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Inspiratory muscle dysfunction in patients with severe obstructive sleep apnoea M-Y. Chien*

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Inspiratory muscle dysfunction in patients with severe obstructive sleep apnoea M-Y. Chien*
Eur Respir J 2010; 35: 373–380
DOI: 10.1183/09031936.00190208
CopyrightßERS Journals Ltd 2010
Inspiratory muscle dysfunction in patients
with severe obstructive sleep apnoea
M-Y. Chien*,#, Y-T. Wu*,#, P-L. Lee",+, Y-J. Chang1 and P-C. Yang+
ABSTRACT: Repetitive inspiratory effort against an obstructed airway and intermittent hypoxia
may be deleterious to the inspiratory muscles in patients with obstructive sleep apnoea (OSA).
We investigated muscular dysfunction by comparing the strength, endurance and fatigability of
inspiratory muscles and knee extensors in patients with newly diagnosed severe OSA compared
with matched controls. The measurements included strength and endurance tests of both
muscles, and a fatigue trial with simultaneous surface electromyography of the diaphragm and
the vastus lateralis during voluntary contractions and in response to magnetic stimulation. To our
knowledge, this is the first investigation to assess peripheral muscle performance in severe OSA
patients versus controls.
Patients in the OSA group exhibited significantly lower strength and endurance in both muscles
than the control group. The fatigue index decreased significantly exclusively in the inspiratory
muscles of OSA patients. Magnetic stimulation-evoked compound muscle action potential
latencies increased and the amplitudes decreased significantly in the diaphragm, but not in the
vastus lateralis after a fatigue test in the OSA group.
In conclusion, a significantly lower functional performance was shown for both inspiratory
muscles and knee extensors in the OSA group. However, higher fatigability was only seen in the
inspiratory muscles of patients with severe OSA.
KEYWORDS: Inspiratory, knee extensors, magnetic stimulation, nerve conduction delay,
obstructive sleep apnoea, surface electromyography
epetitive obstruction of the upper airway
and apnoea/hypopnoea during sleep is a
feature of obstructive sleep apnoea (OSA)
syndrome [1]. An obstructed airway and the
subsequent asphyxia may lead to increased
inspiratory efforts and, hence, the chronic overload of inspiratory muscles [2]. The chronic
overuse of the diaphragm was reported to put
OSA subjects at risk of inspiratory muscles
fatigue [3]. However, whether diaphragm fatigue
actually occurs in OSA patients is still controversial [4–6]. GRIGGS et al. [4] have shown that pleural
pressure relaxation rates during voluntary sniff
maneuvers were prolonged in the morning
compared with the preceding night prior to sleep
in OSA patients. However, MONTSERRANT et al. [5]
reported lack of evidence for diaphragmatic
fatigue during the night in these patients. They
explained that the fatiguing levels of inspiratory
effort generated throughout the night did not
continue for sufficiently long periods to develop
impaired contractility.
R
causes muscle damage [7]. OSA has been
considered a systemic oxidative disorder [8].
Therefore, it is logical to hypothesise that
systemic skeletal muscle dysfunction may
develop in patients with OSA, in addition to
disorders of the upper airway muscles. However,
studies addressing this issue were conducted in
animal models and have shown conflicting
results [9, 10].
AFFILIATIONS
*School and Graduate Institute of
Physical Therapy, College of
Medicine,
#
Physical Therapy Center,
"
Center of Sleep Disorder,
+
Division of Pulmonary and Critical
Care Medicine, Dept of Internal
Medicine, National Taiwan University
Hospital, Taipei, and
1
Dept of Physical Therapy, Chang
Gung University, Tao-Yuan, Taiwan.
CORRESPONDENCE
P-C. Yang
Dept of Internal Medicine
National Taiwan University Hospital
No 1 Jen-Ai Road
Section 1
Taipei 10051
Taiwan
E-mail: [email protected]
Received:
Dec 16 2008
Accepted after revision:
July 16 2009
First published online:
July 30 2009
The purpose of this study was to investigate the
effect of OSA on muscular strength, endurance,
and the fatigability of inspiratory muscles and
peripheral knee extensors in patients with severe
OSA compared with those in the control group.
Comparisons made between these two types of
muscle were aimed to determine whether the
effects of OSA were generalised or specific to the
muscles subjected to increased use.
The unique repetitive deoxygenation–reoxygenation pattern in OSA patients may induce free
radical production and oxidative stress, which
METHODS
15 males aged 40–65 yrs with newly diagnosed
severe OSA who had an apnoea/hypopnoea
index (AHI) of o30 events?h-1 and an Epworth
sleepiness scale (ESS) score of o10 were
recruited at the Sleep Research Centre (National
EUROPEAN RESPIRATORY JOURNAL
VOLUME 35 NUMBER 2
European Respiratory Journal
Print ISSN 0903-1936
Online ISSN 1399-3003
c
373
SLEEP-RELATED DISORDERS
M-Y. CHIEN ET AL.
Taiwan University Hospital, Taipei, Taiwan). The control
group consisted of 15 age-, height- and weight-matched
subjects (AHI ,5 events?h-1) not diagnosed with OSA from
the Sleep Research Centre. Subjects were excluded if they
presented with any active medical diseases, nervous system
diseases, major pulmonary dysfunction, morbid obesity,
diabetes under the control of oral hypoglycemic agents,
alcoholism (o50 g per day) or recent infection. All the
participants at the time of the study were not receiving
pharmacological or mechanical treatment. The study was
approved by the Institutional Ethics Committee (National
Taiwan University Hospital, Taipei, Taiwan), and all subjects
were informed of the procedures in detail and gave their
written informed consent prior to enrolment. This study is a
registered clinical trial at ClinicalTrials.gov (NCT00813852).
Diagnosis of OSA
The definitive diagnosis of OSA depended on an in-laboratory
overnight polysomnography recording system (Embla,
Medcare, Iceland) demonstrating an elevated AHI, which
was calculated as the total episodes of hypopnoeas and
apnoeas per hour of sleep according to the criteria of the
American Academy of Sleep Medicine [1].
The level of daytime sleepiness was assessed using the ESS
score in the morning after nocturnal polysomnography.
Normal values ranged from 2 to 10, with scores o10 indicating
daytime sleepiness [11].
Anthropometrics, pulmonary function tests and physical
activity evaluation
Body weight and height, and circumferences of the neck, waist,
and hip were measured. Body mass index (BMI) and waist-tohip ratio were also calculated. Pulmonary function tests were
performed by using a computerised spirometer (Chestgraph
HI-701; Chest MI Inc., Tokyo, Japan) with the subjects in a
sitting position, according to the standardised procedure [12].
The forced expiratory volume in 1 s (FEV1), forced vital
capacity (FVC) and FEV1/FVC ratio were recorded.
pressure gauge (Model 4103; Boehringer Ingelheim, Norristown,
PA, USA) using standard procedures [12].
Maximal voluntary ventilation (MVV) manoeuvres were used
as the index of inspiratory muscle endurance and for the
fatigue-induced protocol according to the diagnostic recommendations by the Chestgraph HI-701 spirometer [12].
Ventilation time was calculated by the computer automatically.
A previous study by our group reported that diaphragmatic
fatigue could be induced by the two-set MVV manoeuvres
with a 5-min rest in between [14]. The fatigue index was
defined as the post-MVV manoeuvres PI,max divided by the
pre-MVV manoeuvres PI,max, which represents how much the
muscle tension declined upon repetitive contraction. For
routine muscle fatigue measurements, the decrease in force
generated from a maximal volitional contraction is often used
as a fatigue index.
Functional performance and fatigue index of knee
extensors
The Cybex 6000 (Lumex Inc., Ronkonkoma, NY, USA) was
used to measure the strength and endurance of the right knee
extensors. Each subject was instructed to perform five maximal
isometric knee extension contractions at a 60u knee flexion
angle. Each contraction lasted for 5 s, with a resting period of
at least 15 s between trials [15]. The means of five maximal
isometric contraction peak torques (Newton-metre; N-m) were
calculated for data analysis.
The endurance test consisted of 30 cycles of alternative knee
extension/flexion isokinetic contractions at the speed of
180u?s-1. Before each test, subjects performed three submaximal
trials to become familiarised with the test. The muscular
endurance was evaluated by the total work (N-m) generated
during 30 cycles of contractions as the total area under the
torque curve for knee extension movement, which would be
automatically provided by the Cybex system [15].
Physical activity was evaluated with a 7-day recall questionnaire,
which was designed to determine calories expended on all
activities during the previous 7-day period [13]. The total energy
expenditure was the sum of energy consumed by all activities.
After 30 cycles of isokinetic contractions, each participant
performed three maximal isometric knee extension contractions at 60u knee flexion angle again. The fatigue index was
defined as the mean of the peak torques of isometric
contractions at post-endurance test divided by the preendurance value.
Functional performance and fatigue index of inspiratory
muscles
The maximal inspiratory pressure (PI,max) indicative of muscle
strength was measured from residual volume with an aneroid
Magnetic stimulation
Cervical magnetic stimulation (CMS) was performed by a
Magstim 220 stimulator (Magstim, Whitland, Wales, UK)
equipped with a circular doughnut-shaped 90-mm coil
Protocol:
Maximal voluntary
contractions
Magnetic stimulation
Parameters:
Root mean square
Median frequency
CMAP amplitude
CMAP latency
FIGURE 1.
374
Fatigue test
Magnetic stimulation
Maximal voluntary
contractions
CMAP amplitude
CMAP latency
Root mean square
Median frequency
Schematic diagram demonstrating the protocol for the fatigue test. CMAP: compound muscle action potential.
VOLUME 35 NUMBER 2
EUROPEAN RESPIRATORY JOURNAL
M-Y. CHIEN ET AL.
SLEEP-RELATED DISORDERS
a) 400
b)
µV
200
0
-200
-400
90
80
70
µV
60
50
40
30
20
10
0
0
5
10
15
20
25
30
c)
0
5
10
15
20
25
30
35
0
10
20
30
40
Time s
50
60
70
d)
4
µV
2
0
-2
-4
2.5
2.0
µV
1.5
1.0
0.5
0
0
FIGURE 2.
10
20
30
40
Time s
50
60
70
Examples of a, b) raw electromyopgraphy recordings and c, d) root mean square during maximal voluntary contractions in one patient with severe obstructive
sleep apnoea. Diaphragm a) before and b) after fatigue test. Vastus lateralis c) before and d) after fatigue test.
EUROPEAN RESPIRATORY JOURNAL
VOLUME 35 NUMBER 2
375
c
SLEEP-RELATED DISORDERS
M-Y. CHIEN ET AL.
producing a maximum output of 2.5 Tesla (Magstim) using
standard techniques as described previously [16]. Stimulations
were delivered with the maximal output of the stimulator.
Subjects were asked to keep their neck slightly bent forward
for stimulating the phrenic nerve [16], while lying on the
Cybex table with the coil placed below the inguinal ligament
and 2 cm laterally from the femoral artery for stimulating the
femoral nerve [17].
Surface electromyopgraphy recordings for the diaphragm
and vastus lateralis
The surface electromyopgraphy (EMG) signals were simultaneously and continuously acquired by means of bipolar
electrodes from the right diaphragm and the right vastus
lateralis (VL). For the diaphragm, the electrodes were placed in
the seventh or eighth intercostal space on the right side of the
body at the midclavicular line [18, 19]. The electrodes were also
placed on the skin overlying the lower third of the VL muscle
(10–12 cm above the knee joint) and the electrodes were
aligned longitudinally to the direction of the muscle fibres. The
distance between the two electrodes was kept below 2 cm and
the reference electrodes were placed on the sternum and
patella. The skin surface was well prepared and cleaned with
alcohol to obtain a low inter-electrode resistance prior to
positioning the electrodes.
Experimental protocol
All the subjects performed five maximal voluntary contractions (MVCs), followed by five magnetic stimulations.
Subsequently, inspiratory muscle fatigue was induced by two
MVV manoeuvres with a 5-min rest between each trial, while
knee extensor fatigue was induced by 30 repetitions of
isokinetic contractions. Immediately after the fatigue protocols,
another five magnetic stimulations were performed as
described previously and were followed by five MVCs
(,1 min after the fatigue test). The testing protocol is
illustrated in figure 1.
EMG data analysis
All EMG signals were amplified (EMG100A; Biopac Systems
Co., Goleta, CA, USA), band-pass filtered between 10 Hz
to 1,000 Hz, and digitised at a sampling rate of 2 kHz.
Subsequently, the final signal was acquired and analysed
off-line later using commercially available software
(AcqKnowledge 3.9.1 software for Windows; Microsoft Office).
The parameters of the surface EMG (sEMG) signals during
MVCs included root mean square (RMS) values of the amplitude
and median power frequency (MPF). The means of the first three
voluntary sEMG signals (pre- and post-MVV PI,max, pre- and
post-test maximal isometric knee contractions) (fig. 2), and the
first three and the last three breaths during MVV manoeuvres
and during 30-cycle isokinetic endurance test were calculated.
RMS was used to quantify the diaphragm activation, i.e.
combined processes of diaphragm motor unit recruitment and
motor firing rate [20]. The influence of the electrocardiogram on
sEMG signals was minimised by recording from the right side of
the body. To further minimise any signal contamination by
electrocardiogram on the diaphragmatic sEMG signals during
PI,max effort, RMS was measured from the segments between
QRS complexes.
376
VOLUME 35 NUMBER 2
The conduction time of the phrenic nerve and femoral nerve
were measured as the time elapsed between the stimuli
delivered by CMS and the onset of the compound muscle
action potential (CMAP), which was specifically marked by the
first deviation of the signal from baseline (CMAP latencies)
(fig. 3). CMAP latencies and amplitudes provided thereafter
corresponded to the average of five stimulations. The
voluntary EMG and the diaphragm CMAPs are myoelectric
signals that represent different meanings: the voluntary signal
represents the summated electrical activity generated by
asynchronously firing motor units, whereas the diaphragm
CMAPs represents the summated synchronised electrical
activity generated by all motor units after a supramaximal
stimulus of the phrenic nerve [21].
Statistical analysis
Statistical analyses were performed using SPSS version 11.5 for
Windows (SPSS Inc., Chicago, IL, USA). Data were expressed
as mean¡SD. Comparisons of basic characteristics between the
two groups were made by independent unpaired t-tests. The
MVC force and sEMG parameters were analysed using a
repeated measured ANOVA to assess the difference between
the baseline and the post-fatigue test in each group. An a-value
was set at 0.05.
RESULTS
Baseline characteristics of the study group
There was no significant difference in the basic demographic
characteristics, current smokers, and energy expenditure of
daily activities between the two groups except that the OSA
group had significantly higher values of AHI and ESS (table 1).
All the participants had normal FVC, FEV1 and FEV1/FVC
ratio. However, the patients with severe OSA had significantly
lower values of both FVC and FEV1 than the controls.
Functional performance and sEMG parameters at baseline
Patients with severe OSA had significantly lower baseline
strength (PI,max and peak torque values for the knee extensors)
and endurance than the controls at baseline (p,0.05; table 2).
Diaphragmatic sEMG revealed significantly lower MPF in
patients with severe OSA than those in the control group
(p,0.05). sEMG recordings for VL revealed significantly lower
RMS in patients with severe OSA than those in the control
group (p,0.05).The evoked sEMG for the diaphragm response
to CMS showed a significantly longer CMAP latency
(7.28¡0.66 ms) and lower CMAP amplitude (1.4¡0.5 mV) in
patients with severe OSA than those in the control group
(p,0.05). It also showed a significantly longer CMAP latency
(5.41¡0.74 ms) of evoked sEMG for the VL response to
magnetic stimulation in patients with severe OSA than those
in the control group (p,0.05).
Functional performance and sEMG parameters after the
fatigue test
A similar trend was found for the strength decline and
voluntary sEMG parameters of inspiratory muscles and knee
extensors in the two groups (table 2). As the muscles of OSA
patients were weaker than those of the controls, the level of
fatiguing tasks might be relatively higher for the OSA group.
The fatigue index derived during maximal voluntary efforts
was significantly different between the two groups in the
EUROPEAN RESPIRATORY JOURNAL
M-Y. CHIEN ET AL.
SLEEP-RELATED DISORDERS
a) 1.0
TABLE 1
Baseline characteristics of the subjects
0.8
OSA group
mV
0.6
p-value
0.4
Subjects
15
15
0.2
Age yrs
51.3¡6.5
51.2¡7.0
0.979
8
5
0.462
Current smoker#
0
Anthropometrics
-0.2
-0.4
-0.6
-0.8
0
20
40
60
Time ms
80
100
120
Body weight kg
75.0¡8.1
73.6¡7.8
0.625
Body height cm
168.1¡5.8
167.4¡3.7
0.698
BMI kg?m-2
26.6¡3.1
26.3¡3.0
0.786
Neck circumference cm
38.3¡3.2
37.9¡2.1
0.463
Waist circumference cm
90.6¡10.4
89.2¡10.6
0.724
Hip circumference cm
99.8¡6.9
99.1¡7.2
0.656
Waist-hip ratio %
90.8¡8.2
90.0¡8.3
0.829
AHI events?h-1
54.0¡21.7
2.3¡1.0
,0.001
Epworth sleepiness scale
11.1¡3.1
8.3¡3.6
0.033
Sleep efficiency %
83.2¡8.7
92.0¡4.1
0.002
Average Sa,O2 %
92.3¡4.5
96.2¡7.8
0.005
Lowest Sa,O2 %
71.0¡9.0
88.9¡2.7
,0.001
Sleep examination
b) 0.8
0.6
0.4
0.2
mV
Control group
Pulmonary function test
0
FVC L
FVC % pred
-0.2
FEV1 L
FEV1 % pred
-0.4
FEV1/FVC %
Physical activity kcal?kg-1?day-1
-0.6
-0.8
0
20
40
60
80
100 120
Time ms
140 160 180 200
3.8¡0.7
4.3¡0.6
0.040
102.3¡9.4
111.7¡11.4
0.020
3.1¡0.6
3.5¡0.5
0.064
100.8¡11.1
108.2¡8.2
0.047
81.6¡3.7
80.8¡6.6
0.926
35.1¡2.9
38.6¡6.3
0.059
Data are presented as n or means¡
SD,
unless otherwise stated. OSA:
obstructive sleep apnoea; BMI: body mass index; AHI: apnoea/hypopnoea
index; Sa,O2; arterial oxygen saturation; FVC: forced vital capacity; % pred: %
FIGURE 3.
Example of electromyopgraphy recordings of a) the right
predicted; FEV1: forced expiratory volume in 1 s. #: Chi-squared test.
diaphragm and b) vastus lateralis for motor responses (compound muscle action
potential) with magnetic stimulation in a patient with severe obstructive sleep
apnoea.
inspiratory muscles (0.86 versus 0.92; p,0.05), but not in the
knee extensors (0.94 versus 0.95; p.0.05).
The diaphragmatic voluntary sEMG MPF declined significantly from baseline to the end of the second MVV manoeuvre
and returned slightly at post-MVV manoeuvres PI,max (p,0.05;
fig. 4). A similar trend was shown in VL; however, no
statistical significance was detected.
The diaphragmatic CMAP latency and amplitude showed
significant changes after the MVV manoeuvres in the severe
OSA group (latency: 7.28¡0.66 versus 7.48¡0.65 ms; amplitude: 1.4¡0.5 versus 1.2¡0.5 mV; p,0.05). However, there
were no significant changes in CMAP latency and amplitude of
the VL after the endurance test.
DISCUSSION
This study demonstrated that severe OSA patients have
significantly lower functional performance in strength and
endurance, and a prolonged CMAP latency in response to
magnetic stimulation of both the inspiratory muscles and knee
extensors, but only the inspiratory muscles showed significantly increased fatigability in performance and sEMG assessments. This is the first investigation that we know of in
EUROPEAN RESPIRATORY JOURNAL
assessing peripheral muscle performance in severe OSA
patients versus controls.
Methodological considerations
Diaphragm muscle activity can be assessed either as a pressure
or an EMG response which was recorded with surface,
intramuscular needle or oesophageal electrodes. However,
transdiaphragmatic pressure method and oesophageal EMG
have the disadvantage of their invasiveness and discomfort.
Use of intramuscular needle electrodes avoids cross-talk but
contains disadvantages of invasiveness and sampling bias.
sEMG recordings provide a popular, routine tool to investigate
chest wall muscle function but can be confounded by noise and
cross-talk [22]. This is a potential limitation of sEMG. Thus,
electrodes were placed in the way that minimises cross-talk, as
suggested by previous researches [18, 19]. Subjects were well
supported during testing to minimise the activities of the
adjacent trunk muscles.
It was well established that force production by the diaphragm
could be significantly reduced by fatigue induced by periods of
high-intensity voluntary isocapnic ventilation [23]. During a 2min MVV manoeuvre there was a progressive reduction in
ventilation and transdiaphragmatic pressure generation associated with the development of fatigue of the diaphragm [23].
Isocapnic maximal sustained ventilation for 8 min has also
VOLUME 35 NUMBER 2
377
c
SLEEP-RELATED DISORDERS
TABLE 2
M-Y. CHIEN ET AL.
Strength, endurance, and surface electromyographic parameters of inspiratory muscles and knee extensors before
and after the fatigue protocol
OSA group#
Control group#
Pre-test
Post-test
Pre-test
Post-test
PI,max cmH2O
73.3¡22.3
63.1¡20.3"
100.3¡19.2*
92.7¡19.7"
MVV L
130.4¡29.2
Inspiratory muscles
Fatigue index %
85.9¡6.2
Root mean square mV
73.0¡23.2
Median frequency Hz
CMAP latency ms
149.3¡33.0*
92.3¡6.4*
62.2¡20.7"
87.9¡20.4*
74.5¡19.1"
103.6¡14.6
100.3¡13.4
116.5¡17.4*
113.2¡14.5*
7.28¡0.66
7.48¡0.65",+
6.56¡0.76*
6.60¡0.72
1.4¡0.5
1.2¡0.5"
1.7¡0.4*
1.6¡0.4
Peak torque N-m
140.9¡21.3
133.1¡20.0"
167.7¡26.9*
158.9¡20.0"
CMAP amplitude mV
Knee extensors
Endurance N-m
1424.3¡247.1
Fatigue index %
94.6¡5.8
Root mean square mV
1.8¡0.6
1.7¡0.6
2.3¡0.6*
2.1¡0.5
Median frequency Hz
93.7¡11.3
88.6¡13.2+
100.7¡12.1
94.3¡11.2"
CMAP latency ms
5.41¡0.74
5.44¡0.82
5.01¡0.74*
5.00¡0.74
8.8¡3.1
8.5¡2.4
9.7¡2.2
9.6¡2.1
CMAP amplitude mV
1821.3¡277.7*
95.3¡7.4
Data are presented as mean¡SD. OSA: obstructive sleep apnoea; PI,max: maximal inspiratory pressure; MVV: maximal voluntary ventilation; CMAP: compound muscle
action potential; N-m: Newton-metre. #: n515; ": p,0.05, pre-test and post-test comparisons within the group; +: p,0.05, significant group effect by using repeated
measures ANOVA. *: p,0.05, pre-test variable comparisons between groups.
been suggested as fatiguing procedures [12]. Our preliminary
study has also demonstrated that two-set 15-s MVV manoeuvres could induce diaphragmatic fatigue in young healthy
participants [14].
Our study employed MVV manoeuvres and 30 cycles of
isokinetic knee contractions for determining the endurance of
inspiratory muscles and knee extensors, respectively, which,
strictly speaking, were not standardised endurance tests by the
definition. However, they are widely utilised for clinically
evaluating functional muscle endurance [12, 15].
Functional performance of inspiratory muscles and knee
extensors
In this study, inspiratory muscles (diaphragm) and knee
extensors (VL) were selected to explore the effect of the
functional changes observed in OSA patients. The chronic
overloading of inspiratory muscles against an obstructed
upper airway could lead to structural and metabolic adaptations. Peripheral muscle was chosen as a control because it was
considered not to be overloaded during sleep. Several studies
have compared the inspiratory muscles and peripheral
muscles in patients with OSA.
MEZZANOTTE et al. [24] reported a significantly lower PI,max in
severe OSA subjects, but SHEPHERD et al. [25] reported that the
PI,max was not different between the subjects whose AHI was
,20 events?h-1 and .20 events?h-1. In this study, we found
significantly lowered values of PI,max in patients with severe
OSA compared to those without OSA. The weakened
diaphragm would reduce the collapsing force during apnoeas
thereby offsetting the large negative pressure generated by the
378
VOLUME 35 NUMBER 2
diaphragm. However, the cause–effect relationship could not
be determined in the present study.
With regard to the performance of the lower extremity muscles
among OSA patients, little investigation has been performed in
humans. SAULEDA et al. [26] obtained a needle biopsy of
quadriceps femoris in severe OSA patients and found
structural and bioenergetic changes in the skeletal muscles.
Nevertheless, some studies have shown conflicting results
regarding limb muscle performance in OSA animals [9, 10].
Our study is the first investigation that we know of in showing
lower strength and endurance of knee extensors in the OSA
group, but not fatigability. Future studies are needed to
confirm this observation.
It is noteworthy that factors such as nutrition, obesity state and
physical activity have profound effects on muscle performance
[27]. In our study, the groups were matched for the anthropometric parameters; therefore, the difference in muscular
strength could not be attributed to them. However, the
relatively lower physical activity levels might be related to
the lower baseline muscular strength of both examined
muscles in the severe OSA group. In addition, the possibility
that lower values of PI,max and peak torques represent
difference in effort and cooperation between two groups could
not be excluded, even though we gave maximal encouragement to each participant during all the tests.
Fatigability of the inspiratory muscles
Previous studies have shown conflicting results regarding
whether inspiratory muscles fatigue during OSA [4–6]. One
possible reason is the fatigue index may not distinguish
EUROPEAN RESPIRATORY JOURNAL
M-Y. CHIEN ET AL.
a)
SLEEP-RELATED DISORDERS
nervous system to prevent further inspiratory muscle fatigue;
thus acting as a protective mechanism.
Median power frequency Hz
140
120
100
However, significant decreases in CMAP latencies and
amplitudes after MVV manoeuvres developed in patients in
the severe OSA group, thereby suggesting the diaphragm
muscle was responsible for inspiratory muscle fatigue in these
patients. Because peripheral muscle fatigue can result in
persistent muscle fatigue and longer recovery periods, it is
likely that this peripheral neuromuscular fatigue was responsible for the decline in function of inspiratory muscles, i.e.
decreased PI,max and endurance.
*
80
60
40
20
0
Pre PI,max
b)
MVV early
MVV end
Post PI,max
Median power frequency Hz
120
100
Study limitations
This study had several limitations. First, as we did not measure
twitch pressure in response to the stimulation of phrenic
nerves and femoral nerve, this study could not answer whether
the decreased strength of the inspiratory muscle and knee
extensors was due to decreased recruitment and/or decreased
contractility per se. Nevertheless, the study demonstrated
decreased CMAP amplitude that could represent the delayed
neurotransmitter in OSA patients compared with the controls.
80
60
40
20
0
Prevoluntary
FIGURE 4.
The decrease of sEMG amplitudes and power spectra of the
inspiratory muscles found in this study may reflect decreased
motor unit recruitment from a decreased activation [29], or
hypoxia induced decreases in muscle pH that promote fatigue
[30]. Further studies are needed to explore the associated
mechanisms.
Isokinetic
early
Isokinetic
end
Postvoluntary
Group mean values of median power frequency of the a) right
diaphragm and b) vastus lateralis for voluntary contractions before, during and after
fatigue test by maximal voluntary ventilation (MVV) manoeuvres for inspiratory
muscles and isokinetic test for knee extensors. PI,max: maximal inspiratory pressure.
&: obstructive sleep apnoea; h: control. *: p,0.05, significant group effect by
using repeated measures ANOVA.
between different types of fatigue, i.e. central fatigue and
peripheral neuromuscular fatigue. In contrast to the conventional fatigue test induced by MVCs, externally applied
electrical or magnetic stimulations for peripheral nerve roots
that measure the CMAP after stimulation have long been
known to evaluate peripheral neuromuscular function [16, 17].
CMAP measures the peripheral neuromuscular fatigue (especially neurotransmitters) in the muscles bypassing the central
nervous system. EL-KABIR et al. [28] have shown that in patients
with OSA treatment with nasal continuous positive airway
pressure, the twitch transdiaphragmatic pressure did not
improve in response to bilateral CMS. However, the study
included lack of repeated polysomnography and compliance
data of continuous positive airway pressure treatment, and no
control group. Our results revealed a significant decrease in
the sEMG RMS amplitude after MVV manoeuvres but not
CMAP amplitudes in control subjects. These findings indicate
that MVV manoeuvres might induce central fatigue, which
was considered as a pre-emptive fatigue induced by the central
EUROPEAN RESPIRATORY JOURNAL
Secondly, we did not measure lung volume changes before and
immediately after MVV manoeuvres. Thus it may be difficult
to thoroughly interpret the changes in CMAP characteristics.
Previous studies had reported that CMAP amplitude and
latency would be affected by different lung volumes [21, 22].
We assumed both groups in our study were influenced to the
same extent; however, the result showing significant difference
of CMAP amplitude and latency could provide important
information regarding the neuromuscular characteristics of
inspiratory muscles in OSA patients. Future studies should
examine the effect of OSA on inspiratory muscles fatigue by
using comprehensive measurement tools.
Thirdly, the unequal fatiguing tasks produced by OSA and
control participants might complicate the comparison of
fatigue indices. The lower baseline PI,max and peak torques of
knee extensors in the OSA group would bring about the
different fatigue tasks for the OSA and the control group.
According to that, future study should strive to employ a more
standardised fatigue tests for further refinement of this study.
Implications
A significantly lower strength and endurance for inspiratory
muscles and knee extensors of severe OSA patients were found
in comparison with their age and BMI-matched controls.
Therefore, systemic effects of chronic intermittent hypoxia and
reoxygenation on skeletal muscles in OSA populations could
not be completely ruled out. However, higher fatigability
either during voluntary contractions or in response to
magnetic stimulations was only exhibited in the inspiratory
muscles of patients with severe OSA. Peripheral neuromuscular fatigue of the diaphragm might contribute to this
increased fatigability; therefore, we speculated that the
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379
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SLEEP-RELATED DISORDERS
M-Y. CHIEN ET AL.
underlying mechanisms of muscular adaptation to chronic
increase use played a critical role in this pathological state
when compared with the systemic effects on skeletal muscles
occurring in OSA patients.
CLINICAL TRIALS
This study is registered at ClinicalTrial.gov (NCT00813852).
SUPPORT STATEMENT
The authors received financial support from the National Science
Council (Taiwan) (96-2314-B-002-022-MY3).
STATEMENT OF INTEREST
None declared.
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