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H Magnussen

Publications and source records attributed to H Magnussen.

At least 73 records · Page 4Linked to original sources
PubMed2000

Update on sputum methodology.

Over the past few years cellular and biochemical sputum examinations have become important instruments to assess airway inflammation. The aim of this review is to summarize new methodological developments and aspects, which are currently under investigation. The use of isotonic saline has increased safety of inductions in patients with severe asthma and in children. The origin of sputum is better understood, as is the need to standardize the volume and duration of induction. It also needs to be borne in mind that the induction procedure itself is able to cause changes in sputum composition. However, the basic induction and processing procedures have not changed much over the last few years, and therefore the method is still time consuming. The analysis of ECP in lysed sputum cells as a marker for the number of eosinophils has been suggested to overcome this problem, but needs further validation. Furthermore, storage of sputum has been studied, as well as early fixation or freezing of sputum cells to elongate the time between induction and processing. Differential cell counts by flow cytometry are still difficult, but the method has increased knowledge concerning lymphocyte subsets and the activation status of sputum cells. The use of induced sputum to noninvasively measure airway inflammation in clinical trials will offer additional information, but the proper use and interpretation of sputum outcome parameters will need further investigation.

Administration, Inhalation↗
PubMed2000

The concentration of hydrogen peroxide in exhaled air depends on expiratory flow rate.

Hydrogen peroxide (H2O2) is known to be detectable in exhaled air. The present study aimed to determine whether the concentration of exhaled H2O2 depends on expiratory flow rate in order to make inferences on the site of its production within the lung. Breath condensate was collected in cooled Teflon tubes, at three different expiratorv flow rates, in 15 healthy or mild asthmatic subjects. Tests were repeated 2-5 times to assess reproducibility. Mean+/-SEM concentrations of H2O2 at flow rates of 140, 69 and 48 mL.s(-1) were 0.12+/-0.02, 0.19+/-0.02 and 0.32+/-0.03 microM, respectively. These values differed significantly from each other (p<0.001). For comparison, average coefficients of variability within repeated measurements at each of the three flow rates were 68, 62 and 82%, respectively. These data demonstrate that the concentration of exhaled hydrogen peroxide depends on expiratory flow rate. Since flow dependence is an indicator of production within the airways, this result suggests that, to a large extent, the exhaled hydrogen peroxide originates within the airways. However, even under strictly controlled conditions, a high degree of variability persists, which may limit the usefulness of exhaled hydrogen peroxide as a marker of airway inflammation.

Adult↗
PubMed2000

Noninvasive methods to measure airway inflammation: future considerations.

This last contribution to the series focuses on open questions regarding: 1) methodological issues; and 2) the potential clinical application of the noninvasive methods such as induced sputum and the analysis of exhaled air for the assessment of airway inflammation. In addition their potential future role in occupational health and the early diagnosis of neoplastic lesions are briefly discussed. The future clinical application of noninvasive methods will depend on the progress made to improve their practicability, particularly in rendering them less time consuming and cheaper. To assess their clinical value, prospective studies are needed to establish whether patients actually benefit from the results obtained. This is also important to implement the methods into the healthcare system and to obtain adequate financial compensation. Therefore, it is necessary to know: 1) whether the assessment of airwav inflammation can aid in coming to an earlier and better defined diagnosis; 2) whether by repeated monitoring it is possible to avoid exacerbations through earlier interventions; and 3) whether the long-term outcome of patients is improved through knowledge of the type and degree of airway inflammation that is taken into account in selecting the appropriate treatment. In the meantime a wealth of data has become available, both for induced sputum and the analysis of exhaled air, which give these methods the potential to be incorporated into future clinical practice. This, however, will, amongst the other issues, depend on favourable cost-benefit ratios which should also be the subject of future prospective studies.

Breath Tests↗
PubMed2000

The effect of selective and non-selective phosphodiesterase inhibitors on allergen- and leukotriene C(4)-induced contractions in passively sensitized human airways.

Non-selective inhibitors of cyclic nucleotide phosphodiesterase (PDE) block allergen-induced contraction of passively sensitized human airways in vitro by a dual mechanism involving a direct relaxant effect on smooth muscle and inhibition of histamine and cysteinyl leukotriene (LT) release from airways. We investigated the effects of non-selective PDE inhibitors and selective inhibitors of PDE3 and PDE4 in order to determine the involvement of PDE isoenzymes in the suppression of allergic bronchoconstriction. Macroscopically normal airways from 76 patients were sensitized with IgE-rich sera (>250 u ml(-1)) containing specific antibodies against allergen (Dermatophagoides farinae). Contractile responses of bronchial rings were assessed using standard organ bath techniques. Passive sensitization caused increased contractile responses to allergen, histamine and LTC(4). Non-selective PDE inhibitors (theophylline, 3-isobutyl-1-methylxanthine [IBMX]), a PDE3-selective inhibitor (motapizone), PDE4-selective inhibitors (RP73401, rolipram, AWD 12-281) and a mixed PDE3/4 inhibitor (zardaverine) all significantly relaxed inherent bronchial tone at resting tension and to a similar degree. Theophylline, IBMX, zardaverine and the combination of motapizone and RP73401 inhibited the contractile responses to allergen and LTC(4). Pre-treatment with motapizone, RP73401, rolipram or the methylxanthine adenosine receptor antagonist, 8-phenyltheophylline, did not significantly decrease responses to either allergen or LTC(4). We conclude that combined inhibition of PDE3 and PDE4, but not selective inhibition of either isoenzyme or antagonism of adenosine receptors, is effective in suppressing allergen-induced contractions of passively sensitized human airways. The relationship between allergen- and LTC(4)-induced responses suggests that PDE inhibitors with PDE3 and PDE4 selectivity are likely to act in part through inhibition of mediator release and not simply through direct relaxant actions on airway smooth muscle.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Serum immunoglobulin E levels predict human airway reactivity in vitro.

BACKGROUND: Airway hyperresponsiveness to non-specific stimuli is one characteristic feature of airway diseases such as bronchial asthma and chronic bronchitis. Until now, studies aiming to demonstrate a relationship between in vivo conditions associated with airway hyperreactivity and in vitro airway responsiveness have been inconclusive. OBJECTIVE: Since serum immunoglobulin (Ig) E is believed to be one determinant of airway reactivity in vivo, we studied whether in vitro airway reactivity in lung resection material from patients with elevated levels of serum IgE was increased as compared with patients with undetectable IgE. By this approach, we aimed to elucidate the role of circulating IgE for bronchial smooth muscle reactivity in vitro. METHODS: Bronchial rings from nine patients with total serum IgE levels above 200 U/mL and 10 patients with total serum IgE levels below 10 U/mL were passively sensitized, i.e. incubated overnight with buffer or sensitizing serum containing high levels of total IgE (> 250 U/mL). Afterwards, contractile responses to histamine were assessed in the organ bath. RESULTS: Histamine responsiveness was significantly increased in airways obtained from patients with IgE levels above 200 U/mL as compared with airways from patients with IgE levels below 10 U/mL (P < 0.05). Passive sensitization of bronchi from patients with low IgE significantly increased histamine responsiveness, as compared with non-sensitized controls from the same patients (P < 0.05). In contrast, passive sensitization of airways from patients with elevated IgE did not further increase responsiveness. There was no difference in histamine reactivity between non-passively sensitized and passively sensitized tissue preparations from patients with IgE above 200 U/mL and passively sensitized tissues from patients with IgE below 10 U/mL. CONCLUSION: Our findings reveal that elevated levels of serum IgE predict airway hyperresponsiveness to histamine in vitro. At the same time, they indicate that the in vitro model of passive sensitization, in addition to its ability to induce allergen responses, also mimics conditions of non-specific airway hyperreactivity, which are relevant under in vivo conditions.

Aged↗
PubMed2000

Involvement of protein tyrosine kinases in activation of human eosinophils by platelet-activating factor.

Activation of human eosinophils by platelet-activating factor (PAF) involves multiple signal transduction pathways. Among these, protein kinase C has been demonstrated both to mediate respiratory burst and to suppress an alternative pathway of activation of respiratory burst and arachidonic acid metabolism in eosinophils. We utilized inhibitors of protein tyrosine kinases (PTK) to elucidate the role of PTK in PAF-induced activation of eosinophils. Eosinophils were isolated from peripheral blood of atopic donors and stimulated with PAF in the absence or presence of broad-spectrum PTK inhibitors-genistein or lavendustin A; an inhibitor of mitogen-activated protein (MAP) kinase activation-tyrphostin AG126; or an inhibitor of Janus kinase 2 (Jak2)-tyrphostin B42 (AG490). PAF induced superoxide anion (O2-*) generation, leukotriene C4 (LTC4) release, intracellular calcium ion mobilization and tyrosine phosphorylation of multiple eosinophil proteins in a concentration-dependent manner. All of these responses were concentration-dependently inhibited by genistein; lavendustin A also exhibited potent inhibition of PAF-induced LTC4 release. AG126 had no effect on either O2-* generation or LTC4 release, while AG490 inhibited both responses, albeit less effectively than genistein. We conclude that PAF activates PTK in human eosinophils and that this signalling pathway is involved in eliciting respiratory burst and leukotriene production. The specific PTK(s) involved are unknown but may include Jak2.

Blotting, Western↗
PubMed2000

Equivalent asthma control after dose reduction with HFA-134a beclomethasone solution aerosol. Comparative Inhaled Steroid Investigation Group (CISIG).

AIM: The replacement of chlorofluorocarbon (CFC) by hydrofluoroalkane has the potential to improve airway deposition of BDP. We investigated whether HFA-BDP extra-fine solution aerosol 400 microg day(-1) is as effective as CFC-BDP 1000 micro day(-1) in patients with stable, moderate asthma, having persistent bronchial hyperresponsiveness. PATIENTS AND METHODS: One hundred and fifty patients with moderate asthma from 20 centres, on inhaled steroids for < or = 3 months, entered a 4-week run-in period with 1000 microg day(-1) CFC-BDP. Patients were then allocated to a 10-week study phase, receiving CFC-BDP 1000 microg day(-1) or HFA-BDP 400 microg day(-1). Symptom score and PEF were measured daily and recorded as biweekly means. Spirometry, PC20FEV1, blood eosinophils and serum ECP were determined on days 15, 29, 43 and 71, and compared to the last visit of the run-in period. All group members were trained in a quality control centre. RESULTS: Treating the population of the HFA-BDP group (n = 72) and the CFC-BDP group (n = 78) did not show significant differences in terms of symptoms, lung function, airway hyperresponsiveness and serum markers of inflammation at the end of the run-in period and the end of the study phase. CONCLUSION: Using HFA instead of a CFC metered dose inhaler, containing less than half the daily dose of BDP, allows control of symptoms and lung function parameters, without changes in bronchial hyperresponsiveness.

Administration, Inhalation↗
PubMed2000

Trends in bronchial hyperresponsiveness, respiratory symptoms and lung function among adults: West and East Germany. INGA Study Group. Indoor Factors and Genetics in Asthma.

Previous studies have shown higher prevalences of bronchial hyperresponsiveness (BHR), respiratory symptoms and atopic sensitization among adults in Western Germany than in Eastern Germany. One of the aims of the joint project INGA (INdoor Factors and Genetics in Asthma) is to assess incidence, prevalence and trends for asthma, BHR and atopic diseases over a time period of 11 years (1990-2001) in the former West (Hamburg) and East Germany (Erfurt), with special reference to indoor exposure. INGA was designed as a case-control study following a cross-sectional study performed from 1990 to 1992 within the European Community Respiratory Health Survey (ECRHS). The database consisted of 1159 subjects in Hamburg and 731 subjects in Erfurt from the ECRHS (age 20-44). In 1995-1996, 107 cases (diagnosed asthma, positive specific serum IgE, positive skin prick or PD20FEV1< or =2.0 mg methacholine at ECRHS) and 106 controls (none of the previous findings) participated in Hamburg (115 cases and 109 controls in Erfurt). The methodology was identical to the ECRHS and dose-response slopes (DRS) of the methacholine challenge were calculated as an index of responsiveness. In the control group, median values of DRS were 0.028% mg(-1) (1990-1992) and 0.044 (1995-1996) (P<0.01) in Erfurt. Corresponding values for Hamburg were 0.028 and 0.022 (NS). Corresponding values within the case groups were 0.041 and 0.049 (NS) for Erfurt, and 0.069 and 0.052 (P<0.05) for Hamburg. Thus, 4 years after the first survey, we found an increased BHR in the Erfurt control group while the bronchial responsiveness remained unchanged for the Hamburg group. These trends in BHR, which indicate the expected converging tendency between East and West Germany, have to be confirmed within the next INGA-survey in 2000-2001.

Adult↗
PubMed2000

Home-based exercise is capable of preserving hospital-based improvements in severe chronic obstructive pulmonary disease.

We examined the feasibility of home-based walking training to maintain the benefits of a short-term exercise training in patients with severe chronic obstructive pulmonary disease (COPD). After initial recovery from an exacerbation, 46 patients were randomized into a training and a control group, and 30 patients completed the programme (mean +/- SD FEV1, 36 +/- 7% predicted). The training group performed a 10-day walking training programme in the hospital, followed by a 6-month programme of supervised walking training at home, integrated into daily activities. The control group did not have exercise training in the hospital or at home. Until 6 months after discharge, lung function, exercise performance and symptom scores were assessed. Six-minute walking distance in the training group improved from day 1 to day 10 (P<0.001) and this effect was maintained over 6 months (P<0.001). On average, daily walking distance at home was 2308 m and walking was reported on 157 days. Quality of life (QoL) scores changed significantly over 6 months (P<0.001). The control group showed no significant changes in exercise performance or QoL scores throughout the whole study period. Therefore, (i) significant improvements in exercise performance and Chronic Respiratory Disease Questionnaire (CRQ) scores could be achieved after recovery from an exacerbation and (ii) these improvements were maintained after discharge, when supported by a home-based walking training.

Aged↗
PubMed2000

[Role of surgical procedures in the diagnosis and therapy of tuberculosis].

Over the last decades the annual number of surgical intervention for treatment of pulmonary tuberculosis has steadily declined. Despite effective antituberculotic medication, there are still indications for thoracic surgery. The aim of the present study was to give an account of the diagnostic and therapeutic role of surgery of pulmonary tuberculosis. Therefore we analysed all operated patients with pulmonary tuberculosis between 1988 and 1999. In 2% of all patients with pulmonary tuberculosis surgical intervention was performed (n = 35). Their main indication was resection for suspected carcinoma, multi-drug resistance or non-compliance to the medical treatment, decortication because of cavern rupture or empyema, hemoptoe and destroyed lung. A additional indication for surgery was pulmonary aspergilloma caused by superinfection of postspecific cavities. Postoperative complications like bleeding (> 1000 ml) or broncho-pleural fistula occurred in 37%, none of the patients died. Surgery is still a valid option für the treatment of pulmonary tuberculosis. Before surgical intervention, a long term antituberculotic chemotherapy is essential. Patients have to be selected individually because of an increased morbidity. In 10% of all operated patients (n = 1132) with preoperative unidentifiable pulmonary mass the infiltrate was specific aetiology.

Diagnosis, Differential↗
PubMed2000

[nCPAP therapy does not affect respiratory mechanics of patients with sleep-related respiratory disturbances].

We investigated in patients with sleep disordered breathing the influence of long-term nCPAP-therapy on airway mechanics and capillary blood gases. 109 patients (19 women, 90 men, age [mean +/- standard deviation] 59 +/- 10 years, apnea-hypopnea-index 34 +/- 24/h) were treated for 27 +/- 33 months, with a mean pressure of 7.7 +/- 2 mbar, mean usage 5.6 +/- 1.9 h/night. Vital capacity, FEV1, thoracic gas volume and capillary blood gases did not change during therapy, irrespective of the smoking history. However, in a subgroup of 6 patients who were hypoxemic before therapy, there was a significant increase of PaO2 from 63 +/- 4 to 70 +/- 6 mm Hg (p < 0.01). Neither the height of the pressure nor the duration of therapy did influence the course of lung function data.

Female↗
PubMed2000

Respimat (a new soft mist inhaler) delivering fenoterol plus ipratropium bromide provides equivalent bronchodilation at half the cumulative dose compared with a conventional metered dose inhaler in asthmatic patients.

BACKGROUND: Respimat, a possible alternative to the conventional metered dose inhaler (MDI), is a novel, reusable, propellant-free, multidose soft mist inhaler. Respimat slowly releases a metered dose of active substance as a soft mist with a high proportion of the dose in the fine particle fraction, leading to improved lung deposition following inhalation when compared with the conventional MDI. OBJECTIVES AND METHODS: The equipotent bronchodilating efficacy and safety of a combination of fenoterol hydrobromide and ipratropium bromide (F/I) in cumulative doses delivered by either Respimat or pressurised MDI was assessed in a randomised, controlled, double-blind (within device) 4-way crossover study. Forty-three patients with stable asthma (mean FEV(1) 62% predicted) responsive to F/I inhaled cumulatively 16 puffs on each of 4 test days (1 + 1 + 2 + 4 + 8 puffs at 50-min intervals) via Respimat delivering 50/20, 25/20 or 25/10 microg F/I per puff or via MDI delivering 50/20 microg F/I per puff. RESULTS: Cumulative doses of 400/160 and 400/320 microg F/I via Respimat produced bronchodilation (evaluated by average increase in FEV(1) 45-245 min after first inhalation) equivalent to that achieved with a cumulative 800/320 microg F/I via MDI (mean increase in FEV(1) above baseline 0.76, 0.73 and 0.71 litres, respectively). The tolerability of the F/I combination via Respimat was also comparable to that of twice the dose delivered via MDI. CONCLUSION: Therefore, a fenoterol hydrobromide/ipratropium bromide combination delivered by Respimat is as safe and effective as the MDI at half the cumulative dose, on acute administration to patients with asthma.

Administration, Inhalation↗
PubMed2000

The effect of repeated ozone exposures on inflammatory markers in bronchoalveolar lavage fluid and mucosal biopsies.

The aim of this study was to investigate the cellular and biochemical events associated with repeated exposures to ozone. Twenty-three healthy subjects underwent single exposures to 200 ppb ozone and to filtered air (FA), as well as repeated exposures to 200 ppb ozone on 4 consecutive days, each for 4 h of intermittent exercise. Bronchoalveolar lavage was performed and mucosal biopsies were taken 20 h after the single or the last of the repeated exposures. As compared with FA, the single exposure to ozone caused a decrease in FEV(1), an increase in the percentages of neutrophils and lymphocytes, the concentrations of total protein, IL-6, IL-8, reduced glutathione, urate, and ortho-tyrosine in BAL fluid (BALF), but no changes in the cellular composition of biopsy. After the repeated exposure, the effect on lung function was abolished and differential cell counts in BALF were not significantly different from those after FA. However, the concentrations of total protein, IL-6, IL-8, reduced glutathione, and ortho-tyrosine were still increased. IL-10 could only be detected in BALF after repeated ozone exposures. Furthermore, macroscopic scores for bronchitis, erythema, and hypervulnerability of airway mucosa were increased, as well as numbers of neutrophils in bronchial mucosal biopsies. Our data demonstrate that airway inflammation persists after repeated ozone exposure, despite attenuation of some inflammatory markers in BALF and adaptation of lung function.

Adult↗
PubMed2000

Factor analysis of changes in dyspnea and lung function parameters after bronchodilation in chronic obstructive pulmonary disease.

Expiratory airway collapse is a characteristic feature in patients with chronic obstructive pulmonary disease (COPD). We hypothesized that this collapse might mask the effects of bronchodilators during forced expiration but not during forced inspiration, and that accordingly, the improvement in forced inspiration and not that in forced expiration with bronchodilator therapy would be related to changes in the perception of dyspnea. In order to investigate this, we conducted lung function measurements, including measurements of forced inspiration and expiration before and 30 min after inhalation of 400 microg salbutamol, in 61 patients with COPD (mean FEV(1): 38. 3 L; range: 12.9 to 79.5% predicted). The change in dyspnea from baseline was assessed with a standard visual analogue scale (VAS) ranging from -100 to +100. To delineate the relationship between parameters, we used the statistical procedure of factor analysis. Salbutamol induced an improvement of 0.16 +/- 0.02 L (mean +/- SD) in FEV(1), 0.36 +/- 0.04 L in forced inspiratory volume in one second (FIV(1)), 0.30 +/- 0.04 L in inspiratory capacity (IC), and -0.34 +/- 0.07 L in intrathoracic gas volume; the mean VAS score was 36.4 +/- 3.2. Factor analysis demonstrated that the reduction in dyspnea at rest was primarily associated with changes in parameters describing forced inspiration and not with those of forced expiration or lung hyperinflation, including IC. Our data indicate that in patients with COPD, the reduction in dyspnea after inhalation of a beta(2)-adrenoreceptor agonist is closely correlated with the change in parameters of forced inspiration, and particularly FIV(1), but not with changes in parameters of forced expiration or lung hyperinflation.

Albuterol↗
PubMed2000

Human alveolar epithelial cells type II are capable of regulating T-cell activity.

Alveolar epithelial cells type II (AEC-II) express MHC class II on their surface, an important prerequisite for antigen presentation. However, accessory signals are required for an efficient T-cell activation. We therefore isolated AEC-II from tumor-free sections of human lungs obtained by lobectomy/pneumectomy and purified the cells by magnetic-activated cell sorting. Furthermore, we tested the expression of CD54, CD58, CD80, and CD86 on AEC-II and evaluated their accessory function (AF) in cell culture using a coculture of interleukin-2 (IL-2), releasing Jurkat cells and AEC-II. An increased AF is documented by an elevated IL-2 release and expressed as accessory index (AI). In 33 experiments the AF of AEC-II proved to be highly variable. AI ranged between 0.3 and 17.1 with a median of 1.4 (0.3-17.1). Forty-four percent (4-77) of the AEC-II expressed HLA-DR, 44% (12-89%) of the cells expressed CD58, and CD54 was expressed by 55% (16-89%). AEC-II also expressed CD80 and CD86 (38% [0-77%] and 40% [4-68%], respectively). Interestingly, AEC-II released high levels of TGF beta (1730 pg/mL [771-5876]) and the accessory index could be increased (approximately 2-fold) by the addition of neutralizing anti-TGF beta antibodies or radiation. Thus, type II alveolar cells express costimulatory molecules and are able to deliver costimulatory signals for T cells, providing evidence that AEC-II are able to act as antigen-presenting and immunoregulatory cells of the lung. Additionally, the accessory function of AEC-II is under the control of endogenously released TGF beta.

Antigen-Presenting Cells↗