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INVITED REVIEW SERIES:
OBESITY AND RESPIRATORY DISORDERS
SERIES EDITOR: AMANDA J PIPER
Obesity hypoventilation syndrome: From sleep-disordered
breathing to systemic comorbidities and the need to offer
combined treatment strategies
resp_2106
601..610
JEAN-CHRISTIAN BOREL,1,2 ANNE-LAURE BOREL,2,4 DENIS MONNERET,2 RENAUD TAMISIER,2,3
PATRICK LEVY2,3 AND JEAN-LOUIS PEPIN2,3
1
Research and Development Department ‘AGIR à dom’, Meylan, 2HP2 Laboratory, INSERM U 1042, Faculty of
Medicine, Joseph Fourier University, 3Rehabilitation and Physiology Unit, and 4‘DIGIDUNE’ Unit,
Endocrinology Department, University Hospital A. Michallon, Grenoble, France
ABSTRACT
Obesity hypoventilation syndrome (OHS) is defined
as a combination of obesity (body mass index ⱖ
30 kg/m2), daytime hypercapnia (partial arterial carbon dioxide concentration ⱖ45 mm Hg) and sleepdisordered breathing after ruling out other disorders
that may cause alveolar hypoventilation. Through
the prism of the International Classification of Functioning, OHS is a chronic condition associated with
respiratory, metabolic, hormonal and cardiovascular
impairments, leading to a decrease in daily life activi-
ties, a lack of social participation and high risk of hospitalization and death. Despite its severity, OHS is
largely underdiagnosed and the health-related costs
are higher than those of apnoeic or obese eucapnic
patients. The present review discusses the definition, epidemiology, physiopathology and treatment
modalities of OHS. Although nocturnal positive
airway pressure therapies represent first-line treatment and are effective in improving patient outcomes,
there is a need to offer combined treatment strategies
and to assess the effect of multimodal therapeutic
strategies on morbidity and mortality.
The Authors: Jean-Christian Borel, PhD, is the Head of the Research and Development Department at ‘AGIR à dom’, a non-profit home care
provider. He has developed an expertise in the field of non-invasive ventilation, home-based training programmes and integrated care. He carried
out his PhD thesis at the Hypoxia Pathophysiology Laboratory (HP2) on the clinical and cardiovascular consequences of the obesity hypoventilation syndrome, followed by a postdoctoral fellowship on the pathophysiology of the sleep apnoea syndrome in Dr Frederic Series’ team at
the Quebec Heart and Lung Institute.
Anne-Laure Borel, MD, PhD from Grenoble University Hospital, France, has completed a postdoctoral fellowship in Quebec, Canada in Dr
Jean-Pierre Despres’ team of the Quebec Heart and Lung Institute. She is an endocrinologist with a clinical activity focused on obesity and type
2 diabetes. Her research interests are in the field of the cardiometabolic complications of an excess visceral adiposity and more specifically, the
association between sleep-disordered breathing, excess visceral fat and metabolic abnormalities.
Denis Monneret, MSc, PhD, is a pharmacist with a diploma of medical biology from Lille Faculty of Pharmacy, France. His MSc and PhD
degrees specialized in biology of obstructive sleep apnoea and obesity hypoventilation syndrome. After working as Assistant Professor in the
Biochemistry and Hormonology Unit at Grenoble University Hospital, he joined the HP2 Laboratory where he works on oxidative stress and
metabolic biomarkers of obstructive sleep apnoea, and obesity hypoventilation syndrome.
Renaud Tamisier, MD, PhD, is an Associate Professor of Physiology at Grenoble University School of Medicine, France. He works in the HP2
Laboratory and has been involved in both research and clinical studies in sleep-disordered breathing for the last 15 years. His research interests
are mainly on the cardiovascular consequences of intermittent hypoxia and obstructive sleep apnoea. In the last 15 years, he has published over
40 papers in the best international journals of the respiratory and sleep fields.
Jean-Louis Pépin, MD, PhD is Professor of Clinical Physiology and Head of the Clinical Physiology, Sleep and Exercise Department at Grenoble
University Hospital. He is the President of the French Sleep Research Society. His clinical and research interests are mainly on the cardiovascular
consequences associated with chronic and intermittent hypoxia, chronic respiratory failure and non-invasive ventilation.
Patrick Lévy MD, PhD is Professor of Physiology at Grenoble University, France. He is the Head of the HP2 Laboratory (Inserm Unit 1042) and
is the Clinical Vice-President of the European Sleep Research Society. He has been involved in sleep-disordered breathing for the last 25 years,
and his clinical and research interests are mainly on obstructive sleep apnoea. He leads one of the most active research teams on obstructive
sleep apnoea and intermittent hypoxia, which published over 200 manuscripts in the best international journals of the respiratory, cardiovascular
and sleep fields.
Correspondence: Jean-Christian Borel, AGIR à dom, Département Recherche et Développement, 29-31 Bd Des Alpes, 38244Meylan
Cedex, France. Email: j.borel@agiradom.com
Received 13 October 2011; invited to revise 17 October 2011; revised 20 October 2011; accepted 22 October 2011.
© 2011 The Authors
Respirology © 2011 Asian Pacific Society of Respirology
Respirology (2012) 17, 601–610
doi: 10.1111/j.1440-1843.2011.02106.x
602
Key words: cardiovascular diseases, exercise and pulmonary rehabilitation, respiratory structure and function, sleep disorder.
INTRODUCTION
Although obesity, defined by a body mass index (BMI)
ⱖ30 kg/m2, is associated with an increased rate of
death from cardiovascular diseases and certain cancers,1 the mechanisms involved in these relationships
are incompletely understood. Obstructive sleep
apnoea syndrome is commonly associated with obesity2 and is a risk factor for cardiovascular morbidity.3
Beyond obstructive sleep apnoea syndrome, a particular subgroup of obese patients is affected by
chronic respiratory failure, the so-called obesity
hypoventilation syndrome (OHS). These patients are
characterized by a greater morbi-mortality than
obese apnoeic patients, although this condition is
often underdiagnosed. The present work reports definition, epidemiology, physiopathology and treatment
modalities of OHS.
DEFINITION
OHS is defined as a combination of obesity
(BMI ⱖ 30 kg/m2), daytime hypercapnia (partial arterial carbon dioxide concentration ⱖ45 mm Hg) and
various types of sleep-disordered breathing after
ruling out other disorders that may cause alveolar
hypoventilation (severe obstructive or restrictive pulmonary diseases, chest wall disorders, neuromuscular diseases, severe hypothyroidism, and congenital
central hypoventilation syndrome).4 Seventy to 90%
of patients with OHS also exhibit obstructive sleep
apnoea syndrome,5,6 while 10–15% of sleep apnoea
patients referred through sleep laboratories have
diurnal hypercapnia and can be classified as OHS.7
EPIDEMIOLOGY
Although the overall prevalence of OHS has never
been directly assessed in the general population, it is
currently estimated at 3.7/1000 persons in the US
population, which is one of the most overweight in
the world.8 OHS prevalence has been more frequently
assessed in patients referred to sleep clinics with a
potential diagnosis of sleep-disordered breathing,6,9
in patients already diagnosed with obstructive sleep
apnoea (OSA),7,10–13 as well as in a cohort of obese hospitalized patients.14 The prevalence is estimated
between 10% and 20% in patients referred to sleep
laboratories and rises to 20–30% or more in patients
already diagnosed with OSA, as well as in hospitalized
obese adult patients. There is a dose–response relationship between obesity as expressed by BMI and
OHS prevalence.6,7,14 The different estimates of prevalence observed in these studies could be partly
explained by the inclusion of patients with concomitant chronic obstructive pulmonary disease12 or
patients with unstable medical status.14 Over the past
decade, the progression of obesity seems to have staRespirology (2012) 17, 601–610
J-C Borel et al.
bilized in the United States.15 However, extreme
obesity among adults is still increasing.16,17 Thus, it
could be anticipated that both prevalence and incidence of OHS will rise in the near future, and we can
anticipate OHS to be a considerable health burden.
GENERAL HEALTH STATUS,
SOCIOECONOMICAL CONSEQUENCES
AND MORTALITY OF OHS
Among OHS patients admitted to hospital, only
20% had previously received the diagnosis of OHS.14
A large proportion of patients are diagnosed with
OHS only when presenting with acute respiratory
failure.11,18–20 This highlights that OHS is underdiagnosed or that the diagnosis is dramatically delayed.
Yet, OHS patients are more likely to suffer from
congestive heart failure,9 pulmonary hypertension5
and diabetes mellitus9,21 than obese eucapnic OSA
patients. Moreover, the number of hospitalizations in
the past few years,22 as well as the number of admissions in intensive care unit,14 are higher in newly diagnosed OHS patients than in eucapnic obese patients.
As a consequence, the direct health costs (i.e. general
practice services, hospital services, medications) per
year of an OHS patient can reach twice that of an
apnoeic patient23 or an obese eucapnic patient,22 and
about six times that of an age, gender and socioeconomic status-matched control subject.23 Furthermore, labour income and employment rate are lower
in OHS patients than in apnoeic patients or control
subjects.23 The lack of social participation in OHS
patients reflected by high unemployment rates is also
in line with a poor social functioning score reported
through questionnaire SF-36.24 OHS patients experience excessive daytime sleepiness9,24,25 that could be
related to the severity of nocturnal rapid eye movement (REM) sleep hypoventilation (i.e. the higher the
percentage of REM sleep spent in hypoventilation, the
higher the excessive daytime sleepiness).25
Beyond the additional burden of comorbidities
compared with eucapnic obese individuals, OHS
patients have a higher risk of death, particularly when
they are left untreated.14,19 In the study of Nowbar
et al.,14 the mortality rate was 23%, 18 months after
hospital discharge, compared with 9% in eupnoeic
obese patients. OHS patients had a significantly
higher hazard ratio for mortality (hazard ratio = 4.0)
after adjustment for age, gender, BMI, electrolyte
abnormalities, renal insufficiency, history of thromboembolism and history of hypothyroidism. In observational cohorts, mortality rate was reduced when
OHS patients were treated with non-invasive ventilation (NIV),18,26–28 but it may remain higher than longterm mortality rates observed in large cohorts of
obese patients.29
PATHOPHYSIOLOGY
Because most OHS patients in a stable state are
diagnosed when they present to sleep clinics, most
© 2011 The Authors
Respirology © 2011 Asian Pacific Society of Respirology
603
Obesity hypoventilation syndrome
OBESITY HYPOVENTILATION SYNDROME
Hormonal and Metabolic
Leptin resistance
Somatotropic axis impairment
Insulin resistance
Adiponectin
Impairments
Cardiovascular
Endothelial dysfunction
High prevalence of
cardiovascular diseases
Figure 1 Obesity hypoventilation
syndrome: a chronic condition
observed through the prism of the
International Classification of Functioning. CRP, C-reactive protein;
RANTES, regulated on activation,
normal T cell expressed and
secreted.
Low Grade Inflammation
hs-CRP
RANTES
Disabilities
Exercise intolerance
Respiratory
Sleep breathing disorders
Pulmonary volume restriction
Respiratory muscle impairment
Altered ventilatory drive
Excessive daytime sleepiness
Decrease in daily life activities
Poor quality of life
High unemployment rate
High risk of hospitalization
High risk of death
studies looking for determinants of hypoventilation
in obesity have consisted of cohorts of sleep apnoeic
patients.7,9,10,13,30,31 In a recent meta-analysis, Kaw
et al.31 have shown that daytime hypoventilation in
obese sleep apnoeic patients was associated with
severity of sleep apnoea, along with impaired chest
wall mechanics and severity of obesity. These findings
highlight that daytime hypoventilation in obese
patients results from the conjunction of several
factors that interact to overwhelm the compensatory
mechanisms of CO2 homeostasis (Fig. 1).32,33
Respiratory mechanics
A decrease in pulmonary volumes (vital capacity, total
lung capacity, residual functional capacity) has been
reported as a determinant of daytime hypercapnia in
obese patients.6,7,12–14,30 This respiratory restriction,
more pronounced in hypercapnic than in eucapnic
obese patients,6,21,31,34,35 is associated with decreases in
total respiratory system compliance and lung compliance;36 moreover, expiratory flow limitation in awake
subjects can occur at low lung volume.37,38 Taken
together, these alterations increase the work of
breathing.34,39,40
Although mechanisms underlying this pulmonary
restriction are incompletely understood, the decrease
in lung volume is usually related to fat mass41 and to
intrathoracic and abdominal fat distribution.41,42
These fat deposits could have direct mechanical
effects on respiratory function by impeding diaphragm motion, changing the balance of elastic recoil
between chest and lung. Another possible mechanism may be related to the metabolic syndrome and
the low-grade inflammation associated with excess
visceral and intrathoracic adiposity. Lin et al.43 have
shown, in a large cohort study of more than 46 000
subjects without previously known respiratory
© 2011 The Authors
Respirology © 2011 Asian Pacific Society of Respirology
Handicaps
Lack of social participation
High health-related costs
disease, that metabolic syndrome was associated with
a higher risk of restrictive lung impairment after
adjustment for confounders (age, gender, BMI,
physical activity, alcohol consumption). Additionally,
other studies have reported an association between
central adiposity and pulmonary restriction,41,44 and
lower muscle strength in extra-respiratory muscles, as
demonstrated by handgrip.45 Similarly, we have
observed that OHS patients exhibit lower lung function, higher low-grade inflammation21 and higher
waist/hip ratio (an anthropometric marker of central
adiposity) than obese eucapnic patients. The lowgrade inflammation associated with metabolic syndrome and the higher work of breathing46 could
induce specific muscle impairment in OHS leading to
a deterioration in pulmonary function.
Respiratory muscle function
Although studies have shown that weight loss
improves
strength/endurance
of
respiratory
muscles47,48 and sometimes hypoventilation,49 the
question of inspiratory muscles weakness in OHS
remains open. OHS patients are able to temporarily
correct hypoventilation with voluntary breathing (i.e.
hyperventilation).12 Additionally, during spontaneous
breathing34 as well as during hypercapnic-induced
hyperventilation,50 transdiaphragmatic pressure has
been demonstrated higher or at least equivalent
in OHS patients compared with obese eucapnic
patients.34,50 Moreover, we recently observed that OHS
patients exhibited somatotropic axis impairment
compared with eucapnic obese patients. Insulin-like
growth factor-I levels were inversely related to partial
arterial carbon dioxide concentration levels and to
vital capacity, which is an indirect marker of diaphragmatic strength.51 Taken together, these results
suggest that muscle function is slightly impaired and
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does not allow compensation for the overload
imposed on the respiratory system by OHS. The
underlying causes for respiratory muscle dysfunction
that may coexist in OHS include inflammation and
somatotopic axis impairment. Further studies are
needed to explore in detail respiratory muscle structure and function in OHS.
Sleep-disordered breathing encountered
in OHS patients
Obstructive sleep apnoea syndrome
It is largely recognized that most OHS patients suffer
from an obstructive sleep apnoea syndrome52 (Fig. 2)
that could explain or at least contribute to daytime
hypoventilation.31 The pathophysiology of sleep
apnoea is multifactorial and has been discussed in
detail by Isono53 in a previous paper in this series. In
brief, upper airway closure occurs when pharyngeal
dilating forces cannot overcome the collapsing effect
J-C Borel et al.
of the negative transmural inspiratory pressure gradient and the tissue weight.54 Excessive fat deposition
induces an enlargement of soft tissue surrounding the
upper airway, compromising the pharyngeal airspace55 and therefore predisposing the airway to
closure during sleep.54 Moreover, the reduced lung
volume, particularly present in OHS patients,31
reduces the inspiratory-related caudal tracheal traction56 that stabilizes upper airway structures.54
Beyond these anatomical predispositions to sleep
apnoea, it has recently been proposed that fluid shifts
from the legs to the neck during sleep (because of the
recumbent position), contributing to the pathogenesis of sleep apnoea.57,58 Although this hypothesis
remains debated,59 Redolfi et al. have shown that prevention in daytime fluid accumulation in the legs
reduces apnoea/hypopnoea index.60,61 As OHS
patients are likely to exhibit cor pulmonale22 and consequently fluid overload and peripheral oedema, their
upper airway collapsibility might be increased by
nocturnal rostral fluid shift. To test the importance of
this phenomenon, the severity of sleep apnoea and
Figure 2 (a) Polysomnographic pattern of obstructive sleep apnoea syndrome. ABD, abdominal movements; EOG,
electro-occulogram; FLOW, nasal pressure; PTT, pulse transit time (an indirect measure of respiratory effort); SpO2,
oxygen blood saturation; THERM, bucconasal thermistor; THO, thoracic movements. (b) schematic representation of
insufficient post-event ventilatory compensation (adapted from reference 63 with authorization) contributing to the
pathogenesis of diurnal hypoventilation via alteration of ventilatory drive (see text for further details).
Respirology (2012) 17, 601–610
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Obesity hypoventilation syndrome
Figure 3 Polysomnographic pattern of REM sleep hypoventilation. (a) 5-min epoch. A2-C3, electroencephalogram;
ABD, abdominal movements; EOG, electro-occulogram; FLO, nasal pressure; SpO2, oxygen blood saturation;
THER, bucconasal thermistor; THO, thoracic movements. (b) Overnight hypnogram: see the increase in PtCO2 during
rapid eye movement (REM) sleep.
the ratio of central versus obstructive events from
acute exacerbation to a chronic stable condition
remain to be studied.
The pattern of sleep apnoea is a key in the development of hypercapnia in OHS patients. The mean
duration of apnoea and hypopnoea is increased with
a reduced duration and amplitude of interapnoea
ventilation.62 This insufficient post-event ventilatory
compensation63 may contribute to the interaction
between sleep apnoea syndrome and diurnal
hypoventilation. Accordingly, the severity of sleep
apnoea syndrome—appreciated by overnight
apnoea/hypopnoea index—contributes to diurnal
hypoventilation in obese apnoeic patients.31
Central hypoventilation
Another type of sleep respiratory abnormality
encountered in patients with OHS is central hypoventilation (Fig. 3) that is characterized by a sustained
reduction in ventilation associated with a constant or
reduced respiratory drive.25,64 Hypoventilation is more
pronounced during REM sleep64 and the proportion
of REM sleep hypoventilation is associated to awake
ventilatory response to CO2. Indeed the lower awake
© 2011 The Authors
Respirology © 2011 Asian Pacific Society of Respirology
CO2 ventilatory response, the higher the percentage of
REM sleep spent in hypoventilation.25
There is increasing evidence that sleep-breathing
disorders contribute to the pathogenesis of diurnal
hypoventilation via alteration of ventilatory drive.65
Ventilatory drive
Norman et al.65 have recently proposed a computational model that unifies acute hypercapnia during
sleep-breathing events with chronic sustained hypoventilation during wakefulness. In this model, the persistence of elevated bicarbonate concentration after
the sleep period (characterized by repetitive acute
hypercapnia events), possibly due to either alteration
of renal excretion or reduction in ventilatory drive (or
both), further blunts ventilatory response to CO2,
which in turn increases partial arterial carbon dioxide
concentration. In a recent study, we observed that the
improvement in bicarbonate concentration after
1 month of nocturnal NIV was related to NIV-induced
nocturnal oxygen blood saturation improvement.66
This result supports the hypothesis of a link between
nocturnal breathing disorders and daytime hypoventilation (Fig. 2b). Nevertheless, although diurnal
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606
partial arterial carbon dioxide concentration and
bicarbonate concentration were improved after 1month NIV, the ventilatory response to CO2 remained
unchanged, suggesting that other factors may play a
role in respiratory drive impairment in OHS.
The hypothesis of familial impairment of respiratory drive has been evoked, but Jokic et al. have
shown that ventilatory chemoresponsiveness was
similar between first-degree relatives of OHS patients
compared with age- and BMI-matched control
subjects.67 Another hypothesis, supported by animal
studies, is the participation of neurohumoral agents
such as adipokine leptin that acts as a powerful ventilatory stimulant.68,69 In humans, congenital leptin
deficiency exists but is very rare;70 on the contrary, in
obese subjects circulating leptin levels are often
higher than those in lean subjects.71–75 These results
suggest that a central resistance to leptin may occur in
obesity. A possible mechanism for this central resistance could be deficient leptin transport through the
blood–brain barrier.76,77
Inflammation, insulin resistance and
somatotropic impairment in OHS
Obesity is a disease state characterized by chronic systemic low-grade inflammation and associated inflammatory changes in the adipose tissue.78 Inflammatory
status in OHS patients has not been extensively
studied, but Budweiser et al. found that C-reactive
protein, a systemic biomarker of inflammation, was
associated with poor survival.26 We recently observed
that moderate OHS patients had a higher level of highsensitivity C-reactive protein, a higher level of the
proatherogenic chemokine regulated on activation,
normal T cell expressed and secreted and a lower
adiponectin level (an antiatherogenic and insulinsensitizing adipokine) compared with age- and BMImatched eucapnic control subjects.21 Accordingly,
OHS patients exhibited higher insulin resistance,
higher glycated Hb and were more likely to be treated
by glucose-lowering medications. Endothelial dysfunction, an early key event of atherosclerosis and a
strong predictor of incident cardiovascular events,79
was also more impaired in OHS patients compared
with eucapnic obese patients.21 Additionally, the
impairment in somatotropic axis, as demonstrated by
low insulin-like growth factor-I level,51 may contribute
to this endothelial dysfunction.80 Taken together,
these results support a particular cardiovascular risk
associated with OHS and confirm the results of observational cohorts data, demonstrating a higher prevalence of cardiovascular diseases.9,22,26
TREATMENT MODALITIES
Through the prism of the International Classification
of Functioning81 (Fig. 1), OHS is a chronic condition
associated with impairments of body structures
(upper airway, respiratory muscles) or body functions
(control of breathing, sleep, cardiovascular, metabolic), decrease in activities and a lack of social
participation. Thus, in the absence of guidelines on
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J-C Borel et al.
treatment modalities being clearly established in
OHS, clinicians should adapt treatment modalities
aimed at improving specific impairments, dysfunctions and handicaps of each patient. From this perspective, the three main tools available for clinicians
are positive airway pressure therapies (continuous
positive airway pressure (CPAP) and/or NIV), body
weight loss strategies and rehabilitation.
Positive airway pressure therapies to abolish
sleep-breathing disorders
Positive airway pressure therapies (CPAP and/or NIV)
represent the first-line therapy for sleep-breathing
disorders. The choice of nocturnal CPAP or NIV is
often based on the underlying sleep-related respiratory abnormality encountered.82 CPAP is efficient in
reversing diurnal hypoventilation82–85 in OHS patients
presenting mainly OSA-related hypoventilation. Piper
et al.85 have shown that more than 60% of OHS
patients who exhibited an incomplete initial response
to CPAP have a good response after 3 months of CPAP,
suggesting that incomplete immediate response to
CPAP does not preclude midterm efficacy. However,
some OHS patients continue to exhibit sleep
hypoventilation,82,83,85,86 particularly in REM,25,35 even
though upper airway obstruction is abolished with
CPAP, and require NIV to overcome this central
hypoventilation. In contrast to CPAP, NIV is more
expensive and more complex to set up a large range of
ventilatory parameters (ventilatory mode, inspiratory
and expiratory pressures, back-up respiratory rate,
triggering sensitivity, pressurization slope).87 Moreover, residual respiratory events occur frequently in
OHS patients treated with nocturnal NIV. Additional
attention is required to ensure treatment efficacy
and avoid machine-related undesirable respiratory
events.88,89 Thus, in the absence of long-term randomized trials comparing NIV with CPAP in patients with
predominant OSA-related hypoventilation,85 NIV
should be reserved for OHS patients presenting with
primarily central hypoventilation during sleep.
Manufacturers have proposed new ventilatory modes
(example: average volume-assured pressure support,
volume targeting by bi-level positive pressure ventilation90,91 and auto-titrating NIV92), but the efficacy of
these modes needs to be assessed in larger cohort
studies and on a long-term follow-up basis.
Long-term uncontrolled studies have consistently
reported a lower mortality rate in OHS patients
treated with NIV26–28 compared with those in a cohort
principally composed of untreated patients.14 Additionally, these studies have shown an improvement
in gas exchange.26,28 Beyond hypoventilation, basal
atelectasis or coexisting lung disease may lead to
obesity-related hypoxia. Therefore, additional oxygen
therapy may be necessary to correct persistent
hypoxaemia even under efficient positive airway
pressure therapy. Of note, the need for supplemental
oxygen therapy and baseline hypoxaemia have been
shown as independent predictors of mortality.26–28 In a
recent randomized controlled trial including moderate OHS patient, partial arterial oxygen concentration
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Obesity hypoventilation syndrome
was not significantly improved after 1 month of nocturnal NIV.66 Even though baseline hypoxaemia was
very mild, this result supports the concept that
obesity-related hypoxaemia might be more difficult to
correct than hypercapnia. Additionally, this randomized controlled trial failed to demonstrate that shortterm nocturnal NIV could impact favourably on
metabolic, cardiovascular or inflammatory markers
in spite of the improvements in pulmonary function
and sleep parameters. This suggests that positive
airway pressure therapies should not be the only form
of treatment for these patients.66
Effect of body weight loss, changes in lifestyle
habits and rehabilitation programmes
Previous studies have largely documented the benefits of body weight loss to correct or attenuate sleep
apnoea related to obesity. Indeed, Peppard et al.93
have studied a cohort of 690 subjects and demonstrated that 10% weight gain or weight loss were
respectively associated with a 32% increase or a 26%
decrease in the apnoea/hypopnoea index. Intervention studies designed to allow weight loss in obese
patients have largely shown that weight loss achieved
either by bariatric surgery (Roux-en-Y gastric bypass,
vertical-banded gastroplasty)94,95 or by lifestyle
intervention96–99 was associated with an improvement
in sleep-related breathing disorders.
Body weight loss obviously seems to be the etiological treatment in OHS. The correction of OHS related
to weight loss following bariatric surgery has been
addressed in some studies that have reported an
improvement in diurnal hypoventilation, as well
as an improvement in spirometric parameters.49,100–102
Whereas bariatric surgery seems to be an interesting
option for treatment of OHS, two points have to be
considered: first, a multicentre study identified sleep
apnoea syndrome as an independent factor associated with an increased risk of major adverse outcome
during the 30 days following bariatric surgery in a
large cohort of patients;103 and second, recurrent
sleep-disordered breathing, as well as deterioration
of blood gas and spirometric parameters,102 were
observed in a follow-up of bariatric surgery patients,
even though these patients did not regain weight.104
The level of physical activity is another characteristic of lifestyle habits that is associated with sleepdisordered breathing and may be corrected by
lifestyle intervention programmes. Indeed, the level
of physical activity is inversely correlated to the
apnoea/hypopnoea index.93 In addition, an increase
in physical activity is also associated with a decrease
in visceral fat accumulation,105 and with an improvement in low-grade inflammation. Physical activity
also improves metabolic profile and muscle function.
Therefore, OHS patients may benefit from an increase
in physical activity, as well as from weight loss, acting
synergistically to improve the respiratory disturbances and comorbidities of OHS.
Compared with obese eucapnic OSA patients, individuals with OHS exhibit a lower exercise tolerance.106
In contrast, in a study of patients with a range of dis© 2011 The Authors
Respirology © 2011 Asian Pacific Society of Respirology
orders causing chronic respiratory failure and treated
with long-term NIV, Budweiser et al.107 have shown
that OHS patients had a relatively preserved functional capacity (i.e. 6MWD test) compared with
patients with chronic obstructive pulmonary disease
or thoracic restriction. Moreover, among these different causes of respiratory failure, exercise tolerance
was improved after 2 months of nocturnal NIV.108
However, in OHS patients, in spite of correction of
partial arterial carbon dioxide concentration after
3 months of NIV, these patients continued to exhibit
exercise-induced hypoventilation.106 In a recent study
aimed at comparing a low-calorie diet and a physical
activity programme plus respiratory muscles training
versus the same programme without respiratory
muscle training, the former strategy induced greater
improvement in dyspnoea and exercise capacity than
the latter one.109 On the other hand, NIV during exercise training might also be an aid to enhance exercise
capacity in rehabilitation programmes.110 Taken
together, these results suggest that specific exercisebased rehabilitation programmes including NIV and
respiratory muscle training are likely to benefit these
patients, and the onset of NIV could be the appropriate time to start such programmes. Nevertheless, the
best modalities to include in these programmes have
to be determined in order to improve motivation,111
adherence and long-term benefits.
CONCLUSION AND PERSPECTIVES
Although largely underdiagnosed, OHS is characterized by sleep, respiratory, metabolic and cardiovascular impairments leading to a decrease in activities, a
lack of social participation and a higher mortality rate.
Although CPAP/NIV represent first-line therapy to
treat sleep-related breathing disorders, they cannot
be considered as the only therapeutic strategy. Weight
loss strategies (surgical and non-surgical), as well as
changes in lifestyle habits and rehabilitation programmes, should be proposed. Finally, long-term,
large-scale multicentre studies are required to assess
the effect of multimodal therapeutic strategies on
morbidity and mortality.
ACKNOWLEDGEMENT
The authors thank Suzanne Lamothe for language
revision.
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