The effect of corticosteroids on inspiratory muscle performance in humans.

P Weiner, Y Azgad and M Weiner Chest 1993;104;1788-1791 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/104/6/1788

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The Effect of Corticosteroids on InspiratoryMusclePerformancein Humans*

Faith:! Weiner, M.D.; Yair Azgad, M.Sc; and Margalit Weiner, Ph.D.
Functional alterations in the inspiratory mu@des were in marked improvement in both strength and endurance;

evaluated in patients receiving corticosteroids for diseases other than respiratory. Inspiratory muscle strength, as expressed by the maximal inspiratory mouth pressure (Pimax), and inspiratory muscle endurance (PmPeak/
Pimax), using a pressure threshold breathing device, were

the inspiratory muscle strength rose significantly to 112.2 1 cm H,O (p<O.0005) when steroid treatment was 8.
stopped,
123.18.1

and even more significantly

cm H20 [p<OMOO1]), and

6 months
the

later (to

PmPeak/Pimax

evaluated in eight patients with normal pulmonary and inspiratory muscle functions (two patients with rapidly progressive glomorulonephritis, two with glomorulonephri
tis with minimal changes, two with idiopathic thrombocy

rose to 60.63.4 jercent (p<O.OOl) and to 74.73.2 percent (p<O.000l), respectively. We conclude that corti

costeroids have a significant deteriorating effect on respi

ratory muscle function in humans. This weakness is revers

topenic purpura, and endurance

and two with subacute following corticosteroid

thyroiditis). administration.
while

There Al

ible while tapering stemid dosage. Steroid therapy should be reconsidered in patients with underlying lung disease.
(Chest 1993; 104:1788-91)

was a gradual decrease in both inspiratory muscle strength ter 8 weeks of treatment PmPeaklPimax decreased from
84.4 2.4 to 67.9 3.1 percent (p<O.OO1), inspiratory

muscle strength dropped from 126.99.6 to 86.57.4 cm H20 (p<O.005). Gradual steroid dosage tapering resulted C orticosteroids in high doses and for prolonged periods are frequently used in the treatment of many pulmonary 1,2Steroid-induced myopa thy is a well-known clinical entity in patients treated with high doses of corticosteroids.3 However, little
attention has been paid to the effects of chroni

mouth pressure; PmPeak peak pressure; PmPeak/Pimax

inspiratory muscle endurance

FVC = forced vital capacity; Pimax

maximal inspiratory

who received corticosteroids for diseases other than respiratory and had to meet the following criteria: 1. No history or evidence of ans respiratory, cardiovascular, allergic, neuromuscula@, rheumatobogic, or endocrine disease or any disease that might impair muscle function.

2. Normal pulmonary function tests. 3. Normal respiratory muscle function tests.

4. Not taking any medications. The patients' characteristics are summarized in Table 1. Subjects were treated with high doses of cortic()steroids (prednisone, 1 to

For editorial comment see page 1649 administration

function; disorders.4 of chronic

1.5 mgfkg/d) for 8 weeks, when doses were tapered down to

ofcorticosteroids
this question studies

on respiratiry
is of great

muscle
potential

complete withdrawal within 6 weeks.

Tests

although Several

relevance to patients already suffering from respiratory

have been performed in

All measurements were made with the subject seated in a high

back chair to keep posture constant. All tests were perf@rmed before and every 2 weeks after the administration of corticosteroids and up to 3 months. Tests were then repeated following complete withdrawal of the drug and 6 months later.

order to provide definitive

administration

information

on the effects
on respi

of corticosteroids

ratory muscle function in patients with respiratory diseases!58 However, it is impossible to separate the
effects of steroid therapy from the effects of the

Spirometry: The forced vital capacity (FVC) and the FEy were
measured three times on a computerized spirometer (Compact, Vitalograph, Buckingham, England), and the best trialwas reported. Inspiratory Muscle Strength: Inspiratory muscle strength was assessed 1)V measuring the maximal inspiratory mouth pressure
(Pimax), at residual volume, as previously described by Black and

underlying diseases in these patients. Therefore, we examined the effects ofa therapeutic
dosage of corticosteroids on inspiratory muscle func

tion in patients receiving the drug for diseases other than pulmonary with no underlying respiratory or muscular disease.
METHODS Clinical Data
A group of 8 patients,
from 17 to 33 years were

Hyatt.' The value obtained from the best of at least three efforts was used. Inspiratory Muscle Endurance: To determine inspiratory muscle

endurance (PmPeakfPimax), a device similar to that proposed by

Nickerson
nected

and Keens'

was used. Subjects

the inspiratory to which and plunger

inspired
weights

through a two
was con could be added

way Hans-Rudolph to a chamber

valve,

port of which

4 men and 4 women,

studied. All were

with ages ranging

patients

consecutive

externall)@ Inspiratory threshold load was then increased by the progressive addition of 25- to 100-g weights at 2-mm intervals, as was previously described by Martyn and coworkers, rI until the
subjects were exhausted and could no longer inspire. The pressure

*Fmm the Department of Medicine A, Hillel-Yaffe Medical Center, and the Institute for Respiratory Disease, Hadera, Israel. Manuscript received January 6, 1993; revision accepted March 30.

achieved with the heaviest load (tolerated defined as the peak pressure (PmPeak).

for at least 60 s) was

1788

Corticosteroids and Inspiratory Muscle Performance (Weine@ Azgad, Weiner)

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Table 1Characteristics f Patients Included in the Study* o

%1M17RPGN901041102F26ITP60100943M24MCCN6094984M31RPGN901051075F29ST4089976M19MCCN601121037F25ST301011108F33ITP609299Mean Dose, mg'dFEy1, %FVC, SubjectSexAge, yrIndicationtSteroid

SEM25.5

2.061.3 of predicted normal values. MCGN = glomerulonephritis

7.499.6

2.7102.22.2

*Ahl lung function data are expressed as percentage tRPGN = rapidly progressive glomerulonephritis; idiopathic thromhocytopenic psirpura. Statistical Analysis

with

minimal

changes;

ST = ssibacsite

thyroiditis;

ITP =

had normal inspiratory

by the PImax at residual

muscle strength,
volume

as expressed
H20)

Comparisons of the posttreatment versus pretreatment values of respiratory muscle performance in the eight patients were carried out using the two-way repeated measures analysis of variance. RES U LTS

(126.99.6cm

and PmPeakfPlmax as expressed by the relationship between PmPeak and the PImax (84.4 percent), 2.4
before treatment. Following strength administration of corti

costeroids, before treatment

inspiratory the

there
muscle

was a gradual

decrease

in both
although drop in

Spirometry

data for the subjects

and endurance, a significant

are also presented

in Table 1. There was no difference

the rate of decrease was not identical.

initiation of treatment,

Two weeks after

between the posttreatment and pretreatment values in regard to the FEVI/FVC ratio relationship. How ever, there was a small but significant decrease, from 99.62.7 to 94.61.8 (meanSEM [p<O.Ol]) in FEy1 (percentage of predicted normal values) and from 102.22.2 to 90.62.4 (p<O.OOl) in the FVC
(percentage of predicted normal values) following

PmPeak/Plmax was already observed (from 84.4 2.4 to 67.93.1 percent {p<O.OOl]), while inspiratory muscle strength was still reserved at this point and showed a significant drop only at the end of the 4th week of treatment (from 126.9 9.6 to 109.4 10.3 cm H20 [p<O.005J).
At the end of the 8 weeks of treatment, inspiratory muscle performance reached the lowest values. Mean

treatment. The results of the individual irispiratory muscle function are showit in Figures 1 and 2. All subjects

inspiratory

muscle

strength

dropped

to as low as

N.S 160
I
C.,'

130 100 70 40
1--@-I I I I I

E
0
C5

E
a-

/1
Tapering

6 months Time

down Time (weeks)

N.S Not significant

* Statistically significant

FIGURE

1.

Inspiratory

muscle

strength,

as

expressed

by

the

Pimax

at

residsial

volume

before

steroid

treatment, after 8 weeks of treatment (left) and following tapering complete withdrawal of the drag (right).

steroid

dosage and 6 months

after

CHEST I 104 / 6 / DECEMBER, 1993

1789

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100@

80

E
Q.

60
40

Cu

a. E a.

a)

20
0 2 4 6 6

-1/

Time (weeks)
* Statistically significant

down

Tapering

6 months

Time

FmcumsE Inspiratory muscle endurance as expressed by the relationship between PmPeak and the Pmmax, 2. before steroid treatment and after 8 weeks of treatment (left) and following tapering steroid dosage and 6 months after complete withdrawal of the dnmg (right).

86.57.4 cm H20 (p<0.000l),

Pimax decreased to 38.92.4

while the PmPeakl

percent (p<O.000l).

Following gradual reduction of the steroid dose, the patients regained both strength and endurance; the inspiratory muscle strength rose significantly to
112.2 8.1 (p<O.0005) when steroid treatment was

shown the myopathic effects of corticosteroicis on respiratory muscle function in animals.@@16 Ferguson and colleagues'3 found that the histologic changes in the diaphragm were associated with no change in
diaphragrnatic strength but with a fall in PmPeak/

stopped, and rose even more significantly 6 months later (to 123.18.1 [p<O.000l]), as shown in Figure 1. The inspiratory muscle endurance rose to 60.6 3.4
percent (p<O.OO1) and to 74.7 3.2 percent

Pimax. These studies show that steroids may affect respiratory muscles and that myopathy may occur after treatment for 2 weeks or even less. However,
there may be species to humans. differences in susceptibility to

steroid myopathy, and these results are not necessarily

applicable

(p<O.000I), respectively, as seen in Figure 2. At this point in time, the values of both strength and endur aiice statistically were not different from baseline
values. DiscussioN

In this report, we present eight patients with normal

lung and respiratory muscle function, with diseases other than respiratory, who developed severe inspira
tory muscle weakness during treatment with high

Several studies have examined the effects of corti costeroids on respiratory muscle function in humans. Bowyer and colleagues6 found that those patients who showed a marked reduction in hip flexor strength also had reduced inspiratory muscle strength. Melzer and Souhrada7 described four obese patients with steroid dependent bronchial asthma and inspiratory muscle weakness. However, in a previous study by Weiner et
al,m7 it was shown that hyperinflation adversely affects

doses

of corticosteroids.

Tapering

the steroid

dosage

down was clearly associated with regained inspiratory muscle strength and endurance. The reduction in PmPeaklPimax, after 2 weeks of
treatment was striking when compared with the re

served

inspiratory

muscle

strength

at this point

in

time. Glycogen depletion and lactate accumulation are usually associated with reduced muscle endur

ance.'2 Although glycogen depletion

after 2 weeks, in corticosteroid-treated

was not observed,

animals, lactate

levels were significantly elevated in the diaphragms of the animals. ms is possible that the increased lactate
accumulation may have played a role in the reduced

endurance at this point in time, while the strength was still normal. A number of previous studies have
1790

the performance of the inspiratory muscles, in patients with asthma; therefore, the reduction in peak inspi rat()ry mouth pressure may have been due, either partly or completely, to factors other than steroid therapy. There also are anecdotal reports on inspira tory and expiratory muscle weakness following steroid treatment.'5 However, in the vast majority of the cases, respiratory muscle weakness developed following treatment with a combination of steroids and muscle relaxants. ma-2m On the other hand, Picado and coworkers@compared patients who had steroid-dependent bronchial asthma with age- and sex-matched patients who had asthma but were not taking oral steroids. There was no significant difference in respiratory muscle perform
Corticosteroids and Inspiratory Muscle Performance (Weine@ Azgad, Weiner)

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ance between the two patient groups. However, a training effect of the inspiratory and expiratory muscle could have masked respiratory muscle weakness due to steroid myopathy in the prednisone group. Another explanation for the lack of muscle weakness complaints in these asthmatic subjects might be the fact that these patients usually were treated with low doses of steroids. Therefore, although these human studies provide important information, they do not clarify the effects of steroid therapy per se on respiratory muscle function in humans. In a recent study, Wang and colleagnesas have found, in 16 normal volunteers, that prednisone in moderate dosage administered for 2 weeks had no significant effect on respiratory muscles in humans. However, corticosteroids in higher doses and for longer periods of time are frequently used in the treatment of many pulmonary diseases, and the results of the study by Wang et alas are not necessarily applicable to higher doses or longer durations of treatment. Our study shows that patients who receive high dose steroids for several weeks may develop inspira tory muscle weakness, which seems to be reversible following withdrawal of the drug. We were able to isolate the effects of corticosteroids on inspiratory muscle performance from those effects contributed to the underlying disease, by choosing patients who had no pulmonary disease and who had normal pulmonary and respiratory muscle function. Whether similar changes might be observed in patients treated with lower doses of corticosteroids needs to be determined. However, if such changes are encountered frequently, the use of systemic cortico steroids should be limited in patients already suffering from respiratory disease.
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The effect of corticosteroids on inspiratory muscle performance in humans. P Weiner, Y Azgad and M Weiner Chest 1993;104; 1788-1791 This information is current as of May 24, 2012
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