Analysis of nasal resistance regulation mechanism during postural changes in patients with obstructive sleep apnea by measuring heart rate variability

Abstract

Study Objectives:

Changes in nasal resistance (NR) during postural changes are influenced by venous filling pressure and autonomic nervous system mediation, and heart rate variability (HRV) can reflect changes in the autonomic nervous system. This study aimed to explore the regulatory mechanisms of NR in patients with obstructive sleep apnea (OSA) during postural changes.

Methods:

Healthy controls (apnea-hypopnea index < 5 events/h) and patients with OSA were recruited. NR and electrocardiogram data were collected in sitting, supine, left-lateral, and right-lateral postures. HRV parameters were obtained by analyzing the electrocardiogram data from each posture. Subgroups were divided according to sitting–supine NR changes, and HRV parameters were compared between different postures and groups/subgroups.

Results:

In total, 34 healthy controls and 39 patients with OSA (mean apnea-hypopnea index 34.34 ± 22.44 events/h) were recruited. During sitting–supine postural changes, the NR increased in the control group but did not change significantly in the OSA group. None of the autonomic nervous system–related HRV parameters changed significantly. After the groups were divided into NR-elevated and NR-unchanged subgroups, sympathetic activity–related HRV parameters were higher in the NR-unchanged subgroup but only statistically significant in the OSA group. When comparing the left and right postures, there was no significant change in NR; however, the OSA group had lower parasympathetic activity–related HRV parameters when in the right posture.

Conclusions:

During postural changes from the sitting to supine positions, the total NR increases, and this increment is smaller in patients with OSA. This is likely due to overregulation of sympathetic activity, which may occur in patients with OSA.

Citation:

Shi Y, Lou H, Wang H, et al. Analysis of nasal resistance regulation mechanism during postural changes in obstructive sleep apnea patients by measuring heart rate variability. J Clin Sleep Med. 2023;19(4):643–650.

BRIEF SUMMARY

Current Knowledge/Study Rationale: Patients with obstructive sleep apnea often experience nasal obstruction symptoms without a significant increase in nasal resistance. The different regulatory mechanisms of nasal resistance during postural changes may explain why patients with obstructive sleep apnea do not demonstrate high nasal resistance.

Study Impact: Studies have confirmed that patients with obstructive sleep apnea have different mechanisms of nasal resistance regulation, and these are mediated by the sympathetic nervous system. This suggests a new exploratory direction regarding the relationship between obstructive sleep apnea and nasal obstruction and the corresponding regulatory mechanism.

INTRODUCTION

Obstructive sleep apnea (OSA) is characterized by recurrent complete and partial upper airway collapse during sleep, resulting in intermittent hypoxemia, autonomic nervous system (ANS) fluctuation, and sleep fragmentation.¹ The estimated global prevalence is 29% (almost 1 billion people).² Nasal obstruction has been reported to be a risk factor for OSA, regardless of the cause. In 2001, Young et al^3,4 discovered a relationship between nocturnal obstruction and sleep apnea and verified it in a large population. Temporarily increased nasal resistance (NR), such as nasal packing, is also known to cause OSA.⁵ The Starling resistor model may explain this relationship, in which an upstream (nose) obstruction will generate an increased downstream (oropharynx) suction force (negative intraluminal pressure) to maintain an equal tidal volume, thereby contributing to oropharyngeal collapse.⁶

NR is affected by many elements, including posture. In nose-breathing healthy individuals, several studies found that NR increased during postural changes from seated to supine positions.^7–9 However, this phenomenon was not significant in patients with OSA.^10–12 Hanif et al¹³ believed that the above phenomenon is regulated by 2 different mechanisms. First, an increase in the filling central venous pressure, which is generated by the act of lying down, can lead to nasal mucosa congestion and ultimately increase one’s NR.¹⁴ At the same time, a reflex mediated by the ANS is activated that constricts the nasal blood vessel and ultimately reduces NR.^7,15 However, it is unclear which step OSA interferes with to cause the difference in postural NR regulation.

Heart rate variability (HRV) analyzes the variation over time between consecutive heartbeats and is used as a valuable tool to investigate the function of the ANS.¹⁶ By calculating time-domain and frequency-domain measurements, some HRV parameters such as the low-frequency (LF) component, high-frequency (HF) component, and LF-to-HF ratio (LF:HF) have been proven to be associated with the sympathetic nervous system (SNS) and parasympathetic (vagus) nervous system (PNS).⁸

We speculate that there may be different NR regulatory mechanisms underlying postural changes in patients with OSA. This study aimed to explore the influence of postural changes on NR and HRV and how OSA interferes with the NR regulation mechanism.

METHODS

Participants

Participants were recruited from the Sleep Center of Beijing Tongren Hospital, Capital Medical University. The inclusion criteria were as follows: (1) patients between 18 and 65 years of age, (2) those who signed the informed consent form, and (3) those who could accurately complete and finish the examination. The exclusion criteria were as follows: (1) OSA-related surgical treatment history, including uvulopalatopharyngoplasty, tonsillectomy, septoplasty, and nasal valve reconstruction; (2) recent (< 2 weeks) upper respiratory infection or allergic rhinitis (diagnosed by history inquiry, clinical symptoms, and physical examination); (3) use of topical nasal treatments, including decongestants, corticosteroids, and antihistamines; (4) complete nasal obstruction measured using anterior rhinoscopy; and (5) coexisting lung, neurological, cardiovascular, or psychiatric disorders. The study was approved by the Institutional Review Board of Beijing Tongren Hospital (TRECKY2019-109).

Baseline data, including age, body mass index, and Nasal Obstruction Symptom Evaluation (NOSE) score, were collected following acquisition of consent.

Overnight polysomnography

In all participants, polysomnography data were collected using a T3 device (Nox Medical, Reykjavik, Iceland), including nasal cannula pressure, thoracic and abdominal respiratory bands, body position, electrocardiogram, and pulse oximetry for oxygen saturation (SpO₂). The polysomnography data were analyzed by 2 professional technicians following the criteria proposed by the American Academy of Sleep Medicine in 2012. Participants with sleep-disordered breathing–related clinical symptoms and an apnea-hypopnea index (AHI) ≥ 5 events/h were diagnosed with OSA according to the International Classification of Sleep Disorders, third edition (ICSD-3).

Rhinomanometry

An NR6 Rhinomanometer (GM Instruments, Irvine, UK) was used to measure NR during normal breathing. After separately measuring the unilateral NR (including R_left and R_right) values, the NR (R_total) was calculated according to the following equation:

$$\frac{1}{R_{\mathit{\text{total}}}}=\frac{1}{R_{\mathit{\text{left}}}}+\frac{1}{R_{\mathit{\text{right}}}}$$

The examination was started after the participants rested in a sitting posture for more than 15 minutes in a temperature-controlled room. Measurements were performed in sitting, supine, left-lateral, and right-lateral postures. To obtain a stable NR value in each posture while minimizing the influence of the nasal cycle, measurements were taken after maintaining the posture for at least 5 minutes, and the entire measurement time of each participant was limited to 40 minutes. NR increment was calculated using the following equation.

$$\text{sitting}–\text{supine NR increment}={\text{log}}_{10}\left(\text{supine NR}\right)-{\text{log}}_{10}\left(\text{sitting NR}\right)$$

Considering that postural changes had the same effects on the inspiration NR and expiration NR values, only the inspiration NR data are shown in the results, while the expiration NR data are compressed in the supplemental data (Supplemental Table S1 ^{(330.6KB, pdf)} , Table S2 ^{(330.6KB, pdf)} , and Table S3 ^{(330.6KB, pdf)} ).

HRV analysis

Electrocardiograms during postural changes were calculated using SOMTE-PSG (Compumedics, Victoria, Australia) with a 200-Hz sample frequency. The signal was divided into 30-second segments marked with the body position at the time. Segments with poor signals were excluded prior to the subsequent HRV data extraction. In Python 3.8, the biosppy (0.8.0), heartpy (1.2.6), and hrv-analysis (1.0.3) packages were used to preprocess the raw signals, acquire the normal-normal (NN) intervals, and extract the HRV features, respectively ^36–38. Signal preprocessing included a notch filter (0.05 Hz) and a band filter (0.3–70 Hz). Finally, the LF:HF and LF component were selected as the SNS-related HRV parameters. For the PNS-related HRV parameters, the HF component, root mean square of successive NN interval differences (RMSSD), and the proportion of NN50 (the number of pairs of successive NN intervals that differed by > 50 milliseconds) divided by the total number of NN intervals (PNN50) were selected.¹⁶

Statistical analysis

SPSS (version 23.0; IBM Corporation, Armonk, NY, USA) was used for the statistical analysis. Student’s t test and nonparametric tests were used to determine whether the data conformed to a normal distribution. Analysis of covariance was used to observe the differences in HRV variation between the groups. Mean ± standard deviation or median [25th, 75th percentile] values were calculated, and P < .05 was used to indicate a statistically significant relationship between groups. A log₁₀ transformation was used on the NR, HF, LF, and LF:HF values to correct the skewed distribution.

RESULTS

Participant characteristics

A total of 73 participants were recruited for this study (Table 1). The distribution of nasal septal deviation was not statistically different (χ² = 0.828, P = .363); however, self-reported nasal obstruction (NOSE score ≥ 30) was more common in patients with OSA (59.0% vs 32.4%, χ² = 5.174, P = .023).

Table 1.

Baseline characteristics of the study group.

	Total (n = 73)	Control (n = 34)	OSA (n = 39)	P
Age, y	37.22 ± 10.90	32.24 ± 9.88	40.69 ± 10.66	.003
Sex (male/female), n	52/21	20/14	32/7	.039
AHI, events/h	19.02 ± 23.24	1.44 ± 1.68	34.34 ± 22.44	< .001
BMI, kg/m2	25.74 ± 4.57	24.15 ± 4.36	27.13 ± 4.34	.005
NOSE score	28.97 ± 23.40	22.50 ± 23.62	34.62 ± 21.96	.026
Nasal congestion or stuffiness	1.30 ± 1.13	1.12 ± 1.15	1.46 ± 1.10	.195
Nasal blockage or obstruction	1.36 ± 1.23	1.06 ± 1.23	1.62 ± 1.18	.053
Trouble breathing through my nose	1.03 ± 1.14	0.76 ± 1.07	1.26 ± 1.16	.066
Trouble sleeping	0.67 ± 0.94	0.47 ± 0.79	0.85 ± 1.04	.090
Unable to get enough air through my nose during exercise or exertion	1.44 ± 1.20	1.09 ± 1.11	1.74 ± 1.21	.019
Nasal septal deviation, n (%)	24 (32.9%)	13 (38.2%)	11(28.2%)	.456

AHI = apnea-hypopnea index, BMI = body mass index, NOSE score = Nasal Obstruction Symptom Evaluation questionnaire score (0–100), OSA = obstructive sleep apnea.

Differences in NR according to body posture

When the patients’ postures changed from sitting to supine positions, the NR in the control group increased (–0.673 ± 0.157 to –0.578 ± 0.178 [log₁₀Pa/cm³/s], t = –5.558, P < .001), while the NR in the OSA group did not change significantly (–0.672 ± 0.153 to –0.647 ± 0.127 [log₁₀Pa/cm³/s], t = –1.294, P = .203). When their postures changed from the supine to left-lateral positions, the NR did not change significantly in the control group (–0.578 ± 0.178 to –0.565 ± 0.189 [log₁₀Pa/cm³/s], t = –0.474, P = .638); however, the NR was significantly increased in the OSA group (–0.647 ± 0.127 → –0.582 ± 0.201 [log₁₀Pa/cm³/s], t = –2.816, P = .008). Notably, NR values did not differ between the left and right postures in both groups (control group: P = .624; OSA group: P = .436).

Compared with the control group, the NR values in the OSA group did not differ significantly while in the sitting, left-lateral, and right-lateral positions (P = .972, P = .719, and P = .941, respectively). While in the supine posture, the NR appeared to be lower in the OSA group; however, the difference was not statistically significant (P = .059) (Figure 1).

Figure 1. Total nasal resistance (inspiration) variation in different postures.

OSA = obstructive sleep apnea (group).

NR increments were calculated according to different body postural changes and compared between groups. The sitting–supine NR increment was significantly lower in the OSA group (0.095 ± 0.100 vs 0.025 ± 0.122 [log₁₀Pa/cm³/s], P = .010), while the supine-left, supine-right, and left-right NR increment did not differ between the groups (P = .140, P = .185, and P = .735, respectively) (Table S2 ^{(330.6KB, pdf)} in the supplemental material). Pearson’s correlation analysis was performed between AHI scores and sitting–supine NR increment, and the correlation was significantly negative (inspiration: ρ = –0.331, P = 0.004; expiration: ρ = –0.301; P = .010) (Figure 2).

Figure 2. Correlation between AHI and sitting-supine NR increment (inspiration).

AHI = apnea-hypopnea index, NR = total nasal resistance, OSA = obstructive sleep apnea (group).

Difference in HRV according to body posture

When the patients’ postures changed from the sitting to supine positions, the ANS-related HRV parameters did not change significantly in the groups. When comparing the left and right lateral postures, there were no differences in the control group (LF:HF: P = .921; LF: P = .332; HF: P = .311; RMSSD: P = .616; PNN50: P = .930); however, the OSA group had lower PNS-related HRV parameters when in the right posture (HF: P < .001; RMSSD: P = .002; PNN50: P = .001).

Compared with the control group, the SNS-related HRV parameters did not differ in all postures; however, the PNS-related HRV parameters were lower in the supine and right postures (supine: HF, P = .205; RMSSD, P = .058; PNN50, P = .006; right-lateral: HF, P = .041; RMSSD, P = .042; PNN50, P = .001) (Table 2).

Table 2.

HRV parameters at different postures in the control and OSA groups.

HRV Parameters	Sitting	Supine	Left	Right
Control group (n = 34)
SNS-related
LF:HF	0.50 ± 0.19	0.55 ± 0.16	0.53 ± 0.20	0.52 ± 0.16
LF, ms2	3.58 ± 0.47	3.68 ± 0.55	3.59 ± 0.41	3.49 ± 0.50
PNS-related
HF, ms2	3.08 ± 0.46	3.13 ± 0.48	3.06 ± 0.40	2.97 ± 0.46
RMSSD, ms	63.93 ± 28.43	74.46 ± 31.62	64.86 ± 25.88	61.69 ± 30.03
PNN50	1.01 ± 0.41	1.08 ± 0.45	1.07 ± 0.34	1.06 ± 0.44
OSA goup (n = 39)
SNS-related
LF:HF	0.50 ± 0.22	0.51 ± 0.20	0.55 ± 0.20	0.53 ± 0.24
LF, ms2	3.50 ± 0.51	3.50 ± 0.51	3.61 ± 0.58	3.29 ± 0.50†‡§
PNS-related
HF, ms2	3.00 ± 0.56	2.99 ± 0.47	3.06 ± 0.49	2.75 ± 0.43*†‡§
RMSSD, ms	59.51 ± 30.94	60.75 ± 29.05	66.74 ± 33.59	48.11 ± 25.98*†‡§
PNN50	0.79 ± 0.54	0.76 ± 0.51*	0.89 ± 0.45	0.66 ± 0.52*§

*P < .05 compared with control group. †P < .05 compared with sitting posture. ‡P < .05 compared with supine posture. §P < .05 compared with left posture. HF = high frequency, HRV = heart rate variability, LF = low frequency, OSA = obstructive sleep apnea, PNN50 = proportion of NN50 (the number of pairs of successive NN intervals that differ by > 50 ms) divided by the total number of NN intervals, PNS = parasympathetic nervous system, RMSSD = root mean square of successive NN interval differences, SNS = sympathetic nervous system.

Relationship between HRV and NR increment in the 2 groups

When subgrouping was performed to compare the differences in ANS variation between the NR-elevated subgroup and the NR-unchanged subgroup (split according to NR increment ≥ 0.5 [log₁₀Pa/cm³/s]; Figure 2), the OSA group constituted more NR-unchanged participants (21/18 vs 8/26; χ² = 6.972, P = .008). During sitting-to-supine postural changes, an analysis of covariance of the supine HRV parameters was performed after adjusting for the corresponding sitting HRV parameters, age, and body mass index in both the control and OSA groups. The SNS-related HRV parameters tended to be higher in the NR-unchanged subgroup, but these were only statistically significant in the OSA group (control group: LF:HF, P = .137; LF, P = .059; OSA group: LF:HF, P = .036; LF, P = .493). In contrast, the PNS-related HRV parameters were not different between the 2 groups (Table 3).

Table 3.

HRV analysis between NR increment subgroups during sitting–supine postural changes.

Adjusted HRV Parameters (mean ± SE)	Control			OSA
	NR-Elevated (n = 26)	NR-Unchanged (n = 8)	P	NR-Elevated (n = 18)	NR-Unchanged (n = 21)	P
SNS parameter
LF:HF	0.526 ± 0.027	0.610 ± 0.048	.137	0.427 ± 0.047	0.574 ± 0.043	.036
LF, ms2	3.580 ± 0.104	4.007 ± 0.189	.059	3.432 ± 0.126	3.556 ± 0.116	.493
PNS parameter
HF, ms2	3.060 ± 0.092	3.379 ± 0.168	.107	2.986 ± 0.113	2.998 ± 0.104	.943
RMSSD, ms	70.669 ± 6.038	86.797 ± 10.954	.209	59.275 ± 6.685	62.015 ± 6.139	.776
PNN50	1.040 ± 0.080	1.231 ± 0.148	.271	0.804 ± 0.125	0.728 ± 0.115	.672

HF = high frequency, HRV = heart rate variability, LF = low frequency, NR = nasal resistance, OSA = obstructive sleep apnea, PNN50 = proportion of NN50 (the number of pairs of successive NN intervals that differ by > 50 ms) divided by the total number of NN intervals, PNS = parasympathetic nervous system, RMSSD = root mean square of successive NN interval differences, SE = standard error, SNS = sympathetic nervous system.

Correlation between AHI and ANS-related HRV parameters

Pearson’s correlation analysis was performed between the AHI and HRV parameters of patients in different postures. A negative correlation between the AHI and PNS-related HRV parameters was observed only for the supine and right postures. SNS-related HRV parameters were not significantly correlated with AHI in any posture (Table 4).

Table 4.

Correlation between AHI and HRV parameters.

HRV Parameters	AHI
	Sitting	P	Supine	P	Left	P	Right	P
SNS parameter
LF:HF	−0.135	.253	−0.004	.972	0.108	.364	−0.012	.921
LF, ms2	−0.003	.980	−0.256*	.029	0.110	.354	−0.225	.055
PNS parameter
HF, ms2	0.052	.663	−0.285*	.014	0.076	.523	−0.248*	.034
RMSSD, ms	0.065	.582	−0.293*	.012	0.128	.280	−0.268*	.022
PNN50	−0.146	.219	−0.440**	.000	−0.077	.516	−0.346**	.003

*P < .05 with Pearson correlation analysis. **P < .01 with Pearson correlation analysis. AHI = apnea-hypopnea index, HF = high frequency, HRV = heart rate variability, LF = low frequency, PNN50 = proportion of NN50 (the number of pairs of successive NN intervals that differ by > 50 ms) divided by the total number of NN intervals, PNS = parasympathetic nervous system, RMSSD = root mean square of successive NN interval differences, SNS = sympathetic nervous system.

DISCUSSION

By measuring NR in different postures, we confirmed that NR increases when transitioning from a sitting to supine position, and this increment was lower in the OSA group. Through the simultaneous measurement of HRV in each posture, we found that, compared with the NR-elevated subgroup, sympathetic activity was higher in the NR-unchanged subgroup, especially in the comparison within the OSA group. This evidence supports the theory concerning an overregulation mechanism. In addition, a negative correlation was observed between the AHI and PNS activity, which provides more clues regarding the mechanism by which OSA leads to nonelevated NR.

Sitting–supine NR changes

During sitting-to-supine postural changes, the NR increased in both the OSA and control groups, corroborating the findings in a previous study.¹⁷ In 1969, Rundcrantz⁷ found that the NR increased when a healthy person was lying down, which was also verified in a series of subsequent studies.^18,19 The sitting–supine NR increment was lower in the OSA group, which is consistent with a series of previous studies.^10,12,20 In addition, a recent meta-analysis concluded that patients with OSA had a higher NR increment than asymptomatic controls.²¹ It should be noted that 2 studies that contributed to our results enrolled selected patients. One study recruited patients with OSA who were waiting to undergo nasal surgery²² and the other selected those who were suitable for mandibular advancement device treatment.²³ Such selection resulted in a group with a higher proportion of nasal symptoms and nasal diseases, which have been shown to affect sitting–supine NR increment.^7,18

Sitting–supine HRV changes

According to the existing literature, HRV parameter responses to postural changes vary in healthy people. Similar to our study, Hayano et al²⁴ did not find a difference in HRV parameters between sitting and supine postures. In contrast, Ko et al⁸ found that LF:HF and LF values were lower in the supine position, representing a decrease in PNS activity; however, Jiang et al²⁵ believed that the LF:HF ratio was higher in the supine position. A convincing explanation is that not all sympathetic activity changes occur in the same direction as in sitting–supine postural changes. Postural tachycardia syndrome suggests that the supine posture reduces sympathetic activity in some people; however, patients with primary insomnia show improved sympathetic activity,^25,26 indicating that different diseases have different effects on HRV postural changes.

Relationship between HRV and NR increment

The main purpose of this study was to explain why the sitting–supine NR increment was lower in the OSA group by analyzing ANS-related HRV parameters. Using covariance analysis, we found that the sympathetic activity was higher in the NR-unchanged group than in the NR-elevated group, confirming our main hypothesis that sympathetic overregulation nullifies or even reverses the NR increment resulting from the increased filling pressure of nasal vessels. Many studies have shown that the sympathetic nerves are involved in NR changes. Tetraplegic patients showed higher NR and disappearance of the nasal cycle due to disruption of the SNS.^27,28 Notably, the use of adrenergic receptor antagonists (such as prazosin) blocks the regulation reflex mediated by the SNS, resulting in abnormally elevated NR values during sitting–supine postural changes.¹⁴

A previous study demonstrated that patients with OSA have ANS alterations, especially sympathetic hyperexcitability.²⁹ Regrettably, our study only demonstrated a negative correlation between parasympathetic activity and AHI but failed to obtain solid evidence of sympathetic hyperexcitability. Consistent with our results, a worldwide study enrolling 1,247 participants found that awake HRV measures were associated with OSA in some time-domain measures (RMSSD); however, no differences were found in the overall frequency-domain measures (LF:HF, LF, and HF).³⁰ This is likely related to the limitations of HRV measurement, where HRV is primarily affected by the PNS, and when the parasympathetic activity is broadly reduced, the possible OSA sympathetic hyperexcitability is nullified.³¹ In the covariance analysis of the OSA group, the NR-unchanged subgroup had a higher LF:HF; however, the lack of difference in the LF component also reflected the same problem: although the LF component can reflect sympathetic activity, it is also modulated by the PNS.³²

HRV differences between left-right lateral postures

We found that, compared with the left posture, the right posture had no significant difference in NR, while patients with OSA had lower PNS-related HRV parameters while in the right lateral posture. It is difficult to explain why patients with OSA demonstrated differences in parasympathetic activity in the few existing studies.^8,33,34 A possible explanation is that, when lying on the right side, patients with OSA may have minimal airway collapse possibility and heart compression pressure. In addition, Wieslander et al³⁵ found pulmonary circulation asymmetry between the left and right lateral postures; however, their effect on the ANS requires further study.

Limited by the experimental conditions, the results of this study were generated in a specific population (from a single center, excluding patients with nasal mucosa–related diseases and nasal spray use), and further research is needed to explore the universality of the conclusions in the OSA population. Notably, we did not measure the catecholamine or renin-angiotensin levels excreted from multiple points of the nasal cavity and heart, which are the gold standard of sympathetic activity.

When postural changes occur from the sitting to supine positions, the total NR increases, and this increment is smaller in patients with OSA. This difference in NR increment is likely caused by overregulation of sympathetic activity, which may occur in patients with OSA.

DISCLOSURE STATEMENT

All authors have seen and approved this manuscript. This study was funded by the National Natural Science Foundation of China (81970866) and the Beijing Municipal Administration of Hospitals’ Youth Program (grant number QMS20190202). The sponsor had no role in the design or conduct of this research. The authors report no conflicts of interest.

ABBREVIATIONS

AHI,

apnea-hypopnea index

ANS,

autonomic nervous system

HF,

high frequency

HRV,

heart rate variability

LF,

low frequency

NN,

normal-normal

NR,

nasal resistance

OSA,

obstructive sleep apnea

PNN50,

proportion of NN50 (the number of pairs of successive NN intervals that differ by > 50 ms) divided by the total number of NN intervals

PNS,

parasympathetic nervous system

RMSSD,

root mean square of successive NN interval differences

SNS,

sympathetic nervous system