Thorax 1993;48:979-984

Stemomastoid muscle fatigue and twitchmaximum relaxation rate in patients with steroid

dependent asthma

V H F Mak, J R Bugler, S G Spiro

Department ofThoracic Medicine,University CollegeHospital, GowerStreet, LondonWC1 6AUV H F MakJ R BuglerS G SpiroReprint requests to:Dr Vince Mak, Departmentof Respiratory Medicine,St Thomas' Hospital,Lambeth Palace Road,London SE1 7EHReceived 18 February 1993Accepted 29 June 1993

AbstractBackground-Long term oral cortico-steroid treatment is a cause of myopathy-of the skeletal muscles. The effect of longterm treatment with oral corticosteroidson the respiratory muscles is uncertain.Respiratory muscle function and fatiguein sternomastoid muscle were investi-gated in a group of patients with chronicsevere asthma who were taking oral cor-ticosteroids. The results were comparedwith those from a group of patients withchronic airflow limitation who were nottaking oral steroids.Methods-Twelve patients with chronicsevere asthma, taking a mean dailydosage of 8 mg of prednisolone for amean (SD) of 16-8 (9.1) years, were com-pared with patients with chronic airflowlimitation and individually matched forsex, age, and severity of airflow limita-tion. Lung function tests, maximalmouth pressures, and quadriceps andsternomastoid muscle strength weremeasured. The sternomastoid musclewas fatigued by maximal headlift exer-cise to 70% of initial headlift force andthe endurance time noted. Sterno-mastoid fatigue was assessed by twitchmaximum relaxation rate (TMRR)measured in the fresh state and for 30minutes after exercise.Results-There was no significant differ-ence between the control group and thecorticosteroid group for maximal mouthpressures, fresh state TMRR, andquadriceps and sternomastoid strength.The control group had a significantlylonger mean (SD) endurance time thanthe corticosteroid group (121 (47) s v 86(24) s), and also had significantly lessslowing and faster recovery of the TMRRafter exercise. The slowing and recoveryof the TMRR in the corticosteroid group,however, was similar to that previouslyreported for normal subjects.Conclusion-Respiratory muscle weak-ness does not occur more often inpatients taking oral corticosteroids. Thecorticosteroid group was more prone tofatigue than the control group, but wassimilar to normal subjects. This suggeststhat chronic airflow limitation may pro-duce a traning effect on the respiratory

muscles that might be attenuated by longterm oral corticosteroid treatment.

(Thorax 1993;48:979-984)

Despite the widespread use of potent topicalinhaled corticosteroids for the treatment ofasthma, some patients with chronic severeasthma remain dependent on long term oralcorticosteroid treatment to control theirsymptoms. These patients are at risk fromthe well known systemic side effects of oralcorticosteroids, which include adrenal sup-pression, osteoporosis, impaired carbohydratemetabolism, truncal obesity, dermal thinning,and myopathy. Corticosteroid inducedmyopathy has been described mainly in theproximal skeletal muscles'-3 and is usuallyrelated to long term treatment. Myopathy ofthe peripheral muscles has been describedin asthmatic patients given long term oralcorticosteroid treatment4 and also in patientsgiven short periods of treatment with intra-venous steroids.56

Little is known about the effects of longterm oral corticosteroid treatment on thefunction of the respiratory muscles. If cortico-steroid induced myopathy also involves therespiratory muscles, this could predispose toweakness and fatigue of these muscles andsubsequent respiratory failure. To date,studies have not shown obvious respiratorymuscle weakness in patients with respiratorydisease given steroids.478 It is not known,however, if long term corticosteroid treat-ment makes the respiratory muscles prone tofatigue.We have previously described a simple and

sensitive test to detect fatigue in an accessorymuscle of respiration-namely, the slowing ofthe sternomastoid muscle twitch maximumrelaxation rate (TMRR).9 The TMRR of cer-tain muscles in animals is slower in muscleswith myopathy induced by corticosteroids.'°I1Therefore, the TMRR of the sternomastoidmuscle may serve as an indicator of cortico-steroid induced myopathy in the respiratorymuscles in humans.We have investigated respiratory muscle

function and stemomastoid muscle fatiguewith the sternomastoid TMRR technique in agroup of patients with chronic severe asthmarequiring long term oral corticosteroid treat-ment.

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Patients and methodsPATIENTSWe studied 12 patients with chronic severeasthma requiring long term oral cortico-steroid treatment. All had a well documentedhistory of variability of lung function respon-sive to oral corticosteroid treatment, butcould not be weaned off their oral cortico-steroids despite high dose inhaled cortico-steroid medication. All had been taking oralcorticosteroids for at least two years beforethe study. Patients were studied in a stableclinical condition on their minimum main-tenance oral corticosteroid dose plus theirusual medications, which included high doseinhaled corticosteroids (> 1500 pg/day beclo-methasone), inhaled fJ2 agonists, ipratropiumbromide and, in four patients, oral theo-phyllines.

It was possible to individually match thesepatients with a control group of patients withchronic airflow limitation who had nevertaken regular oral steroids. The two groupswere matched for sex, age, height, and indicesof airflow limitation and hyperinflation. Allhad previously received one or two shortcourses (< two weeks) of oral corticosteroidsfor acute exacerbations or as a steroid trialduring the course of their disease, but nonefor at least six months before the study. Thecontrol group was also studied in a stableclinical condition on their usual medication,which included inhaled fJ2 agonists, ipra-tropium bromide and, in five patients, oraltheophyllines. Eight of the 12 were also tak-ing inhaled corticosteroids (<1000,ug/day ofbeclomethasone).We also studied 18 patients with chronic

severe asthma requiring long term oral corti-costeroid treatment whom we could notmatch, and include data from these patientsto compare with the smaller group of 12patients taking corticosteroids.No patients had any evidence of neuro-

pathic or joint disorders that would haveimpaired their ability to carry out the tests onmuscle strength and endurance. Two patientstaking long term oral corticosteroids hadcomplained in the past of muscle weakness,especially of the legs. All patients gave writteninformed consent and the study was approvedby the ethics committee of University CollegeHospital.

LUNG FUNCTION STUDIESAll patients underwent detailed lung functiontests. Spirometry and peak flow were mea-sured with a computerised dry rolling sealspirometer (Gould Pulmograph System 2130,UK). Total lung capacity (TLC) and lungvolume subdivisions were calculated frommeasuring thoracic gas volume in a constantvolume whole body plethysmograph (Fenyvesand Gut, Switzerland). At least three mea-surements were made for each variable.Predicted values were obtained from regres-sion equations given in Cotes."2

RESPIRATORY MUSCLE STRENGTHRespiratory muscle strength was assessed by

maximal mouth pressures with a techniqueadapted from Black and Hyatt.'3 A mouth-piece was attached to a rigid perspex tube 30cm in length and 3 cm internal diameter. Thetube had a 1-5 mm diameter leak hole 15 cmdown its length to prevent closure of the glot-tis during respiratory manoeuvres. The pres-sure generated within the tube was measuredwith a Medex vascular pressure transducer(Medex Inc, Rossendale, UK) attached to theend of the tube. This system has been vali-dated for measuring respiratory pressures andhas a precision of + 2%.'4 Maximum inspira-tory pressure (Pimax) was measured fromresidual volume and maximum expiratorypressure (PEmax) was measured at total lungcapacity with the patients' palms pressingagainst their cheeks to prevent any contribu-tion from the buccal musculature. The maxi-mal pressure sustained for at least one secondwas recorded and the best of four attemptstaken. Reference values previously establishedby our laboratory with this technique wereused. 1'

STERNOMASTOID MUSCLE STRENGTH ANDENDURANCESternomastoid muscle strength was assessedby measuring the maximum voluntary head-lift force. The patients lay on a couch withtheir head and shoulders resting on a pillowat an angle of 30-45 degrees. Patients wereasked to lift their foreheads a few centimetresfrom the resting position and to push as hardas possible against a pad attached to a loadcell (Dyanometer UF-2, Ormed, UK)secured above them. The headlift force thusobtained was recorded on a chart recorderand calculated in Newtons (N). The best offour attempts was taken. Seventy per cent ofthe maximum headlift force was calculatedand marked on the chart recorder. Thepatients were then exercised by performingrepeated maximal headlifts against the fixedpad for two seconds followed by two secondsrest (giving a tension/time index of 50%).This exercise was continued until each sub-ject could not achieve 70% of their initialmaximum headlift force on three consecutiveattempts despite active encouragement. Thetime taken to this point was recorded as theendurance time.

STERNOMASTOID FATIGUESternomastoid fatigue was assessed from thesternomastoid twitch maximum relaxationrate. Full details of this technique have beendescribed previously.9 Briefly, patients werestudied lying at an angle of 30-45 degrees.The right sternomastoid muscle was stimu-lated with two electrodes (3M Red Dot ECGelectrode), one placed on the sternum andthe other placed over the insertion of theaccessory nerve into the body of the muscle.The anterior force vector generated by themuscle contraction was measured with a loadcell (Dyanometer UF-2, Ormed, UK)attached to a curved perspex head pressedfirmly on to the medial (sternal) tendon ofthe muscle. The load cell was in turn

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attached to a custom designed rigid metalframe that allowed adjustments in severaldirections to simplify ideal placement.The muscle was electrically stimulated

with a unidirectional square wave impulse of50,s. Twitches were recorded with a UVlight sensitive chart recorder running at100 mm/s (Micromovements, UK). Initially,maximal stimulation voltage was determinedby measuring the twitch force response toincreasing voltages and was taken as the low-est voltage that gave a maximal twitchresponse (usually 50-80 V). Stimulation volt-age for each patient was set at 10 V above themaximal voltage (to ensure supramaximalstimulation) and all twitches performed at1 Hz with the breath held at end tidal expira-tion. Up to eight twitches could be performedduring each breathhold. At least 24 twitcheswere measured in the fresh state. After theendurance exercise protocol, twitches wererecorded at 1, 2X5, 5, 7-5, 10, 15, and 30minutes, with at least eight twitches on eachoccasion.

All recorded twitches were analysed byhand. The TMRR was taken as the slope ofthe tangent drawn against the steepest part ofthe relaxation curve (usually the initial10-50% of the curve) normalised for the peaktwitch force, and expressed as % force loss/10ms. Any twitch that did not have a smoothrelaxation curve was rejected. At least sixacceptable twitches were used to calculate themean TMRR for each period after exercise.

PERIPHERAL MUSCLE STRENGTHPeripheral muscle strength was assessed fromthe quadriceps muscle with a standardquadriceps chair.'6 The leg was held in pas-sive flexion with an ankle strap attached to acustom built strain gauge. Patients wereasked to make maximal extension movementsat the knee against the ankle strap. The forceproduced was recorded on a chart recorder.The best of four attempts was used and forcewas calculated in Newtons (N). Predictedvalues for quadriceps strength were calculatedfrom equations based on age, sex and height,

Table 1 Mean (SD) data for age and lungfunction

AdditionalControl group Corticosteroid corticosteroid(n = 12) group (n = 12) patients (n = 18)

M/F 6/6 6/6 8/10Age (y) 61-4 (9-3) 59-5 (10-4) 57-1 (14-9)Height (m) 1-63 (0-11) 1-64 (0.11) 1-67 (0-14)Average daily dose N/A 8-00 (2 8) 8-00 (3-11)

prednisolone (mg)Duration of treatment (y) N/A 16-8 (9 1) 13-3 (9-5)Peak flow (1/min) 160 (75) 189 (89) 278 (88)*FEVI(1) 1-10 (0-46) 1 19 (0-55) 1-92 (0.55)*FVC (1) 2-47 (0 74) 2-57 (1-05) 3-19 (0-85)FEV,/FVC (%) 44-5 (12-9) 47-7 (13-5) 59-9 (9.6)*TLC (l) 6-66 (1 85) 6 99 (2*17) 6 14 (1-37)FRC (1) 4-73 (1-65) 4-89 (1-65) 3-75 (1-06)*TLCO (mmol/kPa/s) 5-94 (1-51) 7 05 (2 03) 8-40 (2 80)Kco (mmol/kPa/s/l) 1-32 (0-42) 1-68 (0-53) 1-72 (0-52)

*p < 0 05 between corticosteroid groups.M/F-male/female; N/A-not applicable; FEV,-forced expiratory volume in one sec-ond; FVC-forced vital capacity; TLC-total lung capacity; FRC-functional residualcapacity; TLco-carbon monoxide transfer factor; Kco-transfer factor per unit lungvolume.

and values below 60% of these values weretaken as abnormal (D A Jones, personal com-munication).

STATISTICSStandard statistical methods to calculate themean, standard deviation, standard error ofthe mean, and Pearson's correlation wereused. An unpaired t test was used to analysethe differences between the control group andmatched patients on oral corticosteroids afterensuring- that the two groups had equal vari-ances by means of the F test. A p value of lessthan 0-05 was taken as significant.

ResultsTable 1 gives details of the mean age, steroiddose, duration of treatment, and lung func-tion of the matched corticosteroid group andcontrol group. The two groups were closelymatched in terms of age, height, weight andall indices of lung function. Although thecontrol group had lower indices of gas trans-fer (as would be expected from a group ofpatients with mostly chronic airflow limita-tion induced by smoking rather than asthma),the differences between the two groups didnot reach statistical significance. Also shownin table 1 are the results from the additional18 patients taking corticosteroids who, as agroup, had significantly less severe airflowlimitation than the group of 12 corticosteroiddependent patients. Table 2 summarises therespiratory and quadriceps strength for thethree groups. Only one patient in the smallercorticosteroid group had evidence of quadri-ceps weakness. This patient had previouslyreported muscle weakness, but did not haveabnormal respiratory pressures or weaksternomastoid muscles. Four patients in thecontrol group had evidence of quadricepsmuscle weakness.The mean maximal mouth pressures for

both the matched corticosteroid group andthe control group were similar and within thenormal range for adults as established previ-ously in our laboratory (table 2).'5 In thematched corticosteroid group, however, twopatients had a PImax or PEmax below thenormal range for their sex as did five patientsin the control group. Based on Fisher's exacttest, there was no significant difference in theprevalence of patients with respiratory pres-sures below the normal range between thetwo groups. Of the five patients who hadabnormal respiratory pressures in the controlgroup, three had also had quadriceps weak-ness. In the 18 additional patients on cortico-steroids, three were below the normal rangefor either Pimax or PEmax.The mean sternomastoid muscle TMRRs

in the matched corticosteroid and controlgroups were similar (table 2) and were withinthe normal range established in this labora-tory from 32 normal subjects (mean (SD)9-62 (1-91), range 5-8-13-44% forceloss/l10 ms).The mean (SD) endurance time of headlift

exercise was significantly longer in the control

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Table 2 Mean (SD) values of respiratory and peripheral muscle strength, endurancetime, andfresh state TMRR

Control group Corticosteroid group Additional corticosteroid(n = 12) (n = 12) patients (n = 18)

Pimax (cm H,O) 52-1 (22-4) 66-1 (24 0) 67-4 (26 2)PEmax (cm H,O) 95 7 (49-3) 119-3 (52-1) 96-1 (32 3)Quadriceps MVC (N) 226 (90) 266 (103) 276 (106)Sternomastoid MVC (N) 80-9 (22-5) 82-3 (28-8) 81-1 (24 3)Endurance time (s) 121 (47) 86 (24)* 102 (36)Fresh state TMRR 10 10 (1-95) 10-36 (2 02) 10-94 (2.35)

(% force loss 10 ms)

*p < 0 05 v control group.Pimax-maximum inspiratory mouth pressure; PEmax-maximum expiratory mouthpressure; MVC-maximal voluntary contraction; TMRR-twitch maximum relaxationrate.

110

100

90

81

6

Figure .corticostsignifica

110

100

C,)

a1)LL

Figure,matchetcorticos

costeroid group and this recovered moreslowly after exercise (fig 1). In the controlgroup, two subjects showed little change oracceleration of the TMRR after exercise.These two subjects could have accounted forthe significant differences between the twogroups. If these two controls, together withthe two corticosteroid patients with whomthey were matched, were excluded from theanalysis, however, the mean percentage slow-ing and rate of recovery of the TMRRbetween the two groups still remained signifi-cantly different.The fall and recovery of the TMRR was

similar between the smaller group of patientstaking corticosteroids and the additional 18patients taking corticosteroids (fig 2).

There was no correlation between any ofthe indices of muscle function with the doseof steroids, or with the duration of use ofsteroids, or with the product of these twovariables.

,o- Discussion

We have shown that there is little evidence of0o- respiratory muscle weakness, as assessed by

maximal mouth pressures, in asthmatic

__________________________patients taking long term oral corticosteroid

io- treatment compared with a control group ofpatients with chronic airflow limitation.Patients taking corticosteroids had fresh statesternomastoid TMRRs well within the nor-

0 l E mal range and similar to the control group.Fresh 1 5 10 15 20 25 30 Asthmatic patients taking corticosteroids,

Time after exercise (min) however, had significantly shorter sterno-1 Mean percentage slowing and recovery offresh state TMRR after exercise in the mastoid exercise endurance time with signifi-teroid group (0, n = 12) and the control group (0, n = 12). These are candy mintly differentfrom each other at all times when measured up to 30 minutes. rate slowig of the TMRR and slower

rate of recovery than controls. This suggests

that the sternomastoid muscle in cortico-group compared with the matched cortico- steroid dependent asthmatic patients fatiguessteroid group (121(47)s v 86(24)s, p < 0-05). more easily and takes longer to recover fromDespite less exercise, however, the mean fatigue than in patients with equivalent sever-

percentage slowing from fresh state TMRR ity of airflow obstruction but not taking oralwas significantly greater in the matched corti- corticosteroids.

The prolonged slowing of the TMRR inthe asthmatic group shows a major advantageof the TMRR over the more commonly usedindicator of the fatiguing process, the maxi-

mum relaxation rate (MRR; measured aftertetanic stimulation or maximum voluntarycontractions).'6" After fatiguing exercise,slowing of the stemomastoid TMRR lasts forlonger than the MRR, and seems to follow

the time course of low frequency fatigue.9

Also, the sternomastoid muscle TMRR slowsbefore the loss of force generating capacity,and the degree of slowing and rate of recoveryof the TMRR is related to the precedingload.'8 Therefore, slowing of the TMRR can

indicate if the muscle is undergoing a poten-tially fatiguing load. Comparison of the corti-costeroid group with our previously publishedresults for 10 normal subjects without respi-

ratory disease and exercised to the same

Fresh 1 5 10 15 20 25 30 degree of fatigue9 showed that the slowing

and recovery of the sternomastoid TMRR are(mm)similar (fig 3). Althoug these two grouprs are

2 Mean percentage slowing and recovery offresh state TMRR after exercise in the direcl compa. (thes nor g sujed corticosteroid group (0 n = 12) and the additional 18 patients taking notdirectlycomparable (thenormal subjectsteroids (0). were younger and had a different sex distribu-

c:

a)L-

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100

90

-C,U)LL

80

70

60

Fresh

Figure 3 Mean percentmatched corticosteroid gri(0, n = 10).

mild to moderate airflow obstruction butwere not taking long term oral cortico-steroids. Their findings showed enhancedendurance of both inspiratory and expiratorymuscles but not limb muscles in both asth-matic patients, and patients with chronic air-flow limitation. They also suggested that thiswas due to a training effect that chronic orintermittent episodes of airflow obstruction

PI./ | t had on the respiratory muscles. Our asth-matic patients, however, showed reducedendurance of the sternomastoid muscle com-

pared with patients with chronic airflow limi-tation. This suggests that there is a differencebetween the sternomastoid and other musclesof respiration, or that there is a myopathiceffect from the oral corticosteroids, or thatsteroids attenuated the training effects of achronic respiratory load.

X Another possible explanation for our find-1 5 10 15 20 25 30 ings could relate to differences in the two dis-

Time after exercise (min) eases we have studied. The load on the

age slowing and recovery offresh state TMRR after exercise in the respiratory muscles in chronic airflow limita-oup (0, n = 12) and previously studied normal subjects tion is fairly constant, whereas it may be

intermittent in asthma. All our asthmatic sub-jects, however, were studied in a stable condi-

tion), it is possible that sternomastoid muscle tion and had severe airflow limitation in thefunction in the corticosteroid group is actu- stable state. Therefore, they would have aally normal. The decreased slowing and more similar chronic load to that of the patientsrapid recovery of the TMRR shown by our with chronic airflow limitation together withcontrol group may well be due to a training intermittent exacerbations, so should haveeffect on the accessory muscles of respirationin these patients because of the constant useof these muscles to breathe (supranormal). Ifthis was the case, however, the corticosteroidgroup, which was closely matched for respira-tory impairment, should also have exhibited atraining effect on the sternomastoid muscle.A possible explanation as to why no train-

ing effect was seen in the corticosteroiddependent asthmatic patients could be thatcorticosteroids do actually produce a myo-pathy of the respiratory muscles, but the con-stant use of such muscles in these breathlesspatients keeps the function of the muscles atnormal levels. The protective effect of regularexercise in preventing corticosteroid inducedmyopathy in other muscles has been welldescribed in both animal models' 22 andhuman subjects.2324 Therefore, regular use ofthe respiratory muscles in corticosteroidtreated patients may prevent them frombecoming myopathic. Alternatively, steroidsmay attenuate the training effects of chronicairflow obstruction and stop the muscles frombecoming supranormal. We did not examinethe quadriceps or the sternomastoids of ourasthmatic patients histologically, so we can-not be sure if any had steroid induced myo-pathy. Only one of our asthmatic patients hadevidence of peripheral muscle weakness,whereas four patients in the control grouphad weak quadriceps muscles, so it seemsunlikely that many patients treated with corti-costeroids had a significant peripheral myo-pathy.

Gandevia and colleagues have also foundincreased endurance in the respiratory mus-cles of patients with chronic airflow limitationand asthma.2526 Their asthmatic patients had

exhibited a similar training effect. Also, ourasthmatic patients could have performed lesswell because of bronchospasm induced byexercise. Although we did not measure lungftunction after exercise, no patients com-plained of worsening of asthma after the exer-cises, or required bronchodilators.Few studies have examined the effect of

long term oral corticosteroid treatment on therespiratory muscles of humans. One study hasexamined the effect of a short course of pred-nisolone (20 mg/day for 14 days) on normalsubjects and found no change in respiratorypressures or endurance.7 Picardo et all' exam-ined a group of 34 patients with chronicsevere asthma who had been taking an aver-age dose of 119 mg of prednisolone for amean of 7.9 years (a higher mean dose but ashorter duration of treatment than in ourgroup) and found no difference in respiratoryor peripheral muscle strength when comparedwith a group of age, sex, height, and weightmatched asthmatic patients. The controlgroup was not well matched in terms of respi-ratory impairment, however, with the steroidgroup having a forced expiratory volume inone second (FEVy) of 54-1% of predictedcompared with the control group with anFEV, of 73% (p < 0-001).The clinical effect of therapeutic doses of

corticosteroids on peripheral skeletal muscleis well known,12 but animal models of corti-costeroid myopathy have produced conflict-ing results. Corticosteroids produce selectiveatrophy of fast twitch type II fibres in skeletalmuscles'02728 and in the diaphragms of vari-ous animals,"I 29-31 without change in the pro-portion of type I to type II fibres within themuscle. Although these studies show changes

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occurring within the muscle, the manifesta-tion of the myopathy was variable. Theseinconsistent results may be due to the differ-ent animals used, different corticosteroids,and widely differing dose regimens.

Studies that have examined the enduranceof corticosteroid treated diaphragms have alsogenerated conflicting results; some reportingincreased or unchanged endurance,"29 andothers reduced endurance.31 32 Picardo et a1 8found that respiratory muscle endurance, astested by breathing against an inspiratoryresistance, was similar in a group of 10patients treated with steroids and an anthro-pometrically matched control group. In ourstudy, with patients more closely matched,the group treated with steroids had a signifi-cantly shorter endurance time when the ster-nomastoid muscle was tested by maximalheadlift exercise. If atrophy occurs mainly infast fatigue type II fibres, leaving behind apopulation of fatigue resistant type I fibresthen, theoretically, the muscle should becomeless prone to fatigue. This does not, however,take into account the reduction in mass seenin corticosteroid treated muscles." 29 30

Finally, with regard to the effects of corti-costeroids on the twitch contractile propertiesof muscle, some studies have reported nochange in relaxation rate,293' whereas othershave reported a slowing of relaxation.'0" 30Again, if corticosteroids produce atrophy ofmainly fast twitch type II fibres, the contribu-tion of slow twitch type I fibres shouldbecome more prominent and the relaxationrate of the muscle should become slower. Aslow resting TMRR may therefore be an indi-cation of loss of type II fibres. The meanTMRR of our steroid group was, however,similar to that of normal subjects and that ofthe control group.

In conclusion, although patients treatedwith corticosteroids show no significantreduction in muscle strength or respiratorypressures, there may be a reduced trainingeffect on the respiratory muscles comparedwith patients with a similar respiratoryimpairment.We are grateful to Dr GJ Gibson for his useful comments andcriticisms, and Dr DA Jones for the predicted values forquadriceps strength in normal subjects. VHFM was funded bythe Chest, Heart, and Stroke Association.

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