Impact of obstructive apnea syndrome on upper airway respiratory muscles

doi:10.1016/j.resp.2005.06.012

Respiratory Physiology & Neurobiology

Volume 147, Issues 2–3, 28 July 2005, Pages 263-272

https://doi.org/10.1016/j.resp.2005.06.012 Get rights and content

Abstract

This article reviews studies of upper airway muscles in humans, with emphasis on muscle fiber structural and electrophysiological changes observed in patients with obstructive sleep apnea syndrome (OSAS). The concept of OSAS as a progressive disease is discussed and also possible causes. These include local nervous lesions in the upper airway, both motor and sensory. Previous muscle biopsy studies have given evidence for motor neuron lesions such as, e.g., the phenomenon of type grouping in histological sections. New data obtained with concentric needle EMG recordings from the palatopharyngeus muscles are also presented. In 10/12 OSAS patients there were typical findings indicating motor neuropathy (reduced EMG activity at maximal voluntary effort, long and polyphasic motor-unit potentials and, in two cases, spontaneous denervation activity), whereas such findings were only present in 3/15 patients with habitual snoring. This supports the hypothesis that progression from habitual snoring to the clinical disease of OSAS could be attributed to peripheral neurogenic lesions.

Introduction

Obstructive sleep apneas are caused by repeated episodes of narrowing of the upper airway during sleep, and the site of this narrowing is in the pharynx. This segment of the airway is vulnerable because it lacks substantial bony or rigid support. Thus, the patency is largely dependent on the activity of the pharyngeal dilator muscles. During inspiration, the negative pharyngeal pressure caused by the inflation of the lungs tends to suck the airway closed. This is counteracted by activation of the dilating muscles surrounding the upper airway. An increased inspiratory activity has been shown especially in mm. palatoglossus, palatopharyngeus and levator palatini. In the supine position, when gravity is negatively influencing the width of the upper airway, an increased activity has also been demonstrated in mm. palatoglossus and palatopharyngeus (Mortimore et al., 1995, Mortimore and Douglas, 1997). The diminished activity of the tonically active muscles is the most likely explanation for the increased pharyngeal resistance that takes place during sleep in all persons, including normal subjects.

Section snippets

Muscle activation patterns

The activity of several upper airway muscles is increased during inspiration, thus stiffening and dilating the upper airway to counteract the collapsing influence of negative airway pressure (van Lunteren, 1993). The activity of these muscles is increased by several stimuli. Negative pressure is considered the strongest stimulant, but also increases in pCO₂, decreases in pO₂ and the sensation of cold (inhaled air) enhance the activity in the pharyngeal dilators (Mathew, 1984, Horner et al.,

Natural history of patients with heavy snoring – OSAS

Already at the end of the 60s, when Elio Lugaresi and his co-workers in Bologna began to systematically observe patients with hypersomnia and periodic apneas, they realized that many of the patients reported similar histories. They had been heavy snorers for years, often since their youth, when in their middle age the family began to worry because the snoring became intermittent with breathing pauses. At the same time, diurnal somnolence became apparent. In the late stages of the disease, there

Nervous lesions – a result of snoring, a cause of OSAS?

As mentioned above, it is apparent from the patient histories that a majority have been habitual snorers for years before apneas become apparent. Snoring implies vibration of the tissues that produce the sound. In occupational medicine, it has been shown that longstanding vibration of tissues may cause local nerve lesions (Takeuchi et al., 1986, Brismar and Ekenvall, 1992). It therefore seems possible, that snoring vibrations, repeated every night for several years, might cause neuronal lesions

Discussion

There is convincing evidence that peripheral nervous lesions are common in the upper airway muscles in patients with OSAS, as shown by the quoted studies above. The hypothesis that we propose is the following: the inability of the dilating upper airway muscles to maintain airway patency during sleep is the effect of peripheral nerve lesions, causing partial paresis and/or impaired dilating reflexes at inspiration, worsening over time. There is, however, another possible or maybe additive

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Research related to the duration of respiratory events in obstructive sleep apnea (OSA) has been scarce, perhaps due to the dominant role played by the apnea-hypopnea index (AHI) in the diagnosis and severity estimation of OSA. Lately, however, researchers and clinicians have started to acknowledge the importance of this overlooked parameter. Intuitively, 40-s-long apneas have more harmful physiological and health consequences than 10-s-long apneas. But is this the case? Here, we review the research-based evidence showing physiological, hemodynamic, clinical, sleep quality, and health consequences of long vs. short respiratory events. Most of the reviewed studies support the idea that longer respiratory events have more severe physiological and clinical consequences than shorter events, most probably due to the higher hypoxic burden associated with longer respiratory events. However, a few but highly qualified studies provide clear evidence that short respiratory events have also a deleterious effect on sleep and the physiological and clinical aspects of OSA. The somewhat paradoxical findings that short respiratory events are also associated with a high risk of all-cause mortality is a serious concern. From these results, it is therefore evident that the duration of respiratory events should be quantified when diagnosing and assessing the severity of OSA.
Palatal Sensory Function Worsens in Untreated Snorers but not in CPAP-Treated Patients With Sleep Apnea, Indicating Vibration-Induced Nervous Lesions
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Signs of both motor and sensory nervous lesions have previously been shown in the upper airway of patients with OSA and habitual snorers. Snoring per se may damage all upper airway neurons over time, thereby causing progression to manifest sleep apnea. To test this hypothesis, nonsnoring subjects, untreated snorers, and CPAP-treated patients underwent repeated sensory testing of the soft palate in a prospective long-term study.
Cold detection threshold (CDT) testing at the soft palate and lip with a thermode and nocturnal respiratory recordings were performed in 2008 to 2009 with retesting 6 to 7 years later.
In 25 untreated snorers, palatal CDT worsened from a median (25th-75th percentile range) 4.2°C (3.2-5.9) to 11.0°C (7.0-17.4) (P < .001). The apnea-hypopnea index increased from a median 7.0 to 14.0 events/h (P < .05). There was no significant correlation between changes in CDT and the apnea-hypopnea index. In 21 nonsnoring control subjects, palatal CDT increased from a median 3.2°C to 5.6°C (P < .005). In 19 CPAP-treated patients, palatal CDT did not significantly change; eight patients had improved values. CDTs worsened significantly more in the snorers group than in the control subjects (P < .05) and the CPAP-treated patients (P < .001). There was no significant difference between control subjects and CPAP-treated patients.
CDT worsened considerably over time in untreated snorers, significantly more than in nonsnoring control subjects and CPAP-treated patients. Untreated snorers therefore risk developing poor sensitivity in the upper airway. In contrast, efficient treatment of OSA seems to protect the sensory innervation, as the CPAP-treated group maintained their sensitivity to cold and, in some cases, the sensitivity even improved.
Sex, stress and sleep apnoea: Decreased susceptibility to upper airway muscle dysfunction following intermittent hypoxia in females
2017, Respiratory Physiology and Neurobiology
Citation Excerpt :
Structural changes in upper airway muscles of OSAS patients, including fibre type transitions (Stauffer et al., 1989; Smirne et al., 1991; Series et al., 1995, 1996a,b; Ferini-Strambi et al., 1998; Carrera et al., 2004) and altered metabolic activity (Series et al., 1995; Kim et al., 2014) are reported, consistent with evidence of altered isolated muscle function (Series et al., 1995, 1996a,b, 1999; Carrera et al., 1999, 2004). Inflammation and myopathy (Boyd et al., 2004; Kimoff et al., 2011) have been described in upper airway muscle biopsies from OSAS patients, with evidence too of neuropathic sensorimotor injury in OSAS (Svanborg 2005; Saboisky et al., 2012). Moreover, upper airway muscle functional deficits correlate with airway collapsibility in patients with OSAS (Series et al., 1996a,).
Obstructive sleep apnoea syndrome (OSAS) is a devastating respiratory control disorder more common in men than women. The reasons for the sex difference in prevalence are multifactorial, but are partly attributable to protective effects of oestrogen. Indeed, OSAS prevalence increases in post-menopausal women. OSAS is characterized by repeated occlusions of the pharyngeal airway during sleep. Dysfunction of the upper airway muscles controlling airway calibre and collapsibility is implicated in the pathophysiology of OSAS, and sex differences in the neuro-mechanical control of upper airway patency are described. It is widely recognized that chronic intermittent hypoxia (CIH), a cardinal feature of OSAS due to recurrent apnoea, drives many of the morbid consequences characteristic of the disorder. In rodents, exposure to CIH-related redox stress causes upper airway muscle weakness and fatigue, associated with mitochondrial dysfunction. Of interest, in adults, there is female resilience to CIH-induced muscle dysfunction. Conversely, exposure to CIH in early life, results in upper airway muscle weakness equivalent between the two sexes at 3 and 6 weeks of age. Ovariectomy exacerbates the deleterious effects of exposure to CIH in adult female upper airway muscle, an effect partially restored by oestrogen replacement therapy. Intriguingly, female advantage intrinsic to upper airway muscle exists with evidence of substantially greater loss of performance in male muscle during acute exposure to severe hypoxic stress. Sex differences in upper airway muscle physiology may have relevance to human OSAS. The oestrogen–oestrogen receptor α axis represents a potential therapeutic target in OSAS, particularly in post-menopausal women.
Reducing upper airway collapse at lower continuous positive airway titration pressure
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During respiration, upper airway (UA) collapse occurs when the forces generated from the negative UA pressures exceed the forces produced by the UA muscles; which leads to loose soft tissue at the back of the mouth. At predetermined titration pressure, the Continuous Positive Airway Pressure (CPAP) normally provides a continuous pressurized and humidified air to prevent airway collapse. However, high titration pressures are not always tolerated by patients and may lead to damaging effects including stroke symptoms for cardiovascular disease patients. This paper hypothesizes that superimposed pressure oscillation can modulate the loose tissue and allow unblocking the upper airway passages to help reduce the required titration pressure. Using MRI scans, this paper investigates the effects of using pressure oscillations superimposed on the CPAP to keep the airway open at lower pressure distributions inside the upper airway and consequently increase the patients’ comfort and reduce their rejection to the CPAP.
Neuromuscular function of the soft palate and uvula in snoring and obstructive sleep apnea: A systematic review
2018, American Journal of Otolaryngology - Head and Neck Medicine and Surgery
Citation Excerpt :
3/15 snorers showed signs of moderate nervous lesions with evidence of some polyphasic potentials and slightly reduced interference pattern during maximal contraction of palate [39]. Five normal subjects and 12 snorers had normal EMG [39]. Fogel et al. investigated EMG activity of GG and TP during wakefulness and sleep onset in 12 healthy young men, 13 healthy older men, and 12 men with OSA on CPAP [40].
A collapsible upper airway is a common cause of obstructive sleep apnea. The exact pathophysiology leading to a more collapsible airway is not well understood. A progressive neuropathy of the soft palate and pharyngeal dilators may be associated with the progression of snoring to OSA. The purpose of this study is to systematically review the international literature investigating the neurophysiologic changes in the soft palate and uvula that contribute to progression from snoring to OSA.
PubMed/MEDLINE and 4 other databases were systematically searched through July 4, 2017. Eligibility: (1) Patients: controls, snoring or OSA patients (2) Intervention: neuromuscular evaluation of the palate and/or uvula (3) Comparison: differences between controls, snoring and OSA patients (4) Outcomes: neuromuscular outcomes (5) Study design: Peer reviewed publications of any design.
845 studies were screened, 76 were downloaded in full text form and thirty-one studies met criteria. Histological studies of the soft palate demonstrated diffuse inflammatory changes, muscular changes consistent with neuropathy, and neural aberrancies. Sensory testing studies provided heterogeneous outcomes though the majority favored neuronal dysfunction. Studies have consistently demonstrated that increasing severity of snoring and sleep apnea is associated with worsening sensory nerve function of the palate in association with atrophic histological changes to the nerves and muscle fibers of the soft palate and uvula.
Recent evidence highlighted in this systematic review implicates the role of neurogenic pathology underlying the loss of soft palate and/or uvular tone in the progression of snoring to sleep apnea.
Investigation of smell and taste function in patients with obstructive sleep apnoea syndrome
2019, Journal of Laryngology and Otology

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Impact of obstructive apnea syndrome on upper airway respiratory muscles

Abstract

Introduction

Section snippets

Muscle activation patterns

Natural history of patients with heavy snoring – OSAS

Nervous lesions – a result of snoring, a cause of OSAS?

Discussion

Electroenc. Clin. Neurophysiol.

Exp. Neurol.

Chest

J. Neurol. Sci.

J. Neurol. Sci.

Lancet

Chest

Upper airway muscle inflammation and denervation changes in obstructive sleep apnea

Am. J. Respir. Crit. Care Med.

Palatal muscle electromyogram activity in obstructive sleep apnea

Am. J. Respir. Crit. Care Med.

Patients with obstructive sleep apnea exhibit genioglossus dysfunction that is normalized after treatment with continuous positive airway pressure

Am. J. Respir. Crit. Care Med.

Effects of obesity upon genioglossus structure and function in obstructive sleep apnoea

Eur. Respir. J.

Neurogenic effects on the palatopharyngeal muscle in patients with obstructive sleep apnea

J. Neurol. Neurosurg. Psych.

Muscle fibre type and obstructive sleep apnea

Sleep Res. Online

Obstructive sleep apnea

Adv. Int. Med.

Histological indications of a progressive snorer's disease in an upper airway muscle

Am. J. Respir. Crit. Care Med.

Heavy snorer's disease: a progressive local neuropathy

Acta Otolaryngol.

The role of resistance exercise intensity on muscle fibre adaptations

Sports Med.

Neurogenic muscle hypertrophy

Muscle Nerve

J. Sleep Res.

Evidence for reflex upper airway dilator muscle activation by sudden negative airway pressure in man

J. Physiol. (London)

Afferent pathway(s) for pharyngeal dilator reflex to negative pressure in man: a study using upper airway anaesthesia

J. Physiol. (London)

Motor control of the pharyngeal musculature and implications for the pathogenesis of obstructive sleep apnea

Sleep