Obstructive sleep apnea: a review for the orthodontist

ABSTRACT Introduction: Obstructive sleep apnea (OSA) affects an important part of the population and is characterized by recurrent total or partial obstruction of the upper airway (UA) during sleep, negatively affecting the quality of life of patients in the short and long terms, and constituting an important public health problem for the society. The field of expertise of orthodontists is closely related to the UA, placing them in a strategic position to diagnose air passage failures and intervene when necessary. Orthodontists, as health professionals, must know how to recognize respiratory problems and manage them appropriately, when indicated. Objective: Thus, this paper aims to review and critically evaluate the related literature, to provide orthodontists with updated knowledge on the diagnosis and therapy related to OSA. Science and technology are constantly evolving; thus, the literature was also reviewed considering new technologies available in consumer-targeted applications and devices for the diagnosis, monitoring, and treatment of sleep-disordered breathing.


INTRODUCTION
Breathing is a simple and essential act for the organism, performed millions of times throughout life. The act of breathing takes the oxygen from the air to the cells, and helps to eliminate carbon dioxide, which is a vital process for the metabolic activities of human beings. Any change in this process can trigger health problems. The so-called sleep-disordered breathing (SDB) involves all airflow abnormalities during sleep, from primary snoring without hypoxia, with or without sleep interruption, to obstructive sleep apnea (OSA) with complete blockage of the airway and interruption of the air passage. 1 The number of people affected by OSA is varied, with values estimated at 14% of men and 5% of women 2 to much higher numbers, such as 34% of men and 17% of women. 3 It is believed that the prevalence of OSA in the population may be even higher, since many patients do not have an adequate diagnosis. Respiratory problems can also affect the child population, with adverse manifestations and consequences. 1 Among adults, daytime sleepiness is among the most common symptoms; however, many patients with OSA are asymptomatic. Individuals may experience serious lifelong consequences such as cardiorespiratory failure, hypertension, type 2 diabetes mellitus, and neurophysiological deficits associated with increases in mortality rate. Thus, OSA is an important public health problem for society, and should be investigated to allow the adoption of preventive measures. Orthodontists intervene in the craniofacial complex and thus they can assist in the recognition of SDB, contributing to the identification of dentofacial components involved and, in some cases, to the treatment of OSA, in association with the physician and team. 2 Even though in the past only complete obstruction of the air passage during sleep was considered harmful, currently any form of SDB should be con-

OBSTRUCTIVE SLEEP APNEA (OSA)
Obstructive apnea is the most common type of sleep-disordered breathing. It is characterized by recurrent episodes of partial or total collapse of the upper airway during sleep, leading to reduced (hypopnea) or absent (apnea) airflow lasting at least 10 seconds and associated with cortical excitation or a drop in blood oxygen saturation. 3 Sleep is essential for life.
Thus, the lack of restful sleep can cause difficulties in attention and concentration, reduction in quality of life and productivity, besides favoring the occurrence of accidents, coronary artery disease, heart failure, high blood pressure, obesity, type II diabetes, memory deficits, stroke, and depression. 4 The respiratory system is responsible for the absorption of oxygen from the air and the elimination of carbon dioxide from cells, being formed by the airway (conductive portion) and lungs (respiratory portion). The respiratory tract is the entire path crossed by the air from the nose to the lungs and is divided into upper airway (UA) and lower airway. The UA comprises the nasal cavity, pharynx, and larynx and thus is more relevant for orthodontists because it is close to their area of expertise. The pharynx is a muscular membranous tube that extends from the skull base to the lower border of the cricoid cartilage. 5 The pharynx is divided into three parts (Fig 1): nasopharynx (skull base to the hard palate), oropharynx (soft palate to the upper border of the epiglottis) and laryngopharynx or hypopharynx (tongue base to the lower border of the cricoid cartilage). 5,6 The velopharynx is part of the oropharynx and is located between the soft palate and the posterior pharyngeal wall. The pharyngeal tonsils (adenoids) are aggregates of lymphoid tissue located on the roof of the posterior nasopharyngeal wall. The palatine tonsils are located between the palatine arches bilaterally in the oropharynx. 5 The UA is responsible for swallowing, speech and breathing.
The accomplishment of these tasks depends on the complex interaction of more than 20 muscles that surround the UA: muscles that regulate the soft palate position (levator and tensor palatini), the tongue (genioglossus, geniohyoid, hypoglossus, Figure 1: Upper airway, with areas of the nasopharynx (between skull base and hard palate), oropharynx (soft palate to the upper border of the epiglottis), and hypopharynx or laryngopharynx (from the tongue base to the lower border of the cricoid cartilage). and styloglossus), muscles attached to the hyoid bone (hypoglossus, genioglossus, digastric, geniohyoid and sternohyoid) and muscles of the posterolateral pharyngeal walls (palatoglossus and pharyngeal constrictors). 7,8 These muscles act dilating or constricting the UA lumen. The UA is not a rigid structure (e.g., like the trachea) and is fixed only at its upper (skull base) and lower (cricoid cartilage) ends. The hyoid bone is an important site of attachment for pharyngeal muscles, yet it does not have rigid articulation with other bony structures. Therefore, the pharyngeal cross-sectional area depends on the air pressure existing in the upper airway lumen, which can collapse due to different factors. 9 Contraction of the upper airway dilator muscles (especially the muscles that control the tongue,

OSA DIAGNOSIS AND RISK ASSESSMENT
The diagnosis and severity of OSA are determined by polysomnography, in which several sleep and respiratory parameters are monitored simultaneously. One parameter measured is the apnea-hypopnea index (AHI), which assesses the mean number of apneas and hypopneas per hour of sleep. Apnea is the absence of inspiratory airflow for at least 10 seconds, while hypopnea is a reduction of 30% or more in airflow from baseline associated with a drop in arterial hemoglobin saturation and/or an electroencephalographic awakening. 11 The severity of adult OSA is classified as mild (5≤AHI<15 events/h), moderate (15≤AHI<30 events/h), or severe (AHI≥30 events/h). 11 In children, OSA is diagnosed when they have an AHI of 1 or higher. OSA in children can be categorized as mild (1≤AHI<5 events/h), moderate (5≤AHI<10 events/h), or severe (AHI≥10 events/h). 1 A summary of the values for classifying OSA in adults and children is shown in Table 1. The prevalence of OSA increases with age, being twice as common in men than in women. 3 OSA is also associated with overweight and obesity. 3 Many individuals do not report having sleep disturbances, either because they are asymptomatic or because they do not realize they have the problem. Thus, it is important to apply specific questionnaires (Table 2) to assess the risk of an individual having OSA. 3,12 The Berlin and Stop-Bang questionnaires present high sensitivity for assessing moderate to severe risk for OSA (77 and 90%, respectively), 3 noting that sensitivity is the test ability to correctly identify individuals who have the disease, while specificity is the test ability to correctly identify individuals who do not have the disease. The orthodontist may perform risk assessment for SDB yet diagnosing SDB is outside the scope of dental professionals.
A patient at risk requires referral to a sleep physician for proper diagnosis and a possible referral to the orthodontist for treatment with mandibular advancement devices. 12 There is no specific type of physical finding on examination for OSA. However, the risk of OSA is doubled for overweight individuals and four times higher in obese patients when compared to individuals without these conditions. 3 Examination of the upper airway  Table 3, with a description of some of their advantages and limitations. Subsequently, studies were conducted to assess the association between OSA severity and pharyngeal parameters using submental ultrasound, besides investigating the accuracy of ultrasound to identify patients with severe OSA. Nowadays, the trend is to provide a risk assessment for OSA based on the collapsibility of the airway. 16

TREATMENT MODALITIES OF OSA IN ADULTS
The treatment of OSA must be individualized considering the pathophysiology of the disease, the individual characteristics of patients, and the treatment goals. Therapeutic possibilities include behavioral changes, oropharyngeal exercises, positive air pressure devices (PAP), intraoral appliances, surgeries, and electrical stimulation (Table 4). New technologies are being developed to aid the treatment and monitoring of patients with sleep disorders and will be presented and discussed later.

BEHAVIORAL CHANGES
Weight loss, implementation of physical exercises, positional adjustment, and sleep hygiene measures are positive and non-invasive changes in the treatment of OSA.

Weight loss
Obesity is an important risk factor for OSA since the accumu-

Exercises
Aerobic physical exercises can contribute to weight loss, with positive aspects on cardiovascular and metabolic conditions. However, they are not always easy to adhere to, especially for individuals who already have significant cardiopulmonary diseases. 3 Oropharyngeal exercises are a non-invasive and low-cost alternative for the treatment of primary snoring and mild to moder-

Sleep hygiene
The term "sleep hygiene" refers to the different positive habits that can be implemented to promote an adequate night of sleep, including changes in lifestyle (physical exercise, diet, substance, and medication use) and the environment where the individual sleeps (lighting, noise, temperature, television, cell phone, etc.). 26 The objective of sleep hygiene is to identify factors that can be changed to optimize nocturnal sleep.

Some sleep hygiene habits proposed by the American Sleep
Association include: 27 organizing the bedroom, so that it is peaceful and relaxing; limiting exposure to bright light at night; turning off electronic devices at least 30 minutes before bed; avoiding eating large meals before bed; exercising regularly and maintaining a healthy diet; avoiding caffeine intake in the afternoon or evening; avoid drinking alcohol before bedtime; reducing fluid intake before bedtime. Though important, the American Sleep Association recommends that sleep hygiene measures should be implemented in combination with other therapeutic actions, and never as an isolated approach. 26

Positive air pressure devices (PAP)
The positive air pressure devices (PAPs) prevent the airway from collapsing by generating a flow of pressurized air through a mask fitted to the mouth, nose, or both. The treatment of OSA with PAP is extremely effective and has high-quality sci-  The patients should be instructed about these possible changes and require an adaptation period (usually two to three months).
Patients with temporomandibular joint problems should be evaluated by a specialist in temporomandibular disorder (TMD) and orofacial pain before initiating the use of MAD. However, MADs do not represent a risk factor for the development of TMD signs and symptoms and do not seem to exacerbate preexisting TMD problems. 42 In a 5-year longitudinal study, Martinez-Gomis et al. 43     It is important to note that the present paper addresses the treatment of OSA in adult patients; thus, adenotonsillectomy (standard treatment for pediatric OSA) was not addressed here.

MMAS is an invasive surgery that involves advancement and
Bariatric surgery may also be considered in the treatment of OSA in obese patients. 59

Electrostimulation of the hypoglossal nerve (surgical electrode implantation)
The maintenance of upper airway patency is directly related to the action of oropharyngeal muscles, especially the genioglossus. This therapy aims at stimulating the hypoglossal nerve to increase tongue protrusion and stabilize the UA during inspiration. 3 The treatment of moderate to severe OSA can be performed with hypoglossal nerve stimulation by a surgically implanted neurostimulator. 60 This therapeutic modality is relatively new and appears to be an interesting option for patients who do not tolerate CPAP.
The neurostimulator device is implanted in the chest, approximately 2 to 4 cm below the collarbone, and features a wire for stimulation and a wire with a respiration sensor. The stimulation wire is adapted to the main branch of the hypoglossal nerve by a horizontal incision in the upper part of the neck at the lower border of the submandibular gland. 60 The breath sensor wire is adapted by an incision in the fourth intercostal region, where it is inserted using a tunneling technique. 60 The patient turns on the device before going to sleep and turns it off when awakening, by activating a remote control.

ORTHODONTIC TREATMENT AND ITS POSSIBLE INFLUENCE ON THE UPPER AIRWAY
The field of expertise of orthodontists is closely related to the upper airway. Next, some orthodontic treatment modalities and their relationship with possible changes in upper airway anatomy and breathing pattern will be discussed. This paper does not aim to review the treatment of OSA and UA changes in children. However, some of the orthodontic treatments reported are conducted specifically in this pediatric population and thus will be pertinently discussed.

Headgear
The negative influence of the headgear on the upper airway volume may be assumed, due to maxillary growth restriction.
However, Class II treatment with headgear induces greater dentoalveolar than skeletal changes. Kirjavainen and Kirjavainen 64 reported that treatment with cervical headgear increased the velopharyngeal dimensions yet did not affect the rest of the oropharynx and hypopharynx. Julko et al. 65  According to the authors, a possible explanation for these changes would be the balance theory, according to which the new tongue positioning would apply pressure, promoting changes in the lower dentition. 66 It is believed that all interventions that can potentially affect tongue positioning could promote changes in the upper airway since the tongue base and posterior region constitute the anterior wall of the oropharynx. To date, there is no evidence that Class II treatment with headgear decreases the UA and causes respiratory damage.

Maxillary protraction
Maxillary protraction is performed in growing individuals for the treatment of Class III malocclusion. Systematic reviews demonstrate that maxillary protraction with a face mask can increase the UA dimensions. 67,68 Conversely, studies with a control group do not support this statement. 69,70 In a randomized study, Miranda et al. 71  It is important to note that studies with different functional appliances were included, and most of the 18 studies evaluated used cephalograms (2D) to measure the UA. Amuk et al. 75 conducted a prospective randomized study with a Herbst appliance (associated with RME) and also found an increase in oropharyngeal and hypopharyngeal dimensions. A randomized clinical trial published in 2018 compared the short-term effects of a mandibular advancement device (Twin-block) with a placebo device without advancement (control) and showed a significant reduction of 37% in the AHI of children who used the Twin-block. 76 Studies with longer follow-up periods should be conducted to prove the maintenance of these effects over the years. Despite the possible beneficial effects on the UA, treatment with mandibular advancement devices should be indicated primarily for Class II correction. 2 Adenotonsillectomy is the gold standard treatment for OSA in children.

Rapid maxillary expansion (RME)
Rapid maxillary expansion (RME) is the standard treatment for the correction of the transverse maxillary deficiency. Increases in skeletal and dental dimensions are unquestionable and are already well reported. Due to the proximity to the oral cavity, the volume and area of the upper airway and nasal cavity can be changed by RME. Immediately, RME promotes displacement of circumaxillary sutures in the three planes of space 77  The authors reported a greater reduction in AHI and greater volumetric gains in the UA of the group treated with AT, confirming AT as the gold standard therapy in the treatment of pediatric OSA, and concluding that RME is an adjunct in this process. 82 The American Association of Orthodontics cautions that there is not enough evidence to support the prophylactic indication of RME for the treatment of pediatric OSA; thus, the primary indication should always be the treatment of maxillary constriction. 2

plants (MARPE) or surgery (MISMARPE and SARPE) to surpass
the sutural resistance. Yi et al. 83 found an 8.48% increase in nasopharyngeal volume in 19 individuals (aged 15 to 19 years) with transverse maxillary deficiency treated with MARPE assessed by CBCT. The authors did not find significant differences in oropharyngeal volume and total UA volume. 83 Li et al. 84  Despite the decrease in oropharyngeal volume, the authors did not find an increase in the risk of OSA in setbacks from 4 to 8 mm. 91 Thus, consideration should be given to treating skeletal Class III with double jaw surgery (i.e., mandibular setback associated with maxillary advancement), rather than single jaw mandibular setback surgery.

TOOTH EXTRACTIONS
Treatments with the extraction of first premolars are con-  95 concluded that many studies assessed had methodological flaws (conducted in two-dimensional exams or without direct assessment of respiratory function), and thus there is no evidence that orthodontic treatment with tooth extractions can significantly change the respiratory function and UA size. 95 The same idea was corroborated by Orabi et al. 96 in 2021, in a systematic review with meta-analysis. They concluded that there is no strong evidence to support the concept that premolar extractions in bimaxillary protrusion or crowded patients reduce the pharyngeal airway volume or the minimum cross-sectional area. 96

NEW TECHNOLOGIES: AUXILIARY APPS AND EQUIPMENT
The development of smartphones has enabled the emergence of apps and technological devices that are increasingly inserted into our daily lives. Particularly in the health area, there is a growing interest in sleep issues and respiratory disorders. Personal sleep tracking devices are being widely used and becoming increasingly technologically advanced, raising strong interest from researchers and clinicians in their use as an alternative to conventional tests. 97 In the market, the differences between mobile apps for medical or entertainment purposes are usually unclear. 98 While some seem to work well, meeting the proposed function, others are imprecise or "immature", considering their cycle of technological development, not yet being reliable. 22 The critical point is whether these applications work well enough to provide accurate and reliable data. 97 The American Academy of Sleep Medicine (AASM) advocates that sleep assessment technology devices (SATD), called "consumer sleep technology (CST)", must be strictly assessed and approved by the Food and Drug Administration (FDA) if intended to provide a diagnosis and/or treatment. Thus, considering the unknown potential of SATD to measure sleep or assess sleep disorders, these tools should not replace medical assessment. 98 The use of these technologies for the diagnosis, monitoring, and treatment of SDB is very promising, yet remains in the early stages of development. 22 So far, these devices can be used to improve doctor-patient interaction, when used properly, 98 and considerably improve patient adherence to treatment. 22 In 2018, the AASM published a paper to guide professionals on how to approach patients who are interested in using SATD, recognizing their potential benefits for clinical use; however, considering the lack of scientific validation, most SATD still cannot be used for diagnosis and/or treatment of sleep disorders. 98 There is great potential for SATD for use in research, This new technology provides affordable, inexpensive, and ongoing home monitoring of OSA, yet it has not yet been adequately assessed and its validation is still questionable. Until accuracy is validated and available, smartphone apps and devices for SDB should be used carefully as an adjunct, rather than as the only method of sleep assessment. 22 Most SATDs that offer sleep tracking are found in the form of "wearables" that are worn on the wrist or other body areas such as fingers, head, and torso. Conversely, several companies have developed non-wearable devices that are placed close to the The app provides a permanent record of feedback and accuracy of exercises performed. There was reduction in AHI and in a recent study, authors showed a reduction in AHI and ESS score in 75% of patients using the device after performing daily app exercises for 3 months, compared with a control group.
Orofacial Myofunctional Therapy Users perform 15 minutes of daily voice-activated game play to improve snoring and sleep quality. Users articulate specific phonemes to achieve voice-controlled on-screen objectives. Apps were able to prevent positional OSA, being a cost-effective option in the treatment of POSA. Compliance after 6-months was 79.2%.

Snoretech
Positional obstructive sleep apnea therapy In addition to the general functions of position detection and vibration alarm, this app offers a detailed history of position during sleep, of a period.

SomnoPose ---Sleep Position Monitor
(iOS) user to track sleep using remote sensing of physiological and behavioral signals. 97 The use of these new technologies for the diagnosis, monitoring, and treatment of SDB is promising but is still in the early stages of development. Smartphone apps and linked devices offer affordable, low-cost, continuous data monitoring at home. However, without proper testing and validation, they can be unreliable. 22  It is essential to have an approximation between industry and academia to promote the validation of SATD, so that they may promote real benefits to the individual's health. 98 The development of apps and devices has a great future ahead, yet today they are still not as accurate as other traditional options and should be used with caution.

FUTURE DIRECTIONS
Science and technology are continually advancing and together