State of the art review

Effects of non-­invasive ventilation on sleep in chronic

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hypercapnic respiratory failure
Neeraj M Shah,1,2 Joerg Steier ‍ ‍,1,2 Nicholas Hart,1,2 Georgios Kaltsakas ‍ ‍1,2
1
Lane Fox Clinical Respiratory ABSTRACT (NMD) and rapidly progressive NMD and report
Physiology Centre, Guy’s and St Chronic respiratory disease can exacerbate the normal the relationship between chronic respiratory failure
Thomas’ NHS Foundation Trust,
London, UK physiological changes in ventilation observed in healthy and sleep quality and the effect of non-­ invasive
2
Centre for Human and Applied individuals during sleep, leading to sleep-­disordered ventilation (NIV) treatment. The aim of this review
Physiological Sciences (CHAPS), breathing, nocturnal hypoventilation, sleep disruption is to demonstrate that in patients with chronic
King’s College London, London, and chronic respiratory failure. Therefore, patients with respiratory failure, sleep quality is an important
UK contributor in the aetiopathophysiology and influ-
obesity, slowly and rapidly progressive neuromuscular
disease and chronic obstructive airways disease report ences clinical outcomes, frequently opening a diag-
Correspondence to
Dr Georgios Kaltsakas, Lane Fox poor sleep quality. Non-­invasive ventilation (NIV) is a nostic window to anticipate respiratory issues and
Clinical Respiratory Physiology complex intervention used to treat sleep-­disordered allow for secondary prevention of deterioration,
Research Centre, King’s College breathing and nocturnal hypoventilation with overnight and, lastly, that NIV, by improving sleep quality, has
London Centre for Human & physiological studies demonstrating improvement a role in enhancing health-­related quality of life. Of
Applied Physiological Sciences, course, it should be noted that patients with hyper-
in sleep-­disordered breathing and nocturnal
London, SE1 7EH, UK;
​Georgios.​Kaltsakas@​gstt.​nhs.​uk hypoventilation, and clinical trials demonstrating capnic respiratory failure are still at risk of reduced
improved outcomes for patients. However, the impact on sleep quality due to causes other than hypoventi-
Received 28 May 2023 subjective and objective sleep quality is dependent on lation, including organic sleep disorders, restless
Accepted 23 October 2023 the tools used to measure sleep quality and the patient leg syndrome and psychological disorders, among
Published Online First
18 November 2023 population. As home NIV becomes more commonly many others.
used, there is a need to conduct studies focused on
sleep quality, and the relationship between sleep quality
METHODS
and health-­related quality of life, in all patient groups,
Literature for this review was identified using the
in order to allow the clinician to provide clear patient-­
following terms in Medline and Embase: sleep,
centred information.
sleep pathophysiology, sleep disorders, sleep disor-
dered breathing, polysomnography, sleep apnoea,
obstructive sleep apnoea (OSA), hypoventilation,
respiratory failure, COPD, obesity hypoventilation,
INTRODUCTION neuromuscular disorders, motor neuron disease
Hypercapnic respiratory failure is a severe compli- (MND). No restrictions on dates or study design.
cation of several underlying neuromuscular and English language articles were included. The data-
cardiopulmonary conditions. Symptoms typically bases were searched from inception to April 2023.
present with breathlessness, but in most individuals,
prior to the presentation of daytime hypercapnia,
sleep-­related deterioration of ventilation can be Physiological changes to ventilation during sleep
observed. This can manifest as hypercapnia in rapid in healthy individuals
eye movement (REM)-­sleep at first, but eventually Normal restorative sleep in healthy subjects results
throughout the night. in a subclinical state of reduced alveolar ventilation
In the healthy subject, ventilation is diminished when compared with wakefulness. Tidal volume
with sleep onset and the partial pressure of arterial decreases progressively through the stages of sleep,
carbon dioxide (PaCO2) rises slightly but with little down to almost 13% of the awake tidal volume in
clinical consequence1 2; in patients with chronic REM sleep.1 As a result, minute ventilation also
respiratory disease, pathophysiological changes decreases in parallel. This is affected by increased
occur that lead to hypercapnic respiratory failure. activity of gamma-­ aminobutyric acid-­ secreting
Patients with chronic hypercapnic failure frequently neurones during sleep that act as a depressant of the
report poor sleep quality, which facilitates symptoms central respiratory centre.3 Consequently, a small
of sleepiness, perception of breathlessness and has a increase in the PaCO2 and a small decrease in the
significant impact on the quality of life. This review partial pressure arterial oxygen (PaO2) is observed.1
will discuss the complex interaction between sleep Ventilatory responses to hypoxia and hypercapnia
quality and chronic hypercapnic respiratory failure. are attenuated during normal sleep, due to altered
© Author(s) (or their First, the physiological changes in ventilation (eg, chemosensitivity. During REM sleep, chemosensi-
employer(s)) 2024. No breathing frequency and pattern) during sleep will tivity is less than a third than in wakefulness.4 This
commercial re-­use. See rights be summarised, and a model to explore the patho- minimises any increase in neural drive in response
and permissions. Published physiology of hypercapnic respiratory failure will to the small increase in PaCO2. Upper airway resis-
by BMJ.
be introduced. Next, the review will focus on four tance is increased during sleep, due to loss of naso-
To cite: Shah NM, Steier J, clinical conditions, chronic obstructive pulmonary pharyngeal muscle tone, resulting in increased load
Hart N, et al. Thorax disease (COPD), obesity-­related respiratory failure on the respiratory system.5 6 A degree of bronchoc-
2024;79:281–288. (ORRF), slowly progressive neuromuscular disease onstriction is also observed during healthy sleep,
Shah NM, et al. Thorax 2024;79:281–288. doi:10.1136/thorax-2023-220035    281
 State of the art review

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Figure 1 The neural pathway conducting impulses from the central respiratory centre to the respiratory muscles, displaying where different
conditions cause impairment and therefore hypoventilation. LMN, lower motor neuron; UMN, upper motor neuron.

resulting in a mild increase in lower airway resistance.7 During meet metabolic demand. Clinical conditions that impact on the
REM sleep, a marked loss of intercostal muscle activity has also integrity of the neural pathways between the central nervous
been reported8 resulting in a decrease in tidal volume, and a reli- system and the respiratory muscles (figure 1), and those that
ance on an intact diaphragm to maintain ventilation during this increase dead space ventilation contribute to the development
period. In healthy individuals, these changes are limited and do of hypercapnic respiratory failure. The respiratory muscle load-­
not result in any clinical sequelae, although oxygen saturation capacity ratio is a useful construct to determine the pathophysio-
during sleep is lower than during wakefulness. These changes logical contribution of respiratory and neuromuscular conditions
tend to be exaggerated in individuals with chronic respiratory that lead to hypercapnic respiratory failure.9 Increased load on
diseases and exacerbate nocturnal alveolar hypoventilation, and the respiratory system, reduced respiratory muscle capacity and
thereby contribute to the development of hypercapnic respira- reduced neural respiratory drive, in isolation or in combination
tory failure. lead to an imbalance in the load-­capacity ratio, and can cause
alveolar hypoventilation (figure 2). Furthermore, sleep fragmen-
Pathophysiology of hypercapnic chronic respiratory failure tation is typically a consequence of respiratory-­related arousals
The arterial partial pressure of carbon dioxide is inversely propor- that are associated either with hypoxic, hypercapnic or resistive
tional to alveolar ventilation such that hypercapnic chronic breathing-­related events caused by the underlying condition.10
respiratory failure occurs as a consequence of inadequate alve- Respiratory muscle load is composed of resistive load (eg,
olar ventilation associated with ineffective elimination of carbon airways resistance), elastic load (eg, lung and chest wall compli-
dioxide.9 Alveolar ventilation is determined by the difference ance) and threshold load (eg, intrinsic positive end-­expiratory
between minute ventilation and dead space ventilation, and in pressure). An excess respiratory load can be compensated for
turn, minute ventilation is controlled by neural respiratory drive, by an increase in neural respiratory drive that recruits increased
which determines respiratory muscle pump activity in order to respiratory muscle pump activity, leading to increased ventilation.

Figure 2 Respiratory muscle load-­capacity-­drive relationship displaying changes in sleep in normal subjects and how they contribute to alveolar
hypoventilation. GABA, gamma-­aminobutyric acid.
282 Shah NM, et al. Thorax 2024;79:281–288. doi:10.1136/thorax-2023-220035
 State of the art review

Table 1 Changes to the respiratory muscle load-­capacity-­drive relationship in each condition during sleep, leading to alveolar hypoventilation

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Load Capacity Drive
COPD ► Dynamic hyperinflation ► Loss of intercostal muscle activity during ► Reduced drive during sleep does not compensate
► Bronchoconstriction sleep for increased load/decreased capacity
Obesity ► Smaller lung volumes ► Adipose tissue impairing chest expansion ► Reduced drive during sleep does not compensate
► Airway narrowing ► Reduced diaphragm neuromuscular coupling for increased load/decreased capacity
► Dynamic hyperinflation
► Airway inflammation
► Small airway tidal closure
Slowly-­progressive ► Fibrosis of rib cage/spinal deformities ► Respiratory muscle weakness ► Reduced drive during sleep does not compensate
neuromuscular disease ► Reduce nasopharyngeal dilator muscle for increased load/decreased capacity
function ► Disruption along the neural pathways
Motor neuron disease ► Reduced nasopharyngeal dilator muscle ► Respiratory muscle weakness ► Reduced drive during sleep does not compensate
function ► Phrenic nerve-­induced diaphragm paralysis/ for increased load/decreased capacity
► Increased secretions paresis ► Disruption along the neural pathways
COPD, chronic obstructive pulmonary disease.

The capacity of the respiratory muscle pump is largely determined there is an impaired dilating response of the supraglottic airways
by inspiratory muscle strength and endurance, primarily by the in response to hypercapnia in patients with COPD, resulting in
diaphragm and the extradiaphragmatic muscles. Neural respi- increased upper airway resistance and resistive load.19 Finally,
ratory drive indicates the efferent signal of the central nervous patients with COPD use their intercostal muscles to maintain
system required to match the work of breathing in response to ventilation; loss of the intercostal neuromuscular tone during
the afferent information, including the metabolic demand (eg, sleep will reduce respiratory muscle capacity further.20 The
high body temperature, metabolic acidosis). Neuronal signals combination of these pathophysiological changes in COPD
are transmitted from the respiratory centre in the brainstem directly exaggerates the normal ventilatory changes in healthy
to the respiratory muscles via the spinal cord and peripheral adults during sleep, resulting in sleep hypoventilation and devel-
nerves, including the neuromuscular junctions. Without an opment of hypercapnic respiratory failure.21
intact neuronal tract, the respiratory muscles will not respond to These pathophysiological constraints are reflected in the
increased metabolic demand leading to reduced elimination and symptoms and quality of life, as measured by clinical outcomes
accumulation of alveolar carbon dioxide. There is no difference and standardised validated questionnaires. The Pittsburgh Sleep
between the hypercapnic ventilatory response in older people Quality Index (PSQI) is a widely available tool used to eval-
compared with younger healthy controls both in wakefulness11 uate subjective sleep quality; the higher the score, the worse
and during sleep.12 This demonstrates that the altered ventila- the subjective sleep quality. Studies have demonstrated that
tory response observed in individuals with chronic respiratory poor sleep quality (higher PSQI) is associated not only with an
failure cannot be explained by the effect of advancing age on increased risk of COPD exacerbations,22 but also with reduced
neural respiratory drive. Throughout this review, the respiratory physical activity,23 and worse health-­related quality of life.16 24 25
muscle load-­capacity ratio will be used to explain how COPD, Sleep quality appears to be inversely proportional to the severity
ORRF, slowly progressive NMD and rapidly progressive NMD of COPD.26 In addition, polysomnographic studies have demon-
lead to hypercapnic respiratory failure (table 1), why it contrib- strated that sleep architecture is also disrupted in patients with
utes to sleep fragmentation with development of symptoms, and COPD with reduced sleep efficiency,15 27 reduced total sleep
how NIV can support the patient accordingly. time27 and reduced time spent in REM sleep.28 Poor sleep in
COPD has been associated with increased peripheral airway
Chronic obstructive pulmonary disease resistance,29 and the presence of comorbid OSA in patients
COPD is the most common cause of chronic hypercapnic respi- with COPD can result in worse subjective14 and objective sleep
ratory failure. Many patients with severe COPD complain efficiency.15
of ‘poor sleep’, with 50%–80% of patients reporting sleep Over the past two decades, interest in the provision of domi-
disturbance.13–17 However, despite this high prevalence, there ciliary NIV for the treatment of chronic respiratory failure in
are limited data detailing sleep fragmentation and quality in COPD has increased. Two recent landmark studies resulted in
COPD.18 conditional recommendations in the most recent European Respi-
In patients with COPD, any regular physiological changes ratory Society guidelines30 for the addition of domiciliary NIV
to ventilation during sleep are exaggerated due to the under- to oxygen therapy in patients with COPD with persistent short-­
lying pathophysiology. Due to the lung and airway contribution, term hypercapnia following a severe exacerbation of COPD,31
patients with COPD often have lower oxygen saturation levels, and in stable patients with COPD with chronic respiratory
typically on the steep part of the oxygen-­dissociation curve; such failure.32 These landmark studies provide the clinical evidence
that any further overnight reduction on oxygen saturation will to target carbon dioxide reduction to improve clinical outcome
result in a substantial fall in PaO2. Lung hyperinflation associ- and health-­related quality of life in patients with COPD. Indeed,
ated with expiratory tidal flow limitation in COPD increases recent studies have demonstrated the cost-­effectiveness of domi-
physiological dead space, reduces the capacity of the respira- ciliary NIV in patients with COPD following a recent admission
tory muscles, and increases the elastic load, resulting in further to hospital due to an exacerbation that required acute NIV.33 34
hypoventilation and consequently, hypercapnia. Ongoing bron- Few studies have specifically investigated the effect of domiciliary
choconstriction in COPD facilitates the increase in the resistance NIV on sleep in COPD, although subjective evaluation has been
of the lower airways and increase resistive load. Furthermore, performed in clinical studies as a secondary outcome measure
Shah NM, et al. Thorax 2024;79:281–288. doi:10.1136/thorax-2023-220035 283
 State of the art review
with a Cochrane review detailing the lack of data reporting sleep individuals exhibit daytime hypercapnia in the absence of any

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quality changes in patients with COPD receiving domiciliary other cause. The majority of individuals with OHS (90%) also
NIV.35 Studies have demonstrated no difference in sleep quality suffer from concomitant onbstructive sleep apnoea (OSA),42
with domiciliary NIV when compared with long-­term oxygen but there is evidence to support a continuum for progression of
therapy36 and usual care,37 with either subjective question- hypercapnia in patients with severe OSA through a combination
naire or objective polysomnographic measurements.38 Studies of OSA and OHS to OHS52 53
comparing automated modes of NIV, for example, intelligent Obese individuals report shorter sleep duration and lower
volume-­assured pressure support and average volume assured sleep efficiency,54 55 and worse sleep quality56 57 than controls.
pressure support (AVAPS) with fixed-­pressure support ventila- Respiratory effort-­related arousals may partly explain this sleep
tion, have investigated sleep quality as a primary outcome with disturbance. These are a period of abnormal breathing during
mixed results in terms of reported subjective sleep quality.39–41 sleep, associated with an increased effort and arousal, that do
As the use of domiciliary NIV for chronic respiratory failure and not fulfil the criteria for apnoea or hypopnoea.58 Current data
persistent hypercania following a severe exacerbation of COPD reports that both physiological and psychological factors such as
increases, there is an essential requirement to design clinical mood disturbances impact on sleep quality.59 60 Of interest, in
trials which focus primarily on sleep quality. OHS patients without OSA, time spent in REM sleep was lower
than in controls61 and the presence of OSA did not have any
impact on subjective sleep quality,62 suggesting that hypercapnia
Obesity-related respiratory failure may contribute, rather than the nature of sleep-­ disordered
Obesity increases the load on the respiratory system through a breathing, as the level of PaCO2 elevation is often greater in the
number of pathophysiological mechanisms, making obese indi- OSA and OHS phenotype than the OSA phenotype.
viduals particularly vulnerable to chronic hypercapnic respira- The gold-­standard treatment for ORRF is significant weight
tory failure. Obese individuals breathe at lower lung volumes, loss, which can be successfully achieved by calorie control, exer-
specifically a reduced expiratory reserve volume (ERV), such that cise, bariatric surgery and novel metabolic treatments. Much less
resting breathing occurs at a less compliant part of the pressure-­ significant weight loss can be achieved with NIV alone63 and
volume curve, resulting in increased elastic load,42 close to the NIV accompanied by a comprehensive weight loss programme.64
closing volume of the small airways, potentially leading to tidal Individuals who undergo bariatric surgery demonstrate improve-
airway closure. Furthermore, airway calibre is dependent on ment in sleep architecture (percentage time spent in non-­REM
lung volume; with the change in airway diameter proportional sleep stage III and REM stages of sleep and apnoea/hypopnoea
to the cube root of lung volume.43 As obese individuals breathe index),65 66 with associated improvement in subjective sleep
at this lower lung volume, airway smooth muscles are unloaded, quality.67 68
allowing them to shorten excessively resulting in further airways More immediate correction of obesity-­ related alveolar
narrowing which is exacerbated by the obese proinflammatory hypoventilation and upper airways obstruction can be achieved
state of airways inflammation.44 The airways narrowing results with domiciliary nocturnal NIV. However, there are limited data
in tidal expiratory flow limitation and a resistive load which is reporting the effect on sleep quality after initiation of NIV. In
accompanied by dynamic hyperinflation and intrinsic positive a clinical trial comparing NIV in patients with mild OHS, NIV
end expiratory pressure, and subsequent increase in inspiratory resulted in an improvement in percentage time spent in REM
threshold load.45 Pulmonary compliance is reduced due to the sleep, a reduction in respiratory arousals, a reduction in apnoea/
physical impact on chest wall expansion of obese tissues, and due hypopnoea index, and an increase in nocturnal oxygenation.69
to peripheral small airway closure, again secondary to breathing Another clinical trial comparing NIV and continuous positive
at low volumes, leading to atelectasis.46 In addition, there is a airway pressure (CPAP) in patients with severe OSA and OHS
reduction in diaphragm neuromuscular coupling in response demonstrated that both treatment modalities increased the
to inspired carbon dioxide resulting in less respiratory muscle percentage REM sleep time and reduced the arousal index and
activity for any unit of drive.47 Furthermore, respiratory muscle AHI,70 supporting that nocturnal respiratory support is benefi-
endurance is inversely proportional to increasing body mass cial for sleep quality in patients with ORRF.
index.48 In order to meet the demands of the increase in resistive
and threshold loads and reduced respiratory muscle capacity,
neural respiratory drive increases to attempt to maintain Slowly progressive neuromuscular disorders
adequate alveolar ventilation.49 Indeed, in obese patients with Slowly progressive NMDs include conditions such as congenital
chronic respiratory failure, the neural respiratory drive in the muscular dystrophies, myotonic dystrophy, spinal muscular atro-
awake state, normalised for maximum neural respiratory drive, phies, inflammatory myopathies, metabolic muscle diseases and
is fourfold higher than that observed in healthy subjects.50 As peripheral nerve diseases. While these conditions are rare, the
expected, if the load overwhelms the system’s ability to match the NMD group account for 25% of patients treated with domicil-
demand, alveolar hypoventilation will follow and lead to hyper- iary NIV71 as these patients often develop chronic hypercapnic
capnic respiratory failure for example, during sleep, resulting in respiratory failure with associated morbidity and mortality. As
sleep-­disordered breathing and resultant nocturnal respiratory with COPD and ORRF, sleep disturbance and poor sleep quality
failure. During sleep, the abdominal contents move in a cephalic is a frequently reported complication by patients with NMD.20 72
direction, impeding diaphragm excursion and further reducing The common feature of these conditions is that there is a
ERV, increasing the elastic load. Fatty deposits in the pharyngeal disruption along the neural pathways, with a negative effect on
tissue increase the upper airway collapsibility observed during the efferent signal from the central respiratory centres to the
sleep due to muscle hypotonia, increasing the resistive load. respiratory muscles. This results in respiratory muscle weakness,
As respiratory drive is reduced during sleep, the increased load altered respiratory mechanics and abnormal central control
can overwhelm the compensatory mechanisms resulting in alve- of breathing. Many NMD develop fibrotic changes of the rib
olar hypoventilation.51 The above pathophysiology establishes cage and spinal deformities that result in an increased elastic
in the obesity hypoventilation syndrome (OHS), where obese recoil (and therefore increased elastic load), limiting inspiratory
284 Shah NM, et al. Thorax 2024;79:281–288. doi:10.1136/thorax-2023-220035
 State of the art review
capacity and causing a restrictive ventilatory pattern. In addi- Rapidly progressive neuromuscular disorders

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tion, to reduce the respiratory muscle load and reduce the risk MND is the most common adult-­ onset rapidly progressive
of respiratory muscle fatigue, patients with NMD adopt a rapid neurogenerative disorder of both the central and peripheral
shallow breathing pattern. This ventilatory pattern is char- nervous system. It results in the loss of motor neurones in the
acterised by decreased tidal volume and increased breathing cerebral cortex, the brainstem and the anterior horn of the spinal
frequency, leading to an increased dead space ventilation and cord. Respiratory failure is a common consequence of MND
decreased alveolar ventilation. Decreased alveolar ventilation due to a combination of its effect on the brainstem control of
increases the likelihood of developing hypercapnic respiratory breathing,85 86 and the motor neurones supplying the respiratory
failure. Reduced nasopharyngeal dilator muscle function further muscles; it was the reason for hospital admission in approxi-
leads to increased upper airway resistance due loss of upper mately 30% of patients with MND87 88 and a frequent cause of
airway calibre, and therefore, increases the resistive load. An death.89–92
increased resistance in the upper airway causes greater work of Alveolar hypoventilation is caused by respiratory muscle
breathing, further adding to the load on the diaphragm during weakness as the disease progresses. Progressive degeneration of
inspiration, and in combination with the decreased upper airway the motor neurones innervating the respiratory muscles results
tone during sleep, and diminished neural respiratory drive in in significant respiratory muscle weakness and reduced capacity
different sleep stages leads to nocturnal alveolar hypoventila- of the respiratory muscle pump. Loss of phrenic nerve function
tion. There are sparse data on individual NMD due to relatively results in diaphragm weakness or paralysis, which promotes the
low prevalence rates, particularly with regards to sleep quality. A unopposed caudal movement of abdominal organs in the supine
single study reporting on polysomnographic data in patients with posture, further reducing vital capacity. Expiratory muscles that
NMD demonstrated that apart from nocturnal hypoxia, which is support an effective cough manoeuvre also weaken with disease
unsurprising, sleep architecture was preserved.73 The prevalence progression, resulting in an inability to expectorate secretions
of sleep-­disordered breathing is widely disparate in the literature adequately, facilitating mucoretention and increasing the risk of
due to multiple definitions of hypoventilation, heterogeneity of lower respiratory tract infections, as well as contributing to a
cohorts studied and the degree of weakness involved. Prevalence high airway resistance and increased resistive load.
of hypoventilation in NMD has been reported from anywhere Impaired sleep quality is a frequent and pervasive complaint
between 10% and 62%, depending on the definition of hypoven- among patients with MND93 and presents a particular burden
tilation (daytime PaCO2, daytime base excess, nocturnal SpO2 or on their carers as well.94 More than 60% of patients with MND
report a raised score in the PSQI, indicating worse sleep quality,
nocturnal TcCO2).74
compared with 37% of controls.95 Sleep fragmentation may be
The use of domiciliary NIV to control hypercapnic respiratory
caused by a combination of physical symptoms related to MND
failure has been well established in NMD for several decades. The
(muscle cramps, pain, spasticity and restless legs with period limb
majority of patients with NMD require domiciliary NIV during
movements at night), mood disturbance leading to insomnia and
the course of their illness, and with increasing uptake of the
sleep-­disordered breathing.96 Furthermore, neurodegeneration
therapy, life expectancy has considerably increased.75 The major
of central pathways regulating REM sleep may also lead to REM
indication for initiating domiciliary NIV is nocturnal hypoven-
sleep disorders.97 Time spent in REM sleep was significantly
tilation with or without sleep-­disordered breathing.76 There is
reduced in patients with MND with diaphragmatic dysfunction
evidence for the initiation of NIV prior to the onset of daytime
(suggesting more advanced disease) than those without.98 Of
hypercapnia and there are reports of the benefits of NIV in these
note, in those with diaphragmatic dysfunction, individuals who
patient groups,77 and a number of international guidelines have
demonstrated preserved sternomastoid activity spent more time
been published,78 79 although all referring to the low quality of
in REM sleep than those that did not. This is consistent with data
evidence available. Most frequently, patients are established on from patients with bilateral diaphragmatic paralysis who main-
NIV during an inpatient stay titrating required settings according tained REM sleep by recruiting extradiaphragmatic muscles.99
to polysomnography or limited respiratory polygraphy moni- The mainstay of treatment for hypercapnic respiratory
toring. There is increasing interest in the effectiveness of home-­ failure in MND is NIV. A single clinical trial was performed
based or outpatient set-­up of NIV, to reduce the use of resources, which demonstrated clear survival benefit in patients with
time spent in hospital and increase cost-­effectiveness. Pathways MND without severe bulbar dysfunction.100 A Cochrane review
to employ autotitrating devices and telemedicine support are supported the recommendations of this study, commenting that
currently being developed to support a more outpatient or home-­ further trials will not be possible as it would be unethical to with-
based delivery of the initial titration phase. Autotitrating devices hold NIV in a control arm, given the existing supportive data.101
are non-­inferior in terms of outcomes to standard titration of Subsequent retrospective studies have provided further evidence
NIV devices,80 and home setup of NIV has been demonstrated to for the use of NIV. When compared with matched controls
be both feasible and non-­inferior when compared with inpatient who were not treated with NIV, patients with NIV had longer
setup.81 However, as with COPD and obesity-­related respira- overall survival,102 as well as tracheostomy-­free survival, and
tory failure, few studies investigating the impact of NIV on sleep NIV also provided survival benefit in bulbar-­onset patients.103
quality in NMD have been performed. Polysomnographic data Current work is focused on identifying the specific cohort of
in muscular dystrophy type I82 and late-­onset Pompe disease83 MND patients who most benefit from NIV and the most appro-
demonstrated no deterioration in sleep quality after NIV initi- priate timing of initiation. Bulbar dysfunction was thought to be
ation. A cross-­ sectional subjective assessment of sleep quality a predictor of NIV failure.104 105 Positive pressure applied to the
in a group of various NMD who were already established on airway in patients with MND has been demonstrated to cause
domiciliary NIV demonstrated that more than 50% of patients vocal cord closure, particularly in those with bulbar dysfunc-
reported experiencing poor sleep quality.84 Sleep quality remains tion.106 This has potential consequences for the effective delivery
an important clinical outcome to evaluate when conducting NIV of NIV in this patient group. However, a recent systematic
efficacy trials in this patient group. review has demonstrated that with attention to individual needs
Shah NM, et al. Thorax 2024;79:281–288. doi:10.1136/thorax-2023-220035 285
 State of the art review
(eg, secretion management, interface optimisation and closer NIV,120 it is important to monitor and address potential causes

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ongoing monitoring) bulbar patients can derive considerable as they arise.
benefit from NIV therapy.107 Survival is increased in patients who
are more effectively ventilated (minimal time spent with oxygen
saturation below 90%) overnight than those who are not,108 and Summary
so careful initiation and monitoring is key in these patients. The The physiological changes in ventilation during normal sleep in
optimal timing of NIV initiation remains under investigation. healthy adults are exacerbated in chronic respiratory diseases
Outpatient-­based and home-­based initiation models are increas- that result in alveolar hypoventilation. Simultaneously, sleep
ingly being investigated and compared with the traditional quality is attenuated in patients with conditions leading to
inpatient-­based model; however, novel pathways appear to be chronic hypercapnic respiratory failure. This review has detailed
at least non-­inferior, and may, at best, result in improved clinical the pathophysiological changes that lead to alveolar hypoventi-
outcomes.109 Sleep in MND has been investigated more often as lation and poor sleep quality in COPD, ORRF, slowly progres-
a primary outcome following NIV initiation than in other NMD sive and rapidly progressive neuromuscular conditions. A
conditions. Subjectively, NIV initiation improved sleep quality combination of increased respiratory load, reduced neural respi-
(with a reduction in the PSQI) one month following initiation, ratory drive and respiratory muscle capacity results in a state
and this change was sustained at twelve months.110 Available of alveolar hypoventilation; these pathophysiological changes
polysomnographic data are inconclusive and relate primarily to are accentuated during sleep and can lead to hypercapnic respi-
patient selection for NIV initiation and study design. A small ratory failure. Although the pathophysiological mechanisms
pre/post initiation study demonstrated that NIV improved over- across these groups are well described, the focus of the clin-
night oxygenation without any improvement in the regular sleep ical studies to date have targeted clinical outcomes and health-­
architecture.111 Other retrospective studies have demonstrated related quality of life. Despite this, there are limited published
that NIV initiation increased the time spent in slow wave and data investigating the effect of long-­term NIV on sleep quality.
REM sleep,112 with an improvement in the sleep efficiency and The current data appear to suggest that NIV may have a posi-
the apnoea/hypopnoea index in non-­bulbar patients only,113 as tive impact on sleep quality, with the data for rapidly progres-
well as in both bulbar and non-­bulbar patients.114 However, the sive NMD being more convincing than other groups. Multiple
current literature provides sufficient evidence that NIV signifi- confounding factors, including study design, patient selection,
cantly improves sleep outcomes in MND patients. Identification intervention and different reported outcomes does not permit
of patients who benefit the most (phenotypically and metaboli- conclusions to be clearly drawn. With the increasing use of
cally) and the most appropriate setting for initiation (inpatient, domiciliary NIV in all of these patient groups, supported by the
outpatient or home based) remain key considerations when initi- physiological, clinical and patient-­centred improvement, there
ating NIV in this cohort. is an urgent requirement to focus the effect of treatment with
nocturnal ventilatory support on both subjective and objective
sleep quality with a goal of enhancing adherence and further
Monitoring sleep quality improving outcomes of patients with chronic respiratory failure.
Long-­term NIV is initiated in patients with chronic respiratory
disease not only to improve ventilation, but also to improve Twitter Nicholas Hart @NickHartGSTT
symptoms, quality of life and sleep quality. It is, therefore, Contributors All authors engaged into discussions related to this manuscript,
important to monitor all of these goals. Monitoring sleep quality contributing in writting it and reviewing it.
must be practical and easy to perform both for patients and Funding The authors have not declared a specific grant for this research from any
the clinical team. Frequently used patient-­ reported outcome funding agency in the public, commercial or not-­for-­profit sectors.
measures are the Severe Respiratory Insufficiency questionnaire, Competing interests None declared.
which is a quality of life assessment tool designed for individ- Patient consent for publication Not applicable.
uals receiving home mechanical ventilation with a specific sleep Provenance and peer review Not commissioned; externally peer reviewed.
domain and the PSQI, an assessment of sleep quality.115 Pulse
wave amplitude, which is measured using overnight oximetry, ORCID iDs
Joerg Steier http://orcid.org/0000-0002-1587-3109
can be used to assess sleep fragmentation.116 This is a simple
Georgios Kaltsakas http://orcid.org/0000-0002-7679-0825
home-­based user-­friendly tool to measure sleep quality. Mask
leak is a common cause of poor sleep quality. Telemonitoring
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