Pathophysiology of obstructive sleep apnea

The pharyngeal muscles are essential for effective lung ventilation because they help maintain an open upper airspace for the unhindered passage of air into the lungs. Sleep, especially rapid-eye-movement sleep, however, causes fundamental modifications of pharyngeal muscle tone and reflex responses that in normal individuals lead to airway narrowing and hypoventilation. In individuals with already anatomically narrow upper airways, these effects of sleep predispose them to inspiratory flow limitation (hypopneas), airway closure, and obstructive sleep apnea. Obstructive sleep apnea is a common disorder affecting at least 2% to 4% of North American adults and is associated with serious clinical, social, and economic consequences. This review addresses the physiology and pathophysiology of obstructive sleep apnea, hypopneas, and snoring, that is, the full spectrum of the most common sleep-related breathing events involving the upper airway. Specifically, the anatomical features of the upper airway that are important to its mechanical properties and degree of collapsibility are reviewed. The sites of airway narrowing and closure and the implications for common treatments strategies are also discussed. This article also focuses on the neuromuscular control mechanisms operating in wakefulness and sleep that influence pharyngeal muscle tone and upper airway collapsibility. The effects of sleep on the reflex mechanisms that normally operate to protect the upper airspace from suction collapse during breathing are also addressed. Throughout this review, these mechanisms are discussed with an emphasis on understanding the physiology and pathophysiology of sleep-disordered breathing and obstructive sleep apnea.     

Pathophysiology of adult obstructive sleep apnea

Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive narrowing or collapse of the pharyngeal airway during sleep. The disorder is associated with major comorbidities including excessive daytime sleepiness and increased risk of cardiovascular disease. The underlying pathophysiology is multifactorial and may vary considerably between individuals. Important risk factors include obesity, male sex, and aging. However, the physiological mechanisms underlying these risk factors are not clearly understood. This brief review summarizes the current understanding of OSA pathophysiology in adults and highlights the potential mechanisms underlying the principal risk factors. In addition, some of the pathophysiological characteristics associated with OSA that may modulate disease severity are illustrated. Finally, the potential for novel treatment strategies, based on an improved understanding of the underlying pathophysiology, is also discussed with the ultimate aim of stimulating research ideas in areas where knowledge is lacking.     

Epidemiology of pediatric obstructive sleep apnea

Pediatric obstructive sleep apnea (OSA) has become widely recognized only in the last few decades as a likely cause of significant morbidity among children. Many of the clinical characteristics of pediatric OSA, and the determinants of its epidemiology, differ from those of adult OSA. We systematically reviewed studies on the epidemiology of conditions considered part of a pediatric sleep-disordered breathing (SDB) continuum, ranging from primary snoring to OSA. We highlight a number of methodologic challenges, including widely variable methodologies for collection of questionnaire data about symptomatology, definitions of habitual snoring, criteria for advancing to further diagnostic testing, and objective diagnostic criteria for SDB or OSA. In the face of these limitations, estimated population prevalences are as follows: parent-reported "always" snoring, 1.5 to 6%; parent-reported apneic events during sleep, 0.2 to 4%; SDB by varying constellations of parent-reported symptoms on questionnaire, 4 to 11%; OSA diagnosed by varying criteria on diagnostic studies, 1 to 4%. Overall prevalence of parent-reported snoring by any definition in meta-analysis was 7.45% (95% confidence interval, 5.75-9.61). A reasonable preponderance of evidence now suggests that SDB is more common among boys than girls, and among children who are heavier than others, with emerging data to suggest a higher prevalence among African Americans. Less convincing data exist to prove differences in prevalence based on age. We conclude by outlining specific future research needs in the epidemiology of pediatric SDB.     

Pathophysiology of childhood obstructive sleep apnea: current concepts

The obstructive sleep apnea syndrome (OSAS) is a common and serious condition during childhood. Its pathophysiology remains poorly understood. Although OSAS is related to adenotonsillar hypertrophy in children, adenotonsillar hypertrophy is not likely the sole cause of sleep-disordered breathing in this age group. Rather, large tonsils and adenoids appear to precipitate OSAS in children with underlying abnormalities of upper airway function. Normal children have a relatively narrow upper airway, but maintain airway patency during sleep because of increased upper airway neuromotor tone and an increased central ventilatory drive. We speculate that OSAS occurs in those children lacking the compensatory upper airway neuromotor responses.     

Missing teeth and pediatric obstructive sleep apnea

Background

Missing teeth in early childhood can result in abnormal facial morphology with narrow upper airway. The potential association between dental agenesis or early dental extractions and the presence of obstructive sleep apnea (OSA) was investigated.

Methods

We reviewed clinical data, results of polysomnographic sleep studies, and orthodontic imaging studies of children with dental agenesis (n = 32) or early extraction of permanent teeth (n = 11) seen during the past 5 years and compared their findings to those of age-, gender-, and body mass index-matched children with normal teeth development but tonsilloadenoid (T&A) hypertrophy and symptoms of OSA (n = 64).

Results

The 31 children with dental agenesis and 11 children with early dental extractions had at least 2 permanent teeth missing. All children with missing teeth (n = 43) had clinical complaints and signs evoking OSA. There was a significant difference in mean apnea-hypopnea indices (AHI) in the three dental agenesis, dental extraction, and T&A studied groups (p < 0.001), with mean abnormal AHI lowest in the pediatric dental agenesis group. In the children with missing teeth (n = 43), aging was associated with the presence of a higher AHI (R ² = 0.71, p < 0.0001).

Conclusion

Alveolar bone growth is dependent on the presence of the teeth that it supports. The dental agenesis in the studied children was not part of a syndrome and was an isolated finding. Our children with permanent teeth missing due to congenital agenesis or permanent teeth extraction had a smaller oral cavity, known to predispose to the collapse of the upper airway during sleep, and presented with OSA recognized at a later age. Due to the low-grade initial symptomatology, sleep-disordered breathing may be left untreated for a prolonged period with progressive worsening of symptoms over time.

     

Diagnostic issues in pediatric obstructive sleep apnea

Obstructive sleep apnea syndrome (OSAS) in children includes a spectrum of respiratory disorders with significant morbidities. Diagnosis of OSAS is based on clinical suspicion, history, and physical findings, and confirmation is made by polysomnography. There has been significant progress in recent years in technologies available for diagnosis of OSAS since the consensus statement of the American Thoracic Society in 1996. The current review describes methodologies that are available today for assessment and diagnosis of OSAS in children and summarizes the most recent recommendations of the American Academy of Sleep Medicine Task Force regarding scoring sleep-related respiratory events in children.     

Adenotonsillectomy and orthodontic therapy in pediatric obstructive sleep apnea

Purpose

Rapid maxillary expansion (RME) is an additional treatment in pediatric obstructive sleep apnea (OSA). The aim of this study was to present data about the outcome of adenotonsillectomy (AT) and of RME in a clinical sample of pediatric OSA.

Methods

We consecutively enrolled children with OSA to undergo RME or AT. The age and the severity of OSA are the main factors involved in the choice of treatment. A polysomnography was performed at the baseline (i.e., before treatment, T0) and 1 year after treatment (T1).

Results

A total of 52 subjects fulfilled the inclusion criteria. Twenty-five children underwent AT (group 1) and 22 children underwent RME (group 2). Five children underwent both treatments (group 3). Children in group 2 were older, had a longer disease duration, a higher body mass index (BMI), a lower apnea–hypopnea index (AHI), and a lower arousal index at T0 than children in group 1. After 1 year, BMI percentile and overnight mean saturation increased in group 1 while AHI and arousal index decreased. In group 2, mean overnight saturation increased while AHI decreased. Children in group 3 displayed a significant decrease in AHI from T0 to T1.

Conclusions

Our data demonstrate that both treatments help to improve OSA, and a multidisciplinary approach to treatment is suggested.     

睡眠呼吸暂停低通气综合征问卷对阻塞性睡眠呼吸暂停综合征诊断价值

目的 评价阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的流行病学调查表筛查价值.方法 疑似OSAHS的987例患者为研究对象,按照中华医学会呼吸病学分会睡眠学组睡眠呼吸暂停低通气综合征流行病学调查表进行问卷并行多导睡眠监测.将此问卷表进行量化评分,用克隆巴赫信度系数(α系数)进行信度计算,将各相关因素做方差分析及x2检验,筛选出有统计学意义的因素最后做Logistic回归分析.以鼾声中度以上的打鼾及体质量指数≥25 kg/m2为高危,反之为低危,进行敏感性,特异性,假阳性,假阴性,阳性似然比,阴性似然比,阳性预测值等.结果 疑似OSAHS患者987例,其中男800例(81.05％),女187例(18.95％),年龄18～80岁,平均(47±12)岁,平均体质量指数(29±5) kg/m2.＞60岁者156例(15.81％),≤60岁者831例(84.19％).克隆巴赫信度系数(Cronbach'salpha)是0.803,假阳性者20,假阴性者142,真阳性者742,真阴性者83,问卷的敏感性是83.94％,特异性是80.58％,假阳性率19.42％,假阴性率16.06％,阳性似然比4.32,阴性似然比0.20,阳性预测值0.97,阴性预测值0.37,正确率83.59％.结论 该睡眠调查表对OSAHS筛查具有一定意义,可用于临床OSAHS的初筛,尤其适合在社区和基层医院中推广使用.     

Pathogenesis of obstructive sleep apnea

Obstructive sleep apnea is a fairly common disorder with significant adverse health consequences. However, the pathogenetic mechanisms remain incompletely understood. Upper airway (UA) patency is determined by several neuromuscular and nonneuromuscular factors including (1) UA dilating muscle activity, (2) the collapsing transmural pressure generated during inspiration, (3) changes in caudal traction, (4) vasomotor tone, and (5) mucosal adhesive forces. This review addresses the effect of sleep on UA function and how these factors conspire to cause UA obstruction.     

Central sleep apnea: Pathophysiology and treatment

Central sleep apnea (CSA) is characterized by a lack of drive to breathe during sleep, resulting in repetitive periods of insufficient ventilation and compromised gas exchange. These nighttime breathing disturbances can lead to important comorbidity and increased risk of adverse cardiovascular outcomes. There are several manifestations of CSA, including high altitude-induced periodic breathing, idiopathic CSA, narcotic-induced central apnea, obesity hypoventilation syndrome, and Cheyne-Stokes breathing. While unstable ventilatory control during sleep is the hallmark of CSA, the pathophysiology and the prevalence of the various forms of CSA vary greatly. This brief review summarizes the underlying physiology and modulating components influencing ventilatory control in CSA, describes the etiology of each of the various forms of CSA, and examines the key factors that may exacerbate apnea severity. The clinical implications of improved CSA pathophysiology knowledge and the potential for novel therapeutic treatment approaches are also discussed.     

Home testing for pediatric obstructive sleep apnea syndrome secondary to adenotonsillar hypertrophy

The objective of this study was to determine the accuracy and practicality of home testing for pediatric obstructive sleep apnea syndrome (OSAS) secondary to adenotonsillar hypertrophy. Twenty-one children aged 2-12 years and referred for possible OSAS were studied twice, once at home and once in the sleep laboratory. The home test consisted of two parts: (1) a cardiorespiratory recording of saturation (SaO₂), pulse rate, pulse waveform, electrocardiogram, and respiratory inductive plethysmography; and (2) an 8-hour videotape recording of the sleeping child. In the laboratory, standard nocturnal polysomnography including electroencephalography was performed. Experiences with another 62 children who underwent home testing alone were also reviewed and are reported. At home, saturation, respiratory, and video data were obtained 96.4 ± 13.3% (mean ± SD) 99.4 ± 1.6%, and 90.0 ± 7.8% of the time, respectively. The sleep efficiency was greater at home than in the laboratory, 91.1 ± 3.9% vs. 86.1 ± 7.2%, with a mean difference of 5.0% (P < 0.01). The median environmentally induced movement/arousal index was lower in the home than in the laboratory, 0.0 (inter-quartile range, 0.0-0.3) vs. 2.4/hr (inter-quartile range 1.2–4.2), with a median difference of 2.4/hr (P < 0.001). Study duration, apne/dhypopnea index, desaturation index, respiratory and spontaneous movement/arousal indices, and oxygen saturation during sleep were similar for home and laboratory studies. Although neither sleep state nor PCO₂, (transcutaneous or end-tidal) was measured in the home, this information would have modified patient management in, at most, one case. In the second group of 62 children, exclusively studied at home, all studies were successfully recorded despite a wide range of sleep efficiencies, apne/dhypopnea indices, and desaturation indices. We conclude that home testing, using a simplified cardiorespiratory montage plus video recording, is accurate and of practical use in the routine evaluation of OSAS in patients with adenotonsillar hypertrophy. Pediatr Pulmonol. 1995; 20:241–252 . © 1995 Wiley-Liss, Inc.     

Coagulability in obstructive sleep apnea

BACKGROUND:

Obstructive sleep apnea (OSA) is a common disorder that affects both quality of life and cardiovascular health. The causal link between OSA and cardiovascular morbidity/mortality remains elusive. One possible explanation is that repeated episodes of nocturnal hypoxia lead to a hypercoagulable state that predisposes patients to thrombotic events. There is evidence supporting a wide array of hematological changes that affect hemostasis (eg, increased hematocrit, blood viscosity, platelet activation, clotting factors and decreased fibrinolytic activity).

OBJECTIVE:

To provide a comprehensive review of the current evidence associating OSA with increased coagulability, and to highlight areas for future research.

METHODS:

Keyword searches in Ovid Medline were used to identify relevant articles; all references in the articles were searched for relevant titles. The Web of Science was used to identify articles citing the relevant articles found using the Ovid Medline search. All original peer-reviewed articles, meta-analyses and systematic reviews regarding the pertinent topics between 1990 and present were selected for review.

RESULTS:

Hematocrit, blood viscosity, certain clotting factors, tissue factor, platelet activity and whole blood coagulability are increased in patients with OSA, while fibrinolysis is impaired.

CONCLUSION:

There is considerable evidence that OSA is associated with a procoagulant state. Several factors are involved in the procoagulant state associated with OSA. There is a need for adequately powered clinical studies involving well-matched control groups to address potential confounding variables, and to accurately delineate the individual factors involved in the procoagulant state associated with OSA and their response to treatment.     

Propofol versus dexmedetomidine during drug-induced sleep endoscopy (DISE) for pediatric obstructive sleep apnea

Sleep and Breathing - To test for differences in DISE findings in children sedated with propofol versus dexmedetomidine. We hypothesized that the frequency of ≥ 50% obstruction would be...     

Erythropoietin and obstructive sleep apnea

OBJECTIVE: We tested the hypothesis that repetitive severe hypoxemia resulting from obstructive sleep apnea would increase serum erythropoietin, and that this increase would be attenuated by effective treatment of obstructive sleep apnea. METHODS: We studied healthy untreated patients with obstructive sleep apnea (18 severe and 10 very mild) before and after acute treatment with continuous positive airway pressure, and 12 healthy control subjects free of obstructive sleep apnea. RESULTS: Baseline erythropoietin levels before sleep were similar in the obstructive sleep apnea and control groups. However, erythropoietin levels increased (by 20%, P =.037) in patients with severe obstructive sleep apnea after 3.5 hours untreated (lowest O2, 77% +/- 3%), and decreased after 4 hours of continuous positive airway pressure treatment (P =.001). Erythropoietin responses in patients with severe obstructive sleep apnea were different (F = 4.0, P =.03) from controls, in whom erythropoietin levels remained stable throughout the night (P =.94). Erythropoietin responses were similar in very mild obstructive sleep apnea and controls (P =.58). CONCLUSIONS: Our results indicate that untreated severe obstructive sleep apnea results in increased erythropoietin, which decreases after continuous positive airway pressure treatment. Increased erythropoietin may be a potential reversible mechanism to explain the association between obstructive sleep apnea and cardiovascular disease.     

Individualized therapy for treating obstructive sleep apnea in pediatric Crouzon syndrome patients

Sleep and Breathing - Pediatric patients with Crouzon syndrome have great possibilities of suffering from obstructive sleep apnea (OSA), which is mainly due to midfacial hypoplasia and facial...