis to C5-derived peptides in vitro. We proposed that Gc-globulin may enhance the inflammatory response in lungs by influencing monocyte chemotaxis to C5-derived peptides as it does with neutrophils. Monocyte chemotaxis was measured in blind well chambers by a leading-front technique. Purified human Gc-globulin had no intrinsic chemotactic activity for monocytes at concentrations ranging from 1 fM to 1 microM. However, Gc-globulin, at concentrations as low as 10 pM, increased monocyte chemotaxis over 10-fold in a concentration-dependent fashion when added to non-chemotactic doses of C5a (0.1 nM) and C5a des Arg (0.5 nM). The chemotaxis-enhancing effect of Gc-globulin was specific for C5-derived peptides, as Gc-globulin did not enhance monocyte chemotaxis to other chemoattractants such as leukotriene B4 or formyl-Met-Leu-Phe. The enhancement of monocyte chemotaxis to C5-derived peptides by Gc-globulin was not a nonspecific effect of anionic proteins, as other serum proteins of similar size and charge did not enhance monocyte chemotaxis to C5a des Arg. These results indicate that Gc-globulin enhances the monocyte response to C5-derived peptides and, together with previous work, indicates that its presence in the airways of patients with COPD and ARDS may up-regulate the monocyte inflammatory response in the lungs.

Topics: Antibodies; Cells, Cultured; Chemotactic Factors; Chemotaxis; Complement C5a; Complement C5a, des-Arginine; Dose-Response Relationship, Drug; Humans; Leukotriene B4; Lung Diseases, Obstructive; Monocytes; N-Formylmethionine Leucyl-Phenylalanine; Respiratory Distress Syndrome; Vitamin D-Binding Protein

We studied atrial natriuretic factor (ANF), plasma renin activity (PRA), and plasma levels of leukotrienes (LTs) B4 and C4 in 23 patients with COPD undergoing right cardiac catheterization for suspected pulmonary hypertension. Hemodynamic measurements together with concomitant ANF levels (both in venous and pulmonary artery blood and right atrial and pulmonary artery plasma levels of LTC4 and LTB4, were determined at rest (T0), after 30 min of breathing oxygen (3 L/min) (T1), and after 30 min recovering and breathing air (T2). Patients with effective exacerbation or definitive evidence of left ventricular disease, hypertension, arrhythmias, or vasodilator or diuretic therapy were excluded. Increased levels of ANF, both in peripheral venous blood (117 +/- 65 pg/ml) and the pulmonary artery (153 +/- 75 pg/ml), were found in patients with COPD, with or without pulmonary hypertension. Levels of LTC4 were also significantly increased (366 +/- 406 pg/ml) when compared with our control values. No correlations among ANF, LTC4 values, functional tests, and hemodynamic measurements were found. Brief increased levels of oxygen did not modify ANF or LTC4 plasma levels, either in patients with or without pulmonary hypertension.

Topics: Atrial Natriuretic Factor; Hemodynamics; Humans; Hypertension, Pulmonary; Leukotriene B4; Lung Diseases, Obstructive; Middle Aged; Oxygen Inhalation Therapy; Renin; Respiratory Mechanics; SRS-A

Leukotriene B4 has been found to be increased in the serum of cigarette smokers and some patients with bronchial asthma, as well as in the sputum of patients with cystic fibrosis and COPD. Corticosteroids supposedly may block the formation of LTB4. To determine if the effect of CS on airway disease is by reduction in LTB4, we studied serum LTB4 levels in clinically stable patients with asthma or COPD who were treated with or without CS. The LTB4 was extracted from serum and assayed by radioimmunoassay. Serum LTB4 concentrations, expressed as the mean +/- SD, were 0.36 +/- 0.15 ng/ml in ten normal controls, 0.56 +/- 0.18 ng/ml in nine asthmatic subjects, 0.67 +/- 0.2 ng/ml in eight asthmatic subjects receiving CS, 0.81 +/- 0.19 ng/ml in seven patients with COPD, and 0.97 +/- 0.29 ng/ml in eight patients with COPD receiving CS. Serum LTB4 levels in normal controls differed significantly from all groups with COPD or asthma (p less than 0.01). Levels of LTB4 in asthmatic subjects differed from levels in patients with COPD (p less than 0.03), and levels in asthmatic subjects receiving CS differed from subjects with COPD receiving CS (p less than 0.03). Concentrations of LTB4 within either the COPD or the asthmatic groups were not lower in the patients treated with CS. We conclude that serum LTB4 concentrations are higher in COPD than in asthma or normal controls and that administration of CS is not associated with low LTB4 levels. The beneficial effects of CS in obstructive airway disease appear to be mediated by mechanisms other than reduction of LTB4.

Topics: Adult; Aged; Asthma; Forced Expiratory Volume; Humans; Leukotriene B4; Lung Diseases, Obstructive; Middle Aged; Prednisone; Smoking

In order to investigate the possible role of arachidonic acid metabolites as lipid mediators in cystic fibrosis and chronic obstructive pulmonary disease (COPD), sputum from patients with cystic fibrosis, chronic bronchitis, or bronchiectasis was analyzed for various eicosanoids using a combination of radioimmunoassay and bioassay. Leukotriene (LT) B4, cysteinyl-containing LTs, and prostaglandins (PGs) E2, F2 alpha, 6-oxo-PGF1 alpha, and thromboxane B2 were found in all sputum samples. Saliva, which can contaminate sputum, contained low concentrations of prostanoids but not LTs. Inflammatory cells, including polymorphonuclear leukocytes (PMNs) are present in sputum. Because LTB4 generated by these cells is chemotactic for PMNs, it is suggested that this dihydroxy acid contributes to the inflammation of cystic fibrosis and other diseases characterized by airway obstruction. The source of the cysteinyl-containing LTs is less clear; these LTs may constrict respiratory smooth muscle and/or stimulate mucus formation.

Topics: Adult; Arachidonic Acid; Arachidonic Acids; Cystic Fibrosis; Eicosanoic Acids; Female; Humans; Leukotriene B4; Lung Diseases, Obstructive; Male; Middle Aged; Prostaglandins; Radioimmunoassay; Sputum

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