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Biomedical subjects

D Berdel

Publications and source records attributed to D Berdel.

At least 19 recordsLinked to original sources
PubMed1996

Long-term effects of formoterol and salbutamol on bronchial hyperreactivity and beta-adrenoceptor density on lymphocytes in children with bronchial asthma.

Long-term treatment with short-acting beta 2-sympathomimetic drugs has recently been suggested to be due to a rise in asthma mortality. This effect has been attributed to an increase in bronchial hyperreactivity, a desensitization of beta 2-adrenoceptors and/or a rebound effect after cessation of the therapy. Formoterol, a new long-acting beta 2-symathomimetic drug, has been reported to possess not only bronchodilatation but also antiinflammatory effects. The aim of the present study was to investigate whether long-term effects of salbutamol and/or formoterol could deteriorate asthma management. Therefore, in a trial lasting 90 days, we evaluated the effects of the two drugs on lung function, on the protection they provided against inhalative provocation with histamine, and on tachyphylaxis as monitored by the beta-adrenergic density on mononuclear leukocytes (MNL). Two groups of 11 children each with stable asthma were treated with daily doses of either 4 x 200 micrograms salbutamol or 2 x 24 micrograms formoterol in monotherapy. The lung function was measured six times during the trial period, on day 1, and on day 90, before and after inhaling the drug and at all investigations both with and without histamine provocation. In both groups, the bronchodilatory effect of either formoterol or salbutamol remained constant. The lung function values before and after drug inhalation (specific airway resistance sRAW, forced expiration volume FEV1, vital capacity VC) did not alter significantly. After histamine provocation, the protection was more pronounced in the formoterol group. No changes in the beta-adrenoceptor density on MNL and no significant side effects were seen throughout the trial period. We therefore conclude that formoterol protects significantly better against the bronchial challenge with histamine than does salbutamol. Both drugs did not deteriorate the lung function in asthmatic children. In addition, there was no evidence that long-term treatment leads to a desensitization of beta 2-sympathomimetic effects.

Adrenergic beta-Agonists↗
PubMed1993

[A new beta-2 sympathomimetic drug with longer effectiveness. Comparison with current beta-2 sympathomimetic drugs in therapy of bronchial asthma in childhood].

Inhaled beta-2-agonists are well established for the treatment of bronchial asthma. Treatment in childhood asthma has to take into account the longer night rests and intensive physical activity of the children. The new inhaled beta-2-agonist Formoterol meets these aspects because of the long lasting efficacy. In addition, compliance is increased by easy handling and rare application. Effects of Formoterol in children derived from several studies are presented. In single dose studies, Formoterol (12, 24 mcg) showed a rapid onset of action and in comparison to salbutamol and fenoterol a four-fold respectively two-fold longer lasting spasmolytic effect. The protective effect against unspecific stimuli was comparable but significantly longer. This protection was even more pronounced with a higher dose (24 micrograms). Long-term studies over three months showed that Formoterol (2 x 12 micrograms/day) improved lung function and asthmatic symptoms and protected against histamine and cold-air challenge throughout the study. Formoterol was well tolerated and additional medication could be reduced. Furthermore, we accomplished a high acceptance of treatment with Formoterol for both children and their parents.

Adrenergic beta-Agonists↗
PubMed1991

[Pharmacokinetics and pharmacodynamics of twice-daily unequal administration of theophylline retard pellets in children of various age groups].

To assess the pharmacokinetic parameters of theophylline (Euphylong as retard pellets) children were studied belonging to age groups between 9 to 13 and 5 to 9 years in twice-daily dosage with unequal distribution of the daily doses. For the older children the dose was 400 + 200 mg and for the younger ones 300 + 150 mg theophylline (these quantities represent the evening and morning doses). 16 and 14 children, respectively, completed the studies regularly. Pharmacokinetic evaluation resulted in a markedly parallel course of the individual serum theophylline profiles around the mean value. The average nocturnal concentration from 200 to 600 hours in the morning was higher than the average daytime concentration (11.4 to 10.5 mg/l or 12.3 to 11.4 mg/l). Due to the relatively stable baseline values the clinical parameters improved only slightly, but there were in particular significant changes in the peak-flow profile. In the older children we could also prove that they had a better protection against metacholine provocation. The side effects were generally mild and were in accordance with previous experiences collected with the studied preparation. The dosage scheme with unequal distribution of the total daily dose is recommended, on the basis of the present study, for all patients with rapid theophylline metabolism, i. e. children, habitually strong smokers or if the clearance is accelerated due to endogenous factors.

Adolescent↗
PubMed1990

Diagnostic value of body plethysmographic parameters in healthy and asthmatic young children is not influenced by breathing frequency.

In 16 healthy and 16 asymptomatic asthmatic children (age range 5-8 yr; 8 girls, 24 boys) we studied the influence of breathing frequency on the results and the diagnostic value of body plethysmographic measurements. Airway resistance (Raw), specific airway resistance (SRaw), and thoracic gas volume (TGV) were measured during breathing (or breathing efforts against a closed shutter) at 0.4, 1, and 2 Hz. SRaw was computed by a simplified procedure directly from flow at the mouth vs. box volume-curves. The diagnostic value of each parameter was assessed as the percentage of correctly classified healthy and asthmatic subjects by means of discriminant analysis. When frequency was increased from 0.4 to 1 and 2 Hz mean TGV rose by 5 and 14% in healthy children and by 11 and 21% in asthmatic children, respectively. From 0.4 to 1 Hz mean Raw decreased by 16% (P = 0.002) in healthy children and by 25% (P = 0.0004) in asthmatic children. The differences in Raw between both groups decreased with frequency (3.5, 1.8, and 1.5 cm H2O.L-1.s at 0.4, 1, and 2 Hz, respectively) and those of TGV increased (0.13, 0.21, and 0.23 L). SRaw showed similar frequency characteristics as Raw. As intra-group variability changed in parallel with the differences the diagnostic value of the parameters remained constant with frequency. Simplified SRaw alone and TGV combined with Raw exhibited no differences in their diagnostic values (81-84% correctly classified).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1990

Correspondence between forced oscillation and body plethysmography during bronchoprovocation with carbachol in children.

We compared dose-response curves obtained with the forced oscillation technique (FOT) and with body plethysmography during bronchoprovocation in children. In 40 stable asthmatic children (age, 5-16 yr) we performed challenges with doubling concentrations of inhaled carbachol (0.15-10 mg/mL) until specific airway resistance SRaw had increased by 100% (PC100SRaw). The FOT-response was assessed by total respiratory system resistance (Rrs, cmH2O.1(-1).s) and reactance (Xrs, cmH2O.1(-1).s) from 8 to 26 Hz, expressed as mean Rrs (Rrs), mean Xrs (Xrs), Rrs at 8 Hz (Rrs8), and mean slope of Rrs (dRrs/df). Dose-response curves were analyzed for threshold concentrations (TC) causing a 3 SD change from baseline and sensitivity indices (SI) defined as differences between baseline and postchallenge values (at PC100SRaw) divided by baseline SD. Median TC of Rrs8, Rrs, Xrs, dRrs/df, and SRaw was 0.21, 0.30, 0.34, 0.41, and 0.42 mg/mL, respectively, indicating a slightly higher sensitivity for FOT. Median SI values of SRaw and Xrs (12.0 and 8.2; difference n.s.) were significantly higher than those of the other parameters. Multiple regression analysis revealed only the absolute change of Xrs (delta Xrs), baseline Rrs and age as significantly (P less than 0.001) correlated with the percentage change of SRaw (delta %SRaw). Best correlation (r = 0.86) with delta %SRaw was found for the function: FOT score = -102.5 X delta Xrs X exp(-0.196 X Rrs + 0.038 X age). Provocative concentrations estimated by this FOT score differed from PC100SRaw by less than one (two) concentration steps in 34 (40) out of 40 children.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

Efficacy of formoterol metered aerosol in children.

To evaluate the effect of formoterol MDI (F) in the treatment of bronchial childhood asthma, five studies were performed in a total of 66 young asthmatics. In single-dose studies with 12 micrograms, F showed a rapid onset of action and in comparison to salbutamol a four-times-longer-lasting bronchospasmolytic effect (BSL). In addition, we looked at the BSL and the protective effect (P) in exercise-induced asthma (EIA) after 6, 12, and 24 micrograms. The BSL was not significantly different with respect to onset, magnitude, and duration of action, nor was the P, yet the latter seemed to be superior at 2 and 8 h after 24 micrograms. In a long-term study with 2 X 12 micrograms the patients' clinical well-being could be improved while drug consumption decreased. During another 3-month monotherapy with 2 X 12 micrograms the P in histamine- and cold air challenge was investigated and compared to prestudy values. It could be shown that long-lasting BSL and P did not diminish. Furthermore, there is evidence to suggest an improvement of bronchial hyperresponsiveness after withdrawal of F.

Administration, Inhalation↗
PubMed1990

[Sensitivity and specificity of multi-frequency oscillation methods, body plethysmography and spirometry in 5-8-year-old asthmatic patients].

We compared specificity and sensitivity of the forced oscillation technique with the standard methods of body plethysmography and spirometry in children suffering from asthma (age 5-8 yrs). We investigated 60 healthy and 66 asthmatic children by forced oscillation, plethysmography and spirometry. Mean FEV1% pred was 99.7 and 82.4% in the healthy and asthmatic subjects, respectively, and mean SRaw was 0.68 and 1.18 kPa*s, respectively. Forced oscillation and plethysmography could be measured in all children, whereas 29% of the investigated children failed to perform valid spirometry. Discriminant analysis was used to compare the optimal classification which could be obtained from the measured data with the clinical one. Fixing specificity to 95%, we computed sensitivities of 66% (forced oscillation), 68% (body plethysmography), and 76% (spirometry). We conclude that the diagnostic value of the three methods in young children with asthma is similar. However, the value of spirometry is limited by cooperation in these young children.

Asthma↗
PubMed1990

[Bioequivalence of theophylline retard capsules in children and relation of metabolism to administration route].

The bio-availability of two slow-release theophylline capsules employing different sustained-release principles, was investigated in 12 children suffering from bronchial asthma, on this basis of the renal excretion of the unchanged active substance. With the aid of a model-bound convolution procedure, the completeness and the variability of absorption on multiple dosaging under non-steady-state conditions were established. Depending upon the retardation principle, both the mean bioavailability and its scatter differed from one preparation to the other, one of them being, on average, more completely absorbed than the other, while, at the same time, showing an appreciably more variable bio-availability. In consequence of the first pass metabolisation, the percentage of theophylline that was excreted unchanged in the urine, was greater with the intravenous route of administration than with peroral application. In the case of the secondary metabolite 3-methylxynthine, the situation was reversed.

Adolescent↗
PubMed1990

[Impedance of the respiratory tract of healthy newborn infants--studies using the polyfrequency oscillation method].

Resistance and reactance of the respiratory tract of 40 healthy newborn were measured by means of the polyfrequent oscillation method. Mean resistance had frequency-dependent values between 20.91 and 9.63 cm H2O per litre per second and mean reactance between -29.11 and -3.81 cm H2O/1/s. The resistance--but not the reactance--was found to depend on the body length and the body weight of the infants.

Airway Resistance↗
PubMed1989

Monitoring theophylline levels in serum and saliva using fluorescence polarization immunoassay and Seralyzer.

The reliability and predictive value of salivary theophylline levels was investigated in 58 children who were treated with oral sustained-release theophylline preparations for bronchial asthma. Serum and saliva levels were assessed by fluorescence polarization immunoassay (FPIA), and Seralyzer (reagent strip reflectance photometer method). Forty-six paired serum and saliva samples from 28 patients (Group 1) were used to develop a linear regression formula. This formula was tested on 130 paired serum and saliva samples from 32 patients (Group 2). When saliva theophylline levels were assayed using FPIA, 95% of serum levels were predicted within 30% of the measured value. Using Seralyzer, 95% of serum levels were predicted within 45% of the measured value. For patients with three and more paired serum and saliva specimens, individual regression formulas were determined showing considerable variation. This study indicates that salivary theophylline levels provide for an estimation of serum levels if FPIA is used. The Seralyzer technique is only useful for serum theophylline measurements. Using a special device it is now easier to obtain saliva samples than by conventional methods.

Adolescent↗
PubMed1989

Formoterol and salbutamol metered aerosols: comparison of a new and an established beta-2-agonist for their bronchodilating efficacy in the treatment of childhood bronchial asthma.

In this placebo-controlled, double-blind, single-dose study the new beta-2-agonist formoterol (one puff, 12 micrograms) was intraindividually compared with salbutamol (one puff, 100 micrograms) for onset, magnitude, and duration of bronchodilating efficacy in 15 young asthmatics aged 5 to 14 years with mild to severe asthma. All but one had regular antiasthmatic medication before beginning the study, but none was oral steroid dependent. Both medications produced rapid bronchodilatation within 10 minutes, reflected by a decrease in specific airway resistance (sRaw) with maximum effects at 10 minutes (salbutamol, 51%) and 30 minutes (formoterol, 60%). Significant bronchodilation was present at 10 minutes to 2 hours after inhalation of salbutamol and at 30 minutes to 8 hours after formoterol. Mean percent improvement over baseline was higher for formoterol at all measured times from 30 minutes to 12 hours, when 55% mean decrease in sRaw was still present. The effect of salbutamol was a less than 10% mean decrease in sRaw after 6 hours. The differences in sRaw decrease between the two medications were statistically significant at 4 to 10 hours after inhalation. Neither medication administered as an aerosol caused cardiac side effects. Both had a rapid onset of action and a comparable maximal effect. However, at the doses studied, formoterol produced a larger decrease in sRaw from baseline for longer periods after inhalation than did salbutamol.

Administration, Inhalation↗
PubMed1989

Renal clearance of theophylline and its major metabolites: age and urine flow dependency in paediatric patients.

The renal clearance of theophylline (TH) and its metabolites 1,3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX), and 1-methyluric acid (1-MU) has been studied in 10 children aged 8 months to 14 years. Individual renal clearances were calculated from serum levels and amounts excreted in urine after i.v. administration of the parent drug. The clearance of 1,3-DMU was found to depend both upon urine flow rate and age, which are interrelated. An effect of urinary pH was expected, but was not studied. Consistent age-dependent changes in the relative quantities of metabolites excreted were not observed.

Adolescent↗
PubMed1989

[Oscillatory impedance measurement of the respiratory tract in children].

The author reports on his own experiences with monofrequent and polyfrequent oscillatory impedance measurements of the respiratory tract in childhood. The monofrequent oscillatory process was tested in a total of 10 trials in respect of its suitability to estimate the complex respiratory resistance in the region of lower and upper respiratory tract in a total of 1071 children most of whom were healthy, some children having a diseased respiratory tract, between 3 and 19 years of age. In 268 children the nasal respiratory resistance was measured, in 803 the bronchial respiratory resistance. The polyfrequent oscillation method was compared in 2 examinations with body plethysmography and spirometry in respect of its discriminatory powers between healthy subjects and children suffering from asthma, and in respect of its suitability to prove bronchial hypersensitivity on carbachol provocation, using 93 healthy and 81 asthmatic children. The results of the 12 examinarions are surveyed and discussed.

Adolescent↗