Methotrexate Treatment of Severe Asthma in
ChilIdren
Salomon
Guss, MD,
and
Jay Portnoy,
MD
ABSTRACT.
Seven children from 3
to
14
years
old with
chronic
steroid-dependent
asthma
were
treated with
methotrexate
(MTX).
Asthma in all
of the
patients
had
been
poorly
controlled for
at
least
2
years
despite
the
use
of oral
theophylline
and
inhaled
corticosteroids,
cromo-lyn
and albuterol. All
presented
with
significant
side
effects
as a
result of chronic
systemic
steroid
therapy.
Five
patients
were
atopic
and had been unable
to
tolerate
immunotherapy
because of
systemic
reactions.
Forced
expiratory
volume in
1
second
and
forced
expiratory
flow,
mid-expiratory phase, improved
in
four
patients
after
4 to
6
months of
treatment
with doses
of
MTX
rnigfrom
7.5 to 17.5
mg/wk.
Three
patients
were
able
to
discontinue their
systemic
corticosteroids.
Laboratory
values
including complete
blood cell
count
with
differ-ential and liver enzymes remained
at
baseline in all
except
one
patient,,
who had transient elevation
in
ala-nine aminotransferase and
aspartate
aminotransferase.
One
patient experienced
side effects sufficient
to
require
discontinuation of
MTX. It
is concluded that
MTX
is
effective for
reducing
the need for
systemic
corticoster-oids and for
improving pulmonary
functions
in
some
individuals. The benefits of
MTX
in
this
group of
severe
asthmatics appear
to
justify
the
potential
risks involved
in its
use.
Pediatrics
1992;-89:635-639;-
asthma,
methotrex-ate.
ABBREVIATIONS.
MTX,
methotrexate;
FEVI,
forced
expiratory
volume in 1 second.
Methotrexate
(MTX)
has
recently
been shown
to
be
effective for the
treatment
of
severe
steroid-depend-ent
asthma
in
adults.
13
In
low
doses,
this
drug
has
also been
found
to
be
safe when
given
to
children for
various
inflammatory
diseases such
as
systemic
lupus
erythematosus,
dermatomyositis,
and rheumatic and
psoriatic
arthritis.`7
Its
safety
and
efficacy
in
children
with
severe
asthma
remain
to
be
proven. Since
we
wished
to
reduce the
significant
medication
side
ef-fects and
improve
the
pulmonary
functions of several
children with
severe,
steroid-dependent
asthma,
the
following
open clinical trial
was
performed.
PATIENTS
AND METHODS
Patient Selection
All children
and their
parents
signed
aninformed
consentform
prior
totaking
MTX. Patients
wereselected for MTX
treatmentif
they
had asthma
and
wereunable
todiscontinue oral corticosteroids
Fromthe Sectionof
Allergy/Immunology,
TheChildren'sMercy Hospital,
KansasCity,
MO.Received for
publication Jun
10,1991;accepted Jul
30,1991.Reprint
requests
toU.P.)
SectionofAllergy/Immunology,
TheChildren's
Mercy
Hospital,
KansasCity,
MO 64108.PEDIATRICS
(ISSN
00314005).
Copyright
©
1992by
the American Acad-emyof Pediatrics.despite
aggressive
environmental control and
conventional medical
management.
A
history
of substantial medication-related
toxicity
and poor asthma control
wassought.
Aggressive
conventional medication schedules included inhaled
corticosteroids
atdoses
of
atleast 800
ug/d
of
beclomethosone,
cromolyn
atadose
of
atleast 1 vial
of Intal three times
aday,
albuterol
atadose
of 2 sprays of
ametered dose inhaler
or0.5-mL
nebulizer
solution three times
aday
and
asneeded,
and oral
theophylline
with
blood levels -8
,ug/mL.
Laboratory
studies
performed
prior
tostarting
MTX
included
complete
blood cell count, differential and
platelet
count,
serumprofile including
liver enzymes
(aspartate
aminotransferase,
alanine
aminotransferase,
lactate
dehydrogenase)
and
creatinine,
and
aurinalysis.
Patients
with
significant
liver
enzyme abnormalities
were not
given
MTX. Pretreatment
liver
biopsies
were notper-formned.
All
patients
wereadvised
toavoid
sulfa-containing drugs
and
alcohol-containing beverages
and
syrups."'9
Spirometry
and
achest
roentgenogram
werealso obtained. Peak
flow
metersweregiven
toeach
patient
with instructions
for
keeping
adiary,
atleast twice
aday.
Though
mostpatients
had been
keeping
such
diaries
prior
toinitiating
MTX,
the records tended
tobe
incomplete
and
weregenerally
notuseful.
Treatment
Methotrexate
wasstarted
atadose
of 2.5
mg/wk.
This
dose
wasincreased
by
2.5-mg
increments
every 4 weeks. Once
patients
weretaking
morethan 5
mg/wk,
the
dose
wasgiven
in
twodoses 1
day
each
week.10
All
patients
were seen atleast
every 4 weeks for
clinical evaluation.
Spirometry
and
laboratory
values
aswell
astheophylline
concentrations
weremeasured with each clinic visit.
After the asthma
wasunder control
asindicated
by
reduced
symp-tomsand increased
peak
flows and
spirometry,
anattempt
wasmade
toreduce the
patients'
oral
corticosteroid doses. If control
of
the
asthma deteriorated with this
reduction,
the dose
of MTX
wasagain
increased.
Morning
cortisol concentrations
weremeasured
prior
toreduc-tion
of corticosteroid doses below
aphysiologic
amountfor all
patients
who
wereable
todiscontinue
systemic
corticosteroids.
Once the
serumcortisol
wasdemonstrated
tobe
physiologic,
oral
corticosteroids
werediscontinued.
Corticotropin
stimulation
testshave
notyet
been
performed
onany of these
patients.
RESULTS
Seven
children
were
treated with MTX
starting
in
November
of 1989. Their initial characteristics
are
shown
in
Table
1.
All
had had
poor control
of their
asthma
for
at
least 2 years and had clinical evidence
of steroid
toxicity
such
as
cushingoid
features and
deceleration of their linear
growth
in
relation
to
their
weight.
11'12
Two
patients (C.W.
and
H.L.)
had
steroid-induced
peptic
ulcer disease and
were
being
treated
with
ranitidine. Five
patients
were
atopic
as
demon-strated
by
skin-prick
tests;
however,
none was
able
to
tolerate
immunotherapy
because
of
frequent
sys-temic reactions
and
worsening
of their asthma.
None
of the
patients
considered
for MTX
therapy
had
ab-normal
liver
enzyme
levels,
so
none were
excluded
for that
reason.
The
duration of MTX
treatment
currently
ranges
from 4
to
17
months.
Prednisone doses
prior
to
initi-PEDIATRICS Vol.
89 No. 4
April
1992
635
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TABLE 1.
Initial
Description
of
Patientsand
Drug
Doses*Patient
Age,
Sex
Durationof
InitialPred-
CurrentPred-
Highest
Highest
Allergic Triggers
y
MTX Treat- nisoneDose nisoneDose MTXDose,
MTXDose,
ment,
momg/wk
mg/kg
S.F.
3 F 9 30mg
QOD
None
7.5
0.5
None
H.L. 9 F 4
30
mg
QOD
None 12.5 0.4 MiteC.W. 10 F 17 40
mg
QOD
None 12.5 0.3Tree, grass, weed
A.B.
13 M 1560omg
Qday
20Omg
QOD
12.5 0.2 MiteK.W. 14 M 12 40
mg
Qday
7.5mg
QOD
17.5 0.4Grass,
miteESB.
14 F 1 30mg
QOD
30
mg
QOD
2.5
NA MiteT.M. 11 F 6 40
mg
Qday
40mg
Qday
17.5 0.2 None*Abbreviations:
MTX, methotrexate;
QOD,
every other
day; Qday,
once aday;
NA,
notapplicable.
ation
of
MTX
treatment
ranged
from
30
mg
every
other
day
to
60
mg
daily
as
shown in Table 1. Most
patients
who
experienced
improvement
in
their
asthma
symptoms
noticed this
at
MTX
doses
of
be-tween
7.5
and
10
mg/wk.
One
patient (K.W.)
did
require
12.5
mg/wk
before
he
showed
improvement.
Three
patients (S.F.,
H.L.,
C.W.)
have
now
been able
to
discontinue
their corticosteroids.
Emergency
de-partment
visits
and
hospital
admissions
for
1
year
before
to
1
year after
starting
MTX
are
shown in Table
2.
Though
all
of
these
patients
had
severe
asthma,
their lack
of emergency
department
visits
and
hospi-talizations
suggests
that
their asthma
had been
at
least
somewh-at
controlled
by
their
regimen.
Of the
two
patients (H.L.
and
T.M.)
who did have
large
numbers
of such
visits,
T.M.
did
not
show
improve-ment
with MTX
and
H.L.
was
believed
to
be
noncom-pliant
with
her
medical
therapy.
Linear
growth
and
weight
were
measured
repeat-edly
both
before and after
MTX
therapy
as
shown in
Table
3.
The median
change
in
height
per
weight
was
0.6
cm/kg
before
MTX
and
3.1
cm/kg during
MTX
treatment.
Though change
in
height
was
greater
dur-ing
MTX
treatment
for
only
two
of five
patients (A.B.
and
C.W.),
the
others had
increased
height
in
pro-portion
to
their
weight.
Two
patients (A.B.
and
K.W.)
lost
large
amounts
of
weight during
their 1
year of
MTX
therapy,
reflecting
a
return to
normal
body
proportions.
Spirometry
values
were
obtained
repeatedly
for all
patients
except S.F.,
who
was
too
young
to
perform
a
forced vital
capacity
maneuver
(Fig
1).
All
patients
experienced improved
spirometry
values
except
T.M.
and
E.B.,
who
was
unable
to
take
MTX. In
addition
to
spirometry, patients
were
instructed
to
measure
peak
flows
daily.
One
patient (C.W.)
was
noted
to
have
a
large
amount
of
variability
in
her
peak
flows
which
was
consistently
seen
1
to
2
days
before
each
dose
of
MTX
(Fig 2).
Because
of this
observation,
she
was
switched
to
a
twice-a-week
MTX
regimen
at
the
same
total
weekly
dose
in
an
attempt
to
reduce this
variability.
Her
forced
expiratory
volume
in 1
second
(FEy1)
values
promptly
fell and control of
her asthma
worsened
within 2
weeks,
requiring
a
resumption
of
once-a-week
treatment.
Once
her
asthma
was
again
under
control,
the MTX
dose
was
increased
and
the
weekly variability
resolved. She
was
able
to
discon-tinue
oral
corticosteroids
completely
within the
next
2
months.
Elevated
alanine
aminotransferase
and
aspartate
aminotransferase
developed
in
another
patient (A.B.)
TABLE
2.Yearly Emergency Department
(ED)
Visitsand
Hos-pital
Admissions
From 1 YearBefore
to1 YearAfter
Initiationof
Methotrexate
(MTX)
Therapy
Patient Pre-MTX
During
MTXEDvisits
Admissions
ED visitsAdmissions
S.F.
0 0 0 1H.L. 9 3 3 3
C.W.
2 0 2 0A.B.
0 1 0 0K.W. 0 1 0 0
E.B. 1 0 0
0
T.M. 6 5 5 5
Mean 2.6 1.4 1.4 1.3
at
a
dose
of
15
mg of
MTX
per week.
This
required
him
to
stop
taking
MTX
until the
enzyme levels
returned
to
normal 2 weeks later.
During
this
time
his
pulmonary
function
tests
worsened
(Fig 3),
neces-sitating resumption
of
high-dose daily
corticosteroids.
Once
the
MTX
was
resumed
at
a
lower dose
(1
2.5
mg/wk),
his
FEV1
improved
and
he
was
again
able
to
tolerate
a
taper
of
his steroid
dose.
Unfortunately,
his
asthma has
not
been
as
well controlled
on
the
lower
dose
of
MTX.
The
youngest
patient
we
treated
(S.F.)
was
2.5
years
old
at
the time that MTX
therapy
was
begun.
Because
she
was
unable
to
use
a
metered dose
inhaler,
her
treatment
consisted
of
a
nebulized
mixture
of
albu-terol,
cromolyn,
atropine (1
mg
three times
a
day),
and
intravenous
methylprednisolone
solution
(20
mg
three times
a
day)
as
well
as
oral
theophylline
and
corticosteroids.
Her MTX
dose
was
gradually
in-creased
to
7.5
mg/wk;
the asthma
symptoms
resolved
and oral corticosteroids
were
discontinued
only
after
she
reached
that
dose.
Subsequently,
she
had
been
able
to
reduce her
MTX
dose
to
2.5
mg/wk
without
recurrence
of
symptoms
or a
need
to
resume
oral
corticosteroids. All
cushingoid
features
have
resolved
and
her
growth
has accelerated. She did
not
experi-ence
any adverse effects from
the MTX.
Two
patients
are no
longer
receiving
MTX.
One
of
them
(H.L.)
discontinued
it
after
4
months
because of
lack
of
compliance
with the
treatment
regimen.
When
she
reached
an
MTX
dose of
7.5
mg/wk,
her
asthma
symptoms
completely
resolved.
The
family
discontin-ued all
of her medications
including
oral
corticoster-oids
and MTX without
seeking
medical advice.
For-tunately,
she
displayed
no
evidence
of adrenal
suppression
despite having
received
long-term
oral
corticosteroid
therapy.
Her
asthma has remained
in
636
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TABLE 3.
Change
inHeight (Centimeters)
and
Weight
(Kilograms)
From
1Year
Before
to 1Year
After
Starting
Methotrexate
(MTX)
Therapy*
Patient
Pre-MTX
During
MTXAHeight
AWeight
AHt/AWt
AHeight
AWeight
AHt/AWt
S.F.
+9.6
+3.1
3.1
+6.4
+1.5
4.3
H.L.
+6.0
+5.7
1.1
+3.3
+3.6
0.9
C.W.
+5.2
+8.3
0.6+9.3
+7.3
1.3
A.B.
+2.5
+14.5
0.2
+4.6
-2.8
-1.6
K.W.
+4.5
+9.9
0.4
+3.0
-11.9
-0.2
Mean
±SD
5.6
±2.6
8.3
±4.3
5.3
±2.6
-0.5
±7.4
Median
+5.2
+8.3
+4.6
+1.5
*Two
patients
(T.M.
and
E.B.)
werenotfollowed
long enough
tomeasurethese
changes.
FVC
100
80
60-
40-100
-80
-60
-40
-Pre
Oni
Mtx
NLx
FeV1
100
-80
-60
-
40-MMEF
p
F
rEe
Ed
V
e
d
I
Ir'ev
On
Pre-
On
NLtx
Ilix
Ntx
Mtx
Fig
1.
Percent
predicted
of
spirometry (forced
vital
capacity [FVC];
forced
expiratory
volume
in 1second
[FEV,];
and
forced
expiratory
flow,
mid-expiratory
phase [MMEF])
of
patients
who received
(Mtx).
One
patient (S.F.)
wasunable
toperform
anFVC
maneuverbecause
of her young age.
-Sun
Mon Tue Wed Thu Fri Sat Sun Mon Tue Wedflctato
jutpirt
ahds
fMethotrexate
.
Fiv
. eaoflourptentsd aoreCW
current
takigrMT.sOn
wely
(K.W.)tio
reustpiore
17. mg/wk
boeofmtotrexawe.cudgau
alyemisinaecete
hiforticostaerbtoid regimn.
Ictoiseno
kneownhowlogths
patients(..
wxeillneed
toacbeptratled
thistreantmentwilal have onfct
wt
teirpulonrystatuods.s
Thve
oupatients
presurentediyti
review
suffe
fOme
severe
ashma,
which
theye
pallntwl
haeehdsinceinfancy.
All
were
treated
with maximum
conventional
ther-apy.
They
also
required
frequent
bursts
with
systemic
100.
90-80I
70.
60
50
40
30
20
10
0
Mtxstopped
Mtxre-started
.I
1
2
3
4
5
6
1
8
9
10 11 12
13 14
Month
of~Mtx
Fig
3.
Forced
expiratory
volume
in1 second
(FEVj)
for A.B.
showing
adramatic decrease when the methotrexate
(Mtx)
wasdiscontinued
for
ashort time because
of elevated liver enzymes.
corticosteroids and
eventually
were
unable
to
discon-tinue
them.
Immunotherapy,
which
was
attempted
for
patients
who
were
atopic,
had
to
be
discontinued
because
of
systemic
reactions
and
worsening
of
the
asthma.
These
patients
had
asthma that
was
poorly
controlled,
despite
this
aggressive
treatment.
Some
had
multiple
emergency
department
visits
and
fre-quent
admissions
to
the
hospital.
All
of
these
patients
had
evidence
of
side
effects
due
to
the chronic
use
of
systemic
corticosteroids such
as
increased
body weight, cushingoid
features,
decel-eration
of linear
growth
in
proportion
to
weight,
peptic
ulcer
disease,
mood
swings,
depression,
and
insomnia.
These
patients
were
at
risk
for
development
of
other side
effects
as
well.","2
In
contrast to
the
potentially
severe
and
systemically
global
side
effects
and toxicities of
corticosteroids,
MTX
has
side
effects
that
are more
localized
to
the
liver,
lungs,
gastroin-testinal
tract, and bone
marrow
and
are
therefore
potentially
more
detectable
prior
to
permanent
dam-age.
During
MTX
therapy,
asthma
morbidity
was
sub-stantially
reduced. These
patients
required
fewer
acute
bursts
with
high
doses of corticosteroids.
They
experienced
slightly
fewer
emergency
department
visits
and
admissions
to
the
hospital
and
they
had
a
substantial
improvement
in
their
FEV1
and forced
expiratory
flow,
mid-expiratory phase.
There have been several
reports
involving
adult
asthmatic
patients
who have been shown
to
have
favorable responses
to
MTX.1
'These
studies describe
patients
who
have
been able
to
tolerate
a
reduction
ARTICLES
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of their
systemic
corticosteroid doses
while
receiving
MTX
and thus have had
a
decrease
in
their
steroid-induced side
effects.
Many
of them
were
able
to
discontinue corticosteroids
completely.
In
a
recent
study,
31
cushingoid
adult asthmatics
were
given
15
to
50
mg/wk
of
MTX
for
18
to
28
months. Prednisone
doses
were
reduced
by
more
than
50%
in
24
of
25
patients
and 15
were
able
to
discontinue their
pred-nisone.
Only
15
of these
patients
reported
transient
side
effects,
which included
nausea,
rash,
thinning
of
hair, stomatitis,
and
transient
elevation
of the
liver
enzymes
in
serum
(aspartate
aminotransferase).
These results
as
well
as
our own
differ from those
recently reported by
Erzurum
et
al114
at
National
Jew-ish
Institute
for
Respiratory
Diseases.
This
difference
may be
partially
due
to
the older
age group treated
in
that
study.
Also,
the
doses of
MTX
were
increased
more
rapidly
than
ours
and the duration
of
treatment
was
much
shorter.
None
of
our
patients
were
im-proved by
3
months and this slow
onset
of
improve-ment
has
been observed
in
all other studies
of
MTX.
It is
also
possible
that
patients
seen
at
National
Jewish
may have
had
a
significant
irreversible
component
in
their
airways
disease. Our
patients
did
have
reversi-bility
as
demonstrated
by
improvement
of their
FEy1.
Adverse
effects from
MTX,
even
in
low
doses,
are
known
and have been
reported
in
children and
adults.10
The
more common
side
effects include
an-orexia,
nausea,
vomiting
and
diarrhea,
and
stomati-tiS.
13
A
pruritic
rash that
usually
appears
6
to
12
hours
after
starting
therapy
is
often caused
by
exposure
to
UV
light.
1
5Mild
elevation
of
serum
liver
enzymes,
which
usually
occurs
during
the
3
days
after
MTX is
taken and
may be
transient,
is
commonly
seen
with
a
low
dose
of
MTX.
This
is
not
necessarily
an
indica-tion
to
discontinue the
drug
if the values
return to
normal
prior
to
the
next
MTX
dose.16-19
One
of
the
patients
in
our
group showed elevation
in
the
serum
liver
enzymes which
returned
to
baseline
levels
after
1
week
off the
drug.
Methotrexate
in
high
doses
has
been
reported
to
cause a
picture
of
pneumonitis,
which is
an
idiosyn-cratic reaction
and
not
dependent
on
the
length
of
treatment.23
Another
reported
side
effect
is
pul-monary
fibrosis.13'
15
Both
of
these
may
cause
an
in-crease
in
the
FEV1-forced
vital
capacity
ratio
and
the
emergence of
an
obstructive-restrictive
pattern
in
the
expiratory-inspiratory spirometry
loop.
It is
not
clear
whether
severely
asthmatic
children with
some
de-gree of irreversible
lung damage
are more
prone
to
develop
2pulmonary
side
effects such
as
pulmonary
fibrosis.
A
rare
complication
is
liver
fibrosis and
cirrhosis,
which is
usually
nonprogressive
after the
drug
has
been
stopped.
192'0
This
has been
primarily
observed
with
high
dose of
MTX.
Because
of
this,
a
few
centers
perform
liver
biopsies
as
part
of their
routine
follow-Up.21
This
side
effect
is
very
rare
with
low doses of
MTX
and
usually
affects
patients
with
preexisting
liver
problems
such
as
extremely
obese
patients,
chronic
alcoholics,
and
diabetic
patients.2
Bone
mar-row
suppression
is
rare
in
low-dose
MTX,25
as
is
generalized
vasculitis
with
fever.15'25
MTX is
known
to
be
teratogenic
when taken
early
in
pregnancy.
Reversible
oligospermia
has also been
reported.
26
At
the
present,
MTX is
used
to treat
children with
two
different groups of diseases:
malignancy
and
various
inflammatory collagen
vascular
diseases.
For
the
treatment
of
malignant
2disorders,
doses
of
50
to
150
mg/wk
are
often
used.27
These
doses
are
associ-ated
with
frequent
side
effects.28
Lower
doses such
as
5
to
25
mg/wk
are
used for
the
treatment
of
rheu-matoid
arthritis,
psoriatic
arthritis,
systemic
lupus,
and
polymyositis/dermatomyositis.
These doses
are
believed
to
be
safe and
usually
are
associated
with
only
minor
side
effects.`7
The mechanism
by
which
MTX
affects the asthma
is
not
completely
understood.
It
may be due
to
the
fact
that MTX in low
doses
is
an
anti-inflammatory
drug
that
suppresses
the
small
aiirwa
inflammation
that
is part
of
the asthma pahlgy
L30
The
drugi
a
folic acid
analogue
with
a
variable
half-life that
is
50% bound
to
albumin.'10'31
It is
primarily
excreted
in
the urine via
glomerular
filtration and
active
proximal
tubular
secretion.3
Methotrexate
does
have
a
reduced
clearance
in
renal disease which
requires
a
dose
ad-justment.
The
MTX
dose
required
to
suppress
inflam-mation
is
lower
than
the
immunosuppressive
dose.333
Low
doses
of
the
drug
inhibit both
neutro-phile
chemotaxis and wheal and
flare
responses.354
Recently
it
was
found
to
suppress
the LTB-4
genera-tion in
neutrophils
by
inhibition
of
5-lipoxy~-.enase
and leukotriene
A4
epoxide hydrolase
activity.
1
Low
doses
of
MTX
also inhibit the
primary
and
secondary
antibody
response.
42
Several
drugs
have
been
reported
to
interact
with
MTX. Its
displacement
from
albumin has
been
re-ported
with
barbiturates,
salicylates,
sulfonamide,
tet-racycline, probenecid,
and
phenytoin.3
its
renal
se-cretion
may
be inhibited
by
salicylates, penicillins,
probenecid,
and
sulfonamide.31
Some
drugs-eg,
penicillins,
folic
acid,
cephalothin,
and
corticoster-oids-might
interfere
with its
cellular
uptake,
which
might
be crucial
in
children.8
Bone
marrow
suppres-sion
may be
potentiated
by sulfa-containing drugs.
We
did
measure
theophylline
concentrations
repeat-edly
and,
in
accordance
with the
literature,
they
were
not
affected
by
MTX.
This
was an
open and uncontrolled trial of
MTX
for
treatment
of
severe
asthma in
children.
For
this
reason,
we
cannot
make the
general
statement
that
populations
of asthmatics similar
to
our own
will
respond
differently
to
MTX
than
to
placebo.
We
can
state
that
several of
our
patients
experienced
a
clear
and
unequivocal
response
to
MTX
that
reversed when
the
drug
was
discontinued
and recurred when
it
was
restarted.
The
nature
of
statistical
inference
is
such that
sig-nificant differences between
populations
cannot
be
applied directly
to
individual
patients.
For
this
pur-pose, open
trials such
as
the
current
one can
provide
guidance
to
practitioners
who may
wish
to
provide
this
type
of
treatment
on a
trial basis.
A
patient
either
will
respond
or
will
not
respond.
We
suggest
that
it
is
reasonable
to
try
MTX
when
patients
fail
to
respond
to
conventional
treatment
and
are
at
risk
of
substan-tial
toxicity.
This
toxicity
can
be
both
physical
(from
638
METHOTREXATE FOR ASTHMA
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side
effects of
medications)
and
psychologic
(from
having
to
follow
extremely
difficult medication
regi-mens).
The question
of
patient
compliance is always
of
great importance.
Since
MTX is given on a
once-a-week schedule,
it
has
an
obvious advantage
in
this
respect.
We would therefore ask whether MTX should
be used
in
severe
asthmatics who
are
noncompliant.
The
answer to
this
question
would be
particularly
germane
for the so-called
fatality-prone
asthmatics.
It is
possible that the risk of
asthma
death could
be
greater
than
the
risk of adverse
effects from
MTX. At
this point, there
are
simply
no
data
available
to
justify
its use in
this situation,
but
we
do
suggest
that clinical
trials be
performed
to answer
this
and other questions
pertaining
to
MTX treatment
of asthma.
CONCLUSION
Methotrexate
as an
anti-inflammatory,
immune-modulating
agent
has
proven to
be
effective for
the
treatment
of several
severe
steroid-dependent
asth-matic
children.
It
permitted
them to
decrease their
use
of
systemic
corticosteroids and resulted
in
a
de-crease in
steroid-related side
effects.
Few
signs
of
MTX-related
toxicity were
found
at
doses of
up to
17.5
mg/wk.
Asthma
symptoms
improved
in
most
of
our
patients and
three
were
able
to
discontinue their
corticosteroids completely. Additional clinical
trials
of
this
drug
appear
warranted
to
determine
its
long-term
effects
on
asthmatic
children,
which patients
will
benefit from
it, and
its
indications.
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1992;89;635
Pediatrics
Salomon Guss and Jay Portnoy
Methotrexate Treatment of Severe Asthma in Children
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Salomon Guss and Jay Portnoy
Methotrexate Treatment of Severe Asthma in Children
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