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597 High-dose steroid aerosol and adrenocortical function in children
595
OVERESTIMATIONOFENDOGENOUSCORTISOLIN ASTHMATICS RECEIVING STEROIDS USING A COMMERCIAL IMMUNOASSAY. Malcolm Hill,
597
Pharm. D., Ronald 3. Harbeck, Ph.D., Eleanor Brown, M.T. (ASCP) and Stanley J. Szefler, M.D., Denver, -. Colorado Measurement of plasma cortisol to estimate the degree of adrenal suppression in patients receiving oral corticosteroids is common. We observed discrepancies between cortisols measured by a fluorescence polarization immunoassay (FPIA, Abbott TDx), and those made by a sensitive and specific HPLC assay in patients receiving daily or alternate-day prednisone. Therefore, we compared the accuracy of these 2 methods in measuring cortisol in stripped plasma from normal volunteers spiked with 15.0 ug/dL, as well as 40.0 ug/dL cortisol, normal volunteers (n=19), and asthmatic patients receiving steroids with samples obtained prior to the morning dose (n=24). Analysis of spiked plasma yielded mean cortisols of 14.0 vs. 13.7 ug/dL, and 38.3 vs. 37.3 ug/dL by HPLC and FPIA, respectively. The reproducibility was excellent with 96 C.V. of <4.4% for all. Plasma cortisol in normals yielded a highly significant linear correlation by comparing HPLC and FPIA (r=0.97, p
EFFECT
OF PREDNISONE IN
SUBCLRSSES
ON 100
BRONCHIPL
J. ---
598
PND
PSTHMR. Sudhir Batchu,
S. .._..Seggev, .M.D., M.B.G.G., Columbia, Missouri. Corticosteroids may decrease serum IgG and Igp levels. We determined Igp, and IgG subclass levels in 13 IgM, Id% Ten pat ients were treated asthmat its. with bronchodilators only (group FI), while 9 steroid dependent patients
(group
FIS) received
dilators IV% nephelometry.
and I@,
and
IgM
IgG by et
measured Papadea,
1985)
both
using
ELISG al. ;
WHO Reference Statistical
National
control. employed
broncho-
prednisone(P1.
the
were
standard Serum
whereas age.
IgG
levels
levels
were
group FIS (1218+223mg% levels of
similar
in
test.
older p
(39+15.4y
were
similar
Pt0.30,
in respec-
with were
lower in group p However, (P=0.236),
and both
1940, and the
quality
rank-sum
increased
IgM
from 31:
evaluation
Wilcoxon
IgG
by
were
67/97 for
Group RS was significantly (53.78t13.6~) than group IgR and IgM Pm0.0373). both groups (Pz0.60 and
tively).
measured
subclasses (modified Clin. Chem.
age,
independent
significantly (720+3llmg%)
of than
in
P=0.0022).
IgG2
IgG4 groups
total IgG. We conclude but not Igq and The patients.
decrease
all
equally.
(P=0.318),
(Ps0.2301 when
IgG3
were corrected
for
subclasses
that
P
IgM
levels
IgG, in asthmatic IgG affects
decreases
in
317
HIGH-DOSE STEROID AEROSOL AND ADRENOCORTICAL FUNCTION IN CHILDREN: Palle Prahl, M.D., D.m.Sc., Copenhagen. Increasing the dosage of steroid aerosol one must consider the risk of adrenocortical suppression. .Adrenocortical function has been investigated in 18 children (mean age 12 years) by means of basal s-cortisol, 24 h urinary cortisol excretion and ACTH-stimulation test. The children were treated with budesonide (BU) or beclomethasone d$propionate (BDP) in dosages > 1600 pg/1.73 m /24 h. In patients taking > 2400 ug/1.73 m2/24 h some adrenocortical suppression could be shown. Only 1 patient showed a decreased response to ACTH. Conventional devices for inhalation were changed to a 750 ml spacer device with a oneway valve (Nebuhaler , Astra, Sweden). This increased the urinary cortisol eqcretion in patients taking > 2100 ,ug/1.73 m /24 h. This suggest 8 a decreased systemic influence of the aerosol when administered via a Nebustero'd R baler , which reduces the oropharyngeal deposition of the aerosol. 24 h urinary cortisol excretion was measured in 12 children after treatment with BU and BDP, respectively. Both drugs were inhal2d via a Nebuhaler in dosages >/ 1600 pg/1.73 m /24 h. In 2 patients BU caused a suppression which was less pronounced than that observed following BDP, whereas no difference could be shown in lo patients.
SITE OF SYSTEMIC ABSORPTION OF INHALED ANTIASTHMATIC STEROIDS. B. Jennin s, B.Sc., J. H. Toogood, M.D., Lund, Sweden and London, Canada. It has been suggested, the oropharynx must be the major site of systemic absorption of inhaled steroids and that inhalation of the drug via a spacer should reduce its systemic absorption (Eur .I Clin Pharmacol 31:579, In a comparison of the efficiency of 1987). spacers vs. the metered dose inhaler for delivery of the inhaled steroid, budesonide (Amer Rev Respir Dis 129:723, 1984) we found a significant increase in intrapulmonary drug delivery with the spacers evidenced by higher airflows (p=.O5 by ANOVA for AFEV1) along with an increase in systemic glucocorticoid activity evidenced by neutrophilia (p=.OO2) and reduced serum cortisol levels (A SC, pz.12) and reduced oropharyngeal deposition reflected by reduced candidiasis (A CA, p= < .005). In a separate study (Amer Rev Respir Dis 123:113, 1981), a amall volume spacer similarly reduced the oropharyngeal deposition of inhaled beclomethasone (A CA, p=.OO2), but it reduced intrapulmonary delivery (A PEFR, p=.O4, AFEF and also the amount systemicaf~y7~~s~~b~~'~A SC, p=.OO4). These results indicate (1) the primary site of systemic absorption of metabolically active inhaled antiasthmatic steroids must be the lung; (2) the systemic bioavailability of inhaled steroids is greater with a spacer than with the metered dose inhaler.
OVERESTIMATIONOFENDOGENOUSCORTISOLIN ASTHMATICS RECEIVING STEROIDS USING A COMMERCIAL IMMUNOASSAY. Malcolm Hill,
597
Pharm. D., Ronald 3. Harbeck, Ph.D., Eleanor Brown, M.T. (ASCP) and Stanley J. Szefler, M.D., Denver, -. Colorado Measurement of plasma cortisol to estimate the degree of adrenal suppression in patients receiving oral corticosteroids is common. We observed discrepancies between cortisols measured by a fluorescence polarization immunoassay (FPIA, Abbott TDx), and those made by a sensitive and specific HPLC assay in patients receiving daily or alternate-day prednisone. Therefore, we compared the accuracy of these 2 methods in measuring cortisol in stripped plasma from normal volunteers spiked with 15.0 ug/dL, as well as 40.0 ug/dL cortisol, normal volunteers (n=19), and asthmatic patients receiving steroids with samples obtained prior to the morning dose (n=24). Analysis of spiked plasma yielded mean cortisols of 14.0 vs. 13.7 ug/dL, and 38.3 vs. 37.3 ug/dL by HPLC and FPIA, respectively. The reproducibility was excellent with 96 C.V. of <4.4% for all. Plasma cortisol in normals yielded a highly significant linear correlation by comparing HPLC and FPIA (r=0.97, p
EFFECT
OF PREDNISONE IN
SUBCLRSSES
ON 100
BRONCHIPL
J. ---
598
PND
PSTHMR. Sudhir Batchu,
S. .._..Seggev, .M.D., M.B.G.G., Columbia, Missouri. Corticosteroids may decrease serum IgG and Igp levels. We determined Igp, and IgG subclass levels in 13 IgM, Id% Ten pat ients were treated asthmat its. with bronchodilators only (group FI), while 9 steroid dependent patients
(group
FIS) received
dilators IV% nephelometry.
and I@,
and
IgM
IgG by et
measured Papadea,
1985)
both
using
ELISG al. ;
WHO Reference Statistical
National
control. employed
broncho-
prednisone(P1.
the
were
standard Serum
whereas age.
IgG
levels
levels
were
group FIS (1218+223mg% levels of
similar
in
test.
older p
(39+15.4y
were
similar
Pt0.30,
in respec-
with were
lower in group p However, (P=0.236),
and both
1940, and the
quality
rank-sum
increased
IgM
from 31:
evaluation
Wilcoxon
IgG
by
were
67/97 for
Group RS was significantly (53.78t13.6~) than group IgR and IgM Pm0.0373). both groups (Pz0.60 and
tively).
measured
subclasses (modified Clin. Chem.
age,
independent
significantly (720+3llmg%)
of than
in
P=0.0022).
IgG2
IgG4 groups
total IgG. We conclude but not Igq and The patients.
decrease
all
equally.
(P=0.318),
(Ps0.2301 when
IgG3
were corrected
for
subclasses
that
P
IgM
levels
IgG, in asthmatic IgG affects
decreases
in
317
HIGH-DOSE STEROID AEROSOL AND ADRENOCORTICAL FUNCTION IN CHILDREN: Palle Prahl, M.D., D.m.Sc., Copenhagen. Increasing the dosage of steroid aerosol one must consider the risk of adrenocortical suppression. .Adrenocortical function has been investigated in 18 children (mean age 12 years) by means of basal s-cortisol, 24 h urinary cortisol excretion and ACTH-stimulation test. The children were treated with budesonide (BU) or beclomethasone d$propionate (BDP) in dosages > 1600 pg/1.73 m /24 h. In patients taking > 2400 ug/1.73 m2/24 h some adrenocortical suppression could be shown. Only 1 patient showed a decreased response to ACTH. Conventional devices for inhalation were changed to a 750 ml spacer device with a oneway valve (Nebuhaler , Astra, Sweden). This increased the urinary cortisol eqcretion in patients taking > 2100 ,ug/1.73 m /24 h. This suggest 8 a decreased systemic influence of the aerosol when administered via a Nebustero'd R baler , which reduces the oropharyngeal deposition of the aerosol. 24 h urinary cortisol excretion was measured in 12 children after treatment with BU and BDP, respectively. Both drugs were inhal2d via a Nebuhaler in dosages >/ 1600 pg/1.73 m /24 h. In 2 patients BU caused a suppression which was less pronounced than that observed following BDP, whereas no difference could be shown in lo patients.
SITE OF SYSTEMIC ABSORPTION OF INHALED ANTIASTHMATIC STEROIDS. B. Jennin s, B.Sc., J. H. Toogood, M.D., Lund, Sweden and London, Canada. It has been suggested, the oropharynx must be the major site of systemic absorption of inhaled steroids and that inhalation of the drug via a spacer should reduce its systemic absorption (Eur .I Clin Pharmacol 31:579, In a comparison of the efficiency of 1987). spacers vs. the metered dose inhaler for delivery of the inhaled steroid, budesonide (Amer Rev Respir Dis 129:723, 1984) we found a significant increase in intrapulmonary drug delivery with the spacers evidenced by higher airflows (p=.O5 by ANOVA for AFEV1) along with an increase in systemic glucocorticoid activity evidenced by neutrophilia (p=.OO2) and reduced serum cortisol levels (A SC, pz.12) and reduced oropharyngeal deposition reflected by reduced candidiasis (A CA, p= < .005). In a separate study (Amer Rev Respir Dis 123:113, 1981), a amall volume spacer similarly reduced the oropharyngeal deposition of inhaled beclomethasone (A CA, p=.OO2), but it reduced intrapulmonary delivery (A PEFR, p=.O4, AFEF and also the amount systemicaf~y7~~s~~b~~'~A SC, p=.OO4). These results indicate (1) the primary site of systemic absorption of metabolically active inhaled antiasthmatic steroids must be the lung; (2) the systemic bioavailability of inhaled steroids is greater with a spacer than with the metered dose inhaler.