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Pathophysiology of upper airway obstruction in

obstructive sleep apnea in adults
author: M Safwan Badr, MD
section editor: Nancy Collop, MD
deputy editor: Geraldine Finlay, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Nov 2023.

This topic last updated: Apr 15, 2022.

INTRODUCTION

Obstructive sleep apnea (OSA) is a fairly common disorder with significant adverse
health consequences [1-4]. OSA is characterized by recurrent obstruction of the
pharyngeal airway during sleep, with resultant hypoxia and sleep fragmentation.
The pathogenesis of OSA is due to the interaction between unfavorable anatomic
upper airway (UA) susceptibility and sleep-related changes in UA function [5].
However, the mechanisms linking sleep-related physiologic changes to UA
obstruction in some individuals are not fully understood. In addition, the majority
of studies investigating UA obstruction during sleep have been conducted during
nonrapid eye movement (NREM) sleep, given the difficulty in achieving rapid eye
movement (REM) during invasive studies in the laboratory environment.

This topic will review the effects of sleep on respiratory mechanics, the
determinants of UA patency, and the pathophysiology of UA obstruction during
sleep. The pathophysiology of OSA in children and the clinical features, diagnosis,
and treatment of OSA in children and adults are reviewed separately. (See

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 "Mechanisms and predisposing factors for sleep-related breathing disorders in
children" and "Clinical presentation and diagnosis of obstructive sleep apnea in
adults" and "Obstructive sleep apnea: Overview of management in adults" and
"Management of obstructive sleep apnea in children".)

EFFECT OF SLEEP ON RESPIRATORY MECHANICS

Sleep is accompanied by multiple physiologic changes relevant to ventilation and

respiration ( algorithm 1). Sleep is viewed as a quiet resting period, judging by
the limited movement, decreased responsiveness, and the passive appearance of a
sleeping individual. Sleep is associated with a decreased metabolic rate, loss of the
wakefulness drive to breathe [5], and a subsequent decrease in ventilatory motor
output to respiratory muscles, including upper airway (UA) muscle. Furthermore,
the loss of the wakefulness drive to breathe renders respiration during sleep
critically dependent on the level of chemoreceptor and mechanoreceptor stimuli
[6], and hence susceptible to central apnea and to upper airway obstruction. The
pathogenesis of central apnea is discussed separately. (See "Central sleep apnea:
Pathogenesis".)

Upper airway mechanics

Decreased muscle activity — Reduced UA muscle activity during sleep is a

physiologic phenomenon of little consequence in healthy individuals, but it may
promote UA narrowing in susceptible individuals.

Decreased ventilatory motor output is associated with decreased UA muscle

activity, particularly in muscles that display tonic activity (independent of the phase
of respiration). For example, the tensor palatini demonstrates immediate decrease
in activity with sleep onset, with associated reduction in inspiratory flow [7,8].
Studies investigating respiratory muscle activity at sleep onset demonstrate that
the activity of respiratory pump muscles and UA-dilating muscles changes less
when the dominant electroencephalogram (EEG) waveform is theta (light sleep)
versus alpha (wakefulness) [9].

Changes in caliber and compliance — The sleep state is associated with

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 decreased pharyngeal caliber, increased UA resistance [10], and increased UA
compliance [11]. In other words, the lumen of the UA is smaller and the airway
walls are more deformable during sleep. Thus, sleep renders the UA more
susceptible to closure in the presence of a collapsing transmural pressure.

UA narrowing appears to be a universal finding, resulting in increased turbulent

flow, which may explain why breathing during sleep is audible even in healthy
individuals. A substantial increase in UA resistance leads to increased flow
turbulence, inspiratory flow limitation, and fluttering of the soft palate and UA soft
tissue [12,13]. Snoring is the acoustic corollary of inspiratory flow limitation, which
manifests as a plateau in inspiratory flow despite persistent downstream driving
pressure.

Pressure-flow relationships differ between normal, non-flow-limited breathing

(NIFL) versus high-resistance and flow-limited breathing ( figure 1). Breathing
during wakefulness is non-flow-limited. Likewise, breathing during sleep in non-
snorers is also non-flow-limited. Snoring and flow limitation suggest increased
propensity for UA collapse during sleep. In extreme cases of UA narrowing,
complete closure may occur, leading to obstructive sleep apnea (OSA).

Loss of load compensation — Sleep-related UA narrowing and increased

resistance to flow represent an added internal load on the respiratory system. The
ability of the ventilatory control system to respond to added loads is critical for the
preservation of alveolar ventilation.

Breathing through high-resistance tubing (like a straw) during wakefulness is

associated with an immediate increase in ventilatory effort to maintain alveolar
ventilation and PaCO2. During sleep, loads are not perceived; thus, ventilation
decreases and PaCO2 increases [14,15]. The teleological reason for lack of
immediate load perception is uncertain but may indicate that sleep reigns
supreme, a biological need that is protected through reliance on chemical and
mechanoreceptor feedback. Conversely, impaired resistive load compensation has
been noted in healthy children of patients with OSA. Thus, the ability to
compensate for increased loads may be an inherited trait that contributes to
preservation of upper airway patency during sleep [16].

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 The consequences of decreased load perception during sleep are mild in normal
humans, as increased PaCO2 restores ventilation to near-normal levels. In contrast,
patients with abnormal respiratory mechanics, such as those with chronic
obstructive pulmonary disease (COPD), may experience worsening of respiration
and gas exchange as a result of impaired load compensation. (See "Mechanisms,
causes, and effects of hypercapnia", section on 'Chronic obstructive pulmonary
disease'.)

Thoracic cage dynamics — The relative contributions of the rib cage and
abdominal muscles to tidal volume change during sleep. During non-rapid eye
movement (NREM) sleep, the ratio of the rib cage to abdominal muscle
contribution increases compared with wakefulness. In contrast, the ratio is lower
during rapid eye movement (REM) sleep, when there is loss of intercostal muscle
activity.

It is noteworthy that most of the studies on sleep effect have been conducted
during NREM sleep, since REM is difficult to achieve under instrumented
conditions. REM sleep is associated with muscle atonia affecting many UA dilators
and intercostal muscles, while sparing the diaphragm. During REM, minute
ventilation decreases even more and the respiratory rate becomes more irregular,
particularly during phasic REM sleep [5,17].

Increased arterial carbon dioxide — Relative to wakefulness, sleep is associated

with decreased ventilation and increased PaCO2 ( figure 2). During sleep, PaCO2
rises by 4 to 5 mmHg. This physiologic hypercapnia is due to a combination of
increased UA resistance and decreased ventilatory motor output [18].

Implications — The consequences of physiologic sleep-related changes in

respiratory mechanics depend on individual host factors:

● Individuals with favorable UA anatomy and lung mechanics are able to

sustain rhythmic breathing, normal gas exchange, and stable sleep, albeit at
a higher PaCO2.

● Individuals with intermediate susceptibility to collapse develop snoring and

inspiratory flow limitation, while maintaining stable sleep and breathing.

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 ● Those with highly compromised UAs develop complete UA obstruction.

Similarly, changes in the relative contributions of the rib cage and abdominal
muscles to ventilation are inconsequential in healthy individuals with normal lung
mechanics but may lead to worsening ventilation–perfusion mismatch and hypoxia
in obese individuals and those with pulmonary disease. The ensuing increase in
ventilation may contribute to unstable breathing via activation of peripheral
chemoreceptors.

DETERMINANTS OF UPPER AIRWAY PATENCY

The human upper airway (UA) is a multipurpose conduit serving respiration,

deglutition, and vocalization. The pharyngeal airway lacks structural bony or
cartilaginous support; therefore, it is a deformable tube susceptible to collapse if
sufficient transmural pressure is applied across a compliant pharyngeal wall. The
determinants of pharyngeal compliance or intrinsic "stiffness" are not fully
understood, given the multitude of structures that constitute the pharyngeal wall.

Determinants of UA patency can be broadly divided into two categories: structural

factors and neuromuscular factors. Structural determinants include craniofacial
structure; surrounding soft tissue, including adipose tissue; vascular structures;
and mucosal factors. Neuromuscular factors include ventilatory motor output, UA
muscle activity, and the thoracic-upper airway link via caudal traction. (See 'Effect
of lung volume' below.)

Structural factors

Craniofacial structure — Craniofacial structure is a critical determinant of UA

patency [19,20]. The UA is enclosed in a bony box composed of the mandible,
maxilla, skull base, and cervical spine. A small bony enclosure, or a craniofacial
constraint, such as retrognathia, may result in tissue "crowding," increased
pressure in the tissues surrounding the UA, and increased collapsing transmural
pressure, with resultant inferior displacement of the hyoid bone.

Support for the role of bony structures in the propensity for UA obstruction comes

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 from observational and experimental studies. In a case-control study that used
three-dimensional magnetic resonance imaging (MRI), increased mandibular
length was associated with decreased risk for obstructive sleep apnea (OSA) in
men but not in women [21]. In addition, differences in position of the hyoid bone
between patients with OSA and controls was largely determined by tongue
volume, suggesting that inferior displacement of the hyoid bone in patients with
OSA is due to relative tongue volume and increased surrounding pressure.
Likewise, another study found that the salutary effect of mandibular-advancement
oral appliances may be explained by decreased surrounding tissue pressure [22].

In addition to these studies, there is epidemiologic evidence that differences in

craniofacial indices may contribute to racial and ethnic differences in the
prevalence of sleep apnea [23-25] and may interact with obesity to promote UA
obstruction during sleep.

Soft tissue structures — The UA lumen is surrounded by the soft tissue of the
neck, including connective, adipose, vascular, and lymphatic tissue. Consequently,
factors that increase surrounding tissue pressure tend to promote UA narrowing.

Several soft tissue factors are associated with higher risk of OSA, including
increased tongue size, increased size of lateral pharyngeal walls, and increased
total soft tissue volume [26]. Increased soft tissue may be a heritable trait, as
evidenced by the familial aggregation of UA soft tissue structure in normal
individuals and those with OSA, independent of body mass index (BMI) and neck
circumference [27]. Increased adipose tissue in the UA or the tongue secondary to
obesity may also increase collapsing tissue pressure [28].

Enlarged tonsils can increase the susceptibility to UA obstruction by encroaching

on the pharyngeal lumen. Enlarged tonsils is a recognized risk factor for OSA,
especially in children [29-31]. (See "Mechanisms and predisposing factors for sleep-
related breathing disorders in children", section on 'Enlarged tonsils and
adenoids'.)

Vascular factors

Rostral fluid displacement — Increased vascular volume in the neck (ie, rostral

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 fluid shifts) may promote UA obstruction by increasing surrounding tissue volume
and pressure. Experimentally, vasoconstriction and vasodilatation have been
shown to cause a decrease and increase in UA resistance, respectively [32,33].
Changes in chemical stimuli, such as hypoxia or hypercapnia, may additionally
alter vascular tone and adversely affect UA patency, especially in patients with
unfavorable UA anatomy.

Several small observational studies have consistently demonstrated that, during

recumbent sleep, an increase in rostral volume may contribute to the severity of
OSA, particularly in patients with high volume states (eg, congestive heart failure,
end-stage kidney disease, and refractory hypertension) and that reducing lower
extremity fluid volume (eg, with compression stockings, diuresis) may attenuate
this process [34-40]. As examples:

● In one study of patients with uncontrolled hypertension and OSA, aggressive

diuretic therapy was associated with modest reductions in the apnea-
hypopnea index (AHI; 49 versus 58 events per hour), neck circumference (0.7
versus 1.2 cm) and leg fluid volume (308 versus 418 mL) [35].

● Similarly, another study of non-obese sedentary men with OSA reported that
wearing compression stockings while awake led to measurable reductions in
AHI (23 versus 31 events per hour), together with a 40 percent reduction in
leg volume and neck circumference [40].

● In a study of 17 men with non-severe OSA or no OSA, the infusion of similar

amounts of saline in older men, as compared with younger men, caused a
greater increase in neck circumference and AHI (2 versus 32); however,
substantial methodologic flaws prohibit accurate interpretation of these
results [37].

The role of rostral fluid shifts in intraoperative fluid management for patients with
OSA is discussed separately. (See "Intraoperative management of adults with
obstructive sleep apnea", section on 'Intravenous fluid management'.)

Neuromuscular factors

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 Upper airway muscle activity — Upper airway muscles support multiple critical
functions, including respiration, deglutition, and phonation. The majority of upper
airway muscles demonstrate activity that is independent of the phase of
respiration (tonic activity), whereas some UA muscles demonstrate electrical
activity during one part of the respiratory cycle. (See 'Effect of sleep on respiratory
mechanics' above.)

For example, the tensor palatini demonstrate tonic electrical activity, which
decreases with sleep onset [7,9,41]. It is thought that the tensor palatini stiffens
the UA and decreases pharyngeal collapsibility. By contrast, the genioglossus
demonstrates inspiratory activity (above the tonic level); the genioglossus is
classified as a pharyngeal dilator that is activated before the thoracic pump muscle
to prepare the airway for inspiratory flow.

Decreased activity — The loss of the wakefulness drive to breathe is

associated with a reduction in the electromyography (EMG) activity of the
respiratory pump muscles and UA muscles [9]. Available evidence indicates that a
variety of UA muscles have reduced tonic or phasic activity during non-rapid eye
movement (NREM), thereby promoting UA narrowing and increased UA resistance.

Decreased responsiveness — During wakefulness, application of negative

pressure to the UA is associated with a robust reflex increase in UA muscle activity
[42,43]. Sleep is associated with significant attenuation on the negative pressure
reflex response.

Mechanical corollary — The changes in UA muscle activity and

responsiveness described above are based on electrical activity alone. It is unclear,
however, if these changes are accompanied by mechanical consequence.

Determining the relative contribution of decreased UA muscle activity to sleep-

related narrowing is difficult because of the many influences on UA muscle activity,
such as changes in flow and magnitude of negative pressure. Similarly, the
mechanical corollary of decreased UA muscle responsiveness is also unclear; it
may indicate an attenuation of UA muscles to preserve pharyngeal patency during
physiologic challenges.

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 Changes during rapid eye movement sleep — Rapid eye movement (REM)
sleep is associated with muscle atonia affecting antigravity muscles, particularly
during periods of phasic rapid eye movements. Muscle atonia affects phasic UA-
dilating muscles and the intercostal muscles, but not the diaphragm.

These changes are particularly relevant in patients with neuromuscular disease,

diaphragmatic dysfunction (such as patients with chronic obstructive pulmonary
disease with hyperinflation [44]), or gas exchange defects (such as patients with
interstitial lung disease). In these settings, patients develop hypoventilation and
worsening of gas exchange during REM sleep hypoventilation. This is a form of
sleep-disordered breathing that is different from OSA, although it may be difficult
to distinguish without polysomnography.

It is of note that pharyngeal compliance is not increased during REM sleep [10,45],
despite the attenuated UA-dilating muscle activity. In fact, the retropalatal airway is
less compliant during REM sleep relative to NREM sleep. This finding points to the
significance of additional, non-neuromuscular factors in regulating UA patency.

Effect of lung volume — Changes in lung volume during the respiratory cycle are
paralleled by changes in UA caliber [46]. Independent of UA-dilating muscle
activity, there is an inspiratory increase and an expiratory decrease in UA luminal
size [47,48]. In fact, pharyngeal cross-sectional area reaches a nadir at end
expiration, especially in patients with sleep apnea [49].

The underlying mechanism is the anatomic connection between the intrathoracic

and extrathoracic airways. Accordingly, inspiratory activity displaces the carina and
trachea caudally and stretches the connective tissue linking the trachea to the UA.
Thus, increased UA caliber during inspiration is due to caudal traction on the UA
that is proportional to inspiratory thoracic activity and independent of UA-dilating
muscle activity [50].

From a mechanical standpoint, caudal traction transmits subatmospheric pressure

through the trachea and ventrolateral cervical structures to the soft tissues
surrounding the UA. In this way, caudal traction promotes UA patency by
increasing transmural pressure and/or stiffening the pharyngeal wall [50].

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 Furthermore, increased lung volumes during sleep are associated with decreased
UA collapsibility, perhaps by increasing the longitudinal tension of the pharyngeal
airway [51,52]. Accordingly, inspiratory thoracic activity exerts a salutary effect on
UA patency via caudal traction, with subsequent dilatation and stiffening of the UA.
Decreased lung volume in obesity may contribute to pharyngeal narrowing in
obese individuals though this mechanism. (See "Epidemiology and pathogenesis of
obesity hypoventilation syndrome", section on 'Pathogenesis'.)

PHARYNGEAL OBSTRUCTION DURING SLEEP

The occurrence of upper airway (UA) obstruction during sleep reflects an interplay
between the removal of the wakefulness drive (which helps to maintain airway
patency) and an individual susceptibility to collapse. Although individual risk
factors are known, the precise pathophysiologic pathways leading to UA
obstruction in patients with obstructive sleep apnea (OSA) remain elusive.

As discussed above, the loss of wakefulness drive to breathe results in decreased

UA neuromuscular activity and responsiveness, leading to decreased UA caliber,
increased UA resistance, and increased pharyngeal compliance (see 'Upper airway
mechanics' above). The response to these physiologic changes depends on the
underlying susceptibility to pharyngeal collapse, which is determined by baseline
UA caliber, surrounding tissue pressure, craniofacial structure, and the intrinsic
properties of the UA.

Upper airway mechanics — Sleep-related changes in pharyngeal mechanics are

inconsequential in individuals with favorable UA anatomy, manifesting only by
slight physiologic increase in partial pressure of carbon dioxide (PaCO2). Snoring
occurs in individuals with moderate susceptibility to collapse, leading to fluttering
of the soft palate due to turbulent flow and inspiratory flow limitation. In extreme
cases of UA narrowing, complete closure may occur, leading to OSA.

The UA is a deformable tube, prone to collapse if subjected to a collapsing

transmural pressure, either by intraluminal subatmospheric (negative) pressure
during inspiration and/or by extraluminal surrounding tissue pressure during

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 either phase of respiration. Although UA obstruction during sleep has been
attributed to collapsing intraluminal subatmospheric pressure effectively sucking
the hypotonic pharyngeal airway shut [53], conclusive evidence implicating
negative intraluminal pressure alone is lacking.

Ventilatory motor output — Changes in ventilatory drive may also influence UA

patency. Oscillation of ventilatory motor output during periodic breathing is
associated with pharyngeal narrowing or obstruction at the nadir of ventilatory
motor output, when collapsing pressures are feeble, especially in individuals with a
high propensity for UA collapse [54,55]. In fact, UA narrowing or occlusion occurs
during a spontaneous or induced hypocapnic central apnea, supporting the notion
that negative pressure is not required for the development of UA obstruction [56].
Similarly, in a study examining the mechanics of the pharynx in anesthetized,
paralyzed healthy individuals and those with OSA, the pharynx was patent at
atmospheric pressure in normal individuals and closed in patients with OSA (in the
absence of negative pressure) [57]. Decreased ventilatory output can also be
caused by a physiologic event such as swallowing, which is associated with
transient inhibition of phrenic motor neurons.

Surrounding tissue — This is a significant determinant of UA patency during

sleep. Examples of collapsing extraluminal pressure include passive gravitational
forces, high tissue pressure in humans with mandibular deficiency, large tongue
size, fat deposits in the UA, or pharyngeal wall edema secondary to rostral fluid
shifts in the recumbent position. (See 'Rostral fluid displacement' above.)

Role of expiratory narrowing — Accumulating evidence implicates expiratory

narrowing as a possible mechanism of the initial narrowing. For example, an
obstructive apnea is often preceded by expiratory narrowing of the UA, as
evidenced by increased expiratory resistance [58] or progressive expiratory
narrowing [59,60]. Likewise, induced hypocapnic hypopnea is associated with
expiratory pharyngeal narrowing and increased pharyngeal expiratory UA
compliance [61]. Therefore, UA obstruction may occur at either inspiration or
expiration. Individuals with a high surrounding tissue pressure may be particularly
susceptible to expiratory pharyngeal narrowing under conditions of low ventilatory
motor output and reduced expiratory driving pressure.

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 SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries

and regions around the world are provided separately. (See "Society guideline
links: Sleep-related breathing disorders in adults".)

SUMMARY

● Obstructive sleep apnea (OSA) is characterized by recurrent obstruction of the

pharyngeal airway during sleep, with resultant hypoxemia and sleep
fragmentation. The pathogenesis of OSA, while not completely understood, is
likely due to the interaction between unfavorable anatomic upper airway (UA)
susceptibility to upper airway collapse, and sleep-related changes in UA
function.

● Reduced UA muscle activity during sleep is a physiologic phenomenon of

little consequence in healthy individuals, but it may promote UA narrowing in
susceptible individuals. Changes in UA caliber and compliance and loss of
load compensation during sleep are additional factors that may promote
obstruction. (See 'Upper airway mechanics' above.)

● Despite multiple physiologic sleep-related changes in respiratory mechanics

and a rise in partial pressure of carbon dioxide (PaCO2), not all individuals
develop complete UA obstruction. Individuals with favorable UA anatomy and
lung mechanics are able to sustain rhythmic breathing and normal gas
exchange, whereas those with highly compromised upper airways may
develop complete obstruction. (See 'Implications' above.)

● Determinants of UA patency can be broadly divided into structural, vascular,

and neuromuscular factors. Structural determinants include craniofacial
structure; surrounding soft tissue, including adipose tissue; vascular
structures; and mucosal factors. Vascular factors include rostral fluid shifts
that occur during recumbent sleep. Neuromuscular factors include
ventilatory motor output, UA muscle activity, and the thoracic-upper airway

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 link via caudal traction. (See 'Structural factors' above and 'Neuromuscular
factors' above.)

● A craniofacial constraint, such as retrognathia, can limit the potential space

shared by soft tissue and the airway lumen. Craniofacial features are
heritable traits and may be influenced by racial/ethnic factors. (See
'Craniofacial structure' above.)

● Increased soft tissue surrounding the airway could be due to increased

adipose tissue, enlarged tonsils, or increased vascular volume. (See 'Soft
tissue structures' above and 'Rostral fluid displacement' above.)

● Obesity is a major risk factor for OSA through multiple mechanisms,

including decreased lung volume, increased soft tissue volume, and potential
impairment of the mechanical output of UA muscles. (See 'Determinants of
upper airway patency' above.)

● Although individual risk factors are known, the precise pathophysiologic

pathways leading to UA obstruction in patients with OSA are not well
understood. Important triggers of pharyngeal obstruction during sleep in
susceptible individuals may include changes in upper airway mechanics
during sleep, changes in ventilatory motor output, surrounding tissue
pressure, and expiratory narrowing. (See 'Pharyngeal obstruction during
sleep' above.)

ACKNOWLEDGMENT

The UpToDate editorial staff acknowledges Kathe G Henke, PhD, who contributed
to an earlier version of this topic review.

Use of UpToDate is subject to the Terms of Use.

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 GRAPHICS

Effect of sleep on upper airway mechanics and

alveolar ventilation

Note that several sleep-related changes contribute to decreased

alveolar ventilation and increased arterial PaCO2.

VT: tidal volume; UA: upper airway; VA: alveolar ventilation.

Graphic 102955 Version 1.0

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 Pressure-flow dissociation under inspiratory flow
limitation conditions

Pressure-flow loops depicting two breaths under inspiratory flow limitation

(IFL) and non-flow limitation (NIFL). Note the pressure-flow dissociation
under IFL conditions, with flow reaching a plateau despite increasing driving
pressure.

Graphic 102597 Version 1.0

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 Effect of sleep on ventilation and upper mechanics

During sleep, compared with wakefulness, important changes include decreased

flow and volume (dotted line), augmented supraglottic pressure, and increased
end-tidal PCO2 (dashed line).

EEG: electroencephalogram.

Graphic 102750 Version 1.0

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 Contributor Disclosures
M Safwan Badr, MD No relevant financial relationship(s) with ineligible companies to
disclose. Nancy Collop, MD Grant/Research/Clinical Trial Support: Huxley Medical [Home
sleep testing device]. Consultant/Advisory Boards: Sunrise Medical [Sleep apnea (attended
one-time meeting to provide feedback on technology)]. All of the relevant financial
relationships listed have been mitigated. Geraldine Finlay, MD No relevant financial
relationship(s) with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When
found, these are addressed by vetting through a multi-level review process, and through
requirements for references to be provided to support the content. Appropriately
referenced content is required of all authors and must conform to UpToDate standards of
evidence.

Conflict of interest policy

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