4. DISCUSSION
The prevalence of obstructive sleep apnea with concomitant daytime
drowsiness is between 3 and 7 percent for adult males and 2 to 5 percent
for adult women [1,3]. OSA is defined by recurrent blockage of the
upper airway during sleep, which is associated by episodic hypoxia,
wakefulness, and sleep fragmentation. Upper airway anatomic anomalies,
such as a thicker palate, hypertrophic tonsils, or a thickened pharynx
with decreased neural activity, lead to obstructive apneas and hypopneas
in OSA. OSA causes long-term damage to the cardiovascular, neurologic,
and respiratory systems. According to a meta-analysis, OSA is associated
with increased risks of significant adverse cardiac events, coronary
heart disease, stroke, and cardiac death. OSA is also related to
inflammation, since repeated bouts of hypoxia increase systemic
oxidative stress and contribute to the development of a systemic
inflammatory state.[4] Recent research has discovered higher exhaled
nitric oxide in OSA exhaled air, which contributes to upper airway
inflammation.[5] In this regard, OSA has been associated with the
alteration of voice resonance and articulation through thickened soft
palate, hypertrophic tonsils, or a thickened pharynx and tongue base
lymphoproliferation.[6] However, there has been little research in
the effect of OSA on voice to yet.
A cross-sectional analysis of data from the national longitudinal
research found a relationship between OSA and vocal disorders. People
with OSA symptoms exhibited a higher prevalence of voice abnormalities
than those without OSA symptoms (6.7 percent vs. 4.7 percent) in a study
of 14,794 young adults in the United States.[6] N. Roy et al. also
discovered that 28% of OSA patients had vocal abnormalities, which was
greater than the general population.[7] However, in these research,
vocal abnormalities were assessed by patients’ subjective voice pain,
rather than objective voice characteristics or diseases like BVFL.
The mouth cavity, pharynx, and larynx known as the vocal tract, are
structures that influence speech production. Speech impairment is caused
by functional or structural abnormalities in these structures. The
Bernoulli effect and enhanced pharyngeal dynamic compliance can explain
pharyngeal narrowing and thickening in OSA. As a result, it is assumed
that increased vocal tract compliance leads to OSA resonance and
articulation problems. Many studies have observed vocal alterations
following OSA surgical treatment.[8,9] Eun et al., for example,
found that uvulopalatopharyngoplasty alters the formant frequencies of
vowels, resulting in alterations in resonance after OSA surgery.[8]
However, the changes that occur in the larynx in OSA patients have
received less attention. Elongated epiglottis and redundancy in this
structure can cause collapse and alterations in glottic and supraglottic
structures.[10] Furthermore, Krieger et al. proposed that OSA causes
repeated glottic spasm and paradoxic glottic narrowing.[11]
OSA patients frequently breathe via their mouths, which produces a
reduction in moisture in the inhaled air, leading the vocal cords to
dry. Water loss from the sol layer caused by oral breathing increased
the viscosity of respiratory epithelium and overlaying mucus, increased
tracheal mucus velocity, and reduced mucociliary clearance.[12]
Normal human oral breathing for 15 minutes revealed effects that are
most likely the result of superficial dehydration on the vocal cords and
increased vocal effort.[13] In a research of air inhalation, Hemler
et al. discovered that perturbation measurements were significantly
higher after inhaling desiccated air than ordinary air.[14] Many
research, on the other hand, have observed low phonation threshold
pressures in people exposed to hydrated or ”wet” circumstances.[15]
In summary, OSA patients have long-term mouth breathing, which causes
higher vocal effort due to superficial dehydration of the vocal fold.
As previously stated, there have been few reports on the impact of OSA
on voice. For example, Monoson and Fox and Fox et al. found that the
relationship between OSA and voice disorder and discovered that 60 to
70% of OSA patients exhibited a combination of phonation, articulation,
and resonance abnormalities.[16,17] Based on objective acoustic
parameters, Wei et al. recently showed that OSA patients had vibration
irregularity, inadequate glottal closure, and greater hoarseness
compared to normal individuals.[18]
Unlike prior research that investigated at voice quality, we used a
nationwide cohort study to evaluate at the prevalence of BVFL in OSA
patients. Multiple studies, including the National Institutes of Health
(NIH) epidemiology study, define voice disorder as ”anytime the voice
does not work, perform, or sound as it normally should, so that it
interferes with communication,” implying that it is defined based on
subjective symptoms based on individual judgment.[19] Meanwhile,
BVFLs such as vocal nodules, vocal polyps, and Reinke’s edema are
pathologic changes in the superficial layer of the lamina propria that
otolaryngologists identify with a laryngoscope. These lesions can be
caused by voice abuse, misuse, smoking, alcohol consumption, or
larygopharyngeal reflux (LPR). However, the influence of OSA as a cause
of BVFL has yet to be studied. In this study, the prevalence of benign
vocal fold lesions (BVFL) was reported to be 1.79 times greater in the
OSA group than in the control group. Those who had OSA surgery were 35%
less likely to be diagnosed with BVFL during the study period.
In a subgroup analysis, the HR for BVFL was greater in female OSA
patients than in male OSA patients (HR: 1.22[1.10-1.35]). Females
are more likely to have voice disorders in general, and females had a
greater rate of BVFL in the literature.[20] Female vocal folds
contain less hyaluronic acid in the superficial layer of the lamina
propria, resulting in a lower absorption ability to endure phonotrauma,
according to Butler et al..[21]
Other risk factors for BVFL include being aged from 40 to 60 years (HR:
1.20 [1.09-1.32]), living in a major city (HR: 1.39
[1.23-1.59]), and having a higher socioeconomic status (HR:
1.10[1.01-1.21]). Roy et al. showed that among randomly chosen
participants, the age range of 40–59 years appeared to constitute a
high-risk age group for the reporting of voice problems.[22] Both of
these findings are similar to the findings of Russell et al., who found
that teachers over the age of 50 had higher voice difficulty than
younger teachers.[23] Hur et al. identified health inequalities
among people in the United States with voice difficulties, indicating
that racial minorities and those with low income tend to avoid treatment
owing to a lack of transportation.[24] It is well recognized in the
literature that persons with poor income or insufficient health
insurance face greater hurdles accessing medical services.[25]
Similarly, the greater prevalence of BVFL in metropolitan regions can be
explained.
We used PS matching in our study to reduce selection bias and
confounding variables between the two groups. We used PS matching with
the following characteristics to achieve a fair comparison between
groups: age, gender, residence, socioeconomic status, and underlying
diseases. This is the first study to examine the risk of BVFL in OSA
patients using large-scale real-world data. Although we produced
significant results, there are some limitations that need be addressed
in future study. First, despite the fact that this registry-based method
resulted in a large number of unselected research participants,
information about classic BVFL risk factors such as work environment,
psychological factors, personality traits, voice abuse, and smoking was
insufficient. Second, in our analysis, surgical treatment of OSA was
related with a lower incidence of BVFL. We were unable to compare the
impact of continuous positive airway pressure (CPAP), which is more
often used for OSA therapy, due to a lack of data in the NHIS-NSC
database, as CPAP has only recently become covered by Korean medical
insurance. Third, because OSA was only recognized using diagnostic
codes, the severity of the condition could not be determined.
According to this observational study, OSA is related with an increased
incidence of BVFL. Subgroup analysis revealed that the incidence of BVFL
in OSA patients increased with age, female sex, and high socioeconomic
status. Our study also found that surgical correction of OSA decreased
the incidence of BVFL. Physicians should be aware of the possibility of
developing BVFL in OSA patients, which leads to poor voice outcomes.