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248 Late onset skin and bronchial responses to pollen antigen
245
247 HYDROXYZINE: PHARMACOKINETICS AND 4PFfXPRURITIC EFFECT IN CHILDREN WIht ATIXE'TC [email protected],R. Simona, M.D., K.J. Simons, Ph.D., A.3. Becker, M.D., R.P. Haydey,M.D., Winnipeg, Manitoba The Hl receptor antagonist hvdroxvzine (H) is frequently used as an antipruritic in patients with atopic dermatitis (S.D.). H has 2 ser~lm half-life (tl/Z) in adults of 20.0+4-i hr (Simons, F.E.R., et al, Ann. Roy. &li, Phys. Surg. Can. 15: 276, 1982), and an even more prolonged azpruritic effect. We administered a single dose of H syrup 0.7 mg/kg to l!! children with widespread A.D. Blood samples were obtained before the dose, at hourly intervals for 12 hours after, and at 24 hours. Serum H concentrations (SHC) were measured by HPLC. T1/2, volume of distribution (Vd) and clearance rate (Cl) were calculated. ?ruritis and sleepiness were assessed at the above times using rating scales of O-4+. Results were: weight t1/2 Vd Cl age
EFFICACY OF CORTICOSTEROIDS IN STATUS ASTHMATICUS IN CHILDHOOD. P. S. Gerber, M. D., R. Younger, M. D., H. G. Herrod, M. D., A. Koumbourli Economides, M. D., and L. V. Crawford, M. D. Memphis, Tennessee. Studies on the efficacy of cortisteroid (CS) therapy in status asthma in children have revealed divergent results. Reported here are the preliminary results of an ongoing randomized double-blind investigation comparing CS (methylprednisolone 2 mg/kg followed by 4 mg/kg/24 hr IV) to placebo (P) in childhood status asthma. All patients received conventional fluid, aminophylline, and 62 agonist aerosol therapy. Sixteen patients ages 6 to 17 were evaluated with arterial blood gases at 0, 12, and 24 hr. Pulmonary function tests and pulmonary index (PI) were determined at 0, 12, 24, 36, 48, 72 hr, on discharge from the hospital, and at one week post discharge. Relapse rate was determined by the number of patients requiring emergency room visits or hospitalization during the month immediately post discharge. Nine P and 7 CST patients were enrolled. One patient was omitted from the P group because of clinical deterioration which required breaking of the code. NO significant differences were noted in Pa02, PaC02, FVC, FEVI, PEFR, or MMEF during the initial 72 hr of the study period. The CST group showed significant improvement in the PI, first noted at 12 hr and still present at 72 hr (pc 0.01). Four of 8 patients in the P group relapsed as compared with only one of 7 patients in the CST group. Our results indicate that CS therapy may be important in preventing early relapse in children experiencing an attack of status asthma.
7.w 4.7T;r
23.0 12.0
+ Kg
7.3 2.3
+
19.5
+
30.6
+
The mean oeak mean time-of with increasing Pruritis was from l-24 hrs
gr 9.7 LTkg 8.5 milminlkg SHC was 48.5 + 16.8 ns/ml at a 2.0 + 0.9 hrs.- The tli2 increased age of the patients ir=0.92). significantly decreased (~(0.05) after a single dose of H, over a
SHC range
41.8+13.6
of
to
5.6+2.5
rig/ml.
SHC of
>30 rig/ml were associated wi& sleepiness in some patients. We conclude 1) H has a mean tli2 uf 7.3 hrs in children. 2) The t1/2 of H generally increases with increasing age in childhood, and is shorter in children than in adults. 3) A single H dose has a prolonged antipruritic effect in children with severe A.D.
246 COMPARISON
246 LATE ONSET SKIN
AND BRONCHIAL RESPONSES TO POLLEN ANTIGEN. B. Zweiman, M.D., I‘. Atkins, M.D., G. Martin, M.D., A.L. Levinsm, M.S., and R. Yost, B.S., Philadelphia, PA.
OF AEROSOL INHALATION TECHNIGUES. Jane Unteitio, M D , Warren Richards, M.D., and Joseph A. Church; M.D., Los Angeles, California Bronchodilators administered from metered-dose inhalers (MOIs) are widely used in the treatment of asthma. It has been suggested that the effectiveness of these products may be improved by altering the inhalation technique with which they are taken. Therefore, we compared the efficacy of the traditional closed-mouth technique of MD1 use with one in which the mouth remains open throughout inhalation. The study population included 18 asthmatics, aged 7 to 16 years, whose baseline peak expiratory flow rates (PEFRs) were less than 70% of predicted. PEFR was measured before and 5, 10 and 15 minutes after a single inhalation of isoetharine. The patients were studied on separate days utilizing the closedand open-mouth techniques. On the two study days baseline PEFRs were within 10% of each other, medications were not changed and measurements were obtained at the same time of day. Results are presented in the Table as mean + SEM and statistical analysis was performed with a paired T test. Baseline % Improvement Technique PEFR Over.Baseline n=18 (% predicted) 5 min 10 min 15 min Open 5213 33+7 42+11 52+11 Closed 5313 43+7 43+7 26+7 P 0.3 0.5 0.5 0.4 There was no significant difference in PEFRimprovement at any time when the two techniques were compared. Although the open-mouth technique is effective in producing bronchodilation, there is no apparent advantage over the traditional inhalation technique for children.
We carried out serial measurements of serum neutrophi s rhemotactic activity (NCA) by blind well chamber assay in 7 atopic subjeces following simultaneous skin and inhalation challenges with antigen. Subjects had previously demonstrated immediate and late cutaneous (LCR) as well as immediate and late onset bronchospaetic responses (LBR)following antigen challenge. The mean inhalation sensitivity was 522 2 185 cumulative inhalation units (1 unit = inhalation of 1 PNU/ml), which was associated with meaa FEV reductions of 40 + 5% at 10 minutes and 41 4 10% from 4-8 hours after antigen inhal8tion. Significant increases in NCA accompanied early bronchospasm in 4/7 subjects (72-239% increase) and late bronchoapasm in 597 (84"276% increase). Late increases in serum NCA: (1) correlated with early increases (r = 0.83, ~4.05) but not with the titer of antigen apecifit IgE entFbodies (RAST); (2) occurred at tbe time of late onset bronchospasm but did not correlate in degree with FEV changes or inhaled antigen dose. LCR cor$elatmd with RAST titer (r = 0.84, pc.05) but not the degree-of bronchial or serum NCA responses, Thus, I&R is associated with increases in NW but not with degrees of LCR or RAST titer whereas LCR correlates with RAST titer. This suggests that different factors may govern LCR and LBR.
150
247 HYDROXYZINE: PHARMACOKINETICS AND 4PFfXPRURITIC EFFECT IN CHILDREN WIht ATIXE'TC [email protected],R. Simona, M.D., K.J. Simons, Ph.D., A.3. Becker, M.D., R.P. Haydey,M.D., Winnipeg, Manitoba The Hl receptor antagonist hvdroxvzine (H) is frequently used as an antipruritic in patients with atopic dermatitis (S.D.). H has 2 ser~lm half-life (tl/Z) in adults of 20.0+4-i hr (Simons, F.E.R., et al, Ann. Roy. &li, Phys. Surg. Can. 15: 276, 1982), and an even more prolonged azpruritic effect. We administered a single dose of H syrup 0.7 mg/kg to l!! children with widespread A.D. Blood samples were obtained before the dose, at hourly intervals for 12 hours after, and at 24 hours. Serum H concentrations (SHC) were measured by HPLC. T1/2, volume of distribution (Vd) and clearance rate (Cl) were calculated. ?ruritis and sleepiness were assessed at the above times using rating scales of O-4+. Results were: weight t1/2 Vd Cl age
EFFICACY OF CORTICOSTEROIDS IN STATUS ASTHMATICUS IN CHILDHOOD. P. S. Gerber, M. D., R. Younger, M. D., H. G. Herrod, M. D., A. Koumbourli Economides, M. D., and L. V. Crawford, M. D. Memphis, Tennessee. Studies on the efficacy of cortisteroid (CS) therapy in status asthma in children have revealed divergent results. Reported here are the preliminary results of an ongoing randomized double-blind investigation comparing CS (methylprednisolone 2 mg/kg followed by 4 mg/kg/24 hr IV) to placebo (P) in childhood status asthma. All patients received conventional fluid, aminophylline, and 62 agonist aerosol therapy. Sixteen patients ages 6 to 17 were evaluated with arterial blood gases at 0, 12, and 24 hr. Pulmonary function tests and pulmonary index (PI) were determined at 0, 12, 24, 36, 48, 72 hr, on discharge from the hospital, and at one week post discharge. Relapse rate was determined by the number of patients requiring emergency room visits or hospitalization during the month immediately post discharge. Nine P and 7 CST patients were enrolled. One patient was omitted from the P group because of clinical deterioration which required breaking of the code. NO significant differences were noted in Pa02, PaC02, FVC, FEVI, PEFR, or MMEF during the initial 72 hr of the study period. The CST group showed significant improvement in the PI, first noted at 12 hr and still present at 72 hr (pc 0.01). Four of 8 patients in the P group relapsed as compared with only one of 7 patients in the CST group. Our results indicate that CS therapy may be important in preventing early relapse in children experiencing an attack of status asthma.
7.w 4.7T;r
23.0 12.0
+ Kg
7.3 2.3
+
19.5
+
30.6
+
The mean oeak mean time-of with increasing Pruritis was from l-24 hrs
gr 9.7 LTkg 8.5 milminlkg SHC was 48.5 + 16.8 ns/ml at a 2.0 + 0.9 hrs.- The tli2 increased age of the patients ir=0.92). significantly decreased (~(0.05) after a single dose of H, over a
SHC range
41.8+13.6
of
to
5.6+2.5
rig/ml.
SHC of
>30 rig/ml were associated wi& sleepiness in some patients. We conclude 1) H has a mean tli2 uf 7.3 hrs in children. 2) The t1/2 of H generally increases with increasing age in childhood, and is shorter in children than in adults. 3) A single H dose has a prolonged antipruritic effect in children with severe A.D.
246 COMPARISON
246 LATE ONSET SKIN
AND BRONCHIAL RESPONSES TO POLLEN ANTIGEN. B. Zweiman, M.D., I‘. Atkins, M.D., G. Martin, M.D., A.L. Levinsm, M.S., and R. Yost, B.S., Philadelphia, PA.
OF AEROSOL INHALATION TECHNIGUES. Jane Unteitio, M D , Warren Richards, M.D., and Joseph A. Church; M.D., Los Angeles, California Bronchodilators administered from metered-dose inhalers (MOIs) are widely used in the treatment of asthma. It has been suggested that the effectiveness of these products may be improved by altering the inhalation technique with which they are taken. Therefore, we compared the efficacy of the traditional closed-mouth technique of MD1 use with one in which the mouth remains open throughout inhalation. The study population included 18 asthmatics, aged 7 to 16 years, whose baseline peak expiratory flow rates (PEFRs) were less than 70% of predicted. PEFR was measured before and 5, 10 and 15 minutes after a single inhalation of isoetharine. The patients were studied on separate days utilizing the closedand open-mouth techniques. On the two study days baseline PEFRs were within 10% of each other, medications were not changed and measurements were obtained at the same time of day. Results are presented in the Table as mean + SEM and statistical analysis was performed with a paired T test. Baseline % Improvement Technique PEFR Over.Baseline n=18 (% predicted) 5 min 10 min 15 min Open 5213 33+7 42+11 52+11 Closed 5313 43+7 43+7 26+7 P 0.3 0.5 0.5 0.4 There was no significant difference in PEFRimprovement at any time when the two techniques were compared. Although the open-mouth technique is effective in producing bronchodilation, there is no apparent advantage over the traditional inhalation technique for children.
We carried out serial measurements of serum neutrophi s rhemotactic activity (NCA) by blind well chamber assay in 7 atopic subjeces following simultaneous skin and inhalation challenges with antigen. Subjects had previously demonstrated immediate and late cutaneous (LCR) as well as immediate and late onset bronchospaetic responses (LBR)following antigen challenge. The mean inhalation sensitivity was 522 2 185 cumulative inhalation units (1 unit = inhalation of 1 PNU/ml), which was associated with meaa FEV reductions of 40 + 5% at 10 minutes and 41 4 10% from 4-8 hours after antigen inhal8tion. Significant increases in NCA accompanied early bronchospasm in 4/7 subjects (72-239% increase) and late bronchoapasm in 597 (84"276% increase). Late increases in serum NCA: (1) correlated with early increases (r = 0.83, ~4.05) but not with the titer of antigen apecifit IgE entFbodies (RAST); (2) occurred at tbe time of late onset bronchospasm but did not correlate in degree with FEV changes or inhaled antigen dose. LCR cor$elatmd with RAST titer (r = 0.84, pc.05) but not the degree-of bronchial or serum NCA responses, Thus, I&R is associated with increases in NW but not with degrees of LCR or RAST titer whereas LCR correlates with RAST titer. This suggests that different factors may govern LCR and LBR.
150