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Biomedical subjects

E Derom

Publications and source records attributed to E Derom.

At least 19 recordsLinked to original sources
PubMed2005

Assessment of progression of COPD: report of a workshop held in Leuven, 11-12 March 2004.

Recently performed long term trials have enhanced the insight into the assessment of progression of COPD. The present review focuses on the initial assessment of COPD in general practice and the assessment of disease progression. Several variables may be used to assess this progression, all of which are associated with significant methodological problems. Finding the appropriate mix of outcome measures to capture all aspects of disease progression is a significant challenge.

Belgium↗
PubMed2003

Tiotropium bromide: a long-acting anticholinergic bronchodilator for the treatment of patients with chronic obstructive pulmonary disease.

Prevention and relief of symptoms by regular use of bronchodilators is central to the management of patients with chronic obstructive pulmonary disease (COPD). The bronchodilators in use are beta2-agonists, anticholinergics and theophylline. Since the 1970s the anticholinergic ipratropium bromide has been widely used for the treatment of patients with regular symptoms, but because it has a relatively short duration of action, it needs to be administered four times a day. Tiotropium bromide is a long-acting anticholinergic suitable for once daily administration. It has been developed as a dry powder inhaler for the treatment of patients with COPD. Large clinical trials with administration of the drug for one year have now been published. Compared with placebo and ipratopium bromide, significant and long-lasting bronchodilatation was observed, which was maintained over the year. The bronchodilator effect of tiotropium bromide was accompanied by improvements in other health outcomes. A significant decrease in dyspnoea, improvement in health-related quality of life, and a reduction in the number of COPD exacerbations and hospitalisations were noted. In this review we summarise the clinical development of this compound.

Bronchodilator Agents↗
PubMed2001

Lung deposition and protective effect of terbutaline delivered from pressurized metered-dose inhalers and the Turbuhaler in asthmatic individuals.

We investigated the relationship between pulmonary deposition of terbutaline and bronchoprotection against methacholine and histamine with the Turbuhaler (AstraZeneca, Lund, Sweden) and a pressurized metered dose inhaler (pMDI) in 13 asthmatic patients. The study was done with a randomized, double blind, double dummy, and crossover design. On different days, the provocative concentration of histamine causing a 20% decrease in FEV(1) (PC(20) histamine) and PC(20) methacholine were determined before and at 1.5, 3, and 6 h after inhalation of 0.25 or 0.5 mg of terbutaline sulfate. The Turbuhaler delivered significantly more drug than did the pMDI (% of the nominal metered dose and 95% confidence interval): 20.8% (16.4 to 26.6%) and 16.9% (13.2 to 21.7%) versus 4.8% (3.8 to 6.1%) and 7.4% (5.8 to 9.5%), respectively. Average protection against histamine over 6 h was 0.66 (95% CI: 0.45 to 0.87) doubling concentrations (DC) after inhalation of 0.25 mg and 1.08 (95% CI: 0.87 to 1.29) DC after 0.5 mg terbutaline via pMDI, and 1.07 (95% CI: 0.87 to 1.29) DC after 0.25 mg and 1.24 (95% CI: 1.03 to 1.45) DC after 0.50 mg via Turbuhaler. Protection against methacholine was also dose- and device-dependent. The dose needed to obtain the same pulmonary deposition with the pMDI was 3.14 times greater than with the Turbuhaler, and that needed for the same protective effect was 2.1 and 3.2 times greater for histamine and methacholine, respectively. We conclude that pulmonary deposition of terbutaline was predictive of the clinical response.

Adult↗
PubMed2000

Variability in lung deposition of inhaled drug, within and between asthmatic patients, with a pMDI and a dry powder inhaler, Turbuhaler.

In vitro analysis of inhaled formulations measures, among other parameters, the variability in delivered dose, while a corresponding in vivo analysis also includes the variability caused by patient performance and distribution of drug between the oropharynx and the lungs. In vitro, the dose variability is higher for Turbuhaler(R) than for the corresponding pMDI, whereas in vivo, the converse is true: the variability in lung deposition is significantly higher, both between and within subjects, for pMDI than for Turbuhaler. The observation can be due to several factors such as the non-continuous working principle of inhalation via pMDI as opposed to the continuous working principle of inhalation via Turbuhaler.

Administration, Inhalation↗
PubMed1999

Systemic effects of inhaled fluticasone propionate and budesonide in adult patients with asthma.

We assessed the systemic effects of budesonide (BUD) and fluticasone propionate (FP) in 23 patients with asthma, using a double-blind, placebo-controlled, double-dummy, and cross-over design. The following five treatments were given in a randomized order for 1 wk with a washout period in between of 2 wk: (1) placebo; (2) FP, 200 micrograms twice a day, inhaled from a Diskhaler; (3) FP, 1,000 micrograms twice a day, inhaled from a Diskhaler; (4) BUD, 200 micrograms twice a day, inhaled from a Turbuhaler; and (5) BUD, 800 micrograms twice a day, inhaled from a Turbuhaler. The primary variable was the area under the curve of serum cortisol versus time (AUC0-20), derived from serum samples taken every 2 h over a 20-h period following the last evening dose at 10:00 P.M. The lower doses of BUD and FLU did not cause any adrenal suppression. Compared with placebo, however, FP (1, 000 micrograms, twice daily and BUD (800 micrograms, twice daily) decreased the AUC0-20 by 34 and 16%, respectively. Fluticasone (1,000 micrograms, twice daily) was more suppressive than BUD (800 micrograms, twice daily) (p = 0.0006). The FEV1, measured the morning after the last inhalation, was significantly higher after the active treatments, compared with placebo (p < 0.02), but did not differ between all active treatments. We conclude that high doses of BUD and FP (in particular the latter), inhaled via their respective dry powder inhalers for 1 wk, result in a measurable systemic activity in patients with asthma.

Administration, Inhalation↗
PubMed1998

Onset and duration of action of single doses of formoterol inhaled via Turbuhaler.

The aim of the study was to investigate the time of onset and the duration of the bronchodilating effect of different doses of formoterol administered via Turbuhaler in patients with moderate asthma. Thirty-one patients (five women) with a mean forced expiratory volume in 1 s (FEV1) of 1.97 +/- 0.54 1 and a mean reversibility of 31 +/- 14% of baseline were included in this double-blind, randomized, placebo-controlled and cross-over study. The patients inhaled single doses of placebo, i.e. 6, 12, 24, or 48 micrograms formoterol fumarate, on 5 separate days. Serial measurements of specific airways conductance (SGAW) and FEV1 were performed at regular time intervals for 12 h. The majority of the patients had at least a 50% increase in SGAW within 1-4 min after administration of all active treatments. The maximum increase in FEV1 over placebo was dose-dependent: 12% (6 micrograms), 18% (12 micrograms), 19% (24 micrograms), and 26% (48 micrograms) (P < 0.001). Twelve hours after administration of 6, 12, 24, and 48 micrograms formoterol, the mean increase in FEV1 was still 7%, 15%, 18%, and 27%, respectively, above the value following placebo. Headache was the most frequently reported adverse event in all treatments including placebo. After inhalation of 48 micrograms, three patients experienced mild tremor lasting for less than 1 h; likewise, one patient experienced the same event for 3 h after placebo. Formoterol administered via Turbuhaler10 gave a rapid and dose-related bronchodilating effect lasting for 12 h and was well tolerated.

Adolescent↗
PubMed1998

Neck and abdominal muscle activity in patients with severe thoracic scoliosis.

Patients with severe chronic obstructive pulmonary disease (COPD) do not use the sternocleidomastoid muscles when breathing at rest, but have a greater than normal neural drive to the rib-cage inspiratory muscles, the abdominal muscles, and the diaphragm. Yet the increased activation of the abdominal muscles and diaphragm in such patients has only limited mechanical effects, and this has led to the suggestion that the overall increase in neural drive is simply an automatic response of the respiratory system to a greater than resting stimulation. To test this hypothesis, we examined the pattern of respiratory-muscle activation in eight patients with severe thoracic scoliosis (Cobb angle between 100 degrees and 136 degrees). We recorded electromyograms of the sternocleidomastoid, scalene, rectus abdominis, external oblique, and transversus abdominis muscles; esophageal (Pes) and gastric (Pga) pressures; and the anteroposterior (AP) diameter of the abdomen during resting breathing in the seated posture. All patients had invariable phasic inspiratory activity in the scalenes; and five patients had invariable phasic expiratory activity in the transversus; intermittent expiratory activity in the transversus was also recorded in three patients. In contrast, only one patient had invariable phasic inspiratory activity in the sternocleidomastoid, and only one patient had invariable phasic expiratory activity in the external oblique. The decrease in abdominal AP diameter during expiration was commonly associated with a rise in Pga. These observations therefore indicate that the pattern of respiratory-muscle activation in patients with severe thoracic scoliosis is essentially similar to that seen in patients with severe COPD. This supports the concept that the order of recruitment of the respiratory muscles during breathing is an automatic response of the central controller.

Abdominal Muscles↗
PubMed1997

Broxaterol increases force output of fatigued canine diaphragm more than salbutamol.

We previously demonstrated that broxaterol enhanced recovery of fatigued canine diaphragm. The aim of this study was to compare the inotropic effects of salbutamol and broxaterol on fatigued canine diaphragm. Low-frequency fatigue was induced in 14 mongrel dogs by electrophrenic stimulation, which was continued until transdiaphragmatic pressure (Pdi) at 20 Hz was reduced by 50% or for 1 h. After stabilization of fatigue, the animals received a bolus (18.5 microg/kg) of either broxaterol or salbutamol, followed by a continuous infusion (0.43 microg/kg/min). A second bolus of 74.0 microg/kg, followed by a continuous infusion of 1.72 microg/kg/min, was given after 90 min. Both drugs significantly increased twitch Pdi. Twitch Pdi measured 90 min after the first and second doses of broxaterol increased by 28 +/- 23% and 42 +/- 34%, respectively, whereas the salbutamol-induced increase was clearly smaller (9 +/- 10% and 17 +/- 15%, respectively). Broxaterol increased Pdi at 20 Hz by 25 +/- 28% with the first dose and by 29 +/- 21% with the second dose. In contrast, salbutamol did not alter Pdi at 20 Hz. Neither drug affected Pdi at 100 Hz. We conclude that broxaterol promoted recovery of low-frequency fatigue of the canine diaphragm in vivo in a dose-dependent manner, whereas salbutamol only minimally improved force production by the fatigued diaphragm.

Adrenergic beta-Agonists↗
PubMed1996

The inhalation device influences lung deposition and bronchodilating effect of terbutaline.

The development of new inhalation devices for asthma drugs raises the issue of the relationship between pulmonary deposition and therapeutic effect of inhaled drugs in patients with obstructive lung diseases. We thus conducted a randomized, double-blind and double-dummy, four-period crossover study in 13 patients with moderate asthma (mean age 36 yr; FEV1 59% of predicted), who inhaled 0.25 and 0.5 mg terbutaline sulphate on separate occasions either via a pressurized metered dose inhaler (pMDI) or Turbuhaler (TBH). Pulmonary deposition was 8.1 +/- 2.7% and 8.3 +/- 2.3%, respectively, of the nominal dose for pMDI and 19.0 +/- 7.3%, and 22.0 +/- 8.1% for TBH. The FEV1 increase after 0.25 mg terbutaline sulphate via TBH was significantly greater than after 0.25 mg via pMDI. No significant differences in FEV1 increase were observed between 0.25 mg via TBH, 0.5 mg via pMDI, or 0.5 mg via TBH. Other lung function variables showed similar dose- and device-related changes. We concluded that: (1) the dose of terbutaline sulphate deposited in the lungs is dependent on which inhalation system is used; (2) TBH delivers about twice the amount of drug to the lungs as the pMDI; and (3) the observed difference in deposition is reflected in the bronchodilating effect.

Administration, Inhalation↗
PubMed1995

Theophylline increases oxygen consumption during inspiratory resistive loading.

The effect of theophylline on diaphragmatic blood flow (Qdi) and oxygen consumption (VO2di) was studied in eight lightly anesthetized dogs during quiet breathing and inspiratory resistive loading. Qdi was determined with the radioactive microsphere tracer technique, and VO2di was calculated as the product of Qdi and the diaphragmatic arterio-venous oxygen difference. During quiet breathing, theophylline increased minute ventilation (9.3 +/- 1.7 versus 5.1 +/- 0.4 L/min), mean inspiratory flow (547 +/- 60 versus 378 +/- 56 ml/s), and duty cycle (0.270 +/- 0.042 versus 0.192 +/- 0.024) but did not significantly alter Qdi or VO2di. Conversely, Qdi increased significantly during loaded breathing compared with quiet breathing (37 +/- 4 versus 27 +/- 3 ml/100 g/min) and was further increased by theophylline (45 +/- 7 ml/100 g/min). Theophylline did not alter the tension-time index of the diaphragm (TTdi) during inspiratory resistive loading (0.054 +/- 0.006 versus 0.056 +/- 0.004, p NS) but resulted in a disproportionate and significant increase in VO2di (2.66 +/- 0.53 versus 1.78 +/- 0.26 ml/100 g/min). Similarly, total-body oxygen consumption (VO2TB) during inspiratory loading increased significantly after theophylline (24%), but the tension-time index of the inspiratory muscles (TTi), a measure of the total respiratory load, was unchanged. We conclude that theophylline significantly increases VO2di and VO2TB at the same TTdi and TTi during resistive loading. This enhanced energy expenditure needs consideration in the clinical management of pulmonary disorders that increase the work of breathing.

Animals↗
PubMed1994

Theophylline alters distribution of blood flow to respiratory muscles.

This study was designed to examine the effects of theophylline on respiratory muscle blood flow in 11 lightly anesthetized and spontaneously breathing dogs using the radioactive microsphere tracer technique. During quiet breathing, blood flow to the costal diaphragm (25.1 +/- 13.9 ml/100 g/min) exceeded blood flow to the parasternal intercostals (18.0 +/- 10.2 ml/100 g/min, p < 0.05). Inspiratory resistive loading abolished these differences by increasing blood flow to the parasternal intercostals more than to the diaphragm. Aminophylline (40 mg/kg) significantly increased minute ventilation and tidal transdiaphragmatic pressure (Pdi) swing during quiet breathing but not during inspiratory resistive loading. Theophylline did not affect diaphragmatic blood flow during inspiratory resistive loading while the same Pdi swing and tension-time index (TTdi) were reached. During quiet breathing, however, theophylline significantly (p < 0.05) increased blood flow to the triangularis sterni from 7.9 +/- 5.6 to 18.1 +/- 25.6 ml/100 g/min and to the transversus abdominis from 10.8 +/- 8.4 to 14.6 +/- 10.5 ml/100 g/min and tended to increase blood flow to the costal diaphragm and the parasternals. We conclude that (1) during quiet breathing, but not during inspiratory resistive loading, blood flow to the costal diaphragm exceeded flow to the parasternal intercostals; (2) during quiet breathing, theophylline increased blood flow to the expiratory muscles as it promoted recruitment of expiratory muscles; and (3) theophylline did not affect diaphragmatic blood flow for a given TTdi.

Airway Resistance↗
PubMed1993

Intrapleural quinacrine instillation for recurrent pneumothorax or persistent air leak.

From 1982 to 1990, 27 patients with recurrent pneumothorax or persistent air leak (28 episodes) underwent pleurodesis with intrapleural administration of quinacrine, according to a standardized scheme. A first evaluation was done about 1 month after the intervention. In August 1990, all patients were invited for a second check-up. In 4 patients quinacrine plasma concentrations were determined. There was one early failure. No late recurrences were observed. Neither serious nor late complications were seen with our low-dose regimen. Transient fever was the only constant side effect. In contrast to other chemicals proposed for pleurodesis, quinacrine did not cause major pain. Only very low quinacrine plasma concentrations (peak, < 10 ng/mL) were found. In conclusion, chemical pleurodesis with quinacrine can be considered a safe and effective treatment. The number of administrations as well as the dosage are important to prevent morbidity and recurrence.

Adult↗
PubMed1992

Effects of broxaterol and theophylline on fatigued canine diaphragm in vivo. A randomized, controlled study.

Since broxaterol, a new beta 2-agonist, has been shown to improve contractility of fatigued canine diaphragm in vitro, a controlled, randomized study was designed to assess its effects on fatigued canine diaphragm in vivo, and compare these to the expected inotropic effects of aminophylline. Diaphragm fatigue was induced in 21 dogs using electrophrenic stimulation at 20 Hz until transdiaphragmatic pressure (Pdi) at 20 Hz was reduced to about 50% of its original value. After stabilization of fatigue, animals were randomized in three groups. Aminophylline-treated animals received an intravenous bolus of 20 mg/kg, broxaterol-treated animals were given an initial bolus of 100 micrograms/kg, and control animals obtained an equal load of saline. After 3 h, aminophylline-treated animals and broxaterol-treated animals received a second dose of 20 mg/kg and 200 micrograms/kg, respectively, whereas control animals received a second dose of saline. Pdi was measured every 30 min for 6 h. At therapeutic serum levels, theophylline did not affect Pdi at any stimulation frequency compared with control conditions. In contrast, broxaterol administration resulted in a significant (p less than 0.05) and long-lasting increase in Pdi at low stimulation frequencies. Pdi at 20 Hz thus increased by 20 +/- 16% 90 min after the first bolus, and by 36 +/- 18% 90 min after the second dose. We conclude that (1) broxaterol promotes recovery of low-frequency fatigue in a dose-dependent way, and (2) theophylline does not improve the force output of fatigued canine diaphragm in vivo.

Adrenergic beta-Agonists↗
PubMed1991

Effects of aminophylline on respiratory muscle interaction.

We studied the effects of aminophylline on respiratory muscle interaction during quiet breathing by measuring (1) changes in rib cage and abdominal cross-sectional area, (2) tidal volume, (3) abdominal and esophageal pressure, (4) diaphragm and parasternal intercostal electromyogram (EMG) and parasternal intercostal intramuscular pressure, and (5) triangularis sternl and transversus abdominis EMG, in 14 supine anesthetized dogs. Measurements were done before and 5 and 10 min after administration of progressively increasing doses of aminophylline, reaching a total dose of 5, 10, 20, 40, and 80 mg/kg. In 12 of 14 dogs after aminophylline administration, quiet inspiration became biphasic, or if inspiration was already biphasic under control conditions, the first phase was clearly enhanced after aminophylline administration. Biphasic inspiration was defined as an inspiratory pattern in which rib cage and abdominal expansion showed two distinct phases. First, the onset of inspiration was characterized by a sudden increase in rib cage cross-sectional area often associated with a decrease in abdominal dimensions. During this initial part the parasternals and the diaphragm were electrically silent, confirming that it was achieved by relaxation of expiratory muscles. Further inspiration occurred predominantly through expansion of the abdomen. In the first phase, a pressure drop in the parasternal intercostals was present, presumably due to passive shortening of these muscles caused by expiratory muscle relaxation. On the average, 42 +/- 28% of the rib cage expansion was due to expiratory muscle relaxation at a dose of 80 mg/kg versus 17 +/- 21% under control conditions (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline↗
PubMed1991

Effects of theophylline on canine diaphragmatic contractility and fatigue.

To distinguish the effects of theophylline on respiratory muscle contractility from alterations in respiratory muscle interaction or blood flow, we examined in vitro contractile properties and fatigue of canine diaphragm in two series of experiments. In the first series, a 40-mg/kg aminophylline infusion was given to dogs, and diaphragm strips were removed for in vitro study when stable tissue fixation of the drug was reached. Compared with control bundles examined before aminophylline infusion, no alterations in twitch tension, tetanic tension, or force-frequency characteristics were observed. Moreover, theophylline-treated strips fatigued faster than control strips, whether subjected to repetitive submaximal or maximal contractions (p less than 0.01). In the second series, diaphragm bundles were equilibrated with high theophylline doses (400 mg/L) in vitro, and inotropic effects compared with the results in the first series. Supratherapeutic theophylline concentrations increased force development at low stimulation frequencies (p less than 0.05 at 10 Hz) and significantly elevated twitch-tetanus ratio (p less than 0.01) but did not protect against development of in vitro muscle fatigue. Poor penetration of theophylline in diaphragm bundles in vitro was excluded, since drug concentrations in the muscle bundle and the muscle bath were virtually equal. We conclude that diaphragmatic tissue concentrations correlate well with therapeutic serum and supratherapeutic bath levels and that only high theophylline concentrations increase canine diaphragmatic contractility in vitro. None of the theophylline concentrations studied could protect diaphragm bundles against the development of low- or high-frequency fatigue in vitro.

Animals↗
PubMed1990

Theophylline minimally alters contractile properties of canine diaphragm in vitro.

We examined the effects of theophylline on contractile properties and high-frequency fatigue of canine diaphragm in vitro. Eighteen diaphragm muscle bundles were obtained from 10 anesthetized dogs and equilibrated in oxygenated Krebs solution to 100, 200, or 300 mg/l theophylline. These bundles were compared with 18 matched control bundles from the contralateral hemidiaphragm. No statistically significant differences in twitch tension, tetanic tension, twitch-to-tetanus ratio, time to peak tension, or half-relaxation time were observed. Concentrations of 300 mg/l theophylline, however, significantly (P less than 0.05) increased force production at 10 Hz by 32%. A similar tendency was present at lower concentrations and exhibited a clear dose-response behavior. High-frequency fatigue was similar in control and theophylline-treated bundles. We conclude that supratherapeutic in vitro concentrations of theophylline do not increase maximal tetanic tension and do not protect against muscle fatigue but potentiate relative force production at low stimulation frequencies. This relatively small effect cannot be explained by poor diffusion of the drug in the muscle bundle, because theophylline concentrations in the muscle bath and in the muscle bundle were virtually identical. Moreover, it remains unclear whether this potentially beneficial effect can be achieved at in vivo attainable serum concentrations.

Animals↗