Altered ventilatory responses to exercise testing in young adult men with obstructive sleep apnea

Laboratory for Health and Exercise Science, Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Respiratory medicine (Impact Factor: 3.09). 02/2009; 103(7):1063-9. DOI: 10.1016/j.rmed.2009.01.010
Source: PubMed
Obstructive sleep apnea (OSA) is a disorder characterized by repetitive obstructions of the upper airway. Individuals with OSA experience intermittent hypoxia, hypercapnia, and arousals during sleep, resulting in increased sympathetic activation. Chemoreflex activation, arising from the resultant oscillatory disturbances in blood gases from OSA, exerts control over ventilation, and may induce increases in sympathetic vasoconstriction, contributing to increased long-term risks for hypertension (HTN) and cardiovascular disease (CVD).
To evaluate whether OSA elicits exaggerated ventilatory responses to exercise in young men, 14 overweight men with OSA and 16 overweight men without OSA performed maximal ramping cycle ergometer exercise tests. Oxygen consumption (VO(2)), ventilation, (V(E)), ventilatory equivalents for oxygen (V(E)/VO(2)) and carbon dioxide (V(E)/VCO(2)), and V(E)/VCO(2) slope were measured.
The VO(2) response to exercise did not differ between groups. The V(E), V(E)/VCO(2), V(E)/VO(2) were higher (p< 0.05, 0.002, and p<0.02, respectively) in the OSA group across all workloads. The V(E)/VCO(2) slope was greater in the OSA group (p<0.05). The V(E)/VCO(2) slope and AHI were significantly correlated (r=0.56, p<0.03). Thus, young, overweight men with OSA exhibit increased ventilatory responses to exercise when compared to overweight controls. This may reflect alterations in chemoreflex sensitivity, and contribute to increased sympathetic drive and HTN risk.


Available from: William G Herbert, Jan 14, 2014
Altered ventilatory responses to exercise testing in
young adult men with obstructive sleep apne a
Trent A. Hargens
, Stephen G. Guill
, Adrian Aron
, Donald Zedalis
John M. Gregg
, Sharon M. Nickols-Richardson
, William G. Herbert
Laboratory for Health and Exercise Science, Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic
Institute and State University, Blacksburg, VA, USA
Sleep Disorders Network of Southwest Virginia, Christiansburg, VA, USA
Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA
Human Performance Laboratory, Clinical Exercise Physiology Program, Ball State University, Muncie, IN, USA
Edward Via Virginia College of Osteopathic Medicine, Blacksburg, VA, USA
Health Research Group, LLC, Blacksburg, VA, USA
Received 3 June 2008; accepted 14 January 2009
Available online 13 February 2009
Exercise test;
Background: Obstructive sleep apnea (OSA) is a disorder characterized by repetitive obstruc-
tions of the upper airway. Individuals with OSA experience intermittent hypoxia, hypercapnia,
and arousals during sleep, resulting in increased sympathetic activation. Chemoreflex activa-
tion, arising from the resultant oscillatory disturbances in blood gases from OSA, exerts control
over ventilation , and may induce increases in sympathetic vasocons triction, contributing to
increased long-term risks for hypertension (HTN) and cardiovascular disease (CVD).
Methods: To evaluate whether OSA el icits exaggerated ventilatory responses to exercise in
young men, 14 overweight men with OSA and 16 overweight men without OSA performed
maximal ramping cy cle ergometer ex ercise tes ts. Oxygen con sumption (VO
), ventilation,
), ventilatory equivalents for oxygen (V
), and
slope were measured.
Results: The VO
response to exercise did not differ between groups. The V
, V
, V
were higher (p < 0.05, 0.002 , and p < 0.02, respectively) in the OSA group across all work-
loads. The V
slopewasgreaterintheOSAgroup(p < 0.05). The V
slope a nd
AHI were significantly correlated (r Z 0.56, p < 0.03). Thus, young, overweight men with
* Corresponding author. Department of Human Nutrition, Foods & Exercise, Virginia Polytechnic Institute and State University, 213 War
Memorial Hall (0531), Blacksburg, VA 24061, USA. Tel.: þ1 540 231 6565; fax: þ1 540 231 8476.
E-mail address: (W.G. Herbert).
0954-6111/$ - see front matter ª 2009 Elsevier Ltd. All rights reserved.
available at
journal homepage:
Respiratory Medicine (2009) 103, 1063e1069
Page 1
OSA exhibit increased ventilatory respons es to exercise when compared to overweight
controls. This may reflect alterations in chemoreflex sensitivity, and contribute to increased
sympathetic drive and HTN risk.
ª 2009 Elsevier Ltd. All rights reserved.
Obstructive sleep apnea (OSA) is a sleep disorder prevalent
in approximately 2e4% of the middle-aged adult pop-
Recent estimates, however suggest that over 85%
of those with significant OSA, who would benefit from
treatment, go undiagnosed.
This disorder has been
associated with increased risk for the development of
several adverse health conditions,
and it has recently been
reported that OSA may also independently increase the risk
for cardiovascular morbidity and mortality.
The stron-
gest relationship, however, appears to be that between OSA
and the occurrence of hypertension (HTN), which demon-
strates an independent, doseeresponse relationship
between OSA severity and HTN risk.
The mechanisms linking OSA to HTN are unclear, but
several proposed mechanisms suggest a complex interac-
tion of several factors. Heightened sympathetic nervous
system activation has been demonstrated in OSA, which
persists during waking hours, and is above that which is
seen in obesity alone.
Treatment of OSA with nasal
continuous positive airway pressure (CPAP) has been shown
to decrease sympathetic activity.
Chemoreflexes exert powerful control over ventilation
and contribute directly to sympathetic activation.
activation of the chemoreflexes, and a significantly greater
ventilatory response to acute hypoxic breathing has been
documented in OSA patients at rest
above that which
has been previously noted in obesity alone.
Exercise is
another instance when chemoreflex sensitivity augments,
and recent studies examining individuals with central sleep
apnea (CSA) and congestive heart failure (CHF) demon-
strated an exaggerated ventilatory response to exercise in
CSA subjects, suggesting an enhanced chemosensitivity
above CHF alone.
Significant correlations between CSA
severity and the V
slope, a marker of chemo-
sensitivity and predictor of poor prognosis with CHF, were
also reported.
Limited data is available on the responses to graded
exercise testing in OSA, and no published studies have
examined the ventilatory responses at submaximal and
maximal exercise intensities. Therefore, the purpose of this
study is to evaluate the ventilatory responses to graded
exercise testing in young men with undiagnosed OSA, to
examine whether a possible alteration in chemoreflex sensi-
tivity may be an early clinical sign in the progression of OSA.
Study subjects
Sedentary overweight males with untreated OSA (n Z 14),
and control subjects matched for age, body mass index (BMI),
and central adiposity, but without OSA (n Z 16) were
recruited from the local university community through
campus notices as well as newspaper advertisements.
Subjects were between 18 and 26 years of age and were
classified as overweight according to BMI criteria.
subjects underwent pre-screening which included an initial
qualification questionnaire to identify any potential exclusion
criteria, as well as a detailed health history questionnaire. All
subjects were non-smokers, who were free from acute
respiratory infection during the previous 6 weeks, including
tonsillitis and adenoiditis. Subjects were free from significant
cardiovascular, pulmonary, metabolic, or musculoskeletal
disorders that would preclude maximal aerobic exercise
testing. Subjects were not taking any prescribed vasoactive
medications, hypnotics, sedatives, analgesics, psychotropics,
steroids, or sympathomimetics. Individuals who had partici-
pated in regular physical activity (>3 days per week, >30 min
per day) for the previous 6 months were considered physically
active and excluded.
All methods and procedures, approved
by the Institutional Review Board of Virginia Polytechnic
Institute and State University (Virginia Tech), Blacksburg, VA,
were explained to the subjects, who then read and gave
written informed consent.
Home sleep evaluation
Subjects underwent an unattended, limited home sleep
evaluation consisting of: (1) nasal flow detection via nasal
cannula; (2) finger pulse oximetry; (3) respiratory effort
detection via belts positioned on the upper and lower torso;
and (4) body position detection, to screen for the presence
of OSA, utilizing the Embletta portable device (Embla,
Broomfield, CO). The Embletta device and other portable
systems similar to the Embletta have previously been vali-
dated vs. nighttime polysomnography (PSG).
data were interpreted by a sleep technician and transposed
into an apnea hypopnea index (AHI), with the results veri-
fied by the physician investigator who is a sleep specialist.
Apnea is defined as a cessation of airflow for 10 s or greater.
Hypopnea is defined a 50% or greater reduction in airflow
for at least 10 s coupled with a decrease in oxygen satu-
ration (4%).
Subjects were then classified into either the
OSA group (OSA) (AHI > 5 events h
), or the no-OSA group
(No-OSA) (AHI < 5 events h
Body composition measurement
Subjects completed total body dual-energy X-ray absorpti-
ometry (DXA) scans (version 8.26a:3*, QDR4500A, Hologic
Inc., Bedford, MA) for measurement of fat mass (FM) and
body fat percentage (BF%). Central abdominal fat was
measured from total body DXA scans by examining the
region of interest defined by the top edge of the second to
bottom edge of the fourth lumbar vertebra.
1064 T.A. Hargens et al.
Page 2
measures were conducted and analyzed by one investi-
gator. Weekly scans of an external soft tissue bar (Hologic
Inc.) were completed to ensure quality control for soft
tissue mass measurements. Testeretest reliability data for
this DXA have been reported elsewhere.
Ramp exercise testing
Subjects completed a maximal cycle ergometer exercise
test. Anthropometric measures of height, weight, neck
circumference (NC), waist circumference (WC), and hip
circumference (HC) were measured prior to the exercise
test. Resting heart rate (HR) and blood pressure were
obtained in the seated position, after a minimum of 5 min
of rest. An electronically braked cycle ergometer (Sensor-
, Yorba Linda, CA) was utilized for each exercise
test. A standardized protocol for each subject was utilized,
which has been previously described.
Respiratory gas
exchange measurements were obtained during the exercise
test using a computer controlled, breath-by-breath system
(SensorMedics Vmax 229
, Yorba Linda, CA). Values were
calculated to 10 s averages. Measurements included oxygen
consumption (VO
), minute ventilation (V
), carbon dioxide
production (VCO
), respiratory exchange ratio (RER) and
peak VO
). The two highest 10 s VO
values achieved
during the last minute of exercise were averaged to obtain
the VO
value. The V
and V
ratios were
calculated at several submaximal workloads and at peak
exercise. The V
slope was calculated from exercise
onset to peak as previously described.
Statistical analysis
All statistical analyses were performed using SPSS version
15.0 (SPSS Inc., Chicago, IL). Independent t -tests were used
to evaluate differences in baseline descriptive character-
istics between groups. Effects of group, exercise intensity
(watts), and interactions on ventilatory measures were
evaluated using two-way repeated measures ANOVA.
Pearson r correlations were calculated to explore potential
relationships between select ventilatory measures and AHI.
A value of p < 0.05 was considered statistically significant.
Subject characteristics
Demographic and descriptive characteristics for the study
participants are presented in Table 1. No differences were
noted between groups for age, BMI, NC, WC, HC, BF%, and
central abdominal fat. Central abdominal fat was positively
correlated with AHI (r Z 0.42, p Z 0.02) across all study
Exercise test measures
Heart rate and blood pressure responses did not differ
between the groups at rest or during exercise and these
findings are summarized elsewhere.
The VO
between groups did not differ at any submaximal exercise
intensity or at maximum effort (p Z 1.0), nor did peak work
rate (Watts) achieved (p Z 0.30). As shown in Fig. 1, VE,
, and V
responses were higher in the OSA
group at all workloads (p < 0.05, p < 0.002 and p Z 0.02,
respectively). The V
slope was greater in the OSA
compared to the control group (p Z 0.045) (Fig. 2), and was
positively correlated with AHI (r Z 0.56, p Z 0.001)
(Fig. 3). No difference in the RER between groups was
noted at any submaximal workload or at peak (p Z 0.30).
Peak exercise responses for all subjects are presented in
Table 2. Maximal test endpoints were achieved in both
groups (peak RER > 1.1; peak RPE > 16).
This study is the first to evaluate ventilatory responses to
exercise in young, overweight men with untreated OSA. The
major finding is that OSA, and not obesity, results in
increased ventilatory responses to graded exercise testing
in young men, reflected by significantly greater V
, V
, and V
measures across all submaximal exercise
intensities and peak exercise (Fig. 1). In subjects matched
for age, BMI, BF%, central abdominal fat, and VO
, those
with OSA demonstrated an exaggerated ventilatory
response relative to carbon dioxide output and oxygen
consumption. This finding is in contrast to that findings of
Lin et al.,
which reported no difference between the OSA
and control group in either peak V
or V
Exaggerated V
slope, a marker of chemoreflex
sensitivity, has previously been found to be a potent
predictor of poor prognosis in patients with CHF
a condition frequently seen in patients with central sleep
apnea (CSA) as well as OSA. Artz et al.
found, in middle-
age individuals with CHF and CSA, the V
slope, with
exercise, was greater than those without CSA. They also
reported a significant correlation between the V
slope and AHI (r Z 0.613; p < 0.001).
More recently,
Meguro et al.
also reported a greater V
slope in
middle-aged CHF patients with CSA compared to CHF
subjects without CSA (p < 0.01). To our knowledge, no
studies have examined the response to exercise in OSA
subjects. Results from the current study indicate that this
Table 1 Subject characteristics.
OSA (n Z 14) No-OSA (n Z 16)
Age (years) 22.4 (2.8) 21.4 (2.6)
AHI (events h
1) 22.7 (18.5)
2.5 (1.3)
Height (cm) 171.6 (18.6) 178.2 (6.1)
Weight (kg) 99.6 (13.4) 99.4 (12.4)
BMI (kg m
2) 32.0 (3.7) 31.4 (3.7)
NC (cm) 40.8 (2.1) 40.6 (2.6)
WC (cm) 100.5 (8.1) 95.4 (9.7)
HC (cm) 115.4 (8.1) 110.1 (8.4)
FM (kg) 29.1 (7.6) 26.0 (7.2)
% body fat 28.5 (4.7) 25.9 (4.5)
CAF (kg) 8.7 (2.4) 7.0 (1.9)
Values are means with SD in parentheses. AHI, apnea/hypopnea
index; BMI, body mass index; NC, neck circumference; WC,
waist circumference; CAF, central abdominal fat.
* p < 0.0001.
Ventilatory exercise responses in young men with OSA 1065
Page 3
measure of chemoreflex sensitivity is increased in young
overweight men with OSA. We report a correlation between
the V
slope and AHI similar to that of Artz et al.
(r Z 0.56 vs. 0.61).
Further examination of this relation-
ship with OSA is required.
The possible mechanisms underlying the exaggerated
ventilatory responses may be multifaceted. The repetitive
nocturnal bouts of hypoxia and hypercapnia operant in OSA
have been implicated to induce alterations in the central
and peripheral chemoreceptors.
Narkiewicz et al. previ-
ously demonstrated a tonic activation of the chemorecep-
tors in OSA patients,
and further demonstrated
exaggerated chemoreflex sensitivity in OSA patients
through breathing a hypoxic mixture that resulted in
a greater V
and muscle sympathetic nerve activation in the
OSA group vs. non-OSA controls at rest.
Results of the
current study agree with, and extend those of Narkiewicz
et al.
suggesting that the intermittent nighttime
hypoxia of OSA potentiates increased peripheral chemore-
ceptor sensitivity that persists during waking hours, and
manifests during graded exercise testing. The underlying
mechanisms that contribute to the alterations in chemo-
receptor function are not well understood. Recent
evidence suggests that multiple adaptive mechanisms may
play a role, including alterations in vascular endothelial
function, increased angiotensin II activity, as well increased
generation of reactive oxygen species.
Studies utilizing animal and human models support an
increased peripheral chemoreceptor gain in response to
Figure 2 The individual and mean values of the V
slope of patients with OSA (n Z 14) vs. No-OSA (n Z 16).
0 10203040506070
r = 0.56
p = 0.001
Figure 3 Relation between V
slope and the apneae
hypopnea index (AHI) in 30 overweight young men. The AHI is
a measure of obstructive sleep apnea and its severity, as
assessed by overnight somnography.
Power (Watts)
55 85
145 peak
Power (Watts)
55 85 115
145 peak
55 85 115 145 peak
Figure 1 Submaximal and maximal ventilatory responses
during cycle ergometer exercise in young, sedentary men: (A)
was greater across all workloads in the OSA (n Z 14) vs. No-
OSA (n Z 16) group (*p < 0.05); (B) V
was greater across
all workloads in the OSA vs. No-OSA group (**p < 0.002); (C) V
was greater across all workloads in the OSA vs. No-OSA
group (yp < 0.02).
1066 T.A. Hargens et al.
Page 4
chronic intermittent hypoxia.
Data from these studies
suggest that increased endothelin-1, a potent modulator of
the peripheral chemoreceptors that is produced in the
vascular endothelium, increases chemoreflex sensitivity.
Rey et al. further showed an increased ventilatory response
in animals exposed to hypoxic breathing.
Human studies
in OSA subjects have also reported increases in endothelin-1
or its precursors, and the potential for CPAP to improve
these factors.
. Our finding of an exaggerated ventila-
tory response to ramping exercise in young men with OSA
is consistent with this hypothesized mechanism of
increased chemoreceptor gain due to chronic intermittent
hypoxia, possibly involving related alterations in vascular
endothelial function. Further study is needed to clarify
these adaptive mechanisms, particularly with respect to
effects in exercise.
Another potential mechanism has been suggested by
recent investigations that have reported alterations in the
skeletal muscle function as a result of OSA.
Data from
these studies indicated that OSA patients have a reduced
peak blood lactate response during maximal exercise, as
well as a diminished rate of blood lactate clearance. Taken
together, these findings suggest a defect in muscle oxidative
metabolism in OSA subjects.
While we did not measure
lactate or catecholamine levels in the current study, we
observed no differences in the VO
or RER responses in the
two study groups. This suggests similar oxygen cost at
the same power output, as well as a similar metabolic fuel
mix. Taken together, it is unlikely that possible OSA-related
differences in muscle oxidative metabolism would be
an explanation for exaggerated ventilatory responses
observed here.
One potential limitation is that nighttime PSG testing
was not utilized for OSA diagnosis. Nighttime PSG is the
standard and accepted tool for OSA diagnosis. The Embletta
has been validated relative to PSG results,
but is depen-
dent upon the subject’s ability to properly set up the device
independently. Subjects were provided verbal and visual
instruction by study personnel, written instructions for
device setup, and contact information for study personnel
in case further instruction was needed. Another limitation
was that cycle ergometry was utilized for the ramp exercise
test rather than treadmill walking. Cycle ergometry can
result in lower peak VO
values. In the current study,
however, peak RER values for each group were greater than
maximal criteria (RER > 1.1), suggesting maximal efforts in
all subjects.
In conclusion, the results of the current study
indicate that exercise testing results in exaggerated
ventilatory responses in young, overweight m en wi th
untreated OSA. These responses are suggestive of
alterations in chemoreflex sensitivity and breathing
efficiency in these individuals, beyond that seen with
obesity alone. These findings also suggest t he potential
for clinical exercise testing in improving risk stratifica-
tion and clinical decision making leading to patient
selection for OSA diagnostic testing with PSG.
Respiratory gas exchange equipment for this research
was provided by SensorMedics, Yorba Linda, CA,
a Division of VIASYS Healthcare, Inc. Parts of this
research were supported by a grant from the ResMed
Foundation, La Jolla, CA, and ResMed Corporation, San
Diego, CA. Research conducted in the Laboratory for
Health and Exercise Science, Department of Human
Nutrition, Foods and Exercise, on the campus of Virginia
Polytechnic Institute and State University, Blacksburg,
VA , and the Sleep Disorders Network of Southwest
Virginia, Christiansburg, VA.
Conflict of interest statement
Trent A. Hargens, Stephen G. Guill, Adrian Aron, Donald
Zedalis, John M. Gregg, Sharon M. Nickols-Richardson, and
William G. Herbert have no conflicts to disclose.
Table 2 Cardiopulmonary and perceptual responses to
RER peak RPE peak
OSA (n Z 14)
1 29.6 24.2 1.22 N/A
2 23.5 25.7 1.10 17
3 35.3 25.5 1.10 15
4 26.8 25.9 1.04 19
5 31.3 32.7 1.18 17
6 35.3 22.6 1.04 18
7 21.2 30.5 1.13 17
8 23.6 28.8 1.15 20
9 26.1 26.8 1.11 17
10 27.0 29.6 1.15 16
11 22.1 26.5 1.09 19
12 24.5 31.7 1.22 19
13 29.3 24.7 1.23 19
14 24.0 28.9 1.15 20
Mean (SD) 27.1 (4.5) 27.4 (3.0) 1.14 (0.06) 17.5 (1.6)
No-OSA (n Z 16)
1 24.5 23.4 1.16 16
2 28.9 25.4 1.09 17
3 25.9 27.7 1.16 18
4 25.8 26.0 1.1 18
5 22.7 28.5 1.11 17
6 26.3 23.4 1.11 18
7 19.6 23.9 1.12 17
8 24.9 25.3 1.12 15
9 26.0 23.8 1.15 17
10 25.2 26.5 1.13 20
11 26.5 25.6 1.07 19
12 34.3 27.5 1.19 18
13 31.4 23.2 1.21 16
14 35.1 23.5 1.04 16
15 26.7 28.4 1.14 19
16 44.2 25.6 1.12 18
Mean (SD) 28.0 (5.8) 25.5 (1.8) 1.13 (0.04) 17.4 (1.3)
RER, respiratory exchange ratio; RPE, rating of perceived
Ventilatory exercise responses in young men with OSA 1067
Page 5
1. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The
occurrence of sleep-disordered breathing among middle-aged
adults. N Engl J Med 1993;328(17):1230e5.
2. Kapur V, Strohl KP, Redline S, Iber C, O’Connor G, Nieto J.
Underdiagnosis of sleep apnea syndrome in US communities.
Sleep Breath 2002;6(2):49e54.
3. Young T, Evans L, Finn L, Palta M. Estimation of the clinically
diagnosed proportion of sleep apnea syndrome in middle-aged
men and women. Sleep 1997;20(9):705e6.
4. Somers VK, White DP, Amin R, et al. Sleep apnea and cardio-
vascular disease: an American Heart Association/American
College Of Cardiology Foundation Scientific Statement from
the American Heart Association Council for High Blood Pressure
Research Professional Education Committee, Council on Clin-
ical Cardiology, Stroke Council, and Council On Cardiovascular
Nursing. In collaboration with the National Heart, Lung, and
Blood Institute National Center on Sleep Disorders Research
(National Institutes of Health). Circulation 2008;118(10):
5. Young T, Finn L, Peppard PE, et al. Sleep disordered breathing
and mortality: eighteen-year follow-up of the Wisconsin sleep
cohort. Sleep 2008;31(8):1071e8.
6. Marshall NS, Wong KK, Liu PY, Cullen SR, Knuiman MW,
Grunstein RR. Sleep apnea as an independent risk factor for all-
cause mortality: the Busselton Health Study. Sleep 2008;31(8):
7. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardio-
vascular outcomes in men with obstructive sleep apnoeae
hypopnoea with or without treatment with continuous posi-
tive airway pressure: an observational study Lancet 2005;
8. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of
the association between sleep-disordered breathing and
hypertension. N Engl J Med 2000;342(19):1378e84.
9. Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disor-
dered breathing, sleep apnea, and hypertension in a large
community-based study. Sleep Heart Health Study. JAMA 2000;
10. Grassi G, Facchini A, Trevano FQ, et al. Obstructive sleep
apnea-dependent and -independent adrenergic activation in
obesity. Hypertension 2005;46(2):321e5.
11. Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic
neural mechanisms in obstructive sleep apnea. J Clin Invest
12. Narkiewicz K, Kato M, Phillips BG, Pesek CA, Davison DE,
Somers VK. Nocturnal continuous positive airway pressure
decreases daytime sympathetic traffic in obstructive sleep
apnea. Circula
tion 1999;100(23):2332e5.
ra T, Narkiewicz K,Somers VK. Chemoreflexes e physiologyand
clinical implications. Acta Physiol Scand 2003;177(3):377e84.
14. Narkiewicz K, van de Borne PJ, Pesek CA, Dyken ME,
Montano N, Somers VK. Selective potentiation of peripheral
chemoreflex sensitivity in obstructive sleep apnea. Circulation
15. Narkiewicz K, van de Borne PJ, Montano N, Dyken ME,
Phillips BG, Somers VK. Contribution of tonic chemoreflex
activation to sympathetic activity and blood pressure in
patients with obstructive sleep apnea. Circulation 1998;
16. Narkiewicz K, Kato M, Pesek CA, Somers VK. Human obesity is
characterized by a selective potentiation of central chemo-
reflex sensitivity. Hypertension 1999;33(5):1153e8.
17. Weil JV, Byrne-Quinn E, Sodal IE, Kline JS, McCullough RE,
Filley GF. Augmentation of chemosensitivity during mild exer-
cise in normal man. J Appl Physiol 1972;33(6):813e9.
18. Meguro K, Adachi H, Oshima S, Taniguchi K, Nagai R. Exercise
tolerance, exercise hyperpnea and central chemosensitivity to
carbon dioxide in sleep apnea syndrome in heart failure
patients. Circ J 2005;69(6):695e9.
19. Arzt M, Harth M, Luchner A, et al. Enhanced ventilatory
response to exercise in patients with chronic heart failure
and central sleep apnea. Circulation 2003;107(15):1998e
20. American College of Sports Medicine, Whaley MH, Brubaker PH,
Otto RM, Armstrong LE. ACSM’s guidelines for exercisetesting
and prescription. 7th ed. Philadelphia, PA: Lippincott Williams
& Wilkins; 2005.
21. Pate RR, Pratt M, Blair SN, et al. Physical activity and public
health. A recommendation from the Centers for Disease
Control and Prevention and the American College of Sports
Medicine. JAMA 1995;273(5):402e7.
22. Dingli K, Coleman EL, Vennelle M, et al. Evaluation of
a portable device for diagnosing the sleep apnoea/hypopnoea
syndrome. Eur Respir J 2003;21(2):253e9.
23. Redline S, Tosteson T, Boucher MA, Millman RP. Measurement
of sleep-related breathing disturbances in epidemiologic
studies. Assessment of the validity and reproducibility of
a portable monitoring device. Chest 1991;100(5):1281e6.
24. Collop NA, Anderson WC, Boehlecke B, et al. Clinical guidelines
for the use of unattended portable monitors in the diagnosis of
obstructive sleep apnea in adult patients. J Clin Sleep Med
McNeill G, Van Wijk MC. Usefulness of anthropom-
etry and DXA in predicting intra-abdominal fat in obese men
and women. Obes Res 2000;8(1):36e42.
26. Nickols-Richardson SM, Miller LE, Wootten DF, et al. Distal tibia
areal bone mineral density: use in detecting low aBMD of the
hip in young women. J Clin Densitom 2005;8(1):74e9.
27. Miller LE, Nickols-Richardson SM, Wootten DF, Ramp WK,
Herbert WG. Relationships among bone mineral density, body
composition, and isokinetic strength in young women. Calcif
Tissue Int 2004;74(3):229e35.
28. Kaleth AS, Chittenden TW, Hawkins BJ, et al. Unique cardio-
pulmonary exercise test responses in overweight middle-aged
adults with obstructive sleep apnea. Sleep Med 2007;8(2):
29. Arena R, Myers J, Aslam SS, Varughese EB, Peberdy MA. Peak
VO2 and VE/VCO2 slope in patients with heart failure: a prog-
nostic comparison. Am Heart J 2004;147(2):354e60.
30. Bard RL, Gillespie BW, Clarke NS, Egan TG, Nicklas JM. Deter-
mining the best ventilatory efficiency measure to predict
mortality in patients with heart failure. J Heart Lung Trans-
plant 2006;25(5):589e95.
31. Hargens TA, Guill SG, Zedalis D, Gregg JM, Nickols-
Richardson SM, Herbert WG. Attenuated heart rate recovery
following exercise testing in overweight young men with
untreated obstructive sleep apnea. Sleep 2008;31(1):104e10.
32. Lin CC, Hsieh WY, Chou CS, Liaw SF. Cardiopulmonary exercise
testing in obstructive sleep apnea syndrome. Respir Physiol
Neurobiol 2006;150(1):27e34.
33. Ponikowski P, Francis DP, Piepoli MF, et al. Enhanced ventila-
tory response to exercise in patients with chronic heart failure
and preserved exercise tolerance: marker of abnormal
cardiorespiratory reflex control and predictor of poor prog-
nosis. Circulation 2001;103(7):967e72.
34. Kleber FX, Vietzke G, Wernecke KD, et al. Impairment of
ventilatory efficiency in heart failure: prognostic impact.
Circulation 2000;101(24):2803e9.
35. Arena R, Myers J, Hsu L, et al. The minute ventilation/carbon
dioxide production slope is prognostically superior to the
oxygen uptake efficiency slope. J Card Fail 2007;13(6):462e9.
Pearson SB, Bowker CM, Elliott MW, Hainsworth R.
Interaction of chemoreceptor and baroreceptor reflexes by
1068 T.A. Hargens et al.
Page 6
hypoxia and hypercapnia e a mechanism for promoting
hypertension in obstructive sleep apnoea. J Physiol 2005;
568(Pt 2):677e87.
37. Weiss JW, Liu MD, Huang J. Physiological basis for a causal
relationship of obstructive sleep apnoea to hypertension. Exp
Physiol 2007;92(1):21e6.
38. Prabhakar NR, Dick TE, Nanduri J, Kumar GK. Systemic, cellular
and molecular analysis of chemoreflex-mediated sym-
pathoexcitation by chronic intermittent hypoxia. Exp Physiol
39. Peng YJ, Prabhakar NR. Effect of two paradigms of chronic
intermittent hypoxia on carotid body sensory activity. J Appl
Physiol 2004;96(3):1236e42 (discussion 196).
40. Peng YJ, Overholt JL, Kline D, Kumar GK, Prabhakar NR.
Induction of sensory long-term facilitation in the carotid body
by intermittent hypoxia: implications for recurrent apneas.
Proc Natl Acad Sci U S A 2003;100(17):10073e8.
41. Greenberg HE, Sica A, Batson D, Scharf SM. Chronic
intermittent hypoxia increases sympathetic responsiveness
to hypoxia and hypercapnia. J Appl Physiol 1999;86(1):
42. Rey S, Del Rio R, Iturriaga R. Contribution of endothelin-1 and
endothelin A and B receptors to the enhanced carotid body
chemosensory responses induced by chronic intermittent
hypoxia. Adv Exp Med Biol 2008;605:228e32.
43. Gjorup PH, Sadauskiene L, Wessels J, Nyvad O, Strunge B,
Pedersen EB. Abnormally increased endothelin-1in plasma during
the night in obstructive sleep apnea: relation to blood pressure
and severity of disease. Am J Hypertens 2007;20(1):44e52.
44. Zamarron-Sanz C, Ricoy-Galbaldon J, Gude-Sampedro F, Riv-
eiro-Riveiro A. Plasma levels of vascular endothelial markers in
obstructive sleep apnea. Arch Med Res 2006;37(4):552e5.
45. Jordan W, Reinbacher A, Cohrs S, et al. Obstructive sleep
apnea: plasma endothelin-1 precursor but not endothelin-1
levels are elevated and decline with nasal continuous positive
airway pressure. Peptides 2005;26(9):1654e60.
46. Rey S, Del Rio R, Alcayaga J, Iturriaga R. Chronic intermittent
hypoxia enhances cat chemosensory and ventilatory responses
to hypoxia. J Physiol 2004;560(Pt 2):577e86.
47. Bonanni E, Pasquali L, Manca ML, et al. Lactate production and
catecholamine profile during aerobic exercise in normotensive
patients. Sleep
Med 2004;5
48. Vanuxem D, Badier M, Guillot C, Delpierre S, Jahjah F,
Vanuxem P. Impairment of muscle energy metabolism in
patients with sleep apnoea syndrome. Respir Med 1997;91(9):
Ventilatory exercise responses in young men with OSA 1069
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    • "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. "
    [Show abstract] [Hide abstract] ABSTRACT: 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). 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. 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). Exercise appears not to change anthropometric 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.
    Full-text · Article · Nov 2009 · Sleep And Breathing
  • [Show abstract] [Hide abstract] ABSTRACT: Application of photonics in beam forming and steering for phased-array antennas is addressed in this paper. The feasibility of photonics in space communications systems centers around the basic issues such as the need for photonics and derived benefits, overall performance, and complexity and cost of implementation. Several optical beam forming and steering payloads are assessed for their capability and technology feasibility. Also included are the results of demonstrated proof-of-concept (POC) schemes
    No preview · Conference Paper · Jul 1993
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    [Show abstract] [Hide abstract] ABSTRACT: Obese subjects commonly suffer from exertional dyspnea and exercise intolerance. Preliminary evidence suggests that treatment with nocturnal continuous positive airway pressure (nCPAP) may improve dyspnea in obese patients with obstructive sleep apnea (OSA), but the effect on exercise tolerance is unknown. This study sought to investigate whether nCPAP improves exercise tolerance and exertional dyspnea in obese patients with OSA. Obese patients prescribed nCPAP for moderate/severe OSA and without cardiopulmonary disease were recruited. Patients completed a constant-load exercise test and Baseline and Transitional Dyspnea Index questionnaires (BDI/TDI) at baseline and after one and three months of nCPAP. Primary outcome was change in constant-load exercise time from baseline to one and three months. Secondary outcomes included changes in isotime dyspnea, isotime leg fatigue and BDI/TDI score at one and three months. Fifteen subjects (body mass index = 43 kg m(-2), apnea-hypopnea index = 49(.)hr(-1)) were studied. Constant-load exercise time increased by 2.0 min (40%, p = 0.02) at one month and 1.8 min (36%, p = 0.04) at three months. At one and three months, isotime dyspnea decreased by 1.4 (p = 0.17) and 2 units (p = 0.04), and leg fatigue decreased by 1.2 (p = 0.18) and 2 units (p = 0.02), respectively. BDI/TDI scores were 2.7 (p = 0.001) and 4.5 points (p < 0.001) at one and three months. Peak oxygen consumption and static pulmonary function were unchanged. Nocturnal CPAP improves exercise tolerance and dyspnea in obese patients with OSA. Effects on exercise time and chronic dyspnea were seen after one and three months of nCPAP, while exertional dyspnea was only improved at three months.
    Full-text · Article · Oct 2011 · Respiratory medicine
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