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Neuromuscular injuries in Obstructive Sleep Apnea

Research project The purpose of this project is to demonstrate that an acquired neuromuscular injury in the upper airways caused by many years of traumatic snoring vibrations and tissue stretch is an important risk factor for pharyngeal dysfunction and obstructive sleep apneá (OSA). We also intend to follow up and investigate the effect of different treatment interventions on tissue pathology, healing and function of upper airway tissues. OSA is a prevalent progressive disorder that has severe negative health consequences i.e. cardiovascular disease and stroke. The prevalence of OSA in middle-aged adults ranges from 4-9% in men and 2-24% in women. The health care cost of OSA in Sweden is approximately 1 billion SEK per year. Several factors can predispose an individual to OSA such as obesity and anatomical abnor¬malities. However, indi¬vi¬duals with¬out these recogni¬zed traits and conditions also develop OSA making the etiology and pathophysiology unclear.

We hypothesize that an important risk factor for OSA is an acquired injury in the upper airways caused by traumatic snoring vibrations and tissue stretch. This trauma not only disrupts neuromuscular function of the dilator muscles that maintain the patency of the upper airways during sleep, but also explains the increased incidence of swallowing dysfunction among snorers. In order to test this hypothesis, tissue samples of soft palate from 25 patients with OSA will be analysed for upper airway neuropathy and myopathy as a potential cause of OSA. The severity of histopathological alterations will be correlated to the degree of pharyngeal swallowing dysfunction, as measured by video-fluoroscopic X-ray examination. To further evaluate our theory of vibratory tissue damage, pathological findings in OSA patients will be compared with hand muscles showing vibratory injury after exposure to work related vibrations. We will also investigate if intervention reducing vibrations and stretch of upper airway tissue reverses pathology and improves pharyngeal function 1 year after the treatment (n=30). To assess the healing potential, we will examine activation of myogenic stem cells (satellite cells), signs of fiber regeneration and reversal in tissue pathology.. Samples from 10 healthy individuals will serve as reference. Our pilot study shows that. in the OSA patients, there are not only clear signs of neuromuscular damage and degeneration, but also signs of a disturbed regeneration process. The pathology revealed similarities with alterations that are typical of vibration damage and certain genetic myopathies. The preliminary results indicated a correlation between severity of neuromuscular changes and degree of pharyngeal dysfunction. Intrestingly findings from normal palate muscles of healthy subjects contain fibers with a unique molecular build up. Dystrophin, an important protein for muscle fiber stability and function, seems to be present in a novel isoform. The C-terminal domain of the dystrophin molecule, which links the contractile apparatus to extracellular matrix via cell membrane, is not expressed in a way similar to limb muscles. Moreover, dystrophin C terminus negative fibers also lacked expression for desmin, a ubiquitous cytoskeletal protein in muscles. Although several studies indicate that there is a possible link between snoring and development of OSA but none of them has proved it. If our hypothesis is confirmed, new treatment strategies can be implemented in the clinics. Treatments, which reduce snoring-induced traumatic vibration may improve neuro¬muscular function and thereby prevent, reduce or at least delay the progression of a full-blown OSA. In that case, early treatment has obvious bene¬ficial effects in reducing the risk of future cardiovascular and other serious multisystem unhealthy events. We strongly anticipate that a new approach to the pathogenesis of OSA will change the criteria for which patients need care and this strategy may bring major benefits for the society in terms of allayed suffering and ultimately reduced healthcare costs.

Head of project

Per Stål

Project overview

Project period:

Start date: 2013-10-10

Participating departments and units at Umeå University

Department of Integrative Medical Biology

Research subject

Clinical medicine, Molecular medicine