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Biomedical subjects

H Matthys

Publications and source records attributed to H Matthys.

At least 55 records · Page 3Linked to original sources
PubMed1998

Efficacy of chlorofluorocarbon-free beclomethasone dipropionate 400 micrograms day-1 delivered as an extrafine aerosol in adults with moderate asthma.

Beclomethasone dipropionate (BDP) has been reformulated in a chlorofluorocarbon-free propellant, hydrofluoroalkane-134a (HFA), resulting in an extrafine aerosol which gives improved drug delivery to the airways. The objective of this 6 week, placebo-controlled study was to evaluate the clinical efficacy of HFA-BDP 400 micrograms day-1 in 256 adult patients with moderate asthma. This is a lower daily dose than that recommended for existing BDP inhalers in current treatment guidelines for moderate asthma (NIH publication 95-3659). Another objective was to evaluate whether delivering the 400 micrograms dose as four actuations of 50 micrograms twice daily (HFA-BDP 50 micrograms) provided equivalent asthma control to delivering the dose as two actuations of 100 micrograms twice daily (HFA-BDP 100 micrograms) without the use of a spacer or holding chamber. Both active treatments produced a significant change from baseline in morning peak expiratory flow (PEF), which was significantly larger than that in the placebo group (P < or = 0.017) throughout the study. The mean changes from baseline in morning PEF at weeks 5-6 were 47.0 l min-1 in the combined HFA-BDP group and 16.5 l min-1 in the HFA-placebo group. The two dose strengths were statistically equivalent (P = 0.017 for equivalence testing). The active treatments also produced significant improvements compared with placebo in evening PEF, forced expiratory volume in the first second, forced expiratory flow over 25-75% of vital capacity, sleep disturbance scores and daily beta-agonist use. The study medication was well tolerated, with a low incidence of adverse events. The results from this study demonstrate that a daily dose of 400 micrograms HFA-BDP (given in 50 micrograms and 100 micrograms strengths) provides dose proportionality and effective control in patients with moderate asthma.

Administration, Inhalation↗
PubMed1998

Effects of TGF-beta on eosinophil chemotaxis.

Transforming growth factor-beta (TGF-beta), which can decrease the effects of interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) on eosinophil viability, has been shown to be chemotactic for neutrophils. However, there is little information on its effects on eosinophil chemotaxis. Because TGF-beta has recently been found in increased concentrations in asthmatic sputum, we investigated whether TGF-beta could influence eosinophil migration and eosinophil viability. Purified eosinophils from normal donors were incubated with increasing concentrations of TGF-beta. Chemotaxis was measured with a modified Boyden chamber technique. In addition, eosinophils were incubated for 96 h with either IL-3, IL-5 or GM-CSF (1 ng/ml) together with increasing concentrations of TGF-beta. Eosinophil viability was then determined with propidium jodide and flow cytometry. Eosinophil chemotaxis was significantly increased in the presence of TGF-beta in concentrations between 10(-9) and 10(-4) microg/ml. The optimal concentration of TGF-beta in this assay was between 10(-9) and 10(-8) microg/ml. The chemotactic effect of TGF-beta diminished when higher as well as lower concentrations (between 10[-12] and 10[-3] microg/ml) were employed. In contrast, inhibition of eosinophil survival induced by IL-3, IL-5 and GM-CSF reached its maximum at concentrations of TGF-beta between 10(-4) and 10(-3) microg/ml. From these data we conclude that TGF-beta in low concentrations can induce eosinophil chemotaxis whereas higher concentrations reduce eosinophil survival mediated by IL-3, IL-5 and GM-CSF.

Cell Survival↗
PubMed1998

Inhibition of HLA-DR expression on activated human blood eosinophils by transforming growth factor-beta1.

Peripheral blood, bronchoalveolar lavage and sputum eosinophils of patients with asthma but not peripheral blood eosinophils from normal controls have been shown to express human leucocyte antigen (HLA)-DR on their cell surface. Cytokines implicated in the activation of eosinophils, such as interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), can up-regulate HLA-DR expression. However, little is known about antagonistic factors that might down-regulate HLA-DR expression on eosinophils. In this study we investigated whether transforming growth factor-beta (TGF-beta), which has been shown to reduce survival of activated eosinophils, can also modulate HLA-DR expression on eosinophils. For this purpose, isolated peripheral blood eosinophils were stimulated with IL-3 and GM-CSF for 24 h and HLA-DR expression was measured by flow cytometry. We found that while isolated eosinophils expressed low levels of surface HLA-DR, incubation with GM-CSF and IL-3 increased HLA-DR expression on eosinophils. TGF-beta alone did not change HLA-DR expression on isolated eosinophils. However, co-incubation of eosinophils with TGF-beta and either GM-CSF or IL-3 significantly decreased HLA-DR expression compared to eosinophils incubated with either GM-CSF or IL-3 alone and this was not reversed by addition of IL-5. This effect of TGF-beta on IL-3-induced HLA-DR expression was attenuated dose-dependently in the presence of monoclonal anti-TGF-beta antibodies. Our results suggest that TGF-beta can reduce cytokine-induced HLA-DR expression on eosinophils and could thus influence eosinophil activation.

Cells, Cultured↗
PubMed1998

CD14 expression and soluble CD14 after segmental allergen provocation in atopic asthma.

Allergic asthma is associated with the recruitment of activated inflammatory cells after allergen challenge. Surface expression of CD14 has been proposed as a marker of cell activation and differentiation. We therefore measured CD14 expression on activated macrophages and granulocytes as well as soluble CD14 (sCD14) concentrations in peripheral blood and bronchoalveolar lavage (BAL) following segmental allergen provocation (SAP) with individually standardized doses of allergen in eight patients with allergic asthma. Two segments of the right lung were challenged with allergen. Two segments of the left lung, into which saline was instilled, served as controls. CD14 expression on macrophages and granulocytes was determined by flow-cytometry and concentrations of interleukins and sCD14 were analysed by enzyme-linked immunosorbent assay (ELISA) 10 min and 18 h after challenge. Soluble CD14 concentrations remained unchanged in BAL fluid after saline challenge and 10 min after SAP, but increased significantly 18 h after SAP. Although macrophage numbers increased 18h after SAP, CD14 expression on these cells did not change. Unlike macrophages, granulocyte numbers correlated with sCD14 levels 18 h after SAP while their CD14 expression decreased significantly. Furthermore, sCD14 correlated with interleukin (IL)-13 concentrations 18 h after SAP. An increase in soluble CD14 can be observed 18 h but not 10 min after segmental allergen provocation suggesting local release of this surface antigen. Our findings imply that CD14-mediated cell activation following segmental allergen provocation could play a role in asthmatic inflammation.

Adult↗
PubMed1997

[Noninvasive ventilation in respiratory insufficiency. Indications--methods--limits].

Non-invasive ventilation (NIV) supports alveolar ventilation and represents an alternative to conventional invasive mechanical ventilation in suitable cases of respiratory failure. It usually takes the form of positive airway pressure ventilation, either continuous (CPAP) or bilevel positive airway pressure (BiPAP), applied via a nasal or face mask. NIV is capable of increasing arterial oxygen saturation and lowering pCO2. Initial controlled studies involving patients with severe COLD have shown that, in comparison with conventional invasive ventilation, NIV significantly reduces morbidity, mortality and the duration of hospitalisation. It has also been used successfully to treat respiratory failure due to other pulmonary disorders, neuromuscular diseases, during weaning from invasive ventilation, and as "bridging" therapy in patients awaiting lung transplantation. However, further studies on indications and technique are needed to define more clearly the role of NIV in the clinical setting. For the time being, therefore, NIV should be considered to be experimental, and conventional mechanical ventilation should always be available on standby.

Humans↗
PubMed1997

Pleural disease in patients with AIDS.

Patients infected with HIV are at risk of developing a variety of infectious and malignant pleuropulmonary disorders. The three most common causes of AIDS-related pleural effusions are parapneumonic effusions or empyemas, tuberculosis, and Kaposi's sarcoma. However, the relative frequency of these conditions varies from series to series as well as from one region of the world to another. Pneumocystis carinii is a common pulmonary pathogen in AIDS, but it is rarely the cause of a pleural effusion. By contrast, P. carinii infection is strongly associated with the occurrence of spontaneous pneumothoraces. Pleural complications in AIDS are often difficult to treat and contribute significantly to the high morbidity and mortality of the syndrome. Recent progress in antiretroviral therapy as well as improved supportive care should lead to better survival rates in AIDS in the near future. Unfortunately, this progress may be associated with a growing number of patients with AIDS-related diseases, including the pleural complications discussed here.

AIDS-Related Opportunistic Infections↗
PubMed1997

[Sleep and respiration at an altitude of 6,400 m (Aconcagua, Argentina].

UNLABELLED: Persons at extreme altitudes are known to experience disturbances in the regulation of ventilation and sleep structure. However, except for simulated studies using the decompression chamber, only single events of sleep or ventilation were measured so far in field studies up to an altitude of 5800 m. Modifying a portable sleep lab (Vitalog HMS 5000), we were able to conduct 7 channel polygraphy on our ascent to the Aconcagua up to an altitude of 6400 m. METHODS: In 6 climbers (age 38-62 y, 1 f, 6 m), ECG, EOG, SaO2, chest and abdominal movements, breathing and snoring sounds, body position, nasal and oral airflow were measured 4 weeks prior to the expedition at an altitude of 500 m, at base camp (4200 m) and in 3 climbers at 6400 m (2nd base camp) at the Aconcagua mountain. All participants had a repeat study at 500 m altitude 4 weeks after the expedition. RESULTS: The total number of obstructive apnoeas and hypopnoeas (OA/H) at night increased at an altitude of 4200 m in the mean of all 6 climbers from 36 to 67.7 compared to 500 m altitude, Central Apneas and Cheyne stokes (CA/CS) increased from 6.7 to 45.2. At 6400 m altitude the OA/H fell to 3 and 4 respectively in 2 climbers and CA to 1 and 2 respectively. In one climber, suffering from recurrent snoring with oxygen desaturation at 500 m altitude level, the number of OA/H and CA/CS increased further to 201 and 322, respectively, at 6400 m. Total sleep time including the REM position increased in all 6 climbers by 10% at base camp in comparison to an altitude of 500 m. Whereas the total sleep time remained constant in the 3 climbers at 6400 m altitude, the REM position declined by 10% in comparison to base camp (4200 m). However, significant fluctuations between individuals were noticed. CONCLUSION: Although significant alterations in sleep and breathing are noticeable at altitudes above 300 m, the respiratory drive in healthy subjects provides for a regular ventilation at high frequency at the extreme altitude above 6000 m. Sleep-related breathing disturbances at low altitude appear to be amplified at high altitudes.

Adult↗
PubMed1997

[Physical training of patients with sleep apnea].

PURPOSE: It is a common question of sleep apnoea patients in the sleep lab whether they stand a chance to decrease the symptoms and severity of their disease by physical exercise. As far as we know, there is no data about this specific question until now, even though this has been subject to speculation. A few studies, however, report on an improvement of the respiratory drive (and chemoreceptor sensitivity) after physical exercise in athletes. The aim of this study was to prove whether physical exercise in sleep apnoea patients could improve the symptoms of their disease in an open trial. METHODS: 11 Patients with mild to severe sleep apnoea syndrome (1 f, 10 m, mean age 53.8x) took part in a 6-month period of physical exercise twice a week 2 h each time under the instructions of physical therapists. Before and after the 6mo period a full PSG without CPAP or BIPAP, a bicycle exercise test with lactate profile, echocardiography, blood test, and body weight and body height measurement was performed. Statistical analysis was done using Wilcoxon ranked test and multiple regression analysis. RESULTS: There was no significant bodyweight reduction in all patients after the 6mo period of physical training, no significant difference in either basal SaO2 nor mean SaO2 and no significant improvement in physical status by the p at 4 mmol lactate on the lactate profile. Echocardiographic changes were not found; there was no significant change in the blood pressure profiles during the bicycle test. No cardiopulmonary problems including exercise-induced high blood pressure were reported during the training period. There was, however, a significant decrease of the RDI (p < 0.05), but no significant change in the REM-sleep % of total sleep time (TST) and the TST itself. CONCLUSIONS: There was an improvement of the sleep apnoea syndrome correlated to a decrease of the RDI in the studied patient population due to a possible increase in the respiratory drive or a stabilised muscle tone ine the upper airways after physical exercise, as reported by other authors, because weight reduction could not be the reason in our patients. Our trial showed that the exercise does not increase the severity of symptoms of sleep apnoea by changing the REM/non REM ratio or for any other reasons. A physical training programme for sleep apnoea patients as an additional treatment should therefore be considered.

Adult↗
PubMed1997

[Technical differences in various CPAP and BiLevel CPAP devices].

PURPOSE: Since the first presentations of CPAP by Sullivan 1983 und BiPAP by Sanders 1990 as a successful treatment in obstructive sleep apnoea syndrome, many CPAP and BiLevel-CPAP devices have been developed by several companies around the world. Although all devices work on the same principle of continuous positive airway pressure delivered through nasal or facemasks, there are, however, significant technical differences between these devices, mainly due to different size and different maximum speed of the turbines. As far as we know, the only study concerning this technical difference in the devices was conducted by Raschke in 1995, who found significant differences in the pressure stability of the devices using a very complicated measurement model on volunteers who were breathing on the different devices. We intended to study the technical differences of the devices using a more simple technique in static conditions, but with very exact measurement. METHODS: We measured pressure stability on different inspiration flows and different pressure levels of 8 CPAP's and 4 BiLevel-CPAP's under static conditions using the "Höntzsch Exact ASD-G Messrohr ms 20201-18" flow-measurement device and the "Thommen HM 18.0020.A" pressure-measurement devixe. We measured the noise emission by these devices at different frequency levels using the "Brüel and Kjer Dual Channel Real Time Frequency Analyzer", and measured the speed to reach the adjusted pressure level with the "Multimeter Phillips PM 2518X" and "Oszillograph Phillips PM3350" using the voltage change due to different working of the electric engines at different turbine speeds. We also investigated the different construction of the devices by opening them and analysing the materials used in the devices. RESULTS: The real pressure levels at an adjusted pressure of 10 mbar and at an inspiration flow of 1 Liter/sec range from 8.7 mbar to 15.6 mbar in CPAP's and from 9 mbar to 9.7 mbar in BiLevel devices. At higher inspiration flows the differences are larger, at lower flows smaller. The maximum noise emission in the 10 Hhz spectrum at a distance of 100 cm from the device at an adjusted pressure level of 10 mbar ranged from 29.6 dB to 39.9 dB in CPAP's and 30.4 dB to 42.2 dB in BiLevel-CPAP's. The time to reach an adjusted pressure level of 10 mbar after closing the airway of the device ranged from 0.26 to 0.66 sec in CPAP's and from 0.46 to 0.80 sec in BiLevel devices. CONCLUSION: There are significant technical differences in the different CPAP and BiLevel devices due to different construction of the turbines and electrical engines of these devices. This should be considered when prescribing a device for a sleep apnoea patient. Not every device is suitable for every patient, and quality differences should be considered by all persons involved in the production and prescribing process.

Airway Resistance↗
PubMed1997

Holding chambers for pMDI use.

Spacer devices for pressurized metered-dose inhalers (pMDI) are needed to slow down the aerosol jet and hence to reduce oropharyngeal deposition as well as to overcome coordination problems. A new spacer, JET (Chiesi, Italy), which is less cumbersome to carry, was tested on five healthy volunteers. They inhaled with a slow inspiratory vital capacity maneuver 2 x 100 micrograms doses of the beta 2-agonist salbutamol, labelled with 99mTc, via a pMDI (Butovent, Chiesi) with and without the new JET spacer. The percentage of total delivered activity to the lungs increased with the JET from 14.3 +/- 4.5% to 22.3 +/- 4.1%, while the extrapulmonary deposition (oropharynx and stomach) was reduced from 39.8 +/- 12.2% to 11.0 +/- 3.4%. These results show that the optimal application of the JET can improve therapeutic efficacy by reducing extrapulmonary drug deposition while increasing the drug delivery to the lungs. Use of holding chambers as reservoirs should be avoided as well as frequent cleaning of the spacer.

Administration, Inhalation↗
PubMed1996

Activation of human eosinophils by IL-13. Induction of CD69 surface antigen, its relationship to messenger RNA expression, and promotion of cellular viability.

To study the effect of IL-13 on CD69 expression and cell viability in human eosinophils, purified human peripheral blood eosinophils from healthy donors were incubated with increasing concentrations of IL-13. The expression of CD69 was analyzed by flow cytometry (FACS). Surface expression of CD69, which was absent on untreated eosinophils, was induced by IL-13 at concentrations ranging from 1 ng/ml to 1 microgram/ml in a concentration-dependent manner. In contrast, neutrophils expressed CD69 neither spontaneously nor following incubation with IL-13. Semiquantitative reverse transcription-PCR for CD69 mRNA showed constitutive CD69 mRNA expression in purified human eosinophils. Incubation of eosinophils with IL-13 further increased CD69-specific mRNA. Analysis of intracellularly stored CD69 in eosinophils permeabilized with saponin revealed intracellular binding of anti-CD69 Abs in all isolated eosinophils. After stimulation with 100 ng/ml IL-13 for 24 h, the concentration of intracellular CD69 decreased by 41 +/- 9%. Furthermore, IL-13 at a concentration of 100 ng/ml enhanced eosinophil viability, as assessed by propidium iodide staining after 4 days in culture from 8.6 +/- 5.5% in control medium to 50.7 +/- 6.8% following stimulation with IL-13 treatment. The effect of Il-13 on eosinophil viability as well as that on CD69 expression were both neutralized by anti-IL-13 Abs. In conclusion, our results demonstrate that IL-13 specifically activates human eosinophils, as determined by the expression of CD69 cell surface protein and mRNA expression. Furthermore, IL-13 significantly prolongs eosinophil survival in vitro. The data suggest that IL-13 may play a role in the activation of eosinophils.

Antigens, CD↗
PubMed1996

Prostacyclin modulates granulocyte/macrophage colony-stimulating factor release by human blood mononuclear cells.

Although production and immunological activity of granulocyte-macrophage colony stimulating factor (GM-CSF) have been implicated in the pathogenesis of various disorders, little has been reported concerning the factors involved in the regulation of GM-CSF release. Therefore, we examined the effect of the stable prostacyclin agonist, cicaprost, on the in vitro production of GM-CSF by peripheral blood mononuclear cells (PBMC) obtained from normal subjects by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR). Incubation of PBMC (10(6) cells/ml1) with the bacterial lipopolysaccharide (LPS; 0.1 microgram/ml) for 24 h caused a more than 10-fold concentration-dependent increase of GM-CSF release (401 +/- 58 pg/ml x 10(6) cells-1). Addition of cicaprost (0.01 ng/ml to 1 microgram/ml) resulted in a concentration- and time-dependent reduction of LPS-induced GM-CSF secretion by PBMC with a mean IC50 of 6.7 ng/ml (n = 9). Furthermore, cicaprost also inhibited the LPS-elicited expression of GM-CSF mRNA, as determined by RT-PCR. These results demonstrate that prostacyclin inhibits LPS-induced GM-CSF release and that its effects are related to the level of transcription. Hence, our data suggest that cicaprost or related PGI2 agonists may represent immunomodulators of mononuclear cell function and may offer a therapeutic approach to GM-CSF-mediated inflammatory disorders.

Epoprostenol↗
PubMed1996

Chlorofluorocarbon-free aerosol therapy in patients with pulmonary airflow obstruction.

Following the recognition that the chlorofluorocarbon (CFC) propellants used in all earlier pressurized metered dose inhalers (pMDIs) damage the Earth's protective ozone layer in the stratosphere, alternative aerosol applicators have become mandatory. Therefore it is clear that prescribers have to move away from CFC-containing pMDIs. Today the ozone hole over the South Pole reaches about the size of Europe. This means for the physician to prescribe aerosol therapy completely free of CFCs, e.g. by DPIs and nebulizers or CFC-free pMDIs.

Aerosols↗
PubMed1996

Endobronchial secretion of interleukin-13 following local allergen challenge in atopic asthma: relationship to interleukin-4 and eosinophil counts.

We investigated the secretion of interleukin (IL)-13 into the airways in 10 mild allergic asthmatics by employing local allergen challenge, and compared the data both to IL-4 levels and eosinophil numbers obtained by bronchoalveolar lavage (BAL). Appropriate allergen or saline were endoscopically instilled into different airway segments, which were lavaged 10 min and 18 h after allergen or sham challenge. IL-4 and IL-13 were measured in unconcentrated BAL fluid using a double sandwich enzymes-linked immunosorbent assay (ELISA). Endobronchial allergen challenge induced a highly significant increase in the numbers of eosinophils after 18 h in the allergen exposed segment. Ten minutes following allergen exposure, low levels of IL-4 and IL-13 could be detected, whilst concentrations of both cytokines were significantly raised 18 h following local allergen exposure. In contrast to IL-4, the concentration of IL-13 strongly correlated with the eosinophil numbers found 18 h post-allergen challenge. The results suggest that interleukin-13 is actively secreted during the late asthmatic response in mild asthmatic subjects. In view of its action on eosinophils and other cell types, we conclude that interleukin-13, in addition to interleukin-4, may play an important role in the pathogenesis of eosinophil-related inflammation, such as bronchial asthma.

Adult↗