Effects of Continuous Positive Airway Pressure on the Degree of Sleepiness, Functional Quality of Sleep, and Electrophysiological Hearing Responses in Individuals with Obstructive Sleep Apnea

Abstract

Introduction

Obstructive sleep apnea (OSA) affects nerve impulse transmission in the auditory pathway due to oxygen supply. Continuous positive airway pressure (CPAP) therapy improves oxygen levels, potentially alleviating sleepiness and enhancing central auditory pathway function.

Objective

To longitudinally evaluate the effect of CPAP on the degree of sleepiness, functional quality of sleep, and electrophysiological hearing responses of the central auditory pathways of patients with moderate to severe OSA.

Materials and Methods

There were 31 adults (21 men and 10 women), aged 20 to 70 years, of which 18 were from the group with and 13 from the one without CPAP. All patients underwent three assessments: the first one performed immediately after CPAP prescription; the second, 3 months later; and the third, 6 months after the initial assessment. The Epworth Sleepiness Scale (ESS), the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), auditory brainstem response (ABR), and long-latency auditory evoked potentials (LLAEP) were used for these assessments.

Results

The ESS did not detect any changes in excessive daytime sleepiness levels and the FOSQ-10 showed no improvement in either group. Analysis from ABR revealed a high proportion of altered results in both groups at the three assessment times. During the LLAEP, it was observed that the CPAP group exhibited reduced P2 latencies compared with the non-CPAP group in the second assessment. However, this improvement was not sustained in the subsequent assessment, possibly attributed to OSA-induced damage.

Conclusion

Treatment with CPAP for 6 months did not improve the degree of sleepiness, functional quality of sleep, or electrophysiological response of hearing, demonstrating that OSA can irreversibly harm the individual.

 

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Keywords

sleep apnea obstructive - continuous positive airway pressure - sleepiness - sleep quality - evoked potentials auditory

Introduction

Obstructive sleep apnea (OSA) is a respiratory disorder characterized by narrowing of the upper airways that impairs normal ventilation during sleep, accompanied by hypoxia and sleep fragmentation. [1] [2] These obstruction episodes can be total (apnea) or partial (hypopnea).[3] The estimated prevalence of OSA has increased substantially over the last two decades, between 14 and 55%, depending on gender and age,[4] and in 2019 it was estimated that almost 1 billion people were affected.[5]

Among other treatment options, continuous positive airway pressure (CPAP) has been recommended, in association with educational and behavioral interventions,[6] characterized by the application of constant and continuous positive pressure to the patient's airways.[7] This resource has been highlighted as a mainstay in the treatment of moderate to severe OSA in adults, resulting in improved sleep, quality of life, and reduced risk of cardiovascular and neurocognitive side effects associated with the disease.[7]

Greater tissue oxygenation with CPAP is believed to increase auditory pathway oxygenation and improve functioning. This can be visualized through electrophysiological hearing tests, such as the auditory brainstem response (ABR) and long-latency auditory evoked potential (LLAEP). The first test captures the neuroelectric brainstem response to acoustic stimulation, and the second assesses the integrity of the central auditory pathway and cognitive functions, such as attention, discrimination, recognition, and memory of sounds.[8] [9]

Although some studies have investigated the relationship between OSA and the hearing electrophysiology,[10] [11] [12] most of them focused on ABR assessment, with few studies addressing LLAEP, which is responsible for evaluating cognitive-auditory abilities. Moreover, there is a shortage of studies that monitor electrophysiological responses with CPAP treatment.

Thus, the present study aimed to longitudinally evaluate the effect of CPAP use on the degree of sleepiness, functional quality of sleep, and electrophysiological responses of the central auditory pathways of patients with moderate to severe OSA.

The results of patients who did or did not use CPAP were also compared in a longitudinal follow-up regarding their degree of sleepiness and functional quality of sleep, obtained through the Epworth Sleepiness Scale (ESS), the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), as well as the absolute latencies of ABR waves I, III, and V and interpeak intervals I to III, III to V, and I to V. Furthermore, the P1, N1, P2, N2, and P3 components latencies, and P1 to N1, P2 to N2, and N2 to P3 amplitudes of the LLAEP. The hearing thresholds, the length of CPAP use, and the degree of sleepiness and fatigue will also be related to the ABR and LLAEP responses.

We hypothesize that the CPAP treatment in patients with moderate or severe OSA reduces the levels of sleepiness (ESS), improves the functional quality of sleep and fatigue (FOSQ-10), and improves the functioning of the central auditory pathways (ABR and LLAEP), thus increasing the processing speed and the neuronal network activated during acoustic stimulation.

 

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Materials and Methods

Study Design

This longitudinal study was approved by the institution's Ethics Committee under number 5.449.704. Individuals in the OSA laboratory eligible to participate in the study were invited; those who accepted read and signed an informed consent form.

 

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Data Collection

The inclusion criteria were as follows: having a medical diagnosis of moderate to severe OSA[13] [14] based on polysomnography; being 20 to 70-years-old; not having undergone previously treatment with an intraoral device or CPAP.

Patients with the following conditions were excluded from the study, to avoid interference with the audiological assessment results: cerumen and/or foreign bodies identified through otoscopy; tympanometry types B, C, As, or Ad curves;[15] conductive or mixed hearing loss; moderately severe to profound sensorineural hearing loss;[16] history of using ototoxic medications (aminoglycosides, combination with diuretics, chemotherapeutic agents) and/or hypnotic medications; history of middle-ear disorders (persistent or recurrent otitis media, tympanic membrane perforation, tubal dysfunction); malformation of the external auditory canal; family history of hereditary dysacusis; maternal consanguinity; acoustic trauma or congenital syndromes; diagnosis of neurosyphilis; vascular diseases; cancer with use of ototoxic agents; and the use of mechanical ventilation.

Considering these criteria, 41 individuals were initially included. After 3 months (2^nd assessment), five patients withdrew due to personal issues, mobility difficulties, moving to another city, change in medical prognosis, and so forth, leaving 36 patients. After 6 months (3^rd assessment), another five individuals withdrew for similar reasons, totaling 31 participants (21 men and 10 women).

Hence, patients underwent the procedures at three distinct time points: an initial assessment (baseline), followed by a second and a third assessment. After the initial evaluation, patients were monitored to determine whether they had adhered to CPAP use, as not all of them had obtained the equipment (through purchase, rental, or borrowing).

Therefore, patients who had been using CPAP were included in the “With” group and were invited for the 2^nd assessment after 3 months, and for the third assessment 6 months after starting the treatment. For this group, CPAP was provided on loan from the institute where the treatment was performed, with old devices that did not provide data on the number of hours the equipment was used per night. This information was obtained from self-reporting, and all the patients reported using CPAP effectively for more than 4 hours per night. The configuration of treatment pressure was performed by a physiotherapist. Patients who had not acquired CPAP were included in the “Without CPAP” group and were invited for the second assessment after 3 months, and for the third assessment 6 months after the first.

Altogether, 31 patients were evaluated, of whom 18 used CPAP (With CPAP group) and 13 did not (Without CPAP group). There was a statistically significant difference between the groups regarding sex; most patients without CPAP were males (12 patients), as shown in [Table 1].

Table 1 Characterization of the sample.

	Minimum	Maximum	Mean	SD	t test
Age (years)
With CPAP	46	69	57.11	8.50	t(29): 1.792; p = 0.084
Without CPAP	37	68	51.08	10.27
AHI
With CPAP	15.50	74.10	39.14	17.43	t(29): 0.048; p = 0.962
Without CPAP	16.80	75.10	38.84	17.25
Mean SpO2 (%)
With CPAP	91.00	94.00	89.80	3.80	t(29): -1.501; p = 0.144
Without CPAP	92.00	96.00	93.10	1.40
BMI (kg/m2)
With CPAP	24.20	49.60	32.75	6.31	t(29): 0.264; p = 0.794
Without CPAP	22.80	47.96	32.11	7.23
CPAP use time (hours/night)
Without CPAP	4	8	6.33	1.64
	Female		Male		Chi-squared test
Sex
With CPAP	9 (50.00%)		9 (50.00%)		X2 (1): 6.183 p = 0.013*
Without CPAP	1 (7.69%)		12 (92.31%)

Abbreviations: AHI, apnea/hypopnea index; BMI, body mass index; CPAP, continuous positive airway pressure; kg/m², kilogram per square meter; SpO₂, oxygen saturation level; t, Student's t-test; X², Chi-squared test.

Notes: * Statistically significant.

 

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Procedures

The first assessment included a medical history survey, investigating the otological history and auditory complaints related to attention and memory. Participants also answered the ESS and FOSQ10 and were then sent to a room with a sound booth for acoustic immittance measures, pure-tone audiometry and speech audiometry. The patients were positioned supine on a comfortable stretcher to obtain the LLAEP and ABR; they were also instructed to remain relaxed throughout the procedure. The exam took approximately 60 minutes, having been scheduled as chosen by the patient, based on their perception of the times of the day when they would be more alert.

The ESS consists of eight questions to evaluate the probability that the individual has of dozing off in various everyday situations, and each question can receive a score between zero and three points: 0: no possibility of dozing off; 1: small chance; 2: moderate chance; 3: high chance. Therefore, the results can range from 0 to 24 points. For the analysis, the cutoff point of 9 points or more was used to define excessive daytime sleepiness.[17]

Regarding the FOSQ-10, it is a questionnaire that assesses sleepiness and fatigue before and after treatment for obstructive apnea. The questionnaire is divided into individual subscales to provide the overall score: E1, activity level; E2, vigilance; E3, intimacy and sexual relations; E4: general activity; and E5: social outcomes.

Each question can receive a score between zero and four, with 0 being: I do not perform this activity for other reasons; 1: Yes, extreme sleepiness or fatigue; 2: Yes, moderate sleepiness or fatigue; 3: Yes, little sleepiness or fatigue; 4: I am not sleepy or fatigued. The score is calculated for each subscale, and all five are calculated to produce an overall scale. The results range from 0 to 40 points, with the highest score indicating a better functional sleep state. The result for each subscale is obtained by calculating the average score of the questions. The cut-off score adopted was a score greater than 17.9 indicating better functional sleep quality and a score below this value indicating worse sleep quality results.[18]

After the evaluation through acoustic immittance measures, pure-tone and speech audiometry, taking into account patients' eligibility criteria in this study, two more tests were performed to avoid exam failures due to sleepiness. First, the LLAEP is a cognitive-auditory test that directly depends on patients' active participation, whereas ABR does not require their active cooperation. Stimuli were presented monaurally in both exams.

Their skin was cleaned with NUPREP abrasive paste, and the electrodes were positioned in predetermined positions according to the International Electrode System (IES) 10–10[19] standard to obtain electrophysiological responses. The positions and impedance values (which should be below 5 kOhms) were checked before starting the exam recording.

In ABR, the active (Fpz) and ground electrodes were positioned on the forehead, while the reference electrodes were positioned on the left (M1) and right mastoids (M2). Click stimuli with rarefied polarity at 80 dBnHL were used to elicit responses, at a presentation rate of 27.7 stimuli per second, totaling 2,000 stimuli, in a 20 millisecond analysis window. The filter property was 1,500 Hz low pass and 33 Hz/6/oct high pass.

Two tracings were obtained for each ear to ensure wave reproducibility and the presence of a response, analyzing the absolute latencies of waves I, III, and V, and interpeak intervals I to III, III to V, and I to V.

Normal results of the absolute latencies of waves I, III, and V and interpeak intervals (I-III, III-V, and I-V) were based on the normal values proposed by the Eclipse Ep 25's manual for adults (Interacoustics A/S),[20] as shown in [Table 2]. Normal results had up to two standard deviations (SDs) for absolute latencies and up to one SD for interpeak intervals.

Table 2 Reference values of latencies of waves I, III, and V and interpeak intervals I-III, III-V, and I-V at 80 dBnHL for adults, according to the Eclipse manual.[20]

Intensity	Wave I		Wave III		Wave V		Interpeak interval I-III		Interpeak interval III-V		Interpeak interval I-V
	Lat	SD	Lat	SD	Lat	SD	Lat	SD	Lat	SD	Lat	SD
80 dBnHL	1.37	± 0.10	3.57	± 0.17	5.36	± 0.26	2.20	± 0.17	1.79	± 0.26	3.99	± 0.26

Abbreviations: Lat, latency; SD, standard deviation.

The active electrode was positioned on the vertex (Cz), the reference electrode on the right and left mastoids (M2 and M1), and the ground electrode on the forehead to capture the LLAEP.

Tone burst stimuli were presented at 70 dBnHL to elicit responses, with a presentation rate of 1.1 stimuli per second, totaling 300 stimuli, using a low-pass filter of 100 Hz and a high-pass filter of 1.0 6/oct. The frequent stimulus was the 1,000 Hz tone (85% of the stimuli), and the rare one was the 1,500 Hz tone. Patients were instructed to pay attention to the rare stimuli that appeared randomly among a series of frequent stimuli and mentally count the number of times it appeared.

Two types of tracing were obtained, one corresponding to the rare stimuli and the other to the frequent stimuli. The P1, N1, P2, and N2 were identified in the frequent stimulus tracing and analyzed for each component's absolute latency, in addition to the P1 to N1 and P2 to N2 peak-to-peak amplitudes. In turn, P3 was identified in the rare stimulus tracing and analyzed for its absolute latency, along with the N2 to P3 amplitude.

The results were classified as normal when the absolute latencies were within the range proposed for each age group,[9] and abnormal when the latency was increased or there was no response ([Table 3]).

Table 3 Normal P1, N1, P2, N2, and P3 latency standard per age group.

Component	17–30 years	30–50 years	50–70 years
P1 (ms)	54–73	54–73	54–73
N1 (ms)	83–135	83–135	83–135
P2 (ms)	137–194	137–194	137–194
N2 (ms)	188–231	188–231	188–231
P3 (ms)	225–365	290–380	350–427

Note: Chart based on McPherson.[28]

 

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Statistical Analysis

The percentages of normal and abnormal results per individual were calculated for the qualitative analysis. Next, an inferential analysis using the chi-squared test with continuity correction was performed to investigate the association between the results. The effect size was assessed with the Phi coefficient (φ), with 0.1 being small; 0.3, medium; and 0.5, large.

An inferential analysis was performed for the quantitative analysis, using the Student's t-test to compare the meaning between two variables. Effect sizes were determined as follows, according to Cohen's d (21): 0.20 was considered small; 0.50 was medium; and 0.80 was large. The repeated measures in the Analysis of Variance (ANOVA) test compared the means between three or more variables, considering frequency, ear, and time of assessment as repeated measures factors, as well as grouping factors between subjects. Equality of variance was verified with the Leneve test and sphericity, with the Mauchly test. The effect size was determined by the Eta squared value (η²), according to Cohen (21), with η² of 0.01 being small; 0.06 medium; and 0.14 large. The Bonferroni test was used to perform post-hoc analysis when necessary.

Pearson's correlation coefficient (r) was used for the correlation analysis, following Cohen's recommendation:²¹ 0.10 < r < 0.30 was considered a weak correlation; 0.30 < r < 0.49 was moderate; and r ≥ 0.50 was strong. The significance level was set at 5% (α = 0.05) in all analyses.

 

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Results

The ESS responses differed significantly between the groups (F [1]: 4.484; p = 0.043*; η² = 0.105), with a medium effect size. Individuals who did not use CPAP scored higher in all assessments than those who used it. There was no difference between the three assessments; responses remained stable over time (F [1.588]: 32.913; p = 0.133; η² = 0.014), as shown in [Fig. 1].

Fig. 1 Comparison of scores obtained in the Epworth Sleepiness Scale between the groups in each assessment.

The final FOSQ-10 scores did not differ significantly regarding either the group (F [1]: 1.002; p = 0.325; η² = 0.026) or assessment (F [1]: 1.065; p = 0.338; η² = 0.008), as shown in [Table 4].

Table 4 Scores obtained by FOSQ in each assessment, in groups with and without CPAP.

Assessment	CPAP Group	Minimum	Maximum	Mean	SD
1st	With	12	39	29.056	7.635
	Without	15	38	26.462	8.550
2nd	With	10	40	29.000	9.337
	Without	14	38	27.154	8.345
3rd	With	13	40	31.333	7.852
	Without	12	39	27.615	9.042

Abbreviations: CPAP, continuous positive airway pressure; FOSQ, Functional Outcomes of Sleep Questionnaire; SD, standard deviation.

Likewise, the scores did not differ significantly regarding the group or assessment in subscales E1 (Activity level), E2 (Vigilance), or E3 (Intimacy and sexual relationship). On the other hand, subscale E4 (General productivity) differed significantly between the second and third assessments (F [1]: 4.231; p = 0.027*; η² = 0.024). The score was significantly higher in the third assessment (t = -2.759; p = 0.023*), regardless of the group. Also, subscale E5 (Social outcome) differed significantly between groups (F [1]: 6.074; p = 0.020*; η² = 0.122). Patients with CPAP scored higher than those without in all assessments ([Fig. 2]).

Fig. 2 Comparison of scores obtained in each subscale of the Functional Outcomes of Sleep Questionnaire-10 per group and assessment.

A qualitative analysis was initially performed per individual, calculating the percentage of normal and abnormal results for the absolute latency of each ABR wave and interpeak interval ([Table 5]). A higher percentage of abnormal results was found in the latency of both wave I and interpeak interval I to V. There was no association of ABR results regarding the groups in any assessment (p > 0.05).

Table 5 Percentage of normal and abnormal results for ABR absolute latencies and interpeak intervals per assessment in the groups with and without CPAP.

	Assessment	CPAP Group	Normal	Abnormal	Chi-squared test	Phi coefficient
Wave I	1st	With	3 (16.67%)	15 (83.33%)	X2 (1): 0.241 p = 0.623	0.166
		Without	4 (30.77%)	9 (69.23%)
	2nd	With	7 (38.89%)	11 (61.11%)	X2 (1): 0.292 p = 0.589	0.167
		Without	3 (23.08%)	10 (76.92%)
	3rd	With	4 (22.22%)	14 (77.78%)	X2 (1): 2.061 p = 0.151	0.326
		Without	7 (53.85%)	6 (46.15%)
Wave III	1st	With	9 (50.00%)	9 (50.00%)	X2 (1) < 0.001 p > 0.999	0.038
		Without	7 (53.85%)	6 (46.15%)
	2nd	With	8 (44.44%)	10 (55.56%)	X2 (1) < 0.001 p > 0.999	0.017
		Without	6 (46.25%)	7 (53.85%)
	3rd	With	8 (44.44%	10 (55.56%)	X2 (1) < 0.001 p > 0.999	0.017
		Without	6 (46.25%)	7 (53.85%)
Wave V	1st	With	9 (50.00%)	9 (50.00%)	X2 (1) < 0.001 p > 0.999	0.038
		Without	7 (53.85%)	6 (46.15%)
	2nd	With	9 (50.00%)	9 (50.00%)	X2 (1): 0.074 p = 0.786	0.114
		Without	8 (61.54%)	5 (38.46%)
	3rd	With	7 (38.89%)	11 (61.11%)	X2 (1): 0.001 p = 0.972	0.073
		Without	6 (46.25%)	7 (53.85%)
Interpeak interval I-III	1st	With	8 (44.44%)	10 (55.56%)	X2 (1) < 0.001 p > 0.999	0.017
		Without	6 (46.15%)	7 (53.85%)
	2nd	With	10 (55.56%)	8 (44.44%)	X2 (1): 0.023 p = 0.879	0.093
		Without	6 (46.15%)	7 (53.85%)
	3rd	With	7 (38.89%)	11 (61.11%)	X2 (1): 0.001 p = 0.972	0.073
		Without	6 (46.15%)	7 (53.85%)
Interpeak interval III- V	1st	With	7 (38.89%)	11 (61.11%)	X2 (1) < 0.001 p > 0.999	0.004
		Without	5 (38.46%)	8 (61.54%)
	2nd	With	9 (50.00%)	9 (50.00%)	X2 (1) < 0.001 p > 0.999	0.038
		Without	7 (53.85%)	6 (46.15%)
	3rd	With	5 (27.78%)	13 (72.22%)	X2 (1) < 0.001 p > 0.999	0.033
		Without	4 (30.77%)	9 (69.23%)
Interpeak interval I-V	1st	With	4 (22.22%)	14 (77.78%)	X2 (1): 0.015 p = 0.904	0.096
		Without	4 (30.77%)	9 (69.23%)
	2nd	With	7 (38.89%)	11 (61.11%)	X2 (1): 0.007 p = 0.932	0.084
		Without	4 (30.77%)	9 (69.23%)
	3rd	With	4 (22.22%)	14 (77.78%)	X2 (1) < 0.001 p > 0.999	0.010
		Without	3 (23.08%)	10 (76.92%)

Abbreviations: ABR, auditory brainstem response; CPAP, continuous positive airway pressure; X², Chi-squared test.

The quantitative analysis found no significant differences in any wave absolute latency or interpeak interval latency between either the groups or assessments.

The mean pure-tone thresholds obtained in the first assessment were significantly positively moderately correlated with the interpeak interval I to III only in the right ear (r = 0.385; p = 0.035*). This result demonstrated that the higher the mean auditory threshold, the greater the latency of the interpeak interval I to III in the right ear. The mean auditory thresholds were not correlated with the latencies of waves I, III, and V or with the interpeak intervals III to V and I (p > 0.05). Likewise, the length of CPAP use per night was not significantly correlated with the ABR absolute latencies or interpeak latencies in the 2^nd or 3^rd assessments (p > 0.05). Also, the ESS was not correlated with the ABR absolute latencies or interpeak latencies recorded in any of the ears, in any of the assessments (p > 0.05).

A qualitative analysis was performed per individual, calculating the percentage of normal and abnormal results in each LLAEP component. P2 and N2 had a higher percentage of abnormal results. There was an association in P2 results in the second assessment regarding the group, the group without CPAP had a higher proportion of abnormal results, whereas the “with” group had a higher proportion of normal results, with a large effect size ([Table 6]).

Table 6 Percentage of normal and abnormal LLAEP results in P1, N1, P2, N2, and P3 per assessment in the groups with and without CPAP.

	Assessment	CPAP Group	Normal	Abnormal	Chi-squared test	Phi coefficient
P1	1st	With	15 (83.33%)	3 (16.67%)	X2 (1) < 0.001 p > 0.999	0.080
		Without	10 (76.92%)	3 (23.08%)
	2nd	With	14 (77.78%)	4 (22.22%)	X2 (1): 0.349 p = 0.555	0.195
		Without	12 (92.31%)	1 (7.69%)
	3rd	With	14 (77.78%)	4 (22.22%)	X2 (1) < 0.001 p > 0.999	0.010
		Without	10 (76.92%)	3 (23.08%)
N1	1st	With	16 (88.89%)	2 (11.11%)	X2 (1) < 0.001 p > 0.999	0.057
		Without	12 (92.31%)	1 (7.69%)
	2nd	With	16 (88.89%)	2 (11.11%)	X2 (1) < 0.001 p > 0.999	0.057
		Without	12 (92.31%)	1 (7.69%)
	3rd	With	14 (77.78%)	4 (22.22%)	X2 (1): 0.349 p = 0.555	0.195
		Without	12 (92.31%)	1 (7.69%)
P2	1st	With	12 (66.67%)	6 (33.33%)	X2 (1): 2.590 p = 0.555	0.354
		Without	4 (30.77%)	9 (69.23%)
	2nd	With	15 (83.33%)	3 (16.67%)	X2 (1): 0.715 p = 0.010*	0.533
		Without	4 (30.77%)	9 (69.23%)
	3rd	With	11 (61.11%)	7 (38.89%)	X2 (1): 0.212 p = 0.645	0.148
		Without	6 (46.15%)	7 (53.85%)
N2	1st	With	8 (44.44%)	10 (55.56%)	X2 (1): 0.717 p = 0.397	0.220
		Without	10 (76.92%)	3 (23.08%)
	2nd	With	9 (50.00%)	9 (50.00%)	X2 (1): 1.311 p = 0.252	0.273
		Without	10 (76.92%)	3 (23.08%)
	3rd	With	12 (66.67%)	6 (33.33%)	X2 (1): 0.598 p = 0.439	0.205
		Without	7 (53.85%)	6 (46.15%)
P3	1st	With	16 (88.89%)	2 (11.11%)	X2 (1): 0.159 p = 0.690	0.161
		Without	10 (76.92%)	3 (23.08%)
	2nd	With	16 (88.89%)	2 (11.11%)	X2 (1): 0.159 p = 0.690	0.161
		Without	10 (76.92%)	3 (23.08%)
	3rd	With	13 (72.22%)	5 (27.78%)	X2 (1) < 0.001 p> 0.999	0.033
		Without	9 (69.23%)	4 (30.77%)

Abbreviations: CPAP, continuous positive airway pressure; LLAEP, long-latency auditory evoked potentials; X², Chi-squared test.

Note: * Statistically significant.

The quantitative analysis found a significant difference in P2 between the groups (F(1): 4.409; p = 0.045*; η²= 0.036), the group without CPAP had higher latency values than the one with, regardless of the ear or assessment, although with a small effect size ([Fig. 3]). No difference in P1, N1, N2, or P3 was found.

Fig. 3 Confidence interval for P2 latency by analysis of variance (ANOVA) for the group factor. Abbreviation: ms, milliseconds.

No significant difference was found for any of the amplitudes analyzed, and the mean hearing thresholds, length of CPAP use per night, and ESS scores were not correlated with LLAEP latencies or amplitudes recorded in any of the ears, in any assessment (p > 0.05).

 

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Discussion

The main objective of this study was to evaluate, for a period of 6 months, the effect of CPAP use in patients with moderate to severe OSA on their degree of sleepiness, functional quality of sleep, and electrophysiological responses of the central auditory pathways.

Based on ESS score classifications,[17] both groups had excessive sleepiness. The group with CPAP scored significantly lower than the group without CPAP. Nevertheless, this data had already been observed since the first assessment, this result may be due to selection bias. Although the ESS score decreased in the group with CPAP over time, this difference did not reach the level of significance used in this study, thus remaining stable over time.

From the responses obtained in the ESS, we noticed that the score improved in the group with CPAP, with the symptom of drowsiness being reported in the assessments performed after three and 6 months.

Silveira et al.[22] evaluated CPAP use in patients with OSA for 5 years and found that its continuous use decreased the level of sleepiness and improved the quality of sleep. The level of drowsiness in the CPAP group improved, but it remained at average drowsiness, that is, it did not return to normal.

The FOSQ-10 scores increased in the group with CPAP as treatment progressed – though not reaching the level of significance. On the other hand, the group without CPAP varied little over time, with no improvement in the functional quality of sleep. Nonetheless, the mean values remained abnormal, that is, above 17.9, as proposed by Weaver et al.[18]

This lack of significant improvement in functional sleep quality may be associated with adherence to CPAP. Weaver et al.[18] highlighted the need to use this therapy for 7.5 hours per night to normalize FOSQ-10 values and sleep quality. In the present study, the length of use per night (6.33 hours) may not have been enough to normalize functional sleep quality.

Patients who used and did not use CPAP obtained higher scores in the 3^rd than in the 2^nd assessment in FOSQ-10 General Productivity (subscale E4), indicating an improvement in the levels of concentration (attention) and memory over time. Furthermore, Social Outcomes (subscale E5) scores were higher in the group with CPAP than in the one that did not use it. However, this difference between the groups was observed before beginning CPAP use, with no significant improvement over time in either group. This result may be due to a possible sample selection bias.

Although no significant differences were observed, the qualitative analysis showed a large proportion of patients with increased absolute latency and interpeak latency responses, regardless of the ear or time of assessment. The electrophysiological hearing assessment through ABR found changes in all waves, both in terms of absolute latency and interpeak latencies. The percentage of abnormal results was higher in the latencies of both wave I and interpeak interval I to V for each ear, in all assessments.

Latency refers to the speed of acoustic stimulus transmission.[8] [23] Thus, even after 6 months of CPAP use, neuronal conduction from the auditory system to the brainstem remained increased, indicating that OSA can irreversibly damage the auditory system, to the point that even this technique use may not favor its plasticity.

This study corroborates the results found by Kotterba and Rasche,[24] who evaluated through ABR 20 patients with severe OSA before CPAP use. The authors observed an increase in the latency of wave I and interpeak intervals I to III and III to V, concluding that this finding is probably due to hypoxemia, and pointed out that ABR changes may represent a greater risk for stroke.

The study by Casale et al.[25] found an increased latency of waves I, III, and especially V and interpeak intervals I to V, I to III, and III to V, probably due to the consequences of OSA. The authors concluded that severe OSA can be considered a risk factor for changes in the auditory pathways.

Similar results were found by Matsumura,[26] who reported that 33% of patients with severe OSA had an increase in wave V latency, indicating slower nerve conduction of acoustic stimuli from the auditory pathway to the brainstem. The author also observed a greater change in interpeak I to V latency in patients with moderate and severe OSA.

In line with these results, we can also mention the study by Fu et al.,[27] who evaluated 116 subjects to verify the auditory pathways in patients with moderate OSA. They found a significant difference in the latencies of waves I, III, and V and interpeak intervals I to III, III to V, and I to V, suggesting that the auditory changes worsened according to the severity of OSA.

Regarding the response to treatment, Muchnik et al.[28] evaluated 79 patients with mild, moderate, and severe OSA and found an increase in the latency of waves I, III, and V compared with a group of healthy individuals. Although the patients underwent uvulopalatopharyngoplasty, there were no significant differences in wave latencies before and after the surgery. The authors concluded that the cumulative effects of hypoxia in these patients resulted in delayed ABR latencies. Although it focused on surgical treatment, both Muchnik et al.[28] and the present study found that the ABR examination remains abnormal in patients with moderate to severe disorder even after treatment.

Similarly, Mastino et al.[29] aimed to observe the effect of CPAP on auditory function and verify whether oxidative stress is related to auditory system damage in OSA. They found that the auditory pathways did not present either positive or negative results with this treatment.

The absence of differences in results between the groups (with versus without CPAP) led us to believe that there is a predisposition to changes in the central auditory pathways, as all participants in this research had moderate to severe OSA – which may be permanent, even with treatment.

Moreover, there were changes in all LLAEP components, with a higher percentage of abnormal results in P2 and N2.

In the second assessment, the group without CPAP had a higher percentage of abnormal P2 results than the “with” group, leading us to attribute this change to nocturnal hypoxia, affecting auditory and cognitive functions. Nevertheless, the number of changes in P2 increased again after 6 months of treatment, which indicates that the damage caused by OSA may be irreversible, since there was no significant change in the exams related to the central auditory pathways.

This higher percentage of abnormal P2 and N2 results suggests that the ability of patients with moderate to severe OSA to discriminate and process auditory information had been affected, regardless of CPAP treatment – possibly due to the disorder's damage.

This result corroborates the specialized literature that reports an increase in N2 latency in patients with OSA[10] [30] [31] and demonstrates that it affects the auditory pathways regardless of treatments. It is also similar to the findings by Vakulin et al.,[10] who also described that N2 remained abnormal in patients with severe disorders, regardless of the length of CPAP treatment and high adherence (6 hours per night).

Regarding P2 results, we can mention the studies by Rumbach et al.,[31] Sforza et al.,[32] and Wong et al.,[33] who also found an abnormal P2 in patients with severe OSA. All studies had shorter reassessment intervals than the present one.

Wong et al.[33] investigated patterns of neurocognitive dysfunction in OSA using LLAEP, evaluating 50 individuals with predisposition and 200 without this disorder. They observed prolonged P2 and N2 latencies in patients with a predisposition to OSA. The same result was observed by Donzel-Raynaud et al.,[34] who justified these results based on the damage caused by hypoxia, seemingly due to correlation between abnormal auditory evoked potential and the disorder's severity. In addition to hypoxia, fragmented sleep may also contribute to these changes.

The present study found no significant differences in LLAEP amplitudes in any of the analyses. Akcali et al.[35] examined 27 patients with OSA and 29 healthy individuals to verify the effect of age. Those under 45-years-old were designated as the younger group, while those aged 45 years or older were designated as the older group. The authors observed a decreased amplitude and prolonged latency in the test's components in all patients with OSA. Regarding age, the amplitude of the older group with OSA did not differ from the group without CPAP, suggesting that the LLAEP reveals the effects of the disorder on cognitive function. This may justify the results obtained in the present study, as the mean age of our participants was 54.09 years, and no changes were found in CPAP treatment for up to 6 months, suggesting this timeframe is not enough to increase the number of neurons involved in the cognitive processes of older individuals.

Besides age, other comorbidities commonly found in patients with OSA, such as hypertension, respiratory diseases, and diabetes, may influence the central auditory pathways. Nonetheless, other studies that controlled this variable also found significant changes in their patients' central auditory pathways. Pedreno[11] demonstrated an exclusive effect of OSA on the central auditory pathways.

Although the degree of sleepiness, hearing thresholds, and length of CPAP use in the present study were not correlated with electrophysiological hearing responses in general, a limitation was the lack of information regarding the exact time of OSA onset. Hence, it was impossible to measure the time from the disease onset and diagnosis and accurately determine the moment when the auditory pathways began to suffer possible interference due to lack of oxygenation, causing permanent changes.

This data highlights the importance of public policies aimed at broadly disseminating the effects of OSA to the general population and ensuring that health services can identify risk factors and diagnose it. These strategies could provide individuals with a greater chance of reversing the resulting comorbidities, thus ensuring a better quality of life.

Additionally, this study has other limitations, including the small sample size and the lack of objective data on the exact number of hours used per night and the frequency of use per week, which should be checked in future studies.

 

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Conclusion

Although patients with moderate to severe OSA used CPAP for 6 months, excessive daytime sleepiness (verified with the ESS) remained in both groups, and the functional quality of sleep improved little only in the FOSQ-10's General Productivity subscale. However, this occurred in both groups, indicating the need for an evaluation over longer treatment.

The evaluation of the central auditory pathway at the brainstem level using ABR did not demonstrate any modification with CPAP use for 6 months due to probable factors such as hypoxia, comorbidities, age group (aging), all of which can irreversibly damage patients' bodies. Thus, OSA is a risk factor for the central auditory pathways, as changes were found in all ABR waves.

The evaluation of cortical auditory pathways with LLAEP found a short-term P2 improvement (that is, at 3 months), but it was not maintained in the subsequent assessments. As for the other components, no changes in latencies or amplitudes were found throughout the monitoring time.

 

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Conflict of Interests

The authors have no conflict of interests to declare.

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Publikationsverlauf

Eingereicht: 01. Oktober 2024

Angenommen: 07. Februar 2025

Artikel online veröffentlicht:
07. Juli 2025