Sustained-release theophylline for childhood asthma: evidence for circadian variation of theophylline pharmacokinetics.
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Adolescent↗
Biomedical subjects
H Levison
Publications and source records attributed to H Levison.
Increased incidence of bronchial reactivity in children with a history of bronchiolitis.
To assess bronchial reactivity in children who have had bronchiolitis, we studied 48 children by challenging them with methacholine nine or ten years after admission to hospital with bronchiolitis. Pulmonary function was also evaluated. Fifty-seven percent of children studied had bronchial hyperreactivity. Thirty-three percent of first-degree relatives of those with a positive MCH challenge had a positive response. There was a significant correlation between the occurrence of a positive MCH challenge and a history of recurrent bronchiolitis. Pulmonary function tests demonstrated lower flow rates in the positive responders. Fourteen children had a history of asthma or wheezing, but this did not appear to be severe or frequent, and few required long-term therapy. There appears to be a strong genetic component in the prevalence of bronchial reactivity in these children. Bronchial hyperreactivity may be a risk factor in the development of COPD.
Bronchi↗
Changes in ventilation and chest wall mechanics during sleep in normal adolescents.
The effect of sleep state on ventilation and the mechanics of breathing was studied in nine normal adolescents by use of a respiratory inductive plethysmograph and surface electromyogram electrodes. Minute ventilation was state dependent (P less than 0.01), decreasing by a mean of 8% from wakefulness to nonrapid-eye-movement (NREM) sleep and increasing 4% from NREM to rapid-eye-movement (REM) sleep. These changes were caused by changes in respiratory rate. Tidal volume (VT) was not affected by sleep state (P greater than 0.10). The pattern of breathing during wakefulness was similar to that of REM sleep. During NREM sleep intercostal and diaphragmatic muscle activity increased by a mean of 34% and 11%, respectively, as compared with wakefulness, indicating an increase in the respiratory work load. This was accompanied by a substantial increase in rib cage contribution to VT. REM sleep was associated with a marked decrease in intercostal muscle activity (P less than 0.05) and a diminished rib cage contribution; VT was maintained due to a mean increase of 34% in diaphragmatic muscle activity (P less than 0.05).
Adolescent↗
Chest wall mechanics and pattern of breathing during sleep in asthmatic adolescents.
The effect of sleep state on the ventilatory pattern and chest wall mechanics was studied in 8 asthmatic adolescents (mean age +/- SD, 13.6 +/- 1.3 yr) using a respiratory inductive plethysmograph and surface electromyogram (EMG) electrodes. During rapid eye movement (REM) sleep we observed a mean decrease of 43% in intercostal EMG activity. This was associated with paradoxical inward motion of the rib cage to the extent that the rib cage compartment contributed negatively to tidal volume. Accompanying the abnormal chest wall mechanics there was a mean increase of 45 +/- 38% in diaphragmatic EMG activity, as well as a substantial increase in abdominal contribution to tidal volume. However, despite the increased diaphragmatic activity, tidal volume decreased during REM sleep. The abnormal chest wall mechanics during REM sleep were also associated decreased mean inspiratory flow rates and prolongation of the duty cycle (TI/Ttot). The mean maximal decrease in hemoglobin oxygen saturation during sleep compared with that during wakefulness was 3.9%.
Adolescent↗
The immotile cilia syndrome. A longitudinal survey.
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Adolescent↗
The validity of the transcutaneous oxygen tension method in children with cardiorespiratory problems.
Transcutaneous oxygen tension (tcPO2) was continuously monitored and compared with simultaneous arterial oxygen tension (PaO2) in 68 patients 1.5 to 23 yr of age (mean age, 7.7 yr) with cardiopulmonary disease. Two groups of patients were studied: (1) Patients during cardiac catheterization (56) in whom the PaO2 ranged from 34 to 98 mmHg (mean, 72.4 +/- 17 mmHg) and (2) patients in the Intensive Care Unit (12) in whom the PaO2 ranged from 54 to 158 mmHg (mean, 106 +/- 37 mmHg). Studies lasted for 30 to 210 min (mean, 80 +/- 33.4 min). The overall relation between tcPO2 and PaO2 in the 68 patients studied was r = 0.96 (p less than 0.001). These results indicated that tcPO2 measurement is a reliable method for assessing low as well as high PaO2 values in children and young adults without gross circulatory impairment.
Adolescent↗
Clinical expressions of immotile cilia syndrome.
To date three distinct morphologic types of immotile cilia disorder in man have been recognized. Patients with the disorder have variable clinical manifestations of disease of the upper and lower respiratory tract. Twenty-one patients with immotile cilia syndrome have been evaluated from the standpoint of history, clinical presentation, radiologic changes, pulmonary function tests, and mucociliary clearance. The results have been compared to the pathologic changes noted on ultrastructural examination of the cilia. Although clinical severity does not correlate with the type of abnormality found, a profile of clinical signs and symptoms suggestive of immotile cilia syndrome has emerged. The triad of productive cough, sinusitis, and otitis was a consistent finding in all. Situs inversus occurred in only half of the patients.
Adolescent↗
Pulmonary function and bronchial hyperreactivity in long-term survivors of bronchopulmonary dysplasia.
Nine children with bronchopulmonary dysplasia were studied at a mean age of 8.4 years. Persistent respiratory symptoms were common. Pulmonary function tests demonstrated airway obstruction and abnormal blood gas levels in most. In six of eight children results of methacholine challenge tests were positive, indicating bronchial hyperreactivity. Abnormal chest radiographs persisted in eight children. The bronchial hyperreactivity is a likely consequence of airway damage in infancy and is the probable reason for episodic wheezing in the early years of life. Improvement in expiratory flow rates following bronchodilator inhalation suggests that such therapy may improve function in these children.
Bronchial Provocation Tests↗
Hemoglobin desaturation: its occurrence during sleep in patients with cystic fibrosis.
Sleep studies were performed in 20 clinically stable cystic fibrosis (CF) patients (mean age, 18.2 years) to determine the magnitude of fall in hemoglobin saturation (Sao2) during sleep and to relate these changes to pulmonary function and echocardiographic findings. Five healthy young adults served as controls. In both groups, the maximum fall in Sao2 was seen during rapid eye movement (REM) sleep. The mean maximum fall in the control group during REM sleep was 2.0% (range, 1% to 3%), compared with 7.4% (range, 1% to 23%) in the CF group. Of the 11 patients in whom right ventricular systolic time intervals were obtained, eight of the nine patients with falls in Sao2 greater than 3% during REM sleep had echocardiographic evidence of pulmonary hypertension. Repeated episodes of desaturation during sleep may contribute to the development and progression of cor pulmonale in CF patients.
Adolescent↗
Corticosteroids in status asthmaticus.
Nineteen children who were not steroid dependent and were hospitalized in status asthmaticus were studied to evaluate the effect of corticosteroids. They were randomized into two groups. Each group received salbutamol inhalations and intravenous aminophylline therapy. One group received 7 mg/kg hydrocortisone intravenously every six hours; the other group served as a control. Each group showed significant improvement in clinical score and peak expiratory flow rate after 36 hours; there was no statistical difference in the degree of improvement. Six of ten steroid-treated children and six of nine controls achieved a PEFR of 50% predicted by 36 hours. The response to inhaled salbutamol was similar in each group. The results show that in the first 36 hours of therapy, corticosteroids have no additive effect on the bronchodilator response of aminophylline and salbutamol and do not hasten the recovery of nonsteroid-dependent children in status asthmaticus. Although the results show that an inhaled sympathomimetic drug is beneficial in status asthmaticus, corticosteroid therapy does not increase the responsiveness of the airways to these agents.
Adolescent↗
Response to aerosol salbutamol, SCH 1000, and placebo in cystic fibrosis.
The responses of 20 patients with cystic fribrosis to a B2 agonist, salbutamol, to an anticholinergic agent, SCH 1000, and to a placebo containing difluorodichloroethane and soya lecithin delivered by metered aerosol were compared. Flow rates decreased significantly after placebo (p < 0.05). FEV1 increased significantly after salbutamol (p < 0.05), but the degree of these changes was small. There was a small but significant increase in FVC but no change in flow rates after SCH 1000. Specific conductance increased significantly (p < 0.01) after both salbutamol and SCH 1000. Thoracic gas volume remained unchanged with both drugs and placebo. Four of 20 patients had a clinically significant increase in flow rates with SCH 1000 and three with salbutamol. The consistent increases in sGaw coupled with minimal changes in flow rates, suggest that the physiological effects of both agents is to increase the compressibility of the airway. The results after placebo demonstrate the increased airway reactivity to irritants in cystic fibrosis. In view of this, attention should be paid to the possible irritant effects of inhaled medications.
Adolescent↗
Mechanism of hemoglobin desaturation during rapid-eye-movement sleep in normal subjects and in patients with cystic fibrosis.
To assess the mechanism of the decrease in hemoglobin O2 saturation during rapid-eye-movement sleep, we studied 5 normal subjects 22 to 30 yr of age and 20 patients with cystic fibrosis 9 to 29 yr of age. The largest decrease in arterial O2 saturation, as monitored with an ear oximeter during sleep, occurred during rapid-eye-movement sleep, with a mean +/- SEM decrease of 2 +/- 0.31% in the normal subjects and 7.4 +/- 1.3% in the patients in both groups. Rapid-eye-movement sleep was associated with a significant loss of intercostal and diaphragmatic tonic muscle activity (p < 0.01), as monitored with surface electrodes, and a decrease in the baseline position of the rib cage and abdomen, as recorded by magnetometers (p < 0.01). This suggests a decrease in functional residual capacity, which was accompanied by a consistently lower arterial O2 saturation during rapid-eye-movement sleep. Short periods (< 20 s) of inhibition of phasic respiratory muscle activity during rapid-eye-movement sleep were followed by further decreases in arterial O2 saturation. We conclude that the desaturation during rapid-eye-movement sleep in all subjects was mainly due to a decrease in functional residual capacity, leading to airway closure in the dependent lung regions. The hemoglobin desaturation was further aggravated by transient periods of hypoventilation.
Adolescent↗
Pulmonary function and bronchial reactivity in children after croup.
Ninety-six children who were admitted into hospital with croup 8.5 yr previously were studied to assess lung function, atopic disease, and bronchial reactivity. Although absolute values in pulmonary function showed only small differences, children who have had croup are members of a population that is significantly different from normal children. Thirty-five per cent had heightened bronchial reactivity, as determined by methacholine challenge. There was no increased incidence of atopic disease in the children studied. One can speculate that these children who have had croup may be a population susceptible to developing chronic obstructive airway disease as adults.
Asthma↗
Clinical application of aerosols in pediatrics.
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Aerosols↗
Comparison of the effects of inhaled SCH 1000 and fenoterol on exercise-induced bronchospasm in children.
The effect of 40 microgram of SCH 1000 (ipratropium bromide, an anticholinergic agent) on bronchodilation and suppression of exercise-induced bronchospasm (EIB) was compared with 400 microgram of fenoterol and a placebo in a single-blind controlled study. Twenty-seven randomly selected asthmatic children performed a standardized treadmill exercise challenge and the 17 children who were shown to have EIB continued in the study. Pulmonary function was evaluated before and after drug administration and exercise. When individual results were analyzed and grouped according to the responsiveness of EIB to the drugs, two patterns emerged: (1) the EIB was more severe in those (6/17) children who did not respond to either drug than in the rest of children; (2) the resting pulmonary function was significantly better in the children (4/17) who responded to both drugs than in those (7/17) who responded to fenoterol alone. In conclusion SCH 1000 was shown to be an effective bronchodilator comparable to, but no better than, fenoterol. It had minimal side effects. As an EIB inhibitor it depended on relatively normal base line pulmonary function and only a moderate deterioration following exercise, whereas fenoterol depended on the exercise response alone. Although anticholinergic drugs are not very extensively used, SCH 1000 may be useful in some patients where the beta 2 adrenergic drugs cause signficant side effects or are contraindicated.
Adolescent↗
Oral and inhaled salbutamol in the prevention of exercise-induced bronchospasm.
Oral salbutamol in a dose 0.15 mg/kg of body weight was compared to a total dose of 0.2 mg of salbutamol aerosol in its ability to produce bronchodilation and to prevent exercise-induced bronchospasm (EIB) in 16 asthmatic children in a single-blind crossover study. The degree of bronchodilation seen 120 minutes after the oral salbutamol was equal to that seen 40 minutes after the salbutamol aerosol as assessed by peak expiratory flow (PEF), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow during the middle half of the FVC (FEF25-75%), and maximum expiratory-flow after 75% of the FVC had been expired (V25). With respect to changes in PEF and FEV1, both active agents were equally effective in blocking EIB following a standardized treadmill exercise test. However, in assessing changes in FEF25-75%, and V25 following exercise, the aerosol was slightly but significantly more effective than the oral preparation in blocking EIB. Oral salbutamol was clinically effective in preventing EIB for 4.9 to 5.8 hours. The aerosol route has the advantages of a faster onset of action, fewer side effects, and greater protection against EIB with respect ot small airways function. Nevertheless, for patients who are unable to use a metered aerosol, oral salbutamol is a useful alternative both as a bronchodilator and in preventing EIB.
Administration, Intranasal↗
Dose-response study of oral fenoterol in asthmatic children.
To assess the dose of oral fenoterol, a beta 2-receptor stimulant, which provided optimal bronchodilation with minimal side effects, we studied 12 children using a double-blind crossover comparison of three dose levels, 2.5, 5 and 7.5 mg, and a placebo. ventilatory function, pulse rate, blood pressure and clinical examination were compared over a 3-hour period. Administration of fenoterol resulted in bronchodilation; a maximal effect was seen at 60--90 min lasting over the period of the study. 7.5 mg of fenoterol produced the maximal bronchodilation, but it was not significantly different from 5 mg. Side effects were minimal and no significant drug-response relationship was noted for blood pressure and pulse rate. 5 mg of fenoterol provided optimal bronchodilation with minimal side effects.
Administration, Oral↗
Lung function in children following repair of tracheoesophageal fistula.
Lung function and bronchial reactivity by methacholine challenge were studied in 24 patients seven to 18 years after repair of type I tracheoesophageal fistula. Only one patient had no abnormalities of the variables tested. Thirteen patients had obstructive airways disease, five had a restrictive defect, and 15 had a positive methacholine challenge. It is postulated that continuing subclinical aspiration of esophageal contents causes lung damage and renders the airways hyperreactive.
Adolescent↗