Relationships among nutritional status and skeletal ...

Relationships among nutritional status and skeletal respiratory muscle function in cystic fibrosis: does dietary supplementation make a difference?13 Rhona Lorraine

M Hanning, A Moss,

ABSTRACT skeletal

Cameron and William Relationships

and

respiratory

children with cystic 95 ± 16% predicted).

among

muscle fibrosis Subjects

were muscle

were

indicated

that

respiratory

muscle

not.

changes

Thus,

and

examined

in

16

lung disease (FEy1 assigned to receive

supplementation for 6 mo. Skeletal

at 25% of normuscle strength

changes

in skeletal

muscle

strength,

and

in skeletal

use ofdietary muscle

Am

J Clin

Nutr

and

[weight (kg) voluntary 0.76, P muscle

=

7 y of

that

improved

would

result

University Studies.

1 5 y of age

Research

volunteered

for

fewer than the sample size of 24 on the following calculations: a

main outcome of interest, muscle variation of 8% in CJR Blimkie’s supplementation

Fibrosis

lung disease, and were not receiving or total parenteral nutrition. The

between

the study. which was that we had estimated

we

Cystic

at Chedoke-McMaster

strength, laboratory nutritional

in increased

has a coefficient of (1 2- 14). Because intake muscle

from

diet

strength,

a

I From the Departments of Pediatrics and Physical Education. McMaster University and the Children’s Hospital at Chedoke-McMaster, Hamilton. Ontario, Canada. 2 Supported by the Cystic Fibrosis Foundations of the United States and Canada and by an award from the National Institute of Nutrition (RMH). 3 Address reprint requests to RM Hanning. Department of Pediatrics, Faculty of Health Sciences. HSC 3N1 lH. McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. Received May 19. 1992. Accepted for publication October 19. 1992.

1993;57:580-7.

Printed

in USA.

© 1993 American

Society

for Clinical

Nutrition

Downloaded from www.ajcn.org by guest on July 15, 2011

and power respiratory

Oded

nutritional

function

(CF) and mild were randomly

(or not) noninvasive nutritional mal energy recommendations

analysis

JR Blimkie, M Wilson

and early

NUTRITION one-tailed

test

cepting would

of differences

a risk of a have allowed

groups.

Four

found

the

time

control

were

been

randomly

ordered

records,

basis

aerobic

cycle

sampling

and

lung

ofthe and

6 mo

ergometry, protein

takes

envelope

that

numbers.

muscle-function the

and

tests group.

initial

and

and

to take

shakes,

to achieve

for age and in addition

and

were

tinned

25% ofthe

it was emphasized to their normal

compliance, representing

puddings

according

were drink

to personal energy

and

parking

Dietary-intake

and

meal

at 6 mo. to day,

To

account

the 3 d were

expenses

for the

true

with stick-on decals. to apply each time

were

a Gulick

in the

standard

pro-

of Tanner upper arm,

and thigh,

measuring

thicknesses

modified

were

equation

limb

3-d home food diaries trial (0 mo), at 3 mo,

variation

in intake

( 16) and included

Packard,

evoked

voluntary

lean

taken

of Moritani

and

contractile

strength

measured plantar

at

and

fat cross-sectional

(MVC)

pulses

signals from an oscilloscope

Alto,

CA)

and

To

caused MVC

by prior (24).

voluntary

degree right

technique titative

day week-

paring

because have low

of increasing

occurred.

the

the

the torque

twitch

torque

by computer

until

no

effect

of twitch

contraction, unit

KE,

TI

activation

and

PF

using

after

to that

group

at baseline0

increase

was

before

determined

a modification

of the

of the

evoked

A quanby com-

electrical

isometric

in

potentiation

was measured

supramaximal

1-

Peak TI .ts square-

and McComas (25). MUA was obtained

voluntary

(ITT)]

(PDP-l

further

(MUA)

by

by Belanger of the percent

a maximal

IT

the

limbs with

gauge were am1201 B; Hewlett-

Maynard, MA). ofsingle 50-100

voltage

increment

during

terpolated

evoked

strain (model

analyzed

preclude

of motor EF,

described expression

ulation

and

for the elbow flexors (EF), knee extensors flexors (PF) at joint angles of 90#{176} by using

torque

for

properties

described previously ( 12- 14, 23). Briefly, the into custom-made dynamometers instrumented

Palo

wave

that and

from one

and

of subjects

randomly

allocated

to the

control

group

or the

diet-supplemented

All subjects Control (n=5M,5F)

Age (y) Height (cm) Height-for-age

(percentile)

Weight

(kg)

Percent

expected

weight

for age and height

(%)

Ageatdiagnosis(y)

49.4

± 27.9

of patients

expiratory

volume

with

a Tanner

in 1 s.

Stage

>

15.0

30.7

± 9.2

95.6

±

84.2

SD. Number forced

± 2.8 ±

Subjects Supplemented (n=7M,3F)

10.0 135.7

1.7±

FEV1 (% predicted)t 0

in-

slim-

contraction peak

TI

[in-

response:

1

Characteristics

t FEy,

using

spring-loaded

skinfold

03: Digital Equipment Corporation, was determined by applying a series

reimbursed.

end day ( 17, 18). Three days were considered adequate energy and protein, the main nutrients of interest,

TABLE

with

gauges. Torque displayed on

The from of the

not consecutive

by

the standards girths of the

for determining

strength

were and

strain plified,

assessment

Nutrient intake was assessed were completed at the outset

measured

with midpoint

posterior

used

(22)

procedures were fixed

intake

these foods were to be taken (1 5). To enhance and monitor

subjects were given calendars the different food supplements

gifts

and

Maximal (TT) (KE),

of supplements

recommended

that diets

were

nutrient

areas.

on the number

normal

were

measured

were

DeVries

a supplement was taken. Supplies were monitored, contact with families was maintained by telephone, and supplement use was verified from food records. On testing days all subjects received small

were

ments

blood

to receive diet supplements such as instant breakfast

instructed

weight

Anterior

Isometric

They

recommended

12.1 l.8[2]

± 26.3

1 in brackets.

10.7

± 2.4 ±

15.3

57.7

±

30.8

33.7

± 9.9

92.8

±

(n=6M,3F)

± 2.9 ±

17.1

59.4

± 21.1

10.6

± 2.5

142.0

±

62.1

±

31.3

±

10.1

33.9

±

1 1.3

97.7

±

13.4

91.9

±

19.4

81.5

2.6±2.3[3] ±

9.5 135.0

trial

Supplemented

(n=4M,3F)

142.3

101.4

Control

who c ompleted

2.1

± l.9[l] ±

13.7

16.2 29.3 10.4 1 1.6

2.9±2.3

104.9

±

[3] 17.8


milk

preference.

by com-

Intakes

anthropometric tape measure. These measures were used as a substitute for moment-arm in the normalization of strength measures. Limb girths and circumferential skinfold measure-

respi-

anaerobic

analysis,

(20).

this level with a Harpenden caliper. Forearm, lower leg, and foot lengths were measured on the right side of the body with an

mea-

tests,

analyzed

data

(15).

and

calf

tape.

made in both dietrecords. activity

tests,

were

File

of normal

cedures and compared Whitehouse (2 1). The

analysis.

who were allocated with grocery foods

powders,

(RNI)

intakes

Nutrient

as a percentage

Height

after

Canadian

.4 nthropometri’

and or

study

581

( 16- 19). Nutrient

the

expressed

Diet supplements Subjects provided

with

CF

to

for

of random

IN

ratios

puter

distance

muscle-function

bioimpedance

FUNCTION variance

they

recruited

subject’s

pulmonary-function

for plasma

traveling

measurements were groups: dietary-intake skeletal

and

because

a sealed

of a table

of recruitment

anthropometry, muscle-

Ac-

to diet-supplemented

unaware

the following and control

ratory

or the

within

skeletal were

time

proposed.

trial

of subjects in Table I.

a card

on the

anthropometry

surements, supplement

was

the

allocated

performing

At the

complete

for testing

by selecting

Investigators and

not

demands

groups

had

did

The characteristics the trial are outlined

Subjects

groups

MUSCLE

0.05 and /3 = 0. 10, 12 subjects per group us to detect a difference of 10% between

subjects

be excessive. completing

between

AND

582

HANNING %MUA=ITT-TT/TTX

With

only

two

measurements

measurements were lean cross-sectional limb

area

length)

..lnaerohic

and

by

the

and

limb

to correct aerobic

against

count

was

calculated. any 3-S-s

length

(estimated

advantage

(N/cm2).

Basel,

a constant recorded

force on

Switzerland) (0.08

body

a microcomputer

wt).

and

The

power

er-

patients Hamilton,

rael. is 1 5% (26-29). Each subject performed

pedal

(W)

an all-out

the rate of the drop of variation of the

could mm.

no longer The highest

peak

aerobic

maintain power

continuous,

progressive

(30). Each was increased

stage lasted until the

the cadence of 50 pedal sustained for 2 mm was

the ankle.

and

use

function

Doylestown.

and

PA)

age

(3 1 ).

plethsmograph of predicted Respiratory

re.spiratort’

and

expressed

Lung

and

end

ofthe

impedance

in CF

that

ofothers

cy2 mm, subject

resolutions/ taken as the

Plnwical

has

An assessment

of habitual

physical

from

the

method

of Bouchard

couraged the whole

activity

and The

of body

own

was

on two

entary) sion

not to change their physical-activity project. Activity patterns were

work

(36)

made

at 0, 3,

week

days

to 5 (athletic)

and

incorporated

graded

and

technician were en-

patterns from

as a covariant

during 1 (sedin regres-

analyses.

were St Paul,)

Fasting

was measured Instrument Co.

ofpredicted

measured

analyses

in

values whole-body

and expressed

as percent

and

blood

the

samples

plasma

was

was mouth

assessed

at end

pressures

during

expiration 5-s efforts

with

correction

for absolute

the previously measured percent ofpredicted total

of 10

5

three

with efforts

of effort

percent cycles

volume

by using

value of fixed residual capacity as a lung capacity (33). Respiratory muscle

endurance was measured (35). Briefly, 18 repeated as the

lung

repeated static were performed

and

decline held

5 s of rest. in strength

for

maximal by using

efforts a fixed-

Endurance with

1 s during

the the

was largest

ex-

value

10-s effort

and

the largest of the last two cycles held for 1 s during the effort. RE was measured immediately after respiratory-strength assessment and inspiratory function was measured before expiratory function. A 2-5-mm rest was taken between inspiratory and expiratory maneuvers. Four CF subjects dinate their efforts to complete the RE control

subjects

Body

composition

were

composition

37) by using

not

asked

was the

Valhalla

were unable test. The two

to perform

assessed apparatus

the

endurance

by bioelectrical model

to cooryoungest test.

impedance l990A

(Valhalla

were

obtained

separated

in the and

morning

stored

at -70

#{176}C until analyzed. Plasma albumin was measured by the bromcresol green dye-binding technique (39) with a Unicam spectrophotometer (Cambridge. UK). Transthyretin (prealbumin) and retinol-binding

protein

munosorbent

maximal

(5 mL)

immediately

were

assay

sured by reversed-phase Millford, MA) with

measured

Differences

Because

by enzyme-linked

(40).

HPLC precolumn

(Waters. Millipore Corporation. derivitization with phenyliso-

norleucine

as internal

in muscle

the current

Amino

strength

goal

and

acids

im-

(ELISA)

trol groups at 0 and 6 mo were analysis of variance (ANOVA). as statistically significant.

Body

as a measure by our

et al (38)

values

(36.

body water, calculation.

one weekend day. These were reviewed by the exercise with follow-up phone calls when indicated. Subjects

analysis

first

was

activit’i

Statistical

of the

Care

(37).

and

cycle

metatarsal.

supported

thiocyanate

pressed

third

analysis

been

as described by Lands et al (33). The test was repeated until a maximal effort was reached. This usually occurred within threefive efforts. Maximal pressures had to be maintained for 1 s. Values were expressed as cm H2O and as percent of predicted

duty

fre-

surfaces between

and 6 mo. This was an essential component ofthe study because functional muscle changes may also be induced by changes in activity level. Subjects completed a log oftheir activities, modified

strength

as a percent

volumes

static

muscle

in 1 s (FEy1) II: S and M

(Med Graphics. values (32). muscle strength

by measuring

(34)

a signal

power.

Forced expiratory volume by spirometry (Pulmo-Screen for

at the distal

of bioelectrical

Laboratory Pulmonary

and

was

seen at the Children’s Exercise and the Wingate Institute, Is-

cling test on the Fleisch ergometer at the end of which the power

tA.

were

mea-

standard.

between

supplement

and

measure

ofgood

nutritional

sta-

tus in CF is the achievement of normal growth, the data analyzed statistically to determine which variables were predictive

of a favorable

growth

analysis was used to determine were most predictive of baseline height

for

age

and

which

growth velocity in weight We decided a priori that the outcome sures, height)

categories

outcome. which weight

variables

ofthe

elbow

flexors.

Stepwise-regression

best

over the 6-mo only the single

predicted

mean

expiratory

changes

experimental variable from markers.

most highly with in the regression

possible because all outcome measures significantly correlated with each other. regression equation were energy intake MVC

were most

of the baseline variables as a percent of ideal for

(eg. biochemical

etc) that correlated would be included

con-

assessed by repeated-measures A P value < 0.05 was accepted

strength

growth analysis.

in

period. each of

(weight This

meafor was

within categories were Variables used in the as a percent of RNI. pressure.

mean

and


results in pediatric Nutrition Centre,

of 800

the distal prominences ofthe radius and ulna, distal end of the third metacarpal. between the median and lateral melleioli at

composition

The indexes of interest were peak power attained in interval. mean power (endurance) throughout the 30-

test. and rate of fatigue, determined from off of power. The interindividual coefficient

at a current

and the average values of impedance (1). total fat-free body mass were taken for subsequent

for 30 s at maximal

kp/kg

Diego)

taken to ensure that the upper limbs did not touch other parts ofthe body and that the thighs did not touch each other. Subjects voided before testing. Measurements were repeated in duplicate

was conducted after standardized Subjects pedaled on a cycle

5

test and

strength Strength

(N . m/kg). limb product of limb

moment-arm

San

quency of 50 kHz. Electrodes were placed on the dorsal ofthe right side according to bony landmarks as follows:

potter

(Fleisch-Metabo.

speed

and

investigator.

for mechanical

The Wingate anaerobic test warm-up procedures (26-28). gometer

same

normalized for body mass area (N . m/cm2), and the

lean cross-sectional from

all anthropometric

made

AL

Scientific,

100

exceptions,

were

El

NUTRITION maximum

anaerobic

plasma

transthyretin.

physical

activity.

predicted) Analyses Angeles).

and

aerobic

power,

Covariant sex, and

percent

effects

pulmonary

AND body

of Tanner

function

MUSCLE

fat, and

Stage,

(FEV1

,

FUNCTION

usual

as percent

Growth

were tested. were conducted with BMDPstatistical software (Los Results are presented as mean ± SD unless otherwise

noted.

and

and (Table

values The

estimates

analysis

ranged

stepwise

centage

of expected

significantly muscle

muscle

strength.

a 6-mo intake

change -

and

height

intake,

(r

relationships

with

0.05)

0.05) Amino

in energy equa-

similar

for Tanner

EF. 0.49

+

(.s MVC,

Dietary for

energy

age.

sex,

baseline both

Fig

groups

the RNI. in energy group control

expressed

as percent

height

( 1 5) were

similar

± 22%

respectively:

vs 106

3). Intakes

at baseline Dietary intakes

(to

122

and

± 21%,

control were

other

±

1 7%

nutrients

by a mean

kJ/d

at

vs supplemented, a230%

of RNI

also

intakes

well

in

P

in

0.05). Change 6 mo was significantly

in

control at 6 mo. P < 0.05).

properties

expiratory

spectively, cm

H2O,

air

(PEmax)

different

between

at baseline I 16.2

±

pressures.

control (4 1 , 42):

50.5%

and

and Plmax

vs 124.8

RE

were

supplemented (82.

not

1 ± 2 1 . 1 vs 93.4

± 35.7%),

PEmax

signifi-

groups, (93.7

re-

± 20.0 ±

19.7

vs 93.8 ± 21.7 cm H2O, 103.7 ± 27.7% vs 81.0 ± 17.9%), RE (12. 1 ± 2 1.3% vs 2 1.7 ± 1 3.4% decline). There was also no significant change in Plmax, PEmax, or RE over time. Respiratory function as FE1 (percent predicted) at 6 mo was 77.2

±

groups, baseline

I 3.5%

and

respectively, (Table

95.2

±

which

19.0% was

in control not

significantly

and

supplemented different

from

were gain

apparent and

gain over 6 mo was posenergy intake (percent

fa-

in children

with

a smaller

muscle

CF is similar group

(ad-

CF patients force was

with nega(43). muscle

studies marker

been

used

obese

subjects

(7- 1 1 ) in which of malnutrition.

to monitor and

nutritional

individuals

with

muscle-function abnormalities in body composition or serum significant

muscle

strength

correlation in the

between

current

study

when conventional indexes of nutritional composition and plasma protein biochemThese results indicate that even in relaadolescents with CF. changes in the groups. such as the EF. can serve as in nutritional status. muscle

in patients

with

function

in response

CF should

be specific

to stim-

to the effects

ofnutritional status and independent ofthe effects oflung disease (44) or infection (45). Because recent dietary intake has been found to influence muscle-strength testing (46), measurements in the present ing may

also

study

were

influence

covariant adjustment and energy intake

obtained

2 h postprandially.

muscle-strength

Train-

measurements.

However,

ofthe relationship between muscle for changes in habitual activity did

strength not alter

the statistical significance ofthe association in the present The measures of skeletal muscle strength. anaerobic and with

endurance, CF were

below

those

CF. weight dietary

for

(8. 9). The

in skeletal

tests

and aerobic exercise generally within normal of healthy

tions, muscle If nutritional

Discussion

also

tively healthy children and strength of skeletal muscle a marker for early changes ulation

pattern muscle

of pulmonary function (43). Differprobably explain the discrepancy be-

skeletal

occurred at a time status such as body istry were unchanged.

altered

increased

by more severe malnutrition severely malnourished groups

in starved

47). Thus, in this disease consuming

1).

This study demonstrated that itively associated with increased

has

and

has been in adults

in malnourished patients with failure, and obesity (7- 1 1 ). Our

nervosa reversed the 2-4 wk, before changes

Differences covariant effect of the change on group differences in skeletal muscle strength, power, or endurance. Respiratory muscle strength, as maximal inspiratory (Plmax) cantly

however, and more

function

proteins weight

as a per-

muscle. status

in adolescent and young adult of mild malnutrition. Muscle

Refeeding

anorexia within

6

and

our results and those of other function was shown as a sensitive

change.

status as the failure

muscle been

function

of similar

ages

in the subjects or only slightly

( 1 2-

1 4,

26,

29,

group of patients with mild to moderate lung energy at 100% of normal recommenda-

function status

malnutrition used

children

capacity ranges

study. power

did does

may and

to indicate

not appear to be impaired. indeed relate to muscle function

have

ultimately respiratory

a negative prognosis. muscle

impact

on

Nmax

and

strength

in

respiratory PEmax

in CF (43,

have 48-


20

in skeletal

not be a useful means at any point in time in

(7- 1 1). An

function

et al (43)

function was independent ences in nutritional status

0

and

conditions

muscle

tively influenced, In both the mild

0

MVC disease.

weight

contractile

characteristics been observed chronic renal

to that

ductor pollicis) a similar degree

240

0

of clinical

contractile

tigueability anorexia

lung

in nutritional Nevertheless,

fatigue characteristics of the adductor pollicis investigated as a functional index of nutritional 0

(EF

to moderate

height and age suggests that serial measurestrength may serve as a useful functional index

these patients. Muscle function,

30

our

strength

ofexpected ofmuscle

muscle

CF and

supported

ofchanges of assessing

60

w

increased

with

strength would reflect by growth in subjects

of baseline

90

and

in children

NUTRITION

TABLE Plasma

2 protein

biochemistry

in subjects

randomly

AND

allocated

MUSCLE

to the control Control

(n

FUNCTION

group =

46 0.31 25

(mg/L)

± ±

EAA:TAA

0.307

Valine:g1ycine Taurine(mol/L)

0.771 ± 53±25

±

group

at 0 and 6 mo

Supplemen

7)

6 mo

4 0.14 10 0.019 0.167

±

585

CF

or the diet-supplemented

Baseline Albumin (gIL) Transthyretin (g/L) Retinol-binding protein

IN

43 0.17

± ±

18

23 ±

0.325 0.784 51

±

9)

=

6 mo

Baseline

4 0.0Sf 4 0.023 0.1 19

± ±

ted (n

49 0.30 32 0.302 0.820

5 0.15 9 0.33 0.256

± ± ± ± ±

55±

44 0.19 28 0.326 0.836

14

± 3t

0.03 6 0.024 0.185

± ± ± ±

43±8

SD.

0

t Significant change over time: § Ratio of essential amino acids

< 0.05, jP to total amino

tP