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Screening with limited sleep tests

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One of the drawbacks of limited sleep tests is the lack of sleep variables. A reasonable approach to tackling this issue and increasing their screening power is the use of actigraphy devices. Actigraphy devices objectively measure sleep parameters and average motor activity over a period of days to weeks using a noninvasive accelerometer. Type III and IV devices that use built-in actigraphy have the ability to eliminate awake and artifact time, with the goal of improving the estimation of sleep time and consequently, diagnostic accuracy. Actigraphy also seems to be more accurate than self-reported sleep duration and may be more helpful than sleep diaries in the evaluation of patients with suspected sleep disorders.

Wearable sleep respiratory monitors are gaining attention from the sleep medicine community, and are further simplifying the diagnostic approach. These devices are small, lightweight, less time-consuming to use and set up than conventional PSG, and are capable of screening hundreds of people a day. Wearable sleep-trackers (wristbands, armbands, smartwatches, headbands, rings, sensor clips and in-bed sensors) are relatively low-cost devices and are available without prescription. Their accessibility, usability, novelty and aordability has led to their widespread use and has also helped increase awareness about the importance of sleep in the general population. Despite these potential advantages, there is a paucity of adequate data about their clinical validity, accuracy and reliability as a screening device.

In conclusion, limited sleep studies are cost eective and convenient, and can increase pre-test probability for OSA. Novel devices and emerging technologies are increasingly being used. Artiﬁcial intelligence and telemedicine are expected to deepen our understanding and potentially improve the eciency of limited sleep studies for screening sleep apnoea patients.

Further reading

• Abrahamyan L, et al. (2018). Diagnostic accuracy of level IV portable sleep monitors versus

polysomnography for obstructive sleep apnea: a systematic review and meta-analysis. Sleep Breath; 22: 593–611.

• Ergan B, et al. (2019). European Respiratory Society guidelines on long-term home non-

invasive ventilation for management of COPD. Eur Respir J; 54: 1901003.

• Indications for Polysomnography Task Force, American Sleep Disorders Association Standards

of Practice Committee (1997). Practice parameters for the indications for polysomnography and related procedures. Sleep; 20: 406–422.

• Kapur VK, et al. (2017). Clinical practice guideline for diagnostic testing for adult obstructive

sleep apnea: an American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med; 13: 479–504.

• Pépin JL, et al. (2020). Assessment of mandibular movement monitoring with machine

learning analysis for the diagnosis of obstructive sleep apnea. JAMA Netw Open; 3: e1919657.

• Riha RL, et al. (2023). ERS technical standards for using type III devices (limited channel

studies) in the diagnosis of sleep disordered breathing in adults and children. Eur Respir J; 61:

2200422.

• Smith MT, et al. (2018). Use of actigraphy for the evaluation of sleep disorders and circadian

rhythm sleep-wake disorders: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med; 14: 1209–1230.

• Standards of Practice Committee for the American Sleep Disorders Association (1994).

Practice parameters for the use of portable recording in the assessment of obstructive sleep apnoea. Sleep; 17: 372–377.

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Non-continuous positive

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airway pressure therapies

Johan Verbraecken, Olivier Vanderveken, Marie Marklund, Marijke Dieltjens and Joerg Steier

Therapeutic strategies for patients with OSA may be categorised into three general groups: behavioural, medical and surgical. Treatment decisions should be based on the eect of OSA on daytime symptoms and cardiovascular and metabolic function, rather than on the absolute number of episodes of apnoea or hypopnoea. The ﬁnal goal is to establish a stable oxygen curve and breathing pattern, abolish snoring, the elimination of sleep fragmentation due to upper airway collapse, and enhanced alertness during the daytime.

Lifestyle interventions

First-line treatment of OSA starts with the avoidance of aggravating factors such as weight gain, lack of exercise, smoking and the intake of alcohol, sedatives and muscle relaxants before bedtime, which may inﬂuence the severity of OSA. The relative value of avoiding these factors should be discussed with the patient.

Weight loss

Pharyngeal fat deposits lead to a decrease in pharyngeal patency and underline the risk factor of obesity. Weight loss is recommended in >80% of patients with OSA

Key points

• Although weight loss is highly ecacious in OSA, only 5% of those who are overweight are able to lose weight and keep it o.

• The types of surgery for OSA and snoring are various, with dierent indications, each requiring a speciﬁc expertise.

• MAD therapy is mainly indicated for milder OSA patients without signiﬁcant comorbidities, who are followed-up carefully.

• Positional therapy can be suggested to patients with POSA, preferably those with a nonpathological level of OSA in the nonsupine position (AHI <5 events·h−1).

• Electrical stimulation during sleep, HNS and transcutaneous electrical stimulation have been shown to be safe and ecacious in the treatment of OSA.

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and leads to a decrease in critical closing pressure (P

), consequently decreasing

crit

the severity of OSA. Unfortunately, only 5% of overweight persons are able to lose weight and keep it o. This problem is exacerbated when patients are sleepy during the daytime, tend to snack to stay awake and are too tired to exercise. Therefore, sleep deprivation should be avoided. Most patients who lose weight experience an improvement in apnoea. Based on a large epidemiological study, it was found that a 10% weight loss was associated with a 26% decrease in AHI. Some patients may be substantially better aer a weight loss of only a few kilogrammes, but others may continue to have symptoms despite a signiﬁcant weight loss (50–70 kg). A partial improvement in AHI can be expected in 39% of patients, while a cure of OSA is observed in 23% of cases. Some patients treated with CPAP ﬁnd it easier to lose weight than before treatment, probably because of increased activity during the daytime or decreased ingestion of snacks to increase alertness. Nevertheless, others report a weight gain, which could be related to altered energy expenditure at night. However, weight loss takes time, and only a minority of patients successfully maintain it. As a primary treatment, weight loss should be targeted towards patients with mild-to-moderate OSA, especially if there is no interest in other options. It is also important to emphasise that OSA can recur, even if weight loss is maintained. Bariatric surgery is an eective means to achieve major weight loss and is indicated in individuals with a BMI ≥40 kg·m−2 or those with a BMI ≥35 kg·m−2 with important comorbidities (systemic hypertension, diabetes, OSA) and in whom dietary attempts at weight control have been ineective. Unfortunately, despite the usual massive weight loss obtained with bariatric surgery, cure of OSA is not systematically obtained. Nevertheless, loss of excess body weight by diets and bariatric surgery results in a signiﬁcant improvement in comorbidities and function of the respiratory system, represented by signiﬁcant changes in both static and dynamic lung volumes. Studies have been performed with weight-reducing agents, including phentermine, orlistat (a lipase inhibitor), liraglutide and other glucagon-like peptide-1 agonists, and empagliﬂozin, indicated in obese subjects. Added metabolic beneﬁts may be achieved. Overall, success or failure of weight-reducing interventions is dependent on individual factors, including age, gender, ethnicity and socioeconomic status.

Exercise

Moderate-intensity exercise training is an inexpensive and healthy conservative intervention that may help individual patients with OSA to improve the AHI, quality of sleep and quality of life. In addition, it has been shown to reduce anxiety levels in those with insomnia, even in the absence of weight reduction. A reduction in rostral ﬂuid shi from the lower body, an improvement in upper airway function and changes in body composition could be involved as causal factors.

Smoking cessation

An association between smoking and sleep apnoea has been demonstrated, but smoking cessation is controversial. Wetter et al. (1994) found a dose–response relationship between smoking and AHI. Even secondhand smoke exposure is signiﬁcantly associated with OSA. Cigarette smoking may increase the severity of OSA through alterations in sleep architecture, upper airway neuromuscular function, arousal mechanisms and upper airway inﬂammation. Conversely, smokers in the Sleep Heart Health Study displayed less sleep apnoea than nonsmokers. One potential adverse consequence of smoking cessation is weight gain. This is counterproductive to OSA and may also serve to heighten patients’ anxiety about their appearance, thus thwarting quit attempts.

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Alcohol reduction

Alcohol selectively reduces upper airway muscle tone, and is associated with worsening severity of snoring, altered sleep architecture and AHI as well as lowest oxygen saturation. Additionally, alcohol prolongs respiratory event duration by delaying arousal, and is an important source of calories. Active treatment of OSA can be signiﬁcantly aected by the amount of alcohol intake. Some population-based cross-sectional studies have reported a signiﬁcant association between chronic alcohol intake and OSA, whereas other cross-sectional or longitudinal studies have not.

Avoidance of night sedation

Sedatives, like benzodiazepines and Z-drugs can have adverse eects in some OSA patients (but do not necessarily increase the AHI) while improving sleep eciency and inducing no adverse consequences on alertness the following day.

Sleep hygiene measures

Sleep hygiene measures refer in essence to the impact of daytime exercise and diet, alcohol and smoking in the evening on sleep patterns. Caeine, nicotine and alcohol consumption in particular are not recommended too close to bedtime, given their activating eects. It is also recommended to avoid heavy meals before going to bed. Physical exercise should be carried out regularly and during the daytime, and not within 2 h before bedtime. The overall aim of sleep hygiene is to promote restorative and sucient sleep, including an adequate number of sleep hours. Apart from the advice on diet, exercise and alcohol, tobacco and caeine consumption, other recommendations have emerged from stress reduction measures (cognitive behavioural approaches) and especially from measures designed to control stimulation. In addition, regular bed and wake-up times, and avoidance of daytime naps are clinically relevant.

Role of ENT intervention

Surgical modiﬁcations for OSA include upper airway bypass procedures such as tracheotomy, upper airway surgery, nasal surgery, skeletal modiﬁcations and bariatric surgery.

When considering a non-CPAP therapy, proper investigation of the collapsible segment of the individual patient’s upper airway is of utmost importance. Typically, a thorough clinical ENT examination and a drug-induced sleep endoscopy (DISE) are recommended before an interdisciplinary decision of the choice of a speciﬁc nonCPAP treatment can be made.

Anatomical sleep surgery should be performed addressing the level(s) of collapse in the upper airway in the individual patient. Upper airway surgery can be divided into intrapharyngeal and extrapharyngeal procedures. A more stable ventilatory control seems to be predictive of a more eective surgical treatment for OSA.

In the past, uvulopalatopharyngoplasty was the most performed palatal surgery, while recently, less invasive palatal surgery (expansion sphincter pharyngoplasty and barbed reposition pharyngoplasty) demonstrate similar or better results. Hypopharyngeal surgery includes surgical procedures at the level of the tongue base and/or hypopharynx including the lateral pharyngeal walls and epiglottis. The application of transoral robotic surgery has a potential eectiveness in selected OSA patients.

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Combination therapy, whether it consists of combining a mandibular advancement device (MAD) with positional therapy or multilevel ‘salvage’ sleep surgery, is undervalued and should be prescribed more oen in speciﬁc OSA endotypes in order to increase the overall clinical eectiveness of the OSA therapy.

Role and types of MADs and other oral devices

The MAD (ﬁgure 1) and the tongue-stabilising or -retaining device are anatomical interventions and the most evaluated intraoral devices for patients with OSA. Their mechanism of action is aimed at moving the jaw or tongue forward and widening the upper airway. MADs reduce AHI to similar degrees as CPAP, but MAD is better tolerated and much more preferred by the patients. Custom-made MADs (ﬁgure 2) are superior to thermoplastic ones, but no gold-standard speciﬁc design has been identiﬁed. MADs reduce the pharyngeal collapsibility in a dose-dependent manner, although there is no exact linear relationship between the degree of advancement and the reduction in AHI. The optimal mandibular position, including the chance of treatment success, can be identiﬁed by various techniques that use results from manipulations of the mandible or pharyngeal characteristics during sleep or DISE. A tongue base collapse is related to treatment success and a complete concentric palatal collapse is related to failure, while an epiglottic collapse does not impair the result.

MAD responders have speciﬁc endotypic traits such as a low-to-moderate pharyngeal collapsibility and no physiological traits of OSA, e.g. high loop gain. Beneﬁcial phenotypic traits include younger age, lower BMI and female gender.

In comparisons between MAD and CPAP, it is generally recommended that CPAP should be used, mainly based on the higher decrease of AHI with CPAP over MAD. In mild-to-moderate OSA, MAD might be equally eective as CPAP, because AHI

Figure 1. Mandibular advancement device.

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• Evaluted device design

• Optional mandibular repositioning

Phenotype

• Younger

• Female

• Lower BMI

• Beneﬁcial pharyngeal

chacteristics

• Odontological

considerations

Endotype

• Lower collapsibility

• No nonanatomical OSA traits

Device

Expected bite changes from the forces of the device

General health

• Fewer, less severe comorbidities

Bite with a high risk of negative bite change Bite with less risk of negative bite change Bite aer years of use

MAD

Possible changes in endotype, phenotype,

general health and suitability of the

mechanism of the device, including its quality

• Continuous follow-up of ecacy, bite changes and other side-eects, changed health and OSA-related comorbidities

Long-term outcome

Figure 2. Illustration of success factors for MAD therapy.

values close to the normal range and an equal eect on EDS is oen achieved. There is also some evidence of a higher adherence and patient preference in favour of MAD. During longer term treatment, patients might change their indications for MAD, for instance because of weight increase, deterioration of the disease or bite changes. The relationship between the upper and lower dentitions will change, which can reduce the advancement by the device, if le unadjusted. Follow-up aer 3–17 years in fairly small and well-controlled samples has shown both stable positive eects and increase in AHI.

Modest positive, but variable, eects on BP have been detected in a restricted number of studies. A recent meta-analysis concluded that BP medication was superior for OSA patients with hypertension, and that CPAP, but not MAD, might be helpful as an adjunctive therapy.

According to present knowledge, MAD therapy is mainly indicated for less severe, carefully followed-up OSA patients. More knowledge is needed about the longer term results including adherence and comorbidities, using new grading systems and methods of analysis developed to identify the best candidates for MAD therapy.

Deﬁnition of positional sleep apnoea and role of positional devices

Clinical experience indicates that in the majority of patients with OSA, the frequency and duration of respiratory events are inﬂuenced by body position and sleep stage. In ∼50–60% of OSA patients, there are twice as many respiratory events in the supine sleeping position when compared to the nonsupine sleeping position. The most widely used deﬁnition for positional OSA (POSA) was proposed by Cartwright (1984) and was deﬁned as having a supine apnoea index of at least twice as high as the nonsupine apnoea index; today, researchers use AHI instead of apnoea index. On average, patients with POSA have less severe OSA, have lower BMI, are in general younger or are of similar age as non-POSA patients. They have a better sleep quality and are more alert during the daytime than non-POSA patients.

Patients diagnosed with POSA can beneﬁt from positional therapy, aimed at preventing sleep in the most adverse sleeping position, usually the supine position. However, evaluating the ecacy of positional therapy was hindered by the fact that there are no

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universally used POSA criteria. A new classiﬁcation system was introduced to identify suitable candidates for positional therapy in which the index in the nonsupine posture should be at nonpathological level (AHI <5 events·h−¹ or <10 events·h−¹ at least). The most widely used technique to avoid supine position involves strapping a bulky object (in many cases a tennis ball) to the back of the patient. Several studies have shown that such therapies have a signiﬁcant positive eect on snoring and OSA severity in patients with POSA. However, the bulky object strapped to the back is oen uncomfortable, resulting in low long-term compliance rates. In order to overcome these compliance problems, new neck-worn and chest-worn devices correcting the supine sleeping position by activating a vibration alarm have been introduced to the market (ﬁgure 3). These novel concepts of positional therapy showed promising results in reducing apnoea severity, together with a higher compliance. Meta-analyses conﬁrmed their eectiveness in preventing the supine position and reducing the AHI, although the eect was lower than with CPAP. Short-term compliance was satisfactory, while regular use at 6 months was reported in 41.6% of the patients, with a larger therapeutic eect in patients with mild-to-moderate OSA than in patients with severe OSA.

Positional therapy is not recommended for patients who for any reason (shoulder problems or any other physical disability) cannot avoid the supine posture during sleep. Interestingly, some patients with POSA and non-POSA present dynamic phenotypes: weight reduction may convert a non-POSA patient to POSA and the opposite is also true. In addition, it should be noted that any OSA treatment which could not completely eliminate all breathing abnormalities leaves the patient with a residual OSA that is mainly supine-dependent. In these patients, combination therapy can be a viable option. Overall, positional therapy can yield important reductions in OSA severity, and in some patients leads to the cure of this condition, but only in clearly selected POSA patients. Regular follow-up of these patients is important to secure

Figure 3. Device for positional therapy.

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long-term compliance and to check for a possible weight gain that will reduce the eectiveness of this therapy.

Muscle stimulation and myofunctional therapy (oropharyngeal exercises)

Sleep medicine has seen the arrival of electrical stimulation therapy to target upper airway dilator muscles in OSA patients in recent years. A high level of evidence has been provided in recent literature on the potential clinical eectiveness of hypoglossal nerve stimulation (HNS) therapy in well-selected OSA patients with CPAP intolerance. Proper selection of OSA patients with a moderate-to-severe OSA (AHI 15–65 events·h−¹) is crucial to the role of DISE in order to include patients without complete concentric collapse at the level of the palate, while BMI should not be >35 kg·m−2.

The European Respiratory Society guidelines on non-CPAP therapy have provided the current level of evidence on HNS, recommending that it should not be oered as a primary treatment, but could be considered as a salvage therapy in selected cases.

Following a period of physiological and clinical trials, the area of HNS has reached a renaissance with the publication of the Stimulation Therapy for Apnea Reduction (STAR) trial. 126 participants were implanted the Inspire device stimulating the hypoglossal nerve unilaterally. In this cohort of patients with OSA, the median AHI at 12 months decreased by 68%, from 29.3 events·h−¹ to 9.0 events·h−¹ (p<0.001). The ESS, a secondary outcome parameter, improved signiﬁcantly (mean±

−4.7±5.0 points, p<0.001). The rate of severe adverse events was <2%. Based on these results, the United States Food and Drug Administration approved the system for HNS in OSA.

Using a transcutaneous method of electrical stimulation, the TESLA trial included 36 patients with OSA in a crossover design conﬁrming a modest reduction of the mean oxygen desaturation index of 4.1 events·h−¹ (p=0.026), and in the responder group by 10.0 events·h−¹ (p<0.001). There were no adverse events in this randomised controlled trial using a transcutaneous electrical stimulator.

Finally, the BLAST-OSA trial used a bilateral hypoglossal nerve stimulator in a median position, which is activated by a battery package on the skin when asleep. The trial used the Genio system. 22 out of 27 implanted participants completed the protocol. The AHI decreased from 23.7 events·h−¹ to 12.9 events·h−¹ (p<0.001) at 6 months’ follow-up. Daytime sleepiness, as measured by the ESS, improved as well (p=0.01).

Trials of daytime electrical stimulation to train the tongue ground muscles have previously been reported to improve snoring, but not sleep apnoea severity. Recently, a new methodology using neuromuscular electrical therapy of the tongue muscles has been studied, using the eXciteOSA method for 20 min once daily over 6 weeks. It was found in 115 patients with OSA that 90% of the study population reported a reduction in snoring (p<0.001) and an improvement in the ESS (p<0.001). Overall, electrical stimulation of the upper airway dilator muscles provides an innovative method to treat OSA in a selected cohort of patients, supporting tailored therapeutic solutions for patients with OSA.

Myofunctional therapy is a new approach to non-CPAP therapy, training the movement, strength, endurance and neuromuscular activation of the upper airway, pharyngeal and tongue muscles to facilitate a state in which snoring and OSA are diminished when asleep. Available evidence is weak, but demonstrates a decrease of ∼50% in the AHI, complemented by a symptomatic improvement.

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Pharmacological agents in OSA treatment

Much eort has been made to improve upper airway patency pharmacologically, with limited success. Recent approaches have focused on the combination of atomoxetine (a selective norepinephrine reuptake inhibitor) with oxybutynine (an antimuscarinergic agent), reducing AHI by 62%. Carbonic anhydrase inhibitors such as acetazolamide and sulthiame also hold promise. An improvement aer hypnotics has been described in moderate OSA, with high interindividual variability. Residual EDS is a relatively common condition in OSA, and may in some conditions require wake-promoting drugs. Pitolisant (a selective H3-receptor antagonist/inverse agonist) increases histamine synthesis and release, and promotes wakefulness. Solriamfetol (a dopamine and nonepinephrine reuptake inhibitor) has also received recent interest. Both drugs are eective in symptomatic patients with moderate-tosevere OSA, which opens new therapeutic avenues.