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Biomedical subjects

H Magnussen

Publications and source records attributed to H Magnussen.

At least 19 recordsLinked to original sources
PubMed2006

Randomised trial comparing as-needed versus regular treatment with formoterol in patients with persistent asthma.

PURPOSE: The aim of this study was to demonstrate the equivalent efficacy of inhaled formoterol in asthmatic patients, either given as-needed or on a regular twice-daily schedule. METHODS: Randomised, open 12-week study in patients with mild to moderate asthma not adequately controlled with inhaled glucocorticosteroids alone. Patients received inhaled formoterol as needed or on a regular schedule (2x2 puffs/day with 6 microg formoterol per puff). Patients in the twice-daily formoterol group could use salbutamol as a rescue medication. The primary endpoint was the number of patients with asthma exacerbations in each group. RESULTS: Thirty-nine centres randomised 359 patients. The number of patients with asthma exacerbations showed neither a clinically relevant nor a statistically significant difference between groups: formoterol as-needed: 3.95% (7 of 177); twice daily: 3.45% (6 of 174). Patients in the formoterol as-needed group used significantly less formoterol (-1.5 puffs per day; P<0.0001). Including the saved rescue medication (up to one puff per day), total beta-2 agonist use in the formoterol as-needed group decreased by approximately 2-2.5 puffs per day. Both formoterol treatment schedules were well tolerated. Musculoskeletal pain and tremor were less frequent in the formoterol as-needed group: headaches were slightly more frequent. CONCLUSION: Formoterol given as needed and without additional beta-2 agonist, and formoterol given on a regular basis twice daily, supplemented by salbutamol as a rescue medication, appeared equally effective in this clinical study. Drug consumption was markedly lower in the former group.

Administration, Inhalation↗
PubMed2006

Lung fibroblasts from patients with emphysema show markers of senescence in vitro.

BACKGROUND: The loss of alveolar walls is a hallmark of emphysema. As fibroblasts play an important role in the maintenance of alveolar structure, a change in fibroblast phenotype could be involved in the pathogenesis of this disease. In a previous study we found a reduced in vitro proliferation rate and number of population doublings of parenchymal lung fibroblasts from patients with emphysema and we hypothesized that these findings could be related to a premature cellular aging of these cells. In this study, we therefore compared cellular senescence markers and expression of respective genes between lung fibroblasts from patients with emphysema and control patients without COPD. METHODS: Primary lung fibroblasts were obtained from 13 patients with moderate to severe lung emphysema (E) and 15 controls (C) undergoing surgery for lung tumor resection or volume reduction (n = 2). Fibroblasts (8E/9C) were stained for senescence-associated beta-galactosidase (SA-beta-Gal). In independent cultures, DNA from lung fibroblasts (7E/8C) was assessed for mean telomere length. Two exploratory 12 k cDNA microarrays were used to assess gene expression in pooled fibroblasts (3E/3C). Subsequently, expression of selected genes was evaluated by quantitative PCR (qPCR) in fibroblasts of individual patients (10E/9C) and protein concentration was analyzed in the cell culture supernatant. RESULTS: The median (quartiles) percentage of fibroblasts positive for SA-beta-Gal was 4.4 (3.2;4.7) % in controls and 16.0 (10.0;24.8) % in emphysema (p = 0.001), while telomere length was not different. Among the candidates for differentially expressed genes in the array (factor > or = 3), 15 were upregulated and 121 downregulated in emphysema. qPCR confirmed the upregulation of insulin-like growth factor-binding protein (IGFBP)-3 and IGFBP-rP1 (p = 0.029, p = 0.0002), while expression of IGFBP-5, -rP2 (CTGF), -rP4 (Cyr61), FOSL1, LOXL2, OAZ1 and CDK4 was not different between groups. In line with the gene expression we found increased cell culture supernatant concentrations of IGFBP-3 (p = 0.006) in emphysema. CONCLUSION: These data support the hypothesis that premature aging of lung fibroblasts occurs in emphysema, via a telomere-independent mechanism. The upregulation of the senescence-associated IGFBP-3 and -rP1 in emphysema suggests that inhibition of the action of insulin and insulin-like growth factors could be involved in the reduced in vitro-proliferation rate.

Biomarkers↗
PubMed2006

[Comorbidities of COPD].

Chronic obstructive pulmonary disease (COPD) is often associated with comorbidities. Cardiovascular diseases, weight loss, loss of fat free mass combined with muscle dysfunction, osteoporosis and depression are the main comorbidities in COPD. Cardiovascular comorbidities, weight loss and loss of fat free mass are predictors of mortality of patients with COPD. Thus, the extrapulmonary manifestations are meaningful parameters of clinical assessment. Systemic inflammation is probably the key to the extrapulmonary signs of COPD.

Body Mass Index↗
PubMed2006

[Assurance of process-quality in pulmonary practice by means of a peer-review system--a pilot project].

Quality assurance and quality-management have been well anchored in social legislation for years. Peer-reviews to assure process-quality and quality of outcomes have been conducted repeatedly in centres for pulmonary medicine, facilities for pulmonary rehabilitation as well as centres for sleep-medicine. By means of a pilot study we wanted to investigate if assurance of process-quality is feasible and if a peer review system turns out to be a suitable method in pulmonary practice. Medical reports and/or diagnostic protocols of the investigational procedures such as pulmonary function tests, allergy-tests, induction test of bronchial hyperresponsiveness et cetera were randomly collected from nine patients with bronchial asthma or COPD in each of the 44 participating pulmonary practices and forwarded to three peer-reviewers respectively. 396 selected patient-datasets resulted in 1188 reviews. Peer review was conducted by means of a specially developed checklist of markers of process-quality accompanied by an explanatory manual. Measures of quality were determined for every pulmonary practice and a report of results was generated. The health economical efficacy of the therapy and the diagnostic process as well as an assessment of the overall process was evaluated by means of a visual analogue scale. No deficiencies could be detected in clearly more than half of the assessments. Major deficiencies or an unacceptable result in different items could be detected in every sixth assessment. For every item a graphic ranking in terms of benchmarking was generated for each individual report. Since peers were reviewers and subjects of review at the same time, they can now clearly improve and assure their diagnostic and therapeutic process-quality in patients with bronchial asthma and COPD by means of the experience they gained during the review process, as well as by the assessment they received. We were able to demonstrate that a peer-review-system is appropriate to assure process-quality in pulmonary practice and that it is feasible to achieve a continuous assurance and improvement of quality in the long run.

Asthma↗
PubMed2006

Time course of exhaled hydrogen peroxide and nitric oxide during chemotherapy.

This study was designed to assess the effect of differential leukocyte depletion during chemotherapy by monitoring the levels of exhaled hydrogen peroxide H2O2 and nitric oxide (F(eNO)) present. In 39 patients with lung cancer (chronic obstructive pulmonary disorder up to stage II, median forced expiratory volume in one second 78% predicted), measurements were performed before a cycle of therapy (day 1), at least once during the cycle (day 8: n = 34; day 15: n = 19), and afterwards (days 21-29). There were significant changes in the level of H2O2, F(eNO) and peripheral blood cell differentials over the visits. The level of H2O2 was decreased only on day 15, with a median (difference between the upper and lower quartiles) fall of 31 (57)%, while F(eNO) was reduced only on day 8, by 22 (40)%. Neutrophil numbers were unchanged on day 8 and decreased by 59 (48)% on day 15, while monocyte numbers were decreased on day 8 by 87 (39)%. On days 21-29, values had returned to baseline. Taken together with previous findings, the parallel course of levels of exhaled hydrogen peroxide and neutrophil counts suggests that a major part of exhaled hydrogen peroxide is due to neutrophils via the conducting airways. In contrast, the production of exhaled nitric oxide seems to be primarily associated with monocytes.

Exhalation↗
PubMed2004

Comparison of exhaled nitric oxide analysers.

Currently no published data are available concerning the comparability of different types of NO analysers, making inter-laboratory comparisons difficult. In two sets of experiments we compared 4 and 5 NO analysers, respectively, from 3 different manufacturers using different calibration regimes: calibration with (1) a separate recommended calibration gas for each analyser, (2) a single low concentration for all (394 ppb), and (3) a single high concentration (12.8 ppm). We measured three subjects with known low (L), moderate (M) and high (H) bronchial exhaled nitric oxide concentrations as well as standard gases (SG). In the first set of experiments, calibration regime 1 resulted in the largest differences between analysers (coefficient of variation (CV) for L, M, H, SG: 0.42, 0.22, 0.20, 0.14). The lowest CV between analysers was observed after calibration 2 (0.34, 0.19, 0.12, 0.02). Very similar results were obtained in the second set of comparisons. Thus, differences between analysers existed, but were mainly due to differences in recommended calibration gases/procedures. Only a small part was explainable by deviations from target flow. These differences need to be taken into account when comparing data between laboratories or replacing the calibration gas of an analyser, as well as for the establishment and interpretation of normal values.

Adult↗
PubMed2004

Direct measurement of BDP and 17-BMP in bronchial and peripheral lung tissue after inhalation of HFA- vs CFC-driven aerosols.

Indirect assessments have shown a superior lung deposition of HFA-BDP (Ventolair/Qvar) compared to CFC-BDP (Aerobec). The aim of this study was to assess the concentrations of BDP and its metabolite 17-BMP in airways and peripheral tissue from resected lung specimens after inhalation of these BDP formulations. Immediately prior to surgery for lung cancer, 10 patients inhaled 1000 microg of either CFC-BDP (n = 5) or HFA-BDP (n = 5) Mouthwash was collected after inhalation, and serum before, during, and after surgery. There was no significant difference between CFC and HFA in the concentration of 17-BMP in bronchi (median, 4365 vs 4121 pg/g tissue). After CFC, concentrations of 17-BMP were lower in peripheral tissue (1424 vs 2089 pg/g; ANCOVA, p = 0.001) and in serum taken immediately after inhalation (688 vs 1219 pg/ml, p < 0.01). Furthermore, the CFC group showed a higher concentration of BDP in the mouthwash (17,660 vs 1320 ng/ml, p < 0.05), but the concentration of 17-BMP was lower (452 vs 1028 ng/ml, n.s.). These findings indicate a predominantly peripheral deposition of HFA-BDP, in line with previous data. They also provide evidence for a faster uptake and metabolism of HFA-BDP, probably because BDP is dissolved in HFA and has a smaller particle size distribution than the CFC suspensions.

Administration, Inhalation↗
PubMed2004

[COPD: an inflammatory disease of the airways?].

COPD is characterized by a not fully reversible airflow limitation which is progressive and associated with an abnormal inflammatory reaction of the lungs. Airflow limitation is most often assessed by FEV (1.0). However, FEV (1.0) does not always reflect the course of the disease and does not appropriately describe the functional effect of a pharmacological or non-pharmacological intervention. Measurement of inspiratory parameters, e.g. IC or FIV (1.0), as well as assessment of exercise capacity should therefore be part of functional tests. The abnormal inflammatory reaction of the lungs can be assessed by a variety of methods. However, the characteristic increase of the number of neutrophils does not indicate a new therapeutic target. The term abnormal inflammation of the airways in bronchial asthma as well as in COPD presumably prompted a number of studies investigating the effects of inhalative corticosteroids in COPD. ICS do not alter the course of the disease, however they may reduce the number and severity of exacerbations. Combination of long-acting beta -agonists and ICS exert a better effect than either compound alone. This beneficial effect is difficult to explain by an anti-inflammatory action, as the long acting anticholinergic tiotropium has a comparable symptomatic and functional effect and reduces exacerbations without any known anti-inflammatory component. Future pharmacological therapies should therefore be based on a better understanding of the functional consequences of the disease and its pathogenesis.

Humans↗
PubMed2004

[Respiratory therapist: introduction of a new profession].

Respiratory therapists are healthcare professionals taking care of patients with pulmonary disorders. They are an allied health specialty, practicing under medical direction. The professionalism of nurses and therapists must grow up to act successfully in new fields of medicine, where evidence-based independent action is necessary. Specialized therapists can help us coordinate separated processes (diagnoses, therapy and nursing). The profession "Respiratory Therapist" was created in the United States 50 years ago. We intend to introduce this profession also in Germany. We follow many other countries who have already taken this step. We hope that we can reach yet a higher quality of patient care.

Evidence-Based Medicine↗
PubMed2004

Predictive value of BAL cell differentials in the diagnosis of interstitial lung diseases.

The current authors aimed to quantify how the likelihood for a given diagnosis changes with the knowledge of bronchoalveolar lavage (BAL) cell differentials. As an initial estimate (a priori probability), frequencies of final diagnoses were taken. Using categorisations for cell differentials, a posteriori probabilities were then derived for each disease, according to Bayes. The analysis was performed in three of five groups of diagnoses suspected prior to BAL: interstitial lung disease (ILD; n=710), inflammatory disease (n=583), or lung tumour mimicking ILD (n=455). Overall, out of 1,971 patients, 18.3% had sarcoidosis, 7.7% usual interstitial pneumonia (UIP), 4.4% extrinsic allergic alveolitis (EAA), and 19.0% tumours. In the group with suspected ILD, the likelihood for sarcoidosis increased from 33.7 to 68.1% when lymphocyte numbers were 30-50% and granulocyte numbers were low; the likelihood for UIP increased from 15.8 to 33.3% when lymphocyte numbers were <30% with granulocytes elevated. CD4/CD8 was informative, especially in sarcoidosis and EAA. Despite considerable increases, the likelihood of rare diseases rarely reached appreciable values. Similar results were obtained in the other two groups of suspected diagnoses. In conclusion, these data suggest that bronchoalveolar lavage cell counts per se provide substantial diagnostic information only in relatively frequent diseases, such as sarcoidosis and usual interstitial pneumonia, and are less helpful in infrequent diseases.

Analysis of Variance↗
PubMed2004

Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD.

The aim of this study was to test the hypothesis that use of tiotropium, a new long-acting anticholinergic bronchodilator, would be associated with sustained reduction in lung hyperinflation and, thereby, would improve exertional dyspnoea and exercise performance in patients with chronic obstructive pulmonary disease. A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 187 patients (forced expiratory volume in one second 44 +/- 13% pred): 96 patients received 18 microg tiotropium and 91 patients received placebo once daily for 42 days. Spirometry, plethysmographic lung volumes, cycle exercise endurance and exertional dyspnoea intensity at 75% of each patient's maximal work capacity were compared. On day 42, the use of tiotropium was associated with the following effects at pre-dose and post-dose measurements as compared to placebo: vital capacity and inspiratory capacity (IC) increased, with inverse decreases in residual volume and functional residual capacity. Tiotropium increased post-dose exercise endurance time by 105 +/- 40 s (21%) as compared to placebo on day 42. At a standardised time near end-exercise (isotime), IC, tidal volume and minute ventilation all increased, whilst dyspnoea decreased by 0.9 +/- 0.3 Borg scale units. In conclusion, the use of tiotropium was associated with sustained reductions of lung hyperinflation at rest and during exercise. Resultant increases in inspiratory capacity permitted greater expansion of tidal volume and contributed to improvements in both exertional dyspnoea and exercise endurance.

Aged↗
PubMed2004

Effect of freezing of sputum samples on flow cytometric analysis of lymphocyte subsets.

Sputum samples should be processed shortly after induction to prevent cell degradation. For intermediate storage, freezing of homogenised samples or immediate fixation have been shown to be suitable for cytospins. The aim of this study was to investigate whether freezing or immediate fixation of sputum affect the analysis of lymphocyte subsets by flow cytometry. Selected plugs from 24 sputum samples were homogenised. One aliquot was processed immediately and analysed by flow cytometry. A second aliquot was homogenised, frozen at -20 C after addition of dimethylsulfoxide and stored for a median time of 6 days. In six samples a third aliquot was fixed in formalin after induction and stored for up to 72 h before further processing. Compared to immediate processing, percentages of total lymphocytes and T-suppressor cells were elevated after being frozen, with a minor decrease in the T4/T8 ratio. Proportions of total lymphocytes, T-helper and T-suppressor cells correlated between native and frozen samples, intra-class correlation coefficients being 0.74, 0.85 and 0.70, respectively. The formalin-fixed aliquots could not be analysed with the antibodies used. In conclusion, freezing seems to be a suitable technique to store sputum samples for flow cytometry of CD3, CD4 and CD8 lymphocyte subsets. Its effects were minor compared to the variation between subjects.

Adult↗
PubMed2004

Lung fibroblasts from patients with emphysema show a reduced proliferation rate in culture.

Emphysema is characterised by a loss of alveolar structure, as reflected in elastic recoil and gas exchange. As fibroblasts play a key role in the maintenance of structure, the current authors hypothesised that their proliferation might be constitutively impaired in lung emphysema. Using explant cultures, lung fibroblasts were obtained from resected lungs of 10 patients with emphysema (median forced expiratory volume in one second (FEV1) 40% predicted) and 10 control patients (FEV1, 95% pred). The doubling time (DT) was measured over 4 days under standard conditions (10% foetal calf serum) prior and after cryopreservation. Additionally, in seven samples per group the total population doubling level (PDL) was determined. In emphysema, mean+/-sem DT was 33.6+/-2.8 h compared with 24.8+/-1.4 h in controls. The differences in DT were preserved after cryopreservation. Groups also differed in the initial slope of the PDL plot during long-term culture (up to 35 days). However, the median (range) maximum PDL did not differ significantly between groups (13.8 (7.4-22.6) versus 20.2 (11.2-25.5)). The current authors, therefore, suggest that the reduced proliferation rate in vitro of lung fibroblasts from patients with emphysema reflects a persistent, intrinsic failure of cellular replacement and maintenance in this disease, possibly in relation to pre-term aging.

Aged↗
PubMed2003

Reproducibility of forced inspiratory and expiratory volumes after bronchodilation in patients with COPD or asthma.

The aim of the present study was to assess the reproducibility of changes in forced inspiratory volumes after bronchodilator inhalation. Thirteen patients with chronic obstructive pulmonary disease (COPD) (FEV1, 32-75%pred) and 10 patients with asthma (FEV1, 43-75%pred) inhaled either 200 microg fenoterol or 200 microg oxitropium bromide or placebo, each of them on three occasions, on nine different days in a randomised, cross-over, double-blind fashion. Forced expiratory (FEV1) and inspiratory (FIV1) volumes were measured before and 30 min after inhalation. In patients with COPD, the increase in FEV1 (coefficient of variation) was 221 ml (43%) after fenoterol and 235 ml (33%) after oxitropium; changes in FIV1 were 301 ml (45%) and 360 ml (29%). In patients with asthma, FEV1 improved by 618 ml (26%) and 482 ml (25%), FIV1 by 553 ml (41%) and 475 ml (23%). In less severe COPD or asthma, the reduction in dyspnoea was associated with the improvements in both FIV1 and FEV1, but in severe COPD with the improvement in FIV1 only. The data demonstrate that, at least in terms of relative changes, the reproducibility of bronchodilator responses in terms of FIV1 is similar to that of FEV1 and they underline the assertion of FIV1 being a sensible parameter particularly in severe COPD.

Adrenergic beta-Agonists↗