Sengul et al , 2011 The effect of exercise on obstructive sleep apnea A randomized and controlled trial

Prévia do material em texto

ORIGINAL ARTICLE
The effect of exercise on obstructive sleep apnea:
a randomized and controlled trial
Yesim Salik Sengul & Sevgi Ozalevli & Ibrahim Oztura &
Oya Itil & Baris Baklan
Received: 17 July 2009 /Accepted: 14 October 2009 /Published online: 7 November 2009
# Springer-Verlag 2009
Abstract
Purpose The aim of the study was to assess the effect of
breathing and physical exercise on pulmonary functions,
apnea-hypopnea index (AHI), and quality of life in patients
with obstructive sleep apnea syndrome (OSAS).
Methods Twenty patients with mild to moderate OSAS
were included in the study either as exercise or control
group. The control group did not receive any treatment,
whereas the exercise group received exercise training.
Exercise program consisting of breathing and aerobic
exercises was applied for 1.5 h 3 days weekly for 12 weeks.
Two groups were assessed through clinical and laboratory
measurements after 12 weeks. In the evaluations, bicycle
ergometer test was used for exercise capacity, pulmonary
function test, maximal inspiratory-expiratory pressure for
pulmonary functions, polysomnography for AHI, sleep
parameters, Functional Outcomes of Sleep Questionnaire
(FOSQ), Short Form-36 (SF-36) for quality of sleep and
health-related quality of health, Epworth Sleepiness Scale
for daytime sleepiness, and anthropometric measurements
for anthropometric characteristics.
Results In the control group, the outcomes prior to and
following 12-weeks follow-up period were found to be
similar. In the exercise group, no change was found in the
anthropometric and respiratory measurements (P>0.05),
whereas significant improvements were found in exercise
capacity, AHI, and FOSQ and SF-36 (P<0.05). After the
follow-up period, it was shown that improvement in the
experimental group did not lead to a statistically significant
difference between the two groups (P>0.05).
Conclusions Exercise appears not to change anthropomet-
ric characteristics and respiratory functions while it
improves AHI, health-related quality of life, quality of
sleep, and exercise capacity in the patients with mild to
moderate OSAS.
Keywords Mild to moderate obstructive sleep apnea
syndrome . Breathing exercise . Physical exercise
Introduction
Obstructive sleep apnea (OSA) can be described as a
condition characterized by repetitive obstruction of the
upper airway resulting in oxygen desaturation and awak-
ening from sleep, loud snoring, and increased daytime
sleepiness [1]. Many studies have shown that a link exists
between OSA and cardiovascular disease, chronic heart
failure ischemia, hypertension, obesity, and impaired
glucose tolerance [2, 3]. A number of factors are likely to
play role in development of clinical OSA syndrome
(OSAS) ranging from upper airway anatomy to central
respiratory control mechanisms. The pathophysiology of
OSA is unclear and complex. Several previous studies have
explored pulmonary function in the OSAS patients [4, 5].
Interestingly, OSAS has been found to be highly correlated
Y. S. Sengul (*) : S. Ozalevli
School of Physical Therapy and Rehabilitation,
Dokuz Eylul University,
Inciralti-Izmir TR-35340, Turkey
e-mail: yesim.salik@deu.edu.tr
I. Oztura : B. Baklan
Departments of Neurology, School of Medicine,
Dokuz Eylul University,
Izmir, Turkey
O. Itil
Department of Chest Diseases, Dokuz Eylul University,
Izmir, Turkey
Sleep Breath (2011) 15:49–56
DOI 10.1007/s11325-009-0311-1
with lower airway obstruction, although it is originally
defined as an upper airway disease [4]. In the recent
studies, metabolic factors, especially inflammatory cyto-
kines (IL-1, IL-6, and TNF-α) are implicated for leading to
this condition because of its systemic interactions [6, 7].
Another important effect of pro-inflammatory cytokines is
to cause collapse by leading inflammation in dilator
muscles in the upper airway. Thus, the observed hyper-
cytokinemia, hyperleptinemia, and hyperinsulinemia/viscer-
al adiposity, through central and peripheral effects, may
lead to a collapse of the upper airway during sleep [7, 8].
The most commonly accepted interventions in the
treatment of OSA include administration of continuous
positive airway pressure (CPAP) and oral appliances during
sleep and surgery [9–11]. American Sleep Apnea Associ-
ation considers exercise as a non-pharmacological treatment
modality of sleep disorders [12]. Theoretical reviews and
hypotheses on the effects of exercise in OSA have
suggested thermoregulatory, metabolic, and biochemical
mechanisms although clinical trials on the topic are
inadequate [6, 7, 12, 13].
Hargens et al. [14] indicated that alteration in chemo-
reflex sensitivity and breathing efficiency exists in patients
with OSA. Exercise studies showed that an improvement
occurs in respiratory drive (and chemoreceptor sensitivity)
after physical exercise in athletes. Netzer et al. [15] reported
a significant improvement in apnea-hypopnea index (AHI)
following a 6-month exercise program in the patients with
moderate to severe OSAS. They suggested that improve-
ment of OSA severity might be due to a possible rise in the
respiratory drive or a stabilized muscle tonus in the upper
airway after exercise. Nevertheless, Norman et al. [16]
noted that regular exercise training provided improvement
in sleep by decreasing body weight. Consequently, the
studies have shown that regular physical activity reduces
severity of OSA symptoms either by decreasing body
weight or through positive effects on the respiratory
muscles and sufficiency of breathing (ventilatory abilities)
[13, 15–17].
Our study was planned to assess the effects of physical
and breathing exercise training on pulmonary function,
AHI, and quality of life in order to investigate the place of
exercise in management of OSAS.
Methods
Subjects
Study protocols and written informed consents were
approved by the institutional review committee on clinical
research of the Dokuz Eylul University School of Medi-
cine. The inclusion criteria for this study included men 40
to 65 years of age, in good general health (stability of clinic
state), with OSAS symptoms (snoring, breathing cessations,
and daytime sleepiness), and polysomnographic evidence
(AHI, sleep efficiency percentage, minimum saturation
percentage, and total sleep time) consistent with mild (5<
AHI<15) to moderate (16<AHI<30) OSAS. Medical
conditions that would make exercise dangerous such as
angina pectoris, congestive heart failure, cardiomyopathy,
emphysema, lung cancer, recent upper respiratory surgery,
chronic obstructive pulmonary disease, or other serious
medical problems such as neurological, psychological, and
cooperation problems that would prevent successful partic-
ipation in and completion of the protocol by the subject
served as exclusion criteria.
The participants were divided into control and study
groups according to the table of random numbers. The
control group did not receive any treatment, the study group
received exercise training. Both groups underwent similar
clinical and physiotherapeutic assessment. In addition, the
control group was not advised any information and/or
exercise apart from routine clinical treatment and proposals.
In contrast to the control group, the study group received
breathing exercise (approximately; 15–30 min) and aerobic
exercises (approximately; 45–60 min) lasting progressively
1–1.5 hour three times weekly for 12 weeks.
Exercises were given by a single physiotherapist at the
same time and place for 12 weeks. Exercises were taught to
the patients repetitively until they said "I understood". The
patients were enabled to get used to the exercises by giving
them exercise booklets and requiring them to participate
with sports outfits. Several data such as the patients'
respiration rates, heart rates, and blood pressures were
recorded before and after the exercises. Participants'
dyspnea severity and leg tiredness were evaluated with
Modified Borg Scale [18]. The exercises were maintained
under the control of a physiotherapist.
Breathingexercises Exercises were started with the pursed
lips breathing training in which the patient is taught to
inhale the air through the nose and exhale slowly by
slightly opening his/her lips. During entire breathing
exercises, relaxation training and its importance were
explained to the patients in order to minimize contribution
on the shoulder girdle and neck muscles to breathing. The
patients were placed in appropriate position during dia-
phragmatic and thoracic expansion exercises. For kines-
thetic stimulation, the patient was asked to place his/her
hand on the relevant pulmonary areas to increase the
amount of expiration through resistance in the inspiration
period and through pressure in the expiration period. All
exercises were combined with postural exercises. Exercise
program was progressed according to fatigue severity of
patients. Breathing exercises, which had been done in
50 Sleep Breath (2011) 15:49–56
sitting position, were done resistively in flat position by the
help of gravity and 250-g weights [19, 20].
Aerobic exercises The height of the bicycle was adjusted
specifically for each patient. After the breathing exercises,
the patients did warm up exercises consisted of slow jogging,
calisthenics, and stretching. Then they did aerobic exercises,
resistance, and duration of which were increased according
to the patients' tolerance on bisergo and treadmill. The
training program began at a low to moderate intensity over
the first 1–2 weeks and progressed to a moderate intensity
program. During the treadmill and bicycle exercises, which
were applied at submaximal intensity at 60–70% of
maximal oxygen consumption, it was ensured that the
intensity of fatigue that the patients perceived is at the
interval of 4–5 according to the Modified Borg scale.
During the exercises, the Palco Laboratories Model 400
pulse oxymeter has been used in order to observe the heart
rate and peripheral oxygen saturation. After the bicycle and
treadmill exercises, the exercise program was finished with
the cooling down period which was consisted of low-tempo
walking, posture, and stretching exercises. It was ensured in
all exercises to maintain respiration control [21, 22].
Patients suitable for inclusion criteria were asked if they
had smoking and exercise habits. Anthropometric measure-
ments, pulmonary functions, exercise capacity, quality of
sleep, and health-related quality of health were repeatedly
measured at the end of week 12 in order to describe the
effects of exercise treatments in patients with OSA.
Anthropometric data
Anthropometric measurements including height, weight,
and circumference measurements were obtained before and
after the study. From the height (m) and weight (kg)
measurements, the body mass index (BMI) was calculated
(kg/m2). Circumference measurements were made with a
flexible tape and included neck, upper chest, waist, and hip
circumferences. The waist and hip girths were used to
calculate the waist-to-hip ratio for each individual. A single
investigator performed all measurements.
Skinfold thickness were measured on the right side of
the body with a caliper (Holtain Tanner/Whitehouse
skinfold caliper; Holtain Ltd, UK) to the nearest millimeter.
To assess subcutaneous fat, the skinfold thickness of the
following sites was measured: subscapular, triceps, and
chest in accordance with procedures described by The
American College of Sports Medicine. From the skinfold
thickness, body density was calculated using the predictive
equations proposed by Jackson and Pollock. Relative body
fat was estimated from the equations proposed by Brozek
and colleagues [21].
Pulmonary function testing
Subjects underwent pulmonary function testing to evaluate
the lung functions. Spirometry was performed by an expert
using a Sensormedics Vmax 22 machine (SensorMedics
Inc., Anaheim, CA, USA) conforming to the American
Thoracic Society criteria [23]. Forced vital capacity, first
second forced expiratory volume (FEV1), and FEV1/FVC
values were recorded.
Respiratory muscle strength Mouth pressures were mea-
sured by Sensormedics Vmax 22 (SensorMedics Inc.,
Anaheim, CA, USA) using a previously reported technique
[24]. Inspiratory muscle strength (Pimax) was measured
from functional residual capacity, whereas expiratory
muscle strength (PEmax) was measured near total lung
capacity. Tests were run three times (at the beginning of the
study period, after 3 months, and at the end of the study
period), and three measurements were made in each testing
session.
Exercise testing
The subjects exercised on an electronically braked cycle
ergometer (ercometrics 800, ergoline, Germany) by "Max-
imal incremental cycle ergometry protocols". This protocol
consists of 3 min of rest, followed by 3 min of unloaded
pedaling and by incremental load (3 W per 10 s) until
reaching maximal load [25]. Criteria for terminating
exercise testing include the patient reaching volitional
exhaustion or the test has been terminated by the medical
monitor. Pretest and posttest dyspnea severity and leg
tiredness were evaluated with Modified Borg Scale [18].
Quality of life and sleep
Quality of life was assessed by two questionnaires as OSA
specific measures and a general health-related quality of life
questionnaire. Functional Outcomes of Sleep Questionnaire
(FOSQ), which has been developed specifically for patients
with sleep disorders leading to excessive sleepiness. FOSQ-tr
was applied in a decreased 26-item Turkish version without
the sexual functioning subscale [26].
The general health-related quality of life was assessed
using the Short Form-36 (SF-36) questionnaire. As well as
a transition question, the SF-36 consists of eight multi-item
dimensions, which are physical functioning, role physical
(role limitations due to physical problems), vitality, social
functioning, role emotional (role limitation due to emotion-
al problems), bodily pain, general health, and mental health.
Each of the dimensions is scored from 0 to 100, with higher
scores indicating better health-related quality of life. The
Sleep Breath (2011) 15:49–56 51
SF-36 was administered during a face-to-face interview by
the physiotherapist [27].
Daytime sleepiness evaluation
The subjective sleepiness was assessed using Turkish
Epworth Sleepiness Scale (ESS). The ESS is a question-
naire containing eight items that shows the likelihood of
dozing during typical daytime activities. The dozing
probability ranges from 0 (never) to 3 (high probability).
Normal values range from 2 to 10, with scores >10
indicating daytime sleepiness [28].
Polysomnography
Polysomnography (PSG) evaluation of at least 8 h was
performed on Embla A 10 (Flaga, Reyjavick, Iceland) and
Schwarzer Comlab 32 polysomnographic device (Comlab 32;
Schwarzer Medical Diagnostic Equipment, Baermannstr,
Germany) sleep systems. The following variables were
monitored: four channel EEG (C3/A2-C4/A1-O1/A2-O2/A1
according to the 10–20 international electrode placement
system), right and left electrooculogram, chin electromyo-
gram, and electrocardiogram. Airflow was monitored by nasal
pressure cannula. Respiratory movements were assessed by
thoracic and abdominal strain gauges. Snoring was evaluated
with neck microphone. The oxygen saturation during sleep
was measured continuously using a pulse oxymetry. Leg
movements were recorded by left and right tibial electromyo-
grams. PSG recordings were scored according to the standard
criteria of Rechtschaffen and Kales in 30-s epochs [29].
Data analysis
Statistical analyses of data obtained before and after the
treatment were performed with "SPSS for Windows Ver
11.0" software. Wilcoxon signed rank test was used to
compare the pre- and post-treatment data of the study
groups and chi-square test to compare determined changes
and Mann–Whitney U test to compare the groups.
Statistical significance level was chosen as p values less
than 0.05.
Results
Twenty-five patients were randomized as exercise and
control group and were screened. Twenty patientscomplet-
ed the trial. Data were presented for the control group (CG;
n=10 patients) and exercise group (EG; n=10 patients). All
of the ten patients in the exercise group participated the
training. No problems occurred during the exercises.
Characteristics of the subjects
Baseline characteristics of the subjects for each group are
presented in Table 1. There were no significant differences
in height and weight (P>0.05). Patients in CG (48.0±
7.49 years) were slightly younger than those in the EG
(54.40±6.57 years; P<0.05).
In regard to exercise habits of the subjects, seven subjects
in the exercise group (70%) and nine subjects in the control
group (90%) were found not to physically exercise at all. No
statistically significant difference was found between the
control and exercise groups in exercise and smoking habits
(χ2=1.25, P=0.26; χ2=2.80, P=0.25; Table 1).
Physical changes
BMI, body fat percentage (BF percentage), skinfold
thickness, neck and waist girth measures, and waist-to-hip
ratios were similar in both groups at the baseline and the
end of the 12-week program (P>0.05). The patients'
anthropometric parameters did not change significantly
during the exercise period (P>0.05; Table 2).
Respiratory parameter results
At the baseline, there were no significant differences in all of
the pulmonary function tests, except FEV1/FVC ratio, Pimax,
Exercise group n=10 Control group n=10 P value
Age (year) 54.40 (6.57) 48.0 (7.49) 0.04a
Height (cm) 170.40(6.17) 176.60(5.40) 0.40a
Weight (kg) 86.40(8.04) 88.47(16.24) 0.70a
Percentage of current smoker 30.0 30.0 0.25b
Percentage of Never 60.0 30.0
Percentage of former Smoker 10.0 40.0
Regular exercise 30 10 0.26b
Not regularly exercise 70 90
Table 1 Baseline subject
characteristics of patients with
OSAS
Data are presented as mean±
standard deviation
BMI body mass index
a P values were derived by
Mann–Whitney U test
bP values were derived by chi-
square test
52 Sleep Breath (2011) 15:49–56
and Pemax between the EG and CG. There were increases in
FVC percentage and FEV1/FVC ratio, but unchanged in
Pimax-Pemax and respiratory parameters after exercise. All
pulmonary parameters were the same in both groups (P<
0.05), while the FEV1/FVC ratio was significantly higher in
the CG on follow-up (P>0.05; Table 3).
Responses to the exercise testing
Dyspnea severity after the test was higher in the exercise
group than in the control group at first exercise test (P<0.05).
Significant improvements in MaxVO2, metabolic equivalent
of task (MET), and maximal work load were noted on
follow-up exercise testing in the exercise group (P<0.05).
The dyspnea and leg fatigue severity was the same before
and after the exercise program. However, after the exercise
test, the dyspnea and leg fatigue severity were significantly
decreased (P<0.05). In the control group, they did not
change after exercise test at week 12 (P>0.05). In control
evaluation of the subjects included and not included in the
exercise program, maximal tolerated load was significantly
higher and dyspnea severity perceived following the test was
significantly lower in the exercise group (P<0.01; Table 3).
Quality of life and sleep outcomes
Baseline SF-36 and ESS scores (Table 4) were same in both
groups (P>0.05). However, activity level scores of the
Table 2 Anthropometric changes
Exercise group Control group P**
Pre Post P* Pre Post P*
BMI (kg/m2) 29.79 (2.66) 29.20 (3.07) 0.17 28.42 (5.42) 28.28 (5.52) 0.89 0.41
Neck circumference (cm) 41.15 (1.53) 42.15 (2.79) 0.31 41.30 (3.47) 41.60 (3.10) 0.47 0.54
Waist circumference (cm) 104.25 (5.51) 104.45 (6.85) 0.88 103.5 (14.83) 101.25 (11.57) 0.21 0.16
Waist-hip ratio 0.97 (3.33) 0.97 (3.24) 0.79 0.96 (6.30) 0.96 (5.59) 0.96 0.33
Body density 1.03 (9.38) 1.04 (7.7) 0.17 1.04 (7.23) 1.04 (5.65) 0.29 0.50
Body fat percentage (%) 28.41 (4.01) 26.87 (3.27) 0.17 24.84 (3.06) 25.81 (2.40) 0.29 0.53
Data are presented as mean±standard deviation
BMI body mass index
*P<0.05, Wilcoxon signed rank test
**P<0.05, Mann–Whitney U test
Table 3 Results of pulmonary function tests and the exercise test
Exercise group Control group P**
Pre Post P* Pre Post P*
FEV1% predictive 104.3 (10.65) 96.60 (17.57) 0.13 112.50 (22.03) 103.40 (25.00) 0.11 0.62
FVC% predictive 108.50 (12.06) 98.60 (18.90) 0.05 105.80 (16.85) 99.40 (21.92) 0.11 0.94
FEV1/FVC% 77.0 (4.69) 78.80 (3.80) 0.04 85.50 (4.93) 83.70 (4.74) 0.19 0.05
PE (cmH2O) 122.40 (16.60) 117.40 (23.37) 0.67 113.00 (33.40) 113.00 (33.40) 0.58 0.68
Pİ (cmH2O) 91.90 (31.46) 90.20 (31.51) 0.88 89.20 (36.22) 96.90 (44.88) 0.14 0.97
MaxVO2 (mL/min) 15.38 (3.58) 17.48 (5.63) 0.02 16.6 (4.87) 18.37 (3.52) 0.31 0.47
MET 4.40 (1.00) 5.37 (1.04) 0.02 4.76 (1.40) 5.27 (1.01) 0.26 0.47
Maximum work load (W) 112.50 (35.54) 155.00 (18.11) 0.02 141.50 (35.90) 147.50 (25.50) 0.31 0.40
Data are presented as mean±standard deviation
FEV1 forced expiratory volume in 1 s as a percent of the predicted, FVC forced vital capacity as a percent of the predicted, FEV1/FVC forced
expiratory volume in the first second as a percent of the predicted value/forced vital capacity, Pimax maximal inspiratory pressure, Pemax maximal
expiratory pressure, Max VO2 maximal oxygen consumption, MET metabolic equivalents
*P<0.05, Wilcoxon signed rank test
**P<0.05, Mann–Whitney U test
Sleep Breath (2011) 15:49–56 53
FOSQ-tr were low when the exercise group was compared
to the control group (P<0.05).
The exercise intervention significantly improved SF-36
(vitality and mental health domains) and FOSQ-tr (activity
level subscale; P<0.05). In the control group, they
unchanged after quality of life and sleep at week 12 (P>
0.05). FOSQ-tr, SF-36, and ESS scores (Table 4) were not
significantly different between control and exercise groups
after 12 weeks (P>0.05).
Polysomnography
Means and standard deviation of selected sleep parameters
for both groups are shown in Table 4. There was not a
significant difference between groups. Total sleep efficien-
cy was higher the control group than in the exercise group
(P<0.05). Significant improvements in AHI were noted on
follow-up polysomnograms in the exercise group (P<0.05).
AHI was unchanged in the control group while it was
similar in both groups at the end of 12 weeks (P>0.05;
Table 4).
Discussion
This randomized, controlled trial has shown that supervised
exercise training reduced the severity of OSA. Although
AHI decreased the body weight, BMI and other anthropo-
metric characteristics remained unchanged. Increase in
exercise capacity was less in the control group that was
younger with better quality of life at baseline. For the
patients with OSA, with reduced physical activity, we
found increase in exercise capacity, decrease in leg
tiredness and severity of dyspnea perceived following
exercise, and improvements in quality of life and sleep
parameters of mental health, activity level, and vitality.
Especially anatomy of upper airway is affected by
obesity while opinions exist that metabolic activity of the
visceral (central) fat tissue plays role in development of
sleep apnea [7]. Thus, we determined the sample of our
study as males in whom visceral fat formation occurs
frequently.
Giebelhaus et al. [30] found that no change occurred in
BMI and body weight of the patients with OSA included in
exercise program for 6 months consisting of power and
aerobic exercises. Similarly, Peppard et al. [31] showed that
exercise habits of different extent had no effect on body
shape and composition.
Opinions in the literature are conflicting on that exercise
in the patients with OSAS generates changes in anthropo-
metric features and BMI and, thus, lead changes in AHI
[16, 17, 30, 31]. Type, frequency, and duration of given
exercise differed with no consensus being reached among a
few studies on the effect of exercise on OSA [16, 30]. We
found that supervised exercise of respiratory and aerobic
type for 12 weeks had no effect on BMI, body fat
percentage, neck, waist, and hip circumferences,and
waist-to-hip ratio in our prospective, randomized, con-
trolled study on the effect of mild to moderate OSAS.
Norman et al. [16] showed that improvements occurred
in MET levels and resting blood pressures of the patients
with mild to moderate OSAS receiving aerobic exercise and
diet program for 6 months. Giebelhaus et al. [30] noted that
exercise performance did not change with the program
consisting of aerobic and power exercises in the patients
with severe OSAS.
The fact that neither type of exercise nor patients' groups
were standardized prevented the exercise outcomes to
become clear. In the present study, respiratory and aerobic
exercises we applied for 3 months increased MaxVO2,
MET, and maximal load value. We found decrease in leg
tiredness and dyspnea severity as important determination
Table 4 Results of the polysomnographic and intra- and inter-group differences for the control group and exercise group following the
intervention period
Exercise group Control group P**
Pre Post P* Pre Post P*
AHI 15.19 (5.43) 11.01 (5.28) 0.02 17.92 (6.45) 17.36 (11.18) 0.58 0.11
Sleep efficiency% 80.58 (6.34) 86.35 (13.97) 0.14 89.05 (5.96) 88.30 (9.53) 0.80 0.91
Saturation% 83.90 (4.53) 83.60 (4.48) 0.94 82.50 (5.44) 84.03 (4.50) 0.51 0.94
Total sleep time (min) 361.30 (55.27) 361.16 (79.99) 0.80 388.15 (57.27) 351.82 (89.64) 0.29 0.76
ESS 8.20 (6.14) 7.00 (6.65) 0.40 3.42 (507) 5.30 (4.191) 0.43 0.65
Data are presented as mean±standard deviation
ESS Epworth Sleepiness Scale, AHI apnea hypopnea index
*P<0.05, Wilcoxon signed rank test
**P<0.05, Mann–Whitney U test
54 Sleep Breath (2011) 15:49–56
of exercise capacity. Changes occurred in sleep parameters
with increases in determination of exercise capacity without
changes in breathing reserve during exercise testing. We
believe that these improvements in sleep parameters result
from increase in functional capacity contributing to im-
provement in exercise capacity.
It has been reported that CPAP treatment improves ESS,
mental vitality, and social function domains of SF-36, and
especially "activity level" and "vigilance" subscales of
FOSQ [32, 33]. Decrease in daytime sleepiness with
increased level of physical activity has been shown to
improve quality of sleep and life, especially vitality and
physical role [16, 17]. Studies considered this result as a
positive effect of decreased body weight on quality of life
and sleep. The present study showed that applied exercise
treatment did not change ESS score but significant
improvements occurred in vitality and mental health
subscales of SF-36. At the baseline, “Activity level” score
and total score of FOSQ were better in the control group
than in the exercise group. This remained unchanged in the
control group while changed in the exercise group. We felt
that as with CPAP treatment and improved physical
activity, efficient sleep occurred; and this improved vital
activities such as work productivity and vitality.
Although a number of the studies looking at the effects
of chronic exercise on AHI are low, there are many
hypotheses and theoretical reviews [6, 7, 12]. Basic
hypotheses proposed by Driver and Taylor [12] are those
of thermogenic, conversation of the energy, and body
restoration and are that these mechanisms affect sleep-
awake cycle and slow wave sleep [13]. Netzer and
colleagues [15] studied the effects of exercise in the
patients with sleep apnea based on the idea that chemore-
ceptor sensitivity enhanced following physical exercise in
the athletes, and, thus, breathing improves. As a result of
their study, they advocated that decrease in AHI resulted
from improved muscle tonus of the upper airway or
improved breathing although body weight did not change.
Similarly, Giebelhaus et al. [30] suggested that possible
cause of decrease in AHI, without change in body weight
following 6-month exercise training they give to the
patients with sleep apnea syndrome, was increased strength
of pharyngeal and glossal muscles. Another hypothesis
alternative to decreased severity of OSAS through im-
proved tonus of tongue muscles is that strength of the
respiratory muscles, i.e., inspiratory and expiratory pres-
sures increase with exercise training [34]. Based on the
study by O’Donnel et al., Norman et al. [16] noted that
decrease could occur in apnea and hypopnea with increas-
ing inspiratory and expiratory pressure although they had
no enough data on the topic. In contrast to Norman et al.,
we measured strength of inspiratory and expiratory muscles
and similar to the study by O’Donnell et al.. We found that
exercise did not alter strength of ventilatory muscles
although we give breathing exercises to our study group.
In conclusion, similar to the studies by Netzer [15] and
Giebelhaus [30], the present study found decreased AHI
without change in body weight following exercise in the
patients with OSAS. We, however, do not believe that
decreased AHI might be due to changes in the muscle
groups of upper airway or improved breathing control as
Netzer et al. [15] advocated because aerobic and breathing
exercises we applied in our study did not affect Pimax,
Pemax and other respiratory parameters.
It has been shown that the patients with OSA with
regular physical activity have lower AHI [17, 31]. Several
studies exists reporting that exercise does not change total
sleep time [14, 30] despite others that found improvements
in AHI, total sleep time, and sleep efficiency with exercise
in the patients with OSA [16]. Thus, polysomnographic
results of a few studies on effects of supervised exercise
training are controversial. Decrease in AHI has been found
in all studies while improvement in total sleep time has
been found in only one study. Similar to all other studies,
we found in our study that no change occurred in the
control group although significant decreases were found in
the group receiving regular exercise. Total sleep time and
other polysomnographic results did not change after
exercise. Although we determined in the first follow-up
that the control group had more efficient sleep percentage
than the exercise group, no difference was found after the
follow-up between the two groups because it increased in
the exercise group.
In recent years, "Metabolic hypothesis" has been
proposed in explaining the effects of exercise on quality
of sleep. In addition, inflammation of the upper airway
related to the visceral fat tissue appears as a systemic
condition [7, 34]. It has been advocated that plasma
concentrations of the cytokines leading to airway collapse
and inflammation alters, and their receptor antagonists
increase through exercise [6, 34]. In conclusion, exercise
training we applied to the patients with OSAS surprisingly
found decreased AHI despite no changes in breathing
function and BMI. The resultant decrease was supported by
improved exercise capacity. Thus, an effect of exercise in
OSAS that has been frequently discussed as a metabolic
condition in the literature is to make possible metabolic
changes by increasing which lowered functional activity
level. It will be possible to resolve the discussion through
investigations on plasma levels and further studies with
more patients.
Our study is limited by the small sample size and by
inclusion criteria. Due to the known effects of age and sex
on OSA, interval of age was one of the inclusion criteria
and only males were included in the study and this caused
the study to have a small sample size. The situation has
Sleep Breath (2011) 15:49–56 55
been the same in similar studies which used elaborated
protocols and advanced examinations.
Conflict of interest statement There is no related to the article or the
research described and personal or financial support or author involve-
ment with organizations with a financial interest in the subject matter.
References
1. McNamara SG, Grunstein RR, Sullivan CE (1993) Obstructive
sleep apnea. Thorax 48:754–764
2. Parish JM, Somers VK (2004) Obstructive sleep apnea and
cardiovasculardisease. Mayo Clinic Proc 79:1036–1046
3. Levinson PD, McGarvey ST, Carlisle CC, Eveloff SE, Herbert PN,
Millman RP (1993) Adiposity and cardiovascular risk factors in
men with obstructive sleep apnea. Chest 103:1336–1342
4. Zerah-Lancner F, Lofaso F, Coste A, Ricolfi F, Goldenberg F, Harf A
(1997) Pulmonary function in obese snorers with or without sleep
apnea syndrome. Am J Respir Crit Care Med 156:522–527
5. Öztürk L, Metin G, Cuhadaroğlu C, Utkusavaş A, Tutluoğlu B
(2005) FEF (25–75)/FVC measurements and extrathoracic airway
obstruction in obstructive sleep apnea patients. Sleep Breath 9
(1):33–38
6. Santos RV, Tufik S, De Mello MT (2007) Exercise, sleep and
cytokines: is there a relation? Sleep Med Rev 11:231–239
7. Vgontzas AN, Bixler EO, Chrousos GP (2005) Sleep apnea is a
manifestation of the metabolic syndrome. Sleep Med Rev 9
(3):211–224
8. Boyd JH, Petrof BJ, Hamid Q, Fraser R, Kimoff RJ (2004) Upper
airway muscle inflammation and denervation changes in obstruc-
tive sleep apnea. Am J Respir Crit Care Med 170:541–546
9. Lim J, Lasserson TJ, Fleetham J, Wright J (2006) Oral appliances
for obstructive sleep apnoea. Cochrane Database Syst Rev 25(1):
CD004435
10. Sundaram S, Bridgman SA, Lim J, Lasserson TJ (2005) Surgery
for obstructive sleep apnoea. Cochrane Database Syst Rev 19(4):
CD001004
11. Giles TL, Lasserson TJ, Smith BH, White J, Wright J, Cates CJ
(2006) Continuous positive airways pressure for obstructive sleep
apnoea in adults. Cochrane Database Syst Rev 19(3):CD001106
12. Driver HS, Taylor SR (2000) Exercise and sleep. Sleep Med Rev
4(4):387–402
13. Youngstedt SD, O’Connor PJ, Dishman RK (1997) The effects of
acute exercise on sleep: a quantitative synthesis. Sleep 20(3):203–214
14. Hargens TA, Guill SG, Aron A, Zedalis D, Gregg JM, Nickols-
Richardson SM, Herbert WG (2009) Altered ventilatory responses
to exercise testing in young adult men with obstructive sleep
apnea. Respir Med 103(7):1063–1069
15. Netzer N, Lormes W, Giebelhaus V, Halle M, Keul J, Matthys H,
Lehmann M (1997) Physical training of patients with sleep apnea.
Pneumologie 51:779–782
16. Norman JF, Von Essen SG, Fuchs RH, McElligott M (2000)
Exercise training effect on obstructive sleep apnea syndrome.
Sleep Res Online 3(3):121–129
17. Hong S, Dimsdale JE (2003) Physical activity and perception of
energy and fatigue in obstructive sleep apnea. Med Sci Sports
Exerc 35(7):1088–1092
18. Weiser PC, Mahler DA, Ryan KP, Hill KL, Greenspon LW (1993)
Dyspnea: symptom assessment and management. In: Hodgkin JE,
Conors GL, Bell CW (eds) Pulmonary rehabilitation: guidelines to
success, 2nd edn. JB Lippincott Company, Philadelphia, pp 478–
511
19. Nici L, Donner C, Wouters E et al (2006) American Thoracic
Society/European Respiratory Society statement on pulmonary
rehabilitation. Am J Respir Crit Care Med 173(12):1390–1413
20. Bianchi R, Gigliotti F, Romagnoli I, Lanini B, Castellani C,
Binazzi B, Stendardi L, Grazzini M, Scano G (2004) Chest wall
kinematics and breathlessness during pursedlip breathing in
patients with COPD. Chest 125(2):459–465
21. Dwyer GB, Davis SE (2005) ACSM’s health-related physical fitness
assessment manual. Lippincott Williams &Wilkins, Philadelphia
22. American College of Sports Medicine (2003) The ACSM Fitness
Program. ACSM fitness book. Human Kinetics, Hong Kong
23. American Thoracic Society (1995) Standardization of spirometry,
1994 update. American Thoracic Society. Am J Respir Crit Care
Med 152:1107–1136
24. Black LF, Hyatt RE (1969) Maximal respiratory pressures: normal
values and relationship to age and sex. Am Rev Respir Dis
99:696–702
25. American Thoracic Society (2003) ATS/ACCP statement on
cardiopulmonary exercise testing. Am J Respir Crit Care Med
167:211–277
26. Izci B, Firat H, Ardıc S, Kokturk O, Gelir E, Altınors M (2004)
Adaptation of Functional Outcomes of Sleep Questionnaire
(FOSQ) to Turkish population. Tuberk Toraks 52:224–230
27. Brazier J, Harper R, Jones N, O’Cathain A, Thomas KJ,
Usherwood T, Westlake L (1992) Validating the SF-36 health
survey questionnaire: new outcome measure for primary care.
BMJ 305(6846):160–164
28. Johns MW (1991) A new method for measuring daytime
sleepiness: the Epworth Sleepiness Scale. Sleep 14(6):540–545
29. Rechtschaffen A, Kales A (eds) (1968) A manual of standardized
terminology, techniques and scoring system for sleep stages of
human subjects. Brain Research Institute, UCLA, Los Angeles
30. Giebelhaus V, Strohl KP, Lormes W, Lehmann M, Netzer N
(2000) Physical Exercise as an adjunct therapy in sleep apnea—an
open trial. Sleep Breath 4(4):173–176
31. Peppard PE, Young T (2004) Exercise and sleep-disordered
breathing: an association independent of body habitus. Sleep 27
(3):480–484
32. Moore P, Bardwell WA, Ancoli-Israel S, Dimsdale JE (2001)
Association between polysomnographic sleep measures and
health-related quality of life in obstructive sleep apnea. J Sleep
Res 10(4):303–308
33. Marshall NS, Barnes M, Travier N, Campbell AJ, Pierce RJ,
McEvoy RD, Neill AM, Gander PH (2006) Continuous positive
airway pressure reduces daytime sleepiness in mild to moderate
obstructive sleep apnoea: a meta-analysis. Thorax 61(5):430–
434
34. O’Donnell DE, McGuire M, Samis L, Webb KA (1998) General
exercise training improves ventilatory and peripheral muscle
strength and endurance in chronic airflow limitation. Am J Respir
Crit Care Med 157:1489–1497
56 Sleep Breath (2011) 15:49–56
	The effect of exercise on obstructive sleep apnea: a randomized and controlled trial
	Abstract
	Abstract
	Abstract
	Abstract
	Abstract
	Introduction
	Methods
	Subjects
	Anthropometric data
	Pulmonary function testing
	Exercise testing
	Quality of life and sleep
	Daytime sleepiness evaluation
	Polysomnography
	Data analysis
	Results
	Characteristics of the subjects
	Physical changes
	Respiratory parameter results
	Responses to the exercise testing
	Quality of life and sleep outcomes
	Polysomnography
	Discussion
	References
<<
 /ASCII85EncodePages false
 /AllowTransparency false
 /AutoPositionEPSFiles true
 /AutoRotatePages /None
 /Binding /Left
 /CalGrayProfile (Gray Gamma 2.2)
 /CalRGBProfile (sRGB IEC61966-2.1)
 /CalCMYKProfile (ISO Coated v2 300% \050ECI\051)
 /sRGBProfile (sRGB IEC61966-2.1)
 /CannotEmbedFontPolicy /Error
 /CompatibilityLevel 1.3
 /CompressObjects /Off
 /CompressPages true
 /ConvertImagesToIndexed true
 /PassThroughJPEGImages true
 /CreateJDFFile false
 /CreateJobTicket false
 /DefaultRenderingIntent /Perceptual
 /DetectBlends true
 /DetectCurves 0.0000
 /ColorConversionStrategy /sRGB
 /DoThumbnails true
 /EmbedAllFonts true
 /EmbedOpenType false
 /ParseICCProfilesInComments true
 /EmbedJobOptions true
 /DSCReportingLevel 0
 /EmitDSCWarnings false
 /EndPage -1
 /ImageMemory 1048576
 /LockDistillerParams true
 /MaxSubsetPct 100
 /Optimize true
 /OPM 1
 /ParseDSCComments true
 /ParseDSCCommentsForDocInfo true
 /PreserveCopyPage true
 /PreserveDICMYKValues true
 /PreserveEPSInfo true
 /PreserveFlatness true
 /PreserveHalftoneInfo false
 /PreserveOPIComments false
 /PreserveOverprintSettings true
 /StartPage 1
 /SubsetFonts false
 /TransferFunctionInfo /Apply
 /UCRandBGInfo /Preserve
 /UsePrologue false
 /ColorSettingsFile ()
 /AlwaysEmbed [ true
 ]
 /NeverEmbed [ true
 ]
 /AntiAliasColorImages false
 /CropColorImages true
 /ColorImageMinResolution 150
 /ColorImageMinResolutionPolicy /Warning
 /DownsampleColorImages true
 /ColorImageDownsampleType /Bicubic
 /ColorImageResolution 150
 /ColorImageDepth -1
 /ColorImageMinDownsampleDepth 1
 /ColorImageDownsampleThreshold 1.50000
 /EncodeColorImages true
 /ColorImageFilter /DCTEncode
 /AutoFilterColorImages true
 /ColorImageAutoFilterStrategy /JPEG
 /ColorACSImageDict <<
 /QFactor 0.40
 /HSamples [1 1 1 1] /VSamples [1 1 1 1]
 >>
 /ColorImageDict <<
 /QFactor 1.30
 /HSamples [2 1 1 2] /VSamples [2 1 1 2]
 >>
 /JPEG2000ColorACSImageDict <<
 /TileWidth 256
 /TileHeight 256
 /Quality 10>>
 /JPEG2000ColorImageDict <<
 /TileWidth 256
 /TileHeight 256
 /Quality 10
 >>
 /AntiAliasGrayImages false
 /CropGrayImages true
 /GrayImageMinResolution 150
 /GrayImageMinResolutionPolicy /Warning
 /DownsampleGrayImages true
 /GrayImageDownsampleType /Bicubic
 /GrayImageResolution 150
 /GrayImageDepth -1
 /GrayImageMinDownsampleDepth 2
 /GrayImageDownsampleThreshold 1.50000
 /EncodeGrayImages true
 /GrayImageFilter /DCTEncode
 /AutoFilterGrayImages true
 /GrayImageAutoFilterStrategy /JPEG
 /GrayACSImageDict <<
 /QFactor 0.40
 /HSamples [1 1 1 1] /VSamples [1 1 1 1]
 >>
 /GrayImageDict <<
 /QFactor 1.30
 /HSamples [2 1 1 2] /VSamples [2 1 1 2]
 >>
 /JPEG2000GrayACSImageDict <<
 /TileWidth 256
 /TileHeight 256
 /Quality 10
 >>
 /JPEG2000GrayImageDict <<
 /TileWidth 256
 /TileHeight 256
 /Quality 10
 >>
 /AntiAliasMonoImages false
 /CropMonoImages true
 /MonoImageMinResolution 600
 /MonoImageMinResolutionPolicy /Warning
 /DownsampleMonoImages true
 /MonoImageDownsampleType /Bicubic
 /MonoImageResolution 600
 /MonoImageDepth -1
 /MonoImageDownsampleThreshold 1.50000
 /EncodeMonoImages true
 /MonoImageFilter /CCITTFaxEncode
 /MonoImageDict <<
 /K -1
 >>
 /AllowPSXObjects false
 /CheckCompliance [
 /None
 ]
 /PDFX1aCheck false
 /PDFX3Check false
 /PDFXCompliantPDFOnly false
 /PDFXNoTrimBoxError true
 /PDFXTrimBoxToMediaBoxOffset [
 0.00000
 0.00000
 0.00000
 0.00000
 ]
 /PDFXSetBleedBoxToMediaBox true
 /PDFXBleedBoxToTrimBoxOffset [
 0.00000
 0.00000
 0.00000
 0.00000
 ]
 /PDFXOutputIntentProfile (None)
 /PDFXOutputConditionIdentifier ()
 /PDFXOutputCondition ()
 /PDFXRegistryName ()
 /PDFXTrapped /False
 /Description <<
 /CHS <FEFF4f7f75288fd94e9b8bbe5b9a521b5efa7684002000410064006f006200650020005000440046002065876863900275284e8e5c4f5e55663e793a3001901a8fc775355b5090ae4ef653d190014ee553ca901a8fc756e072797f5153d15e03300260a853ef4ee54f7f75280020004100630072006f0062006100740020548c002000410064006f00620065002000520065006100640065007200200035002e003000204ee553ca66f49ad87248672c676562535f00521b5efa768400200050004400460020658768633002>
 /CHT <FEFF4f7f752890194e9b8a2d7f6e5efa7acb7684002000410064006f006200650020005000440046002065874ef69069752865bc87a25e55986f793a3001901a904e96fb5b5090f54ef650b390014ee553ca57287db2969b7db28def4e0a767c5e03300260a853ef4ee54f7f75280020004100630072006f0062006100740020548c002000410064006f00620065002000520065006100640065007200200035002e003000204ee553ca66f49ad87248672c4f86958b555f5df25efa7acb76840020005000440046002065874ef63002>
 /DAN <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>
 /ESP <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>
 /FRA <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>
 /ITA <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>
 /JPN <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>
 /KOR <FEFFc7740020c124c815c7440020c0acc6a9d558c5ec0020d654ba740020d45cc2dc002c0020c804c7900020ba54c77c002c0020c778d130b137c5d00020ac00c7a50020c801d569d55c002000410064006f0062006500200050004400460020bb38c11cb97c0020c791c131d569b2c8b2e4002e0020c774b807ac8c0020c791c131b41c00200050004400460020bb38c11cb2940020004100630072006f0062006100740020bc0f002000410064006f00620065002000520065006100640065007200200035002e00300020c774c0c1c5d0c11c0020c5f40020c2180020c788c2b5b2c8b2e4002e>
 /NLD (Gebruik deze instellingen om Adobe PDF-documenten te maken die zijn geoptimaliseerd voor weergave op een beeldscherm, e-mail en internet. De gemaakte PDF-documenten kunnen worden geopend met Acrobat en Adobe Reader 5.0 en hoger.)
 /NOR <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>/PTB <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>
 /SUO <FEFF004b00e40079007400e40020006e00e40069007400e4002000610073006500740075006b007300690061002c0020006b0075006e0020006c0075006f00740020006c00e400680069006e006e00e40020006e00e40079007400f60073007400e40020006c0075006b0065006d0069007300650065006e002c0020007300e40068006b00f60070006f0073007400690069006e0020006a006100200049006e007400650072006e0065007400690069006e0020007400610072006b006f006900740065007400740075006a0061002000410064006f0062006500200050004400460020002d0064006f006b0075006d0065006e007400740065006a0061002e0020004c0075006f0064007500740020005000440046002d0064006f006b0075006d0065006e00740069007400200076006f0069006400610061006e0020006100760061007400610020004100630072006f0062006100740069006c006c00610020006a0061002000410064006f00620065002000520065006100640065007200200035002e0030003a006c006c00610020006a006100200075007500640065006d006d0069006c006c0061002e>
 /SVE <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>
 /ENU (Use these settings to create Adobe PDF documents best suited for on-screen display, e-mail, and the Internet. Created PDF documents can be opened with Acrobat and Adobe Reader 5.0 and later.)
 /DEU <FEFF004a006f0062006f007000740069006f006e007300200066006f00720020004100630072006f006200610074002000440069007300740069006c006c0065007200200037000d00500072006f006400750063006500730020005000440046002000660069006c0065007300200077006800690063006800200061007200650020007500730065006400200066006f00720020006f006e006c0069006e0065002e000d0028006300290020003200300031003000200053007000720069006e006700650072002d005600650072006c0061006700200047006d006200480020>
 >>
 /Namespace [
 (Adobe)
 (Common)
 (1.0)
 ]
 /OtherNamespaces [
 <<
 /AsReaderSpreads false
 /CropImagesToFrames true
 /ErrorControl /WarnAndContinue
 /FlattenerIgnoreSpreadOverrides false
 /IncludeGuidesGrids false
 /IncludeNonPrinting false
 /IncludeSlug false
 /Namespace [
 (Adobe)
 (InDesign)
 (4.0)
 ]
 /OmitPlacedBitmaps false
 /OmitPlacedEPS false
 /OmitPlacedPDF false
 /SimulateOverprint /Legacy
 >>
 <<
 /AddBleedMarks false
 /AddColorBars false
 /AddCropMarks false
 /AddPageInfo false
 /AddRegMarks false
 /ConvertColors /ConvertToRGB
 /DestinationProfileName (sRGB IEC61966-2.1)
 /DestinationProfileSelector /UseName
 /Downsample16BitImages true
 /FlattenerPreset <<
 /PresetSelector /MediumResolution
 >>
 /FormElements false
 /GenerateStructure false
 /IncludeBookmarks false
 /IncludeHyperlinks false
 /IncludeInteractive false
 /IncludeLayers false
 /IncludeProfiles true
 /MultimediaHandling /UseObjectSettings
 /Namespace [
 (Adobe)
 (CreativeSuite)
 (2.0)
 ]
 /PDFXOutputIntentProfileSelector /NA
 /PreserveEditing false
 /UntaggedCMYKHandling /UseDocumentProfile
 /UntaggedRGBHandling /UseDocumentProfile
 /UseDocumentBleed false
 >>
 ]
>> setdistillerparams
<<
 /HWResolution [2400 2400]
 /PageSize [595.276 841.890]
>> setpagedevice