Search PubMed⌕ Search

Biomedical subjects

H Magnussen

Publications and source records attributed to H Magnussen.

At least 55 records · Page 3Linked to original sources
PubMed2001

Flow cytometric analysis of lymphocyte subpopulations in bronchoalveolar lavage fluid after repeated ozone exposure.

As known from studies in animal and human subjects, ozone can exert effects on the immune response including allergic sensitisation and allergen responsiveness. The objective of the present study was to assess the changes in lymphocyte subsets in bronchoalveolar lavage fluid (BALF) after single and repeated ozone exposures. Twenty-three healthy subjects underwent single exposures to 200 ppb ozone or filtered air (FA), as well as repeated exposures to 200 ppb ozone on four consecutive days, each during 4 h of intermittent exercise. Bronchoalveolar lavage was performed 20 h after the single exposure or the last of the repeated exposures. Lymphocytes were identified by sideward scatter and CD45 expression, and their subsets by eight different panels of antibodies. Checksums were calculated to assess the validity of the results. The percentage and the absolute number of lymphocytes, mostly comprising T-lymphocytes (CD2+; overall mean 98.8%), increased after single (P < 0.05; each), but not after repeated ozone exposure, compared with FA (7.4 vs 5.8 vs 6.5%; 680 vs 419 vs 301 x 10(3)). In addition, we observed small but statistically significant changes in the proportions of lymphocyte subpopulations. The percentage of CD4+ lymphocytes increased after single (P < 0.05) and repeated ozone exposure (P < 0.01), whereas the percentage of CD8+ cells decreased after repeated exposure (P < 0.05). The proportion of activated lymphocytes (CD25+) was elevated after repeated, compared with single, ozone exposure (P < 0.01), and the percentages of natural killer (NK) cells were decreased after both single (P < 0.05) and repeated (P < 0.01) exposures. Our data suggest that single but not repeated ozone exposures cause a change in absolute numbers of lymphocytes in BALF, whereas the proportions of lymphocyte subsets are affected by single as well as repeated exposures.

Adult↗
PubMed2001

Freezing of homogenized sputum samples for intermittent storage.

BACKGROUND: Among the reasons that restrict the application of sputum induction in outpatient settings is the need for processing of samples within 2 h after induction. OBJECTIVE: The aim of our study was to assess whether freezing is suitable for intermediate storage of sputum samples before processing. METHODS: We compared differential cell counts between two sputum aliquots derived from the same sample. One aliquot was processed within 2 h after production and one, after it had been frozen under addition of dimethyl-sulfoxid (DMSO) and stored up to 10 days at -20 degrees C. Thirty-five samples were frozen immediately prior to preparation of cytospins, and 10 samples were frozen at an even earlier stage, directly after homogenization. RESULTS: In both sets of experiments we observed a significant relationship between frozen and native samples regarding macrophages, neutrophils and eosinophils, as indicated by respective intraclass correlation coefficients of 0.96, 0.96, and 0.93 in the first, and of 0.92, 0.96 and 0.77 in the second experiments. CONCLUSION: Our results indicate that the freezing of sputum samples at different stages of processing does not alter sputum morphology to an extent that affects the results of differential cell counts.

Adult↗
PubMed2001

In patients with chronic bronchitis a four week trial with inhaled steroids does not attenuate airway inflammation.

Systemic corticosteroids have been recommended as a therapeutic option in patients with moderate to severe COPD. In an early stage of the disease, i.e. chronic bronchitis with mild or no airflow obstruction, a trial with inhaled steroids could reveal potential benefits, particularly in terms of a modulation of airway inflammation. We therefore investigated the effect of inhaled fluticasone (1000 microg day(-1)) on markers of airway inflammation in 19 patients with chronic bronchitis (mean+/-SEM FEV1, 83.4+/-3.0% predicted; FEV1/VC, 67.5+/-2.4%) in a double-blind, cross-over, placebo-controlled manner. Visits were performed before and after two 4-week treatment periods. separated by a 4-week washout period. Lung function, the concentration of exhaled nitric oxide, differential cell counts in induced sputum and the number of cells positive for iNOS, as well as the levels of LDH, ECP, neutrophil elastase and IL-8 in sputum supernatants were determined. Although the total cell number decreased significantly after fluticasone (geometric mean 12.3 vs. 7.7 x 10(6)/ml; P<0.05) it was not significantly different from the change observed after placebo (14.2 vs. 10.6 x 10(6)/ml; n.s.). None of the other parameters showed statistically significant changes after fluticasone or placebo and the results did not depend on the presence of airway hyperresponsiveness. We conclude that in patients with chronic bronchitis short-term treatment with inhaled corticosterids did not improve lung function or inflammatory parameters to an extent which was statistically significant as compared to spontaneous variability.

Administration, Inhalation↗
PubMed2001

Combined inhalation of nitric oxide and oxygen in patients with moderate to severe COPD: effect on blood gases.

Inhaled nitric oxide (NO) has been reported to improve oxygenation in patients with COPD if administered in combination with oxygen (O2). Little, however, is known about the variability of these effects and the potential influence of body position. Twenty-six spontaneously breathing patients with moderate to severe COPD inhaled clean air, O2(FiO2, 0.29), 5 ppm NO, 5 ppm NO+O2, 10 ppm NO+O2, 10 ppm NO, and again clean air in an upright position. Blood gas analysis from arterialized capillary blood was performed after each inhalation. Tests were repeated on different days to assess the variability of the response. Furthermore, eight patients were studied in both upright and supine position while inhaling 5 ppm NO in the presence or absence supplemental O2. As compared to clean air, NO led to a mean decrease in PaO2 of -0.9 mmHg at 5 ppm and of -2.8 mmHg at 10 ppm NO. Similarly, NO+O2 led to a dose-dependent fall in PaO2 of -1.8 and -3.6 mmHg, respectively, as compared to O2. Average within-subject variation (SD) of the effects elicited by 5 and 10 ppm NO was 2.4 and 2.3 mmHg without additional O2, and 4.7and 5.3 mmHg with O2. The effects of 5 ppm NO+O2 differed significantly between upright and supine position; as compared to O2 alone, mean (SD) changes were -3.7 +/- 5-8 vs. +1.1 +/- 4.9 mmHg, respectively. Our findings suggest thatthe addition of NO to inhaled oxygen, when given in an upright position, does not lead to an improvement of PaO2 in patients with moderate to severe COPD. Furthermore, it turned out that it was not possible to define responders and non-responders to inhaled NO on an individual basis, since the variability ofthe responses was similar to the mean

Administration, Inhalation↗
PubMed2001

Provocation by eucapnic voluntary hyperpnoea to identify exercise induced bronchoconstriction.

The International Olympic Committee Medical Commission (IOC-MC) requires notification for use of a beta(2) agonist at the Winter Olympic Games in Salt Lake City. This notification will be required seven days before the event and must be accompanied by objective evidence that justifies the need to use one. The IOC-MC has expressed the viewpoint that, at present, eucapnic voluntary hyperpnoea (EVH) is the optimal laboratory challenge to confirm that an athlete has exercise induced bronchoconstriction (EIB). The EVH test recommended was specifically designed to identify EIB. EVH has been performed in thousands of subjects in both the laboratory and the field. The test requires the subject to hyperventilate dry air containing 5% carbon dioxide at room temperature for six minutes at a target ventilation of 30 times the subject's forced expiratory volume in one second (FEV(1)). The test conditions can be modified to simulate the conditions that give the athlete their symptoms with exercise. A reduction in FEV(1) of 10% or more of the value before the test is considered positive.

Asthma, Exercise-Induced↗
PubMed2000

The therapeutic effect of theophylline in mild obstructive sleep Apnea/Hypopnea syndrome: results of repeated measurements with portable recording devices at home.

Theophylline has been recommended in the literature as a therapeutic option in mild OSAHS. In mild obstructive sleep apnea/hypopnea syndrome (OSAHS), night-to-night variability of parameters of sleep-disordered breathing has been determined rarely, we therefore compared the results of serial measurements of sleep apnea/hypopnea parameters under the effects of placebo and theophylline. To this end, we measured the individual variability of the apnea-hypopnea index (AHI) for seven consecutive nights using a portable sleep apnea recording device, in 14 subjects (2 women, 12 men, mean age +/- [standard deviation] 50 +/- 8 years), treated with placebo or theophylline in a double blind, randomized crossover fashion, whose polysomnographically measured AHI was 13 +/- 5 /hour. Under theophylline treatment in comparison with placebo we observed a small but significant decrease in mean (of seven days) AHI at home (9.2 +/- 7.7 to 6.7 +/- 6.1 /hour), which was independent of body position. The night-to-night variability of AHI at home was high (9. 2 +/- 8.9 /hour; range: 0-31.4 /hour) and proved to be independent of body position and alcohol consumption. - In mild OSAHS, repeated measurements of sleep related breathing events should be performed. Theophylline showed a small but clinically insignificant potencial to reduce AHI.

Adult↗
PubMed2000

Up-regulation of human eosinophil leukotriene C4 generation through contact with bronchial epithelial cells.

OBJECTIVE AND DESIGN: We studied the effect of contact with bronchial epithelial cells on the functional activity of human eosinophils, measured as the production of a bronchoconstrictor lipid mediator, leukotriene C4 (LTC4) to determine the role of cell-cell interaction in activation of airway eosinophils. MATERIALS AND METHODS: Eosinophils were isolated from peripheral blood of atopic donors. Epithelial cells were obtained from the bronchi of surgically resected lung lobes and cultured to confluence on collagen-coated plates. Eosinophils were stimulated with platelet activating factor (PAF) or serum opsonized zymosan (SOZ) after incubation with or without epithelial cells. Leukotriene C4 (LTC4) was assayed in supernatants by enzyme immunoassay. RESULTS: Bronchial epithelial cells did not produce LTC4 in response to PAF or SOZ. Eosinophils pre-incubated in collagen-coated plates for 1 h produced LTC4 in response to both PAF (130 +/- 53 fmol/10(6) eosinophils at 10 micromol/l PAF, 5 min) and SOZ (1,900 +/- 550 fmol/10(6) eosinophils at 2 mg/ml SOZ, 15 min). Eosinophils co-incubated with bronchial epithelial cells for 1 h produced significantly higher quantities of LTC4 in response to both PAF (310 +/- 94 fmol/10(6) eosinophils; P<0.01) and SOZ (5,500 +/- 1,500 fmol/10(6) eosinophils; P<0.001). Ligation of the common beta2 integrin subunit (CD18) with a monoclonal antibody inhibited PAF-stimulated and augmented SOZ-stimulated LTC4 generation by eosinophils alone but had marginal effects on the epithelium-dependent up-regulation. CONCLUSIONS: Contact with bronchial epithelial cells up-regulates the responsiveness of human eosinophils, a finding that has significant implications in the pathology of asthma.

Asthma↗
PubMed2000

The effect of the enantiomers of formoterol on inherent and induced tone in guinea-pig trachea and human bronchus.

The long-acting beta2-adrenoceptor agonist formoterol is, like all other members of this class of drugs, used as a racemate in the clinic. While the effects of the individual enantiomers have been studied on airway smooth muscle from guinea pig, comparable data on human bronchial smooth muscle are scanty or absent. Therefore, we compared the effects of the enantiomers of formoterol on inherent and induced tone in isolated human bronchi with that on guinea-pig trachea in vitro. The human bronchi either were studied under resting tension conditions or were precontracted with 10 microM carbachol or 0.1 mM histamine. The guinea-pig trachea was precontracted with 0.01, 0.1 or 1 microM carbachol. The racemate and (R,R)-formoterol caused a concentration-dependent relaxation of all preparations with an EC50 of about 1 nM. In the guinea-pig trachea, the concentration-effect curve for formoterol was moved to the right in response to an increased concentration of carbachol. In both human bronchus and guinea-pig trachea, (S,S)-formoterol was more than 1,000 times less potent than (R,R)-formoterol. Thus the relaxing effect of formoterol in human airways as well as in guinea-pig trachea was shown to lie with the (R,R)-enantiomer. Notably, (S,S)-formoterol did not exert any contractile effects within the tested concentration range in either airway preparation. Therefore, we conclude that with regard to relaxant effects the pure (R,R)-enantiomer of formoterol does not offer a benefit over the racemate.

Adrenergic beta-Agonists↗
PubMed2000

Monitoring central and peripheral airway inflammation in asthma.

Invasive methods involving bronchoscopy allow identification of the site of airway inflammation, although within the peripheral airways further distinctions are difficult. The method of induced sputum refers only to the central airways, and the analysis of exhaled NO to the airways as a whole. Therefore there is still a need for more refined tools to asses airway inflammation.

Asthma↗
PubMed2000

Efficacy and duration of action of the antileukotriene zafirlukast on cold air-induced bronchoconstriction.

The objectives of the study were to assess the magnitude of the effect of the leukotriene receptor antagonist, zafirlukast, against cold air-induced bronchoconstriction following the first dose and to assess magnitude and duration after 5 days of dosing. Nineteen patients with asthma were included. In a randomized cross-over design, either zafirlukast 20 mg or 80 mg b.d. or placebo were given over 5 days. Challenges were performed 3 h post first dose and 3, 8, 12 and 24 h post last dose. The authors assessed the provocative ventilation rate necessary to achieve a 10% (PV10) and 20% (PV20) fall in forced expiratory volume in one second. The median PV20 3 h post first dose was 69.1 L x min-1 for zafirlukast 80 mg compared to 40 L x min-1 for placebo (p=0.004). The corresponding median value for zafirlukast 20 mg was 59.9 L x min-1 (p=0.06). At steady state the differences in PV20, between zafirlukast 80 mg and placebo were significant at 8 h and 12 h post last dose. The corresponding difference for zafirlukast 20 mg was statistically significant at 8 h post last dose. The analysis of PV10 yielded compatible results. There was no significant protection 24 h after last dose. This study has demonstrated that zafirlukast offers significant protection against cold air-induced bronchoconstriction in asthma. The degree and duration of protection were dose-dependent. However, there was a large interindividual variability for the protective effect of this leukotriene receptor antagonist.

Administration, Inhalation↗
PubMed2000

Flow cytometric analysis of the effect of dithiothreitol on leukocyte surface markers.

Pretreatment with dithiothreitol (DTT) is necessary to dissolve mucus in samples of induced sputum prior to analysis. However, DTT may affect cell surface markers which are essential for lymphocyte subtyping. Therefore, the aim of this study was to evaluate the effect of DTT on an appropriate panel of surface markers. Peripheral blood leukocytes were used because these cells, in contrast to sputum cells, could be obtained without DTT treatment. Peripheral blood from healthy donors was incubated with either DTT according to standard sputum procedures or phosphate-buffered saline (PBS), washed and incubated with fluorochrome-labelled antibodies. After lysis of erythrocytes, analysis was performed using a calibrated flow cytometer. Leukocyte populations were identified by their light scattering properties. For analysis, fluorescence intensity was compared between DTT- and PBS-treated samples. After treatment with DTT, fluorescence intensity was significantly increased in CD16-positive granulocytes; it was reduced in CD2-positive lymphocytes, CD45-positive lymphocytes and CD14-positive monocytes (p < or = 0.001). These changes occurred in all samples. The fluorescence intensity of CD3-, CD4-, CD8-, CD19-, CD56- and histocompatibility leukocyte antigen DR-positive lymphocytes was not altered by DTT. However, there were statistically significant (p<0.001), although small, changes in the percentages of leukocytes. The present data demonstrate that, although dithiothreitol as used in sputum analysis affects some surface markers of peripheral blood leukocytes, comparability between samples concerning lymphocyte surface markers is preserved. Therefore, it is suggested that treatment of sputum samples with dithiothreitol does not invalidate the immunocytochemical analysis of lymphocytes.

Adult↗