Download Corticosteroids in Asthma* Rationale, Use, and Problems

Corticosteroids
in Asthma*
Rationale, Use, and Problems
Paul A. Greenberger
C
or
M.D.,
orticosteroids
for patients
inhaled
are the
experiencing
in the
presence
asthma.
of status
maintenance
roids
into
the
Asthma
Heart,
of oral
are very
in hospitalized
corticosteroids
are
patients
permits
by
Blood
the
expert
Institute,
or with
increased
stimuli.”
obstruction,
mucus
panel
of the
“is a lung
treatment;
airway
with
(2) airway
over
time,
experience
even
disease
remission,
the
is reeither
of
degree
of bronchial
and
hypersecretion
of
either
patient
lasting
months
or
permanently.
For the acutely
wheezing
patient
with asthma,
it is preferable
to administer
an effective
dosage
of oral or
systemic
corticosteroids
rather
than to withhold
them.
For
ambulatory
torily
with
patients
whose
bronchodilators,
asthma
is not managed
cromolyn,
and avoidance
ures
in patients
with IgE-mediated
costeroids
usually
provide
effective
Indeed,
in some
effective
antiasthma
patients,
asthma,
control
inhaled
corticosteroids
even if the
A potent
and
The
FOR
administration
duce the inhospital
fatality
tration
of oral corticosteroids
wise
symptomatic
emergency
room
desirable
8Fmm
but
for
Division
route
noncompliant
status
cine,
This
Chicago
requests:
Avenue,
Dr.
Greenberger
Chicago 60611
Allergy-Immunology,
In the
improvements
Department
School, Chicago.
Northwestern
University
Medical
study was supported
by USPHS
NIAID
RR000048,
and the Ernest
S. Bazley
Grant
Memorial
Hospital
and Northwestern
University.
Reprint
as
a
of administration
patients.78
Both
budesonide,
adminisasthma,
control
supplemental
was
of
terbutaline
of patients
responsiveness,
a study
and
study
with
responsiveness
with
nate
despite
as compared
groups
had
as
mean
differences
the
budesonide-treated
reduced
bronchial
hyper-
to terbutaline-treated
patients.3
experienced
bronchial
lessened
for which
one explanation
is enrollment
in
effective
management
of asthma.
In another
budesonide
improved
during
1 year of treatment,
airway
an average
of fourfold
as compared
placebo-treated
and triamcinolone
patients.4
as well
that
although
results
corticosteroids,
In addition
as minimize
in patients
bronchial
and
help
the
need
on
morphologic
patients
the
patients
These
grounds
based
with
inhaled
improve
bronchial
hyperresponsiveness
to the empiric
observations
many
reduce
for other
inhaled
corticostecells in bronchial
with asthma,
but
hyperresponsiveness.”
clinically
in asthma,
dipropio-
inhalation
treatment
in reduced
suggest
by
with
inflammatory
Long-term
resulted
Beclomethasone
acetonide
wheezing
mucus
accumulation,
lysosomal),
persists.
justifying
use
experimental
Al 11403,
to Northwestern
grant
East
membrane
suppression
findings
for
if systemic
1 week
of mucosal
of
sug-
Other
eral
cytes,
data
effects
and
basophils,
blood
demonstrating
cells
have
not their
of corticosteroids
and
prevention
of
after
allergen
chalof the early
bronchial
Corticosteroids
but
(vascular
and
response
blockage
corticosteroids
previously.
mast
stabilization
of inflammation,
the late bronchoconstrictive
lenge.
Some
data support
response
of Medi-
303
agonists
(and posbe more efficient
can
gest benefits
that could
rationalize
their
administration
in
the
management
of asthma.
Corticosteroids
have
been
associated
with
reduction
of bronchial
mucosal
edema,
avoid
such
provide
for
However,
corticosteroids
to the emergency
asthmaticus,
of Allergy-Immunology,
re-
adminisor other-
helps
corticosteroids,
acetonide,
essential
some
with
asthma
or recidivism
at times
helps
from asthma.
The
to acutely
wheezing
administered
or triamcinolone
of patients
the
corticosteroids
with
treatment”
of corticosteroids
treatment
rate
patients
room 6 Parenterally
methylprednisolone
less
CORTICOSTEROIDS
need
in
residual
volume.
During
corticosteroids
have been
groups,
after
2 years,
did not have significantly
responsiveness
data
of systemic
reduced
improve
reductions
newly
diagnosed
mild
effective
symptomatic
hyperresponsiveness.
between
on biopsy
RATIONALE
demonstrate
not yet improved.
corticosteroid,
with
more
biopsy
specimens
had not lost their
monotherapy
will
significant
patients
compared
to patients
treated
with
inhaled
terbutaline.
Bronchial
hyperresponsiveness
to histamine,
as measured
by the provocative
concentration
to cause a 15% decline
in
FEY1, was 7.0 mg/ml
in both groups
initially.
After 6 weeks,
the
budesonide-treated
patients
had
reduced
bronchial
roids
provide
However,
with beta-adrenergic
respiratory
effort
FEy1 has
inhaled
medications.
inhaled
cortiof asthma.
6 to 12 h before
residual
capacity
and
hours
after parenteral
nocturnal
satisfacmeas-
require
measurements
administered
along
sibly theophylline),
patients
a variety
the prednisone-requiring
functional
the initial
rates
be documented.’
and
asthma
inflammation;
to
flow
can
tered
to patients
associated
with
National
disease
responsiveness
Asthma
causes
a variable
airway
inflammation,
and
far
reduction
characteristics:
(1) airway
obstruction
that
(but not completely
so in some
patients)
(3)
may
therapeutic
20 to 60 mg adminisinhalation
of corticoste-
in stable
as defined
spontaneously
and
chest consymptoms
the
in expiratory
changes
clinically
of oral corticosteroids.
To address
the use
in asthma,
this manuscript
will be divided
use, and problems.
Lung,
following
versible
maintenance
corticosteroid
asthmaticus
dosages
bronchi
as
While
less and often
consist
of prednisone,
tered
on alternate
days.
Effective
or discontinuation
of corticosteroids
into rationale,
of asthma.
wheezing,
and other
administered
drugs
Oral
antiasthma
valuable
disabling
dyspnea,
controlled
of systemically
patients,
effective
exacerbations
are
to prevent
wheezing
of ineffectively
high
most
corticosteroids
pharmacotherapy
striction,
nocturnal
dosages
F.C.C.P
been
inhibit
in vitro
include
administered
proliferation
mediator
reduction
release.
of periph-
presumably
pulmonary
eosinophils,
lymphoand monocytes.
There
are experimental
that
418$
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corticosteroids
Corticosteroids
in vitro
increase
in Asthma (Paul A
Greenberger)
the
actions
of lipocortin,
pholipase
corticosteroids
A2.
contribute
to
increase
major
enzymes
their
(subsensitivity)
USE
OF
administration
for
reversibility
patients
department
who
therapy,
it
nasal
can
be
essential
to
In the
inability
to speak
muscles
of respiration
corticosteroids
a full
or has
necessary
therapy.
be
There
no data
corticosteroid
continued
patients
single
to support
doses
such
6 h.
The
high-dose
from
several
days
have
pulse,
therapy
the
in-
to 1 week
greatly
dose
of prednisone,
and
can
be
ized
patients
most
preserve
integrity
Sequence
day prednisone
should
be
of the
of
Hospitalization
HPA
should
taken
in
to a
axis.
One
be advised.
the morning
effective
in
the
or
conThe
to
Use of Corticosteroids
After
for Status
Asthmaticus
1. Clear with parenteral
or oral corticosteroids
Convert
to prednisone,
50 to 60mg
each morning
3. Reexamine
in 5 to 7 days
after
discharge;
convert
to
prednisone,
50 mg, on alternate
mornings
and begin
2.
inhaled
corticosteroids’
4. Decrease
prednisone
5 to 10mg every 2 weeks if patient
is
stable
5. Daily prednisone
course for increased
respiratory
symptoms or change in status
6. Discontinue
prednisone
if possible
and continue
inhaled
corticosteroid
7. Administer
stress corticosteroids
and prednisone
as pretreatment
before future surgery
‘At this time, it is appropriate
to discuss
some
corticosteroid
side effects, alternative
therapies,
and benefits from effective
control of asthma.
An information
sheet
can be helpful.
no
of distribution
in well-characterwill
be
as yet unknown.
in the absence
of asthma
and
For many
patients,
corticosteroids
or even their
is
can
of
their
the
will perdiscontin-
formulation
a short
in the
effective
dosage
in
daily
help
hospitaliza-
adults
and
in
days.
beta-adrenergic
provide
satisfactory
control
of asthma
in ambulatory
As there
is increasing
emphasis
on long-term
use
patients
who
it necessitates
appropriate
cough
with
asymptomatic
will require
such that inhaled
drugs
Failure
to recognize
such
many
mg
can
and
weight
for several
combined
with
of inhaled
corticosteroids,
ness to teach and maintain
Some
respiratory
of prednisone
treatment
to 60
g
occasional
of an upper
course
is 40
as 200
of beclomethasone
experiences
setting
department
2 mg/kg
of body
corticosteroids
corticosteroid
actuation
is not available
as concentrated
as the
products.
with
asthma
emergency
The
ng per
is 6 times
but
usually
infection,
topical
be administered
250
States
marketed
a patient
children,
Inhaled
a potent
countries,
containing
United
prevent
a
strategy
prednisone,
of prednisone
factors
patient.
A concentrated
daily.
agonists
patients.
version
to alternate
dose
of prednisone
In a
pred-
or elimination
findings
differences
is incomplete
Budesonide,
in other
exacerbations,
short-
patient
has required
long-term
before
the hospitalization,
day
differences
triggering
by the
moderate
is sufficient.
required
daily
mI/mm/kg),
These
that
with
of volume
of high-dose
topical
of oral corticosteroids
of age.
available
and if the chest
is clear and the patient
is asymptomatic,
decision
can be made
as to whether
continued
prednisone
or not. If the
corticosteroids
(2.0
min).’4
suggest
administration
mit reduction
tions.
intermittent
in terms
clearance
210
consideration
of
potential
avoidance
acting
corticosteroid.
One method
of use of corticosteroids
is to discharge
the patient
recommending
prednisone,
50 to
60 mg daily
for 5 to 7 days. The patient
should
be examined
is necessary
days.
reductions
high dosages
of inhaled
agonists.
Supplemental
exacerbations
of asthma
alternate
identified
11kg),
currently
When
be
converted
an inexpensive,
0.6
life (about
dipropionate
1,000
time
tolerating
were
half
twice
of
should
at which
vs patients
years
4
administration
as hydrocortisone,
can be managed
1 week
of daily
prednisone
of patients
whose
asthma
differences
(about
and
uation.
In the United
States,
beclomethasone
dipropionate
or triamcinolone
can be administered
up to 16 to 20 times
per day, and flunisolide,
8 times
daily,
in patients
over 12
be given and
is unknown.
corticosteroids
improved
morning
of
to 300 mg, or methylprednisowith administration
every
prednisone,
50 mg, can
the most
effective
dosage
every
of
administered
Effective
asthma
by pharmacodynainic
Pharmacotherapy
alone
use
a paradoxical
with
explained
when a patient
findings
such
to 6 h. Alternatively,
repeated
although
mg
of
doses
sentence,
should
cludes
hydrocortisone,
200
lone, 40 to 50 mg intravenously
treatment
effective
without
further
delay.
Indeed,
acute severe
asthma
and displays
virtually
corticosteroids,
nisone
to determine
trial
administer
or
larger
considered
2 weeks
day prednisone,
and beta-adrenergic
may be necessary
during
but usually
comparison
symptomatic
patients,
amto severe
symptoms,
and as
every
of alternate
CownCosTERoIDs
systemic
are
dosages
to 50 to 60 mg on alternate
tried.
patients
prednisone
of acutely
have mild
prednisone
can be reexamined
of 5 to 10mg
and have
as a
refractoriness
themselves
to the emergency
improved
with
beta-adrenergic
other
the
patient
Most
symptoms.
oral
The
Corticosteroids
have presented
and have
not
flaring,
with
asthma.’
a diagnostic-therapeutic
is
to convert
of phos-
asthmaticus,’
accessory
along
action
of respiratory
corticosteroids
presents
with
as
in
of corticosteroids
from the perspective
bulatory
patients
who
a modality
inhibit
eicosanoid
production
by
of phospholipase
A2 could
receptor
number
of beta-adrenergic
status
in
of
benefits
beta-adrenergic
role,
the reversal
The
that
A reduction
via inhibition
explanations
corticosteroids.
Oral and
for
inhaled
bined
need
asthma
and COPD
to be determined.
Despite
the
theophylline
ance
measures,
sifled
therapy
be
may
may
and
basis
only
noncorticosteroid
drugs.
CHEST
as
with
com-
of each
asthma,
modality
to
for asthma,
dreaded
even
on
adverse
effects.
use of beta-adrenergic
in addition
to appropriate
agonists,
avoid-
of asthma
be provided
When
/ 101 / 6 / JUNE,
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inhaled
CORTICOSTEROIDS
produce
exacerbations
cannot
are
be administered
therapeutic
be administered
not
with
where
the contributions
Also in cough
equivalent
the
widespread
and cromolyn,
that
otherwise
in patients
trial
REGARDING
Corticosteroids
a long-term
but
results
corticosteroids
of a diagnostic-therapeutic
PROBLEMS
inspiration
perhaps
4 to 7 days of prednisone,
can actually
reach
distal
airways.
“subclinical”
asthma
is one of the
disappointing
part
corticosteroids
may
relieve
symptoms.
physician
awareinhaler
technique.’
may
require
by currently
daily
1992
corticosteroids
I Supplement
intenavailable
are
419$
and after ten years of treatment
with inhaled
steroids.
Eur
Respir J 1988; 1:883-89
12 Peers SH, Flower
RJ. The role of lipocortin
in corticosteroid
actions. Am Rev Respir Dis 1990; 141:S18-S21
13 Fraser CM, Venter JC. Beta-adrenergic
receptors:
relationship
of primary
structure,
receptor
function,
and regulation.
Am Rev
Respir Dis 1990; 141:S22-S30
14 Creenberger
PA, Chow MJ, Atkinson
AJ Jr, et al. Comparison
of prednisolone
kinetics
in patients
receiving
daily or alternateday prednisone
for asthma.
Clin Pharmacol
Ther 1986; 39:163-
15 Reed CE. Aerosol steroids as primary
treatment
of mild asthma.
N Engl J Med 1991; 325:425-26
16 Fauci AS, Dale DC, Balow JE. Glucoeorticosteroid
therapy:
mechanisms
of action and clinical
considerations.
Ann Intern
Med 1976; 84:304-15
17 Spiro HM. Is the steroid
ulcer a myth? N EngI J Med 1983;
309:45
18 Greenberger
PA, Hendri
11W, Patterson
R, et al. Bone studies
in patients
on prolonged
systemic
corticosteroid
therapy
for
asthma.
Clin Allergy 1982; 12:363-68
68
CHEST/lOl
Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21648/ on 05/12/2017
I 6 I JUNE,
1992
/ Supplement
421S
and after ten years of treatment
with inhaled
steroids.
Eur
Respir J 1988; 1:883-89
12 Peers SH, Flower
RJ. The role of lipocortin
in corticosteroid
actions. Am Rev Respir Dis 1990; 141:S18-S21
13 Fraser CM, Venter JC. Beta-adrenergic
receptors:
relationship
of primary
structure,
receptor
function,
and regulation.
Am Rev
Respir Dis 1990; 141:S22-S30
14 Creenberger
PA, Chow MJ, Atkinson
AJ Jr, et al. Comparison
of prednisolone
kinetics
in patients
receiving
daily or alternateday prednisone
for asthma.
Clin Pharmacol
Ther 1986; 39:163-
15 Reed CE. Aerosol steroids as primary
treatment
of mild asthma.
N Engl J Med 1991; 325:425-26
16 Fauci AS, Dale DC, Balow JE. Glucoeorticosteroid
therapy:
mechanisms
of action and clinical
considerations.
Ann Intern
Med 1976; 84:304-15
17 Spiro HM. Is the steroid
ulcer a myth? N EngI J Med 1983;
309:45
18 Greenberger
PA, Hendri
11W, Patterson
R, et al. Bone studies
in patients
on prolonged
systemic
corticosteroid
therapy
for
asthma.
Clin Allergy 1982; 12:363-68
68
CHEST/lOl
Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21648/ on 05/12/2017
I 6 I JUNE,
1992
/ Supplement
421S