Pathogenesis of obstructive sleep apnea (OSA) and the prevalence of residual excessive sleepiness in

Pathogenesis of obstructive sleep apnea (OSA) and the prevalence of residual excessive sleepiness in patients treated with CPAP

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Papathanasiou L. Constantine, MD, Otorhinolaryngolgist

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Dr Dimitrios N. Gelis, MD, Otorhinolaryngologist, DDS, PhD, with special interest in Medical Nutrition, Complementary Medicine, Vitamin D, Medical properties of Red Wine.

Damaskinou 46, Korinthos 20100, Greece tel. 00302741026631, 00306944280764

www.gelis.gr, www.orlpedia.gr, www.allergopedia.gr, www.gkelanto.gr, www.pharmagel.gr

Obstructive sleep apnea (OSA) is characterised by repetitive episodes of upper airway occlusion during sleep.The pathogenesis of obstructive sleep apnea (OSA) has been under investigation for over 29 years, during which a number of factors that contribute to upper airway (UA) collapse during sleep have been identified. In patients with sleep apnea hypopnea (OSAH) volumetric MRI studies and computer-based analysis techniques permited the objective quantification of  the volume of the tongue, soft palate, parapharyngeal fat pads, and lateral pharyngeal walls.

 

It has been demonstrated that the upper airway calibre reduction during sleep  due to enlargement of the total soft tissue (tongue, uvula, tonsilar pillars, adenoids, soft palate, blood vessels, lymphoid tissue, pharyngeal fat pads, muscles and pharyngeal mucosa) [1] is crucial to the development of OSA in many patients. Enlargement of the soft tissues through hypertrophy, inflammation, or edema may reduce the diameter of the UA. Soft tissue edema is considered as largely responsible for this thickening [6], possibly resulting from inflammation. OSA has been shown to be associated with a variable degree of nasal inflammation, uvula mucosal congestion and airway hyperreactivity.

 

The upper airway inflammation, whose clinical importance is uncertain, is characterised by leukocytes infiltration and interstitial oedema. In addition, recent data has shown the presence of neutrophilic inflammation in the lower airways. The current opinion is that airway inflammation is caused by the local, repeated mechanical trauma related to the intermittent airway occlusion typical of the disease. Another potential mechanism involves the intermittent nocturnal hypoxemia that through the phenomenon of the ischemia-reperfusion injury may induce the production of oxygen free radicals and therefore cause local and systemic inflammation.

 

Finally, a state of low-grade systemic inflammation may be related to obesity per se with the pro-inflammatory mediators synthesised in the visceral adipose cells. Several authors stress the role of circulating and local inflammatory mediators, such as pro-inflammatory cytokines, exhaled nitric oxide, pentane and 8-isoprostane as the determinants of inflammation in OSA [7]. MRI studies have demonstrated increased soft tissue mass surrounding the UA and, hence, reduced UA size in the retropalatal and, to a lesser extent, the retroglossal area of OSA patients compared with control subjects [2, 3, 4]. The larger the volumes of the lateral pharyngeal walls, tongue, and total soft tissue, the greater are the odds of OSA [4].

 

Thickening of the lateral pharyngeal walls appears to be the predominant factor in OSA patients [5]. The impairment of upper airway (UA) mechanoreceptor sensitivity and reflexes that maintain pharyngeal patency and respiratory control system instability, have also been identified as possible mechanisms facilitating UA instability. This suggests that OSA may be a heterogeneous disorder, rather than a single disease entity. Therefore, the extent to which various pathogenic factors contribute to the phenomenon of repetitive collapse of the UA during sleep probably varies from patient to patient.

 

Further elucidation of specific pathogenic mechanisms in individuals with OSA may facilitate the development of new therapies that can be tailored to individual patient needs according to the underlying mechanism(s) of their disease [6]. More easily and rapidly than MRI [8], acoustic pharyngometry can be used to assess the UA caliber [9] and its change in OSAH patients [10].

 

Obstructive sleep apnea (OSA) is characterized by repetitive pharyngeal collapse during sleep. Increased intrinsic UA collapsibility that is generally observed in OSAH patients [11] is due to decreased transmural pressure and increased pharyngeal wall compli­ance.

 

Continuous positive airway pressure (CPAP ) provides a pneumatic splint for the nasopharyngeal airway and is a safe, simple treatment for the obstructive sleep apnoea syndrome [12].. CPAP eliminates respiratory events and reduces sleepiness in OSAH patients. The relative risk of having residual excessive sleepiness (RES) has been found to be  5.3 (95% CI 1.6-22.1), when Epworth Sleepiness Scale (ESS) score  before treatment was >or=11. As 230,000 obstructive sleep apnoea patients are currently treated in France by continuous positive airway pressure, more than 13,800 of them might suffer from residual excessive sleepiness[13]. 

References

1. Schwab RJ, Pasirstein M, Pierson R, Mackley A, Hachadoorian R, Arens R, Maislin G, Pack AI. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. Am J Respir Crit Care Med. 2003 Sep 1;168(5):509-10.

2. Schellenberg JB, Maislin G, and Schwab RJ. Physical findings and the risk for obstructive sleep apnea. The importance of oropharyngeal structures. Am J Respir Crit Care Med 162: 740–748, 2000.

3. Schwab RJ, Gefter WB, Hoffman EA, Gupta KB, and Pack AI. Dynamic upper airway imaging during awake respiration in normal subjects and patients with sleep-disordered breathing. Am Rev Respir Dis 148: 1385–1400, 1993.

4. Schwab RJ, Gupta KB, Gefter WB, Metzger LJ, Hoffman EA, and Pack AI. Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing. Significance of the lateral pharyngeal walls. Am J Respir Crit Care Med 152: 1673–1689, 1995.

5. Schwab RJ, Pasirstein M, Pierson R, Mackley A, Hachadoorian R, Arens R, Maislin G, and Pack AI. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. Am J Respir Crit Care Med 168: 522–530, 2003.

6. Ryan CM, Bradley TD. Pathogenesis of obstructive sleep apnea. J Appl Physiol. 2005 Dec;99(6):2440-50.

7. Sabato R, Guido P, Salerno FG, Resta O, Spanevello A, Barbaro MP. Airway inflammation in patients affected by obstructive sleep apnea. Monaldi Arch Chest Dis. 2006 Jun;65(2):102-5.

8. Marshall I, Maran NJ, Martin S, Jan MA, Rimmington JE, Best JJ, Drummond GB, Douglas NJ. Acoustic reflectometry for airway measurements in man: implementation and validation. Physiol Meas. 1993 May;14(2):157-69.

9. Brooks LJ, Castile RG, Glass GM, Griscom NT, Wohl ME, Fredberg JJ. Reproducibility and accuracy of airway area by acoustic reflection. J Appl Physiol. 1984 Sep;57(3):777-87.

10. Jung DG, Cho HY, Grunstein RR, Yee B. Predictive value of Kushida index and acoustic pharyngometry for the evaluation of upper airway in subjects with or without obstructive sleep apnea. . J Korean Med Sci. 2004 Oct;19(5):662-7.

11. Malhotra A, Pillar G, Fogel R, Beauregard J, Edwards J, White DP. Upper-airway collapsibility: measurements and sleep effects. Chest. 2001 Jul;120(1):156-61.

12. Sullivan CE, Issa FG, Berthon-Jones M, Eves L. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet. 1981 Apr 18;1(8225):862-5.

13. Pépin JL, Viot-Blanc V, Escourrou P, Racineux JL, Sapene M, Lévy P, Dervaux B, Lenne X, Mallart A. Prevalence of residual excessive sleepiness in CPAP-treated sleep apnoea patients: the French multicentre study. Eur Respir J. 2009 May;33(5):1062-7. 


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