The main findings of the present study can be summarized as follows: (1) in a cohort of 951 patients with OSA, 15% of patients reported symptoms of dysphagia; (2) higher OSA symptoms, greater sleepiness, anxiety/depression, concomitant gastroesophageal reflux, and female gender were independently associated with dysphagia symptoms; (3) FEES confirmed the presence of dysphagia in almost all symptomatic patients with OSA, which was mainly related to delayed pharyngeal reflex, poor oral control, and bolus propulsion deficit.
Based on an EAT-10 score ≥ 3, 15% of patients with OSA presented with symptoms of dysphagia. The prevalence of dysphagia symptoms in the general population was 8%, using the same questionnaire and cut-off . The present results suggest that a diagnosis of OSA may nearly doubles the prevalence of dysphagia symptoms. The literature suggests that dysphagia in patients with OSA may be the result of three main mechanisms. Firstly, it was hypothesized that dysphagia may derive from a sensory alteration of the pharynx secondary to low-frequency vibrations, intermittent hypoxia, and inflammatory changes [3, 21]. Secondly, a motor component has been described. In fact, patients with OSA exhibit altered appearance and increased fatigability of orofacial and pharyngeal musculature, as well as altered composition of muscle fibres [4, 22]. Finally, altered swallowing-breathing integration has been reported [3, 5, 23].
The prevalence of dysphagia symptoms of our cohort confirms the results of the Japanese study , which reported a prevalence of 16%. Although with different questionnaires, both studies used multiple items-patient-reported tools to investigate dysphagia symptoms. The assessment of dysphagia symptoms should not be limited to one single open question on swallowing function, due to its insufficient diagnostic performance . It appears advisable to integrate the assessment of patients with OSA in clinical practice with a validated, rapid, and dysphagia-specific tool, such as the EAT-10, that can help the identification of candidates for an in-depth swallowing assessment, preventing dysphagia-related complications. Early identification of dysphagia would allow reducing dysphagia-related pulmonary, nutritional, and psychosocial consequences [25,26,27]. Among these, preventing the development of aspiration pneumonia is particularly important in this population, being OSA itself is a risk factor for pneumonia [28, 29].
The present study identified several independent factors associated with dysphagia symptoms, which may additionally guide clinicians in the selection of patients at higher risk of dysphagia. The former includes female gender, OSA symptomatology, anxiety/depression, and gastroesophageal reflux. The multivariate analysis was performed including almost 85% of the overall sample because of missing values. Indeed, excluded patients showed comparable anthropometrical and clinical characteristics compared to the rest of the population, except for a higher prevalence of anxiety and depression and neurological conditions without known association with dysphagia. However, anxiety and depression were significant predictors of dysphagia in the multivariate analysis, and the neurological diseases that may act as confounder in the diagnosis of dysphagia were excluded from the study, thus, we believe that the risk of selection bias was low and did not interfere with the validity of our results.
The association with the female gender was unexpected. OSA is more prevalent in males and both the pathophysiology and the evolutionary anatomic changes pose male patients at higher risk of more severe disease in respect to women [29,30,31,32]. To the best of our knowledge, the mechanisms and pathophysiology of sleep apnea are not gender-related, and females with OSA should not be at higher risk of dysphagia. Furthermore, to date, a gender effect on swallowing function was not recognized . One study reported a similar trend for higher prevalence of dysphagia in OSA females patients . The authors hypothesized that the observation was influenced by confounding factors, such as aging. The present study seems not to support this hypothesis. In the absence of clear evidence, future studies should shed light on the association between gender and dysphagia in OSA.
Interestingly, age was not associated with dysphagia symptoms in our sample. Previous studies reported conflicting evidence, favoring [8, 34] and in contrast to our result . It is known that dysphagia prevalence increases with aging . The lack of association between age and dysphagia symptoms in the present study, might suggest that dysphagia arises as a consequence of OSA itself and not from the normal aging process.
Analogously, no association was found between OSA severity and dysphagia symptoms, in accordance with previous reports [8, 34, 35]. Conversely, we found that dysphagia symptoms were more frequently reported by patients with a higher burden of OSA-related symptoms and greater daytime sleepiness. Excessive daytime sleepiness does not seem to be associated with OSA severity as measured by AHI . The main hypotheses are that excessive daily sleepiness might be either the effect of REM-dependent OSA or the result of lower oxygenation during sleep [38,39,40]. As repetitive nocturnal hypoxemia has been identified in OSA patients with impaired swallowing , it may be hypothesised that it could represent the common underlying mechanism of dysphagia and excessive daytime sleepiness in OSA. However, we did not find an association between dysphagia symptoms and SpO2 indices. Future studies should provide a more in-depth insight on the association between dysphagia and daily sleepiness in OSAS, investigating other polysomnographic indices and objective measures of dysphagia.
Affective symptoms are common in patients with dysphagia . The relation between dysphagia and anxiety and depression may be bidirectional. On one hand, dysphagia may arise as a consequence of the effects of medications on swallowing function . Moreover, anxiety and depression might influence the perception of swallowing, with patients being more prone to report dysphagia symptoms. On the other hand, dysphagia may increase the prevalence of affective symptoms by altering eating habits and limiting social participation .
Gastroesophageal reflux is known to be associated with OSA . We found a significant association between symptoms of gastroesophageal reflux and symptoms of dysphagia in OSA. Dysphagia and gastroesophageal reflux disease have been reported to be concomitant conditions in other populations [45,46,47]. In patients with gastroesophageal reflux, dysphagia was associated with cricopharyngeal incoordination  and delayed airway closure , potentially related to reflux-induced sensory impairment.
It could be speculated that symptoms of reflux may simulate symptoms of dysphagia recorded by the EAT-10. In patients who underwent FEES, both objective signs and subjective symptoms of LPR were investigated. No significant differences were found in the EAT-10 scores between patients with and without LPR, regardless of the scale used to assess it. Thus, this result seems to confirm that, in the study sample, the EAT-10 recorded symptoms of dysphagia and not symptoms of reflux, corroborating the finding by Caparroz on the fact that dysphagia and LPR, although may be concomitant, are not associated conditions in OSA . However, as this analysis was based on the small sample size of patients who underwent FEES, the potential for an influence of reflux (either gastroesophageal or laryngopharyngeal) on the EAT-10 scores should be recognized and the prevalence data should be interpreted cautiously.
FEES confirmed the presence of dysphagia in 97% of the symptomatic patients who accepted the examination. Other studies instrumentally assessing swallowing function in OSA reported a lower frequency of signs of dysphagia, ranging from 20 to 77% . Previous studies included both symptomatic and asymptomatic patients. Our results may suggest that the selection of OSA candidates to swallowing assessment based on a standardized patient-reported tool could increase the appropriateness of the instrumental examination. However, the high rate of FEES refusal in our study may be responsible for the higher prevalence of instrumentally documented dysphagia, by selecting more symptomatic or concerned patients. Therefore, future studies on larger samples should confirm the present data.
At FEES, patients with OSA exhibited impaired swallowing safety and reduced swallowing efficiency. The main pathophysiological mechanism of dysphagia was a delayed pharyngeal response, aligned with previous findings [35, 50, 51]. Other motor deficits, such as reduced propulsion of the bolus, were also reported but in a smaller portion of the sample. It confirms that both sensory and motor changes associated with OSA impairs swallowing function, but the sensory component seems to be predominant.
The study has some limitations. First, we investigated the prevalence of dysphagia symptoms and of dysphagia as objectively diagnosed by instrumental assessment. This choice was related to the feasibility of analyzing dysphagia on a large sample (N = 951). Indeed, the EAT-10 represents an easy-to-use and rapid tool, whereas instrumental swallowing assessments, either with FEES or videofluoroscopy, are minimally invasive procedures. Nevertheless, using a patient-reported outcome might have underestimated the real prevalence of dysphagia because of poor awareness of patients. Conversely, as the study was conducted in an academic institution, the prevalence of dysphagia symptoms in OSA may have been overestimated due to a referral bias of more complicated OSA patients. Second, as previously stated in the discussion, although patients who refused and patients who accepted FEES did not significantly differ for main factors influencing OSA and dysphagia, the large number of symptomatic patients with OSA who refused to undergo the FEES might have led to a selection bias. Finally, being an observational study on a large sample size, standard polysomnographic indices routinely used in clinical practice were investigated. The present study failed to detect an association between polysomnographic indices and dysphagia symptoms in patients with OSA. However, measuring more specific arousal indices and providing a full characterization of obstructive hypopneas could lead to different results. Future studies should expand the investigation including other polysomnographic indices.