The pharmacokinetics and the pulmonary function were studied in asthmatic children aged 7 to 14 years, treated in once-a-day administration with sustained-release theophylline formulation (Theodur^®), and compared with twice daily administration. The mean time to reach maximum concentration (Tmax) in serum, in once-a-day administration (taken ao 9:00AM) was 8.6 hours, where the maximum concentration (Cmax) was 18.3μg/ml and the minimum concentration (Cmin) being 3.4μg/ml. In comparison with twice daily administration (taken at 9:00AM and 900PM), the serum theophylline concentration at 5:00AM, 7:00AM and 9:00AM were significantly higher (P<0.01). There was a significant correlation between Cmax in once-a-day and twice daily (r=0.660 P<0.05). The pulmonary function showed a significant improvement at 5:00AM in once-a day.
From these results, we assert that once-a-day administration of sustained-release theophylline formulation (Theodyr^®), is useful to inhibit the morning dip in asthmatic children. However, drug monitoring in required to prevent unexpected overdoses, and twice daily administration should be choiced for the treatment of sever asthmatic children to maintain serum concentration wihtin the effective range during day time.

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The results of a survey for a prospective study on the prognosis of infantile bronchial asthma are presented. In the addition, investigation into the factors associated with prognosis are also described. One hundred and thirty eight patients diagnosed as having infantile bronchial asthma in outpatients of Kudanzaka Hospital (Tokyo), during the period of 1972 to 1982, were studied. Out of 93 patients who answered the questionnaire 29 (31.2%) were in remission (no attack), 14 (15.1%) had several mild attacks every year which required no medication, 43 (46.2%) were in better condition but still had several attacks which needed medication, and the remaining 7 patients (7.5%) showed no remarkable change. On the basis of the foregoing results, the factors associated with these prognosis were investingated. There was a strong tendency toward poor prognosis in those cases which showed a high value of IgE, an IgE-RAST positive finding for house dust, milk and egg white.

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We have evaluated a safer and simpler method of inducing bronchospasm through inhalation of ultrasonically nebulized distilled water (UNDW). Inhalation of UNDW was continued for four min. at a fixed load of UNDW 1.6±0.3ml/min. The reproducibility, r, of the test as determined on the basis of FEV_1.0 was 0.96, while by MMF it was 0.84., demonstrated statistical significant correlation. A significant correlation of the test was confirmed in different groups with different degree of severity of asthmatic symptoms. Mean fall in FEV_1.0 is 28.0±17.1% for mild cases, 39.4±10.0% for moderate cases and 60.4±11.3% for severe cases, respectively.
Using this method, bronchial respose was assessed in 53 children with bronchial asthma. Mean % fall in FEV_1.0 was 38.4±22.1% and in MMF is 50.6±23.4%. These results suggest that this method is useful in supporting a diagnosis of bronchial asthma.

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We evaluated the prophylactic effect of ketotifen against the onset of asthma in seventy-three infants with moderate or severe atopic dermatitis without history of asthma. Thirty-three infants (male 17, female 16, mean age 10.8months) did not receive ketotifen or other antiallergic drugs (control group). Fourty infants (male 21, female 19, mean age 13.7 months) received 0.8mg/day ketotifen for one year (ketotifen group). Both groups were followed for one year to evaluate the first asthmatic attack and the changes of serum IgE and RAST (mite, egg white, cow milk).
During this one year study, mild asthmatic attacks were observed in 21 infants (63.3%), moderate or severe asthmatic attacks were observed in 5 infants (15.2%) of the control group. Mild asthmatic attacks were observed in 16 infants (43.2%), moderate or severe asthmatic attacks were observed in 4 infants (10.8%) of the ketotifen group. The occurrence of first asthmatic attack was significantly lower in ketotifen group (P<0.05).
During this one year study, serum IgE elevated in 33 infants (69.7%) of the control group, in 10 infants (32.3%) of the ketotifen group (P<0.001). There were no significant differences in those two groups in the changes of RAST (mite, egg white, cow milk).

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Eighteen cases, who had visited the department of pediatrics of Doai Memorial Hospital and died from asthma, were analyzed from the asthmatic conditions during 12 months before death.
The daily record of their asthma attacks was expressed as monthly asthma attack score. The change of this score during 12 months before their death could be divided into five patterns. They were; acute exacerbation type in a short period, recurrent type with frequent moderate to severe attacks, relapsing type, sudden death type after the short convalscent stage following frequent severe attacks and sudden unexpected type. In sudden unexpected type, most of them were adlescent, without the history of medication by steroid and of admission with asthma attacks and died recently after 1980. In other types, most of them had the history of medication by oral steroid and that of admission with asthma attacks except sudden death type after the short convalscent stage. Their history of life-threatening attack was found only in two cases and only about a half of them had the history of admission with asthma attacks during 12 months before dath.

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We examined clinical symptoms and the changes of the MEFV curve under the conditions of different inhalation flow rates in patients with childhood asthma who inhaled β-stimulant with MDI. A total of 18 subjects with an average age of 11.6 years; 12 boys and 6 girls were studied. The result was that every case indicated a good rate of improvement after inhalation, and a deep slow 3-seconds inhalation of the metered-dose aerosol showed higher tendency to improve the pulmonary function than a deep fast 1-second inhalation.
In the third trial, we examined the effects of variations in inhalation volume on the changes of the MEFV curve in asthmatic children who inhaled β-stimulant with MDI. A total of 20 subjects with an average age of 11.4 years; 14 boys and 6 girls were studied. The result was that every case indicated good improvement, and an inhaling aerosol from the point of FRC showed higher tendency to improve the pulmonary function than that of RV.

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To investigate the combined effects of inhaled DSCG with β-stimulant for the prevention of bronchospasm induced by hyperosmolar challenges, 10 asthmatic children had eight hyperosmolar challenge tests in a randomised order. 3 tests were performed at 15min after the inhalation of either saline (control: C), DSCG (D), or salbutamol (S). 5 tests were performed at 180min after the inhalation of either C, D, S, salbutamol followed by DSCG (S→D) or DSCG mixed with salbutamol (S+D). Although FEV_1.0 significantly increased untill 180min after inhalation in groups of S, S→D and S+D, there were no significant differences between each group. No synergetic effect occurred in the bronchodilating response to the inhalation of DSCG with salbutamol. In both the D and S groups, the dose of hypersaline provoking the 20% decrement in FEV_1.0 (PD₂₀) increased at 15min after inhalation. This protective effect of inhaled DSCG almost disappeared at 180min. PD₂₀ in both the S→D and S+D groups significantly increased as compared to the S group at 180min after inhalation (p<0.05). There were, however, no significant differences in PD₂₀ between the S→D and S+D groups. To evaluate further whether PD₂₀ was influenced by doses of inhaled DSCG, PD₂₀ was measured at 180min after the inhalation of 10mg/ml or 20mg/ml of DSCG. PD₂₀ did not significantly increase in 20mg/ml of DSCG.
This suggests that the combination of inhaled DSCG with salbutamol may produce a synergetic protective effect against the hyperosmolar challenge test.

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