SLEEP, Vol. 28, No. 12, 2005 1554 Nasal Acoustic Reflection in OSAHS—Li et al

INTRODUCTION

OBSTRUCTIVE SLEEP APNEA-HYPOPNEA SYNDROME (OSAHS) IS CHARACTERIZED BY EPISODES OF COM-PLETE OR PARTIAL PHARYNGEAL OBSTRUCTION during sleep and is combined with excessive daytime sleepiness or at least 2 other major symptoms.1 Patients with OSAHS have a high-er rate of automobile and work-related accidents and an increased risk of cardiovascular disease and cardiopulmonary disorder.2,3 Nasal continuous positive airway pressure (CPAP) is the treat-ment of choice in OSAHS patients, acting by blowing pressurized air through the nasal passages to prevent airway collapse. Several researchers have suggested that nasal obstruction may exacerbate OSAHS through increased nasal resistance, necessitating a higher inspiratory pressure, pressure changes resulting from Bernoulli’s effects, or mouth opening during sleep.4,5 Furthermore, nasal

symptoms have been reported in approximately 60% of CPAP users and may adversely affect CPAP use.6,7 Nevertheless, the de-cision to prescribe CPAP for patient with OSAHS in sleep labo-ratories may often be made without formally assessing patients’ nasal configuration and morphology, and nasal function generally may be overlooked as a factor in patients’ intolerance of nasal CPAP. Nasal surgery has been used as a component of the surgical treatment of snoring and OSAHS, and nasal resistance has been proven to play a role in contributing to obstructive sleep apnea.8,9 However, little information has been published concerning the relationship between objective nasal dimensions and tolerance of CPAP.10

Acoustic reflection is a noninvasive technique for determin-ing the internal dimensions of the airway of varying cross-section developed by Fredberg et al.11 This technique estimates the up-per-airway cross-sectional area or volume from the behavior of an incident sound wave and its subsequent reflection, and computed this as a function of distance from the mouth. Although some components have been modified to extend its clinical application in the past 20 years, the principle remains valid.12 In this study, acoustic reflection was used to measure the nasal cavity instead of the upper airway via the oral route, as we have done in our previous research. We therefore first assessed an in-vitro nasal-airway model to assess the validity of nasal acoustic reflection and identify the accuracy of the measurements obtained and then investigated relationships between nasal airway caliber, clinical outcomes, and tolerance of CPAP in patients with OSAHS.

Acoustic Reflection for Nasal Airway Measurement in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome Hsueh-Yu Li, MD1,2; Heather Engleman1; Chung-Yao Hsu, MD1,3; Bilgay Izci, MSc1; Marjorie Vennelle, RGN1; Melanie Cross, MD1; Neil J Douglas, MD1

1Department of Sleep Medicine, Royal Infirmary, Edinburgh, UK; 2Department of Otolaryngology, Sleep Center, Chang Gung Memorial Hospital, Tai-pei, Taiwan; 3Department of Clinical Neuroscience, Kaohsiung Medical University, Kaohsiung, Taiwan

Disclosure StatementThis was not an industry supported study. Dr. Douglas has received research support from ResMed, Ltd; and has participated in the Medical Advisory Board of ResMed, Ltd. Drs. Li, Engleman, Hsu, Izci, Vennelle, and Cross have indicated no financial conflicts of interest.

Submitted for publication February 2005Accepted for publication August 2005Address correspondence to: Neil J Douglas, MD, Department of Sleep Medicine, Royal Infirmary Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, UK; Tel: 44 0 131 242 1836; Fax: 44 0 131 242 1776; E-mail: n.j.douglas@ed.ac.uk

Study Objective: To measure nasal dimensions and explore relationships between these and patients’ use of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).Design: Prospective single-blind study.Setting: A tertiary-care, sleep disorders referral center. Patients: Sixty OSAHS patients (52 men, mean age 51 years, body mass index (BMI) 36.1 ± 9.4 kg/m2).Measurements: After in-vitro validation, acoustic reflection was used to measure the nasal minimal cross-sectional area (MCSA), mean area, and volume in OSAHS patients receiving CPAP treatment. Variables from sleep studies included the apnea-hypopnea index (AHI), titration pressure, and CPAP use (hours per night) after 3 months. Median MCSA was used to categorize subjects into small and large MCSA groups. Correlation and regression analyses were conducted to investigate the relationship be-tween results of polysomnography and nasal acoustic reflection. Results: At baseline the small and large MCSA groups were not different (P > .05) in BMI, age, mask type, or previous nasal stuffiness, but there were more women in the smaller MCSA group (P = .02). CPAP use was

significantly lower in the small MCSA group (P = .007), but apnea-hy-popnea index and titration pressure were indistinguishable between the 2 groups. Furthermore, CPAP use correlated significantly and positively with MCSA (r = 0.34, P = .008), mean area (r = 0.27, P = .04), and volume (r = 0.28, P = .03). Step-wise multiple regression models revealed that MCSA was a predictor of the CPAP compliance (R2 = 0.16, P = .002), and MCSA (P = .001) and age (P = .04) were predictive factors of CPAP compliance (R2 = 0.22). Nasal dimensions were not related to subjective nasal stuffiness.Conclusions: CPAP use in patients with smaller nasal passages was lower than in those with larger passages. Objective measurement of na-sal dimension may be more reliable than subjective self-report of nasal symptoms in identifying patients with OSAHS who might struggle with CPAP therapy. Keywords: Obstructive sleep apnea/hypopnea syndrome, acoustic re-flection, titration pressure, complianceCitation: Li HY; Engleman H; Hsu CY et al. Acoustic reflection for nasal airway measurement in patients with obstructive sleep apnea-hypopnea syndrome. SLEEP 2005;28(12): 1554-1559.

SLEEP, Vol. 28, No. 12, 2005 1555 Nasal Acoustic Reflection in OSAHS—Li et al

Aims

The primary analysis was to assess the association between na-sal area and compliance with CPAP. The secondary aim was to determine the relationship between nasal area and CPAP titration pressure.

MATERIALS AND METHODS

Nasal Model

A cylindrical Perspex tube (Figure 1), 10 cm in length, with 3 narrowing cross-sectional areas corresponding to nasal valve, anterior part of middle turbinate, and middle portion of the mid-dle turbinate, respectively,13 was used as a model to validate our acoustic reflectometer in assessing nasal dimensions. This nasal model is derived from our previous airway model with valida-tion.14 Fifteen measurements were obtained on 3 occasions over a 5-day period.

Pilot Study

At the beginning of the clinical study, we performed measure-ments of nasal acoustic reflection in 10 patients at diagnosis and 3 months after CPAP therapy to assess any impact of CPAP therapy on nasal dimensions.

Clinical Patients

This study was performed prospectively at a sleep disorders referral center. Patients had been diagnosed with OSAHS through polysomnography. Those patients with an apnea-hypopnea index (AHI) ≥ 15 and either an Epworth Sleepiness Scale score ≥ 10 or sleepiness while driving were eligible and invited by letter to par-ticipate in this study. Patients aged less than 16 or greater than 80 years, those residing 100 miles or more away from the Edinburgh Sleep Centre, or with serious coexisting lung, neurologic, cardio-vascular, psychiatric, or sleep disorder were excluded. Study par-ticipants were drawn from the Sleep Clinic population with the permission of the local ethics of medical research committees.

Sleep Study

Overnight polysomnography (Compumedics, Abbotsford, Aus-tralia) was performed using our usual techniques1 to document the

sleep and breathing for every patient. The AHI was defined as the total number of apnea and hypopnea episodes per hour of sleep, with apneas defined as a 10-second breathing pause and hypop-neas as a 10-second event during which there is continued breath-ing but the nasal pressure or thoracoabdominal movement is re-duced by at least 50% from the previous baseline during sleep.1 The single technician who scored the sleep studies was blind to acoustic-reflection measurement. After polysomnography, patients with an AHI > 15 and symp-toms of OSAHS were CPAP titrated and then issued a Sullivan 6 CPAP unit (ResMed, Sydney, Australia) set at the appropri-ate fixed pressure for 3 months, since this period correlates with long-term CPAP use.15 Use of CPAP was expressed by the usage time of CPAP per night, calculated by total CPAP machine run time divided by number of nights available for use.16 A device measuring the patient’s breathing on the CPAP machine was used to accurately measure the use time of CPAP.16 Patients complain-ing of nasal stuffiness were treated with nasal decongestants and, if that did not work, then given heated humidifiers.

Acoustic Reflection

The acoustic reflection technique used in this study was con-ducted in the laboratory, which have been implemented in our previous research for assessment of upper airway caliber.17,18 A commercialized nasal probe consisting of rigid polyvinyl chloride tube 1.2 cm in internal diameter and 5 cm in length (RhinoSleep, Lynge, Denmark) was used to connect the acoustic reflection in-strument to the subjects’ nasal alae. Acoustic reflection measure-ments were performed in a quiet room to decrease the effect of environmental noise on the signals, with a single physician per-forming all acoustic reflection measurement in this study. Sub-jects accommodated to the supine position for 3 minutes before acoustic reflection was measured. During measurement, the nasal probe was held parallel to the nasal ridge with a tight connection to the nasal alae but a minimum of distortion of the nose. Five recordings were taken automatically in quick succession at each testing, and all traces recorded were stored, amplified, and ana-lyzed by computer (Figure 2) and integrated into a 2-dimensional graph with the X axis representing distance into the nasal cavity and the Y-axis, the cross-sectional area relative to this distance. The shaded portion of this sample demonstrates the range (50-

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120 mm) generally used to detect cross-sectional area in the nasal cavity (Figure 3).19 From the traces, measurements were made of minimal cross-sectional area (MCSA), mean nasal area, and nasal volume, which were calculated automatically with coefficient of variation of 5% to 10% from our previous measurements in air-way models14 similar to those previously described for upper air-way caliber.18,20 In this study, acoustic reflection parameters were calculated by averaging the right and left nasal measurements to minimize the effect of the nasal cycle. Measurement of acoustic reflection was performed 3 months after CPAP therapy, when pa-tients returned for recording of objective CPAP use.

Statistical Analysis

The Wilcoxon signed-ranks test was used to compare changes in nasal dimensions after CPAP therapy in 10 patients who partici-pated in the pilot study. Patients were divided into 2 groups based on their measurements of MCSA for comparison using a median split analysis. The small MCSA group had values less than 1.15 cm2 and the large group MCSA ≥ 1.15 cm2. Continuous, normally distributed variables (age, titration pressure, and CPAP use) were compared between these 2 groups with independent t tests. Vari-ables that were not normally distributed (BMI and AHI) were compared with the Mann-Whitney tests. Sex ratios and mask-type ratios (nasal or full face) were compared χ2 tests. Spearman correlation coefficients were used to investigate the associations between acoustic reflection parameters (MCSA, mean area, and volume) and sleep parameters (AHI, titration pres-sure, and compliance). Using CPAP compliance as the dependent variable and using sex, age, body mass index, MCSA, mean area, volume, and AHI data as independent variables, multivariate re-gression models were applied to investigate the predictors of out-comes. Statistical analyses were performed using the SPSS 11.0 for Windows (SPSS Inc., Chicago, IL). Results are expressed as mean ± SD. A P value of less than .05 was considered signifi-cant.

RESULT

In-Vitro Airway Model

Figure 4 shows the actual and acoustic reflection-measured ar-eas of the Perspex airway model. The MCSA was underestimated by 3% (0.190 cm2 instead of 0.196 cm2), while the mean area was underestimated by 15% (0.574 cm2 instead of 0.676 cm2) and vol-ume was measured as 6.03 cm2 (a 15% underestimation).

Pilot Study of Changes in Acoustic Reflection With CPAP

The clinical characteristics of the pilot group (n = 10) were first compared with the rest of the cohort (n=50) to examine the possible selection bias and the results showed no significant dif-ferences in sex (P = .5), age (P = .07), BMI (P = .86), AHI (P = .08), titration pressure (P = .73), and MCSA (P = .06). There were no significant changes in acoustic reflection dimensions observed after 3 months of CPAP therapy in MCSA (P = .72), mean area (P = .23), or volume (P = .16).

Main Study Patients

Sixty patients (52 men and 8 women) participated in the study, ranging in age from 29 to 77 years, and in BMI from 25.9 kg/m2 to 78.3 kg/m2. Anthropometric data for patients in the 2 MCSA groups are shown in Table 1. Comparisons between these 2 groups showed no significant difference (P > .05) in age, BMI, previous existence of nasal stuffiness, and mask type. However, sex ratios were significantly different (P = .02) with significantly more women in the small MCSA group (Table 1).

Comparison of Sleep Parameters Between Small and Large MCSA Groups

The MCSA of this study population varied from 0.7 to 1.1 cm2 in the small MCSA group and from 1.15 to 1.4 cm2 in the large MCSA group. Comparisons of sleep-study variables between the 2 groups revealed a significant difference in CPAP use (P = .007) (Table 1), with lower CPAP use in the smaller MCSA group.

Figure 3—The plot of acoustic reflection in a patient with obstruc-tive sleep apnea-hypopnea syndrome. The X axis represents the dis-tance leaving the source of the sound wave, and the Y axis represents the area relative to distance. The arrow pinpoints the narrowest area chosen as the minimal cross-sectional area (MCSA). The mean area and volume were obtained with the use of an algorithm from 50 to 120 mm.

Figure 4—The areas of the airway model, with the measured area as the broken curve and the actual-area profile as the full curve.

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Correlations Between Acoustic Reflection and Polysomnography Parameters

CPAP use correlated significantly with MCSA (r = 0.34, P = .008) (Figure5), mean area (r = 0.27, P = .04), and volume (r = 0.28, P = .03). There was no other significant correlation between acoustic-reflection parameters and AHI or titration pressure (Ta-ble 2).

Multivariate Regression

Step-wise multiple regression models revealed that MCSA was a predictor of the CPAP compliance (R2 = 0.16, P = .002), and MCSA (P = .001) and age (P = .04) were predictive factors of CPAP compliance (R2 = 0.22).

DISCUSSION

In this study, acoustic reflection was used to investigate the associations of nasal dimensions with patients’ use of CPAP ther-apy. We found that CPAP compliance was significantly different between small and large MCSA groups, with lower CPAP use in the smaller MCSA group. Compliance correlated significantly and positively with MCSA. Multivariate regression revealed that MCSA was an independent predictor explaining a significant pro-portion of CPAP compliance. A previous study using tube models to validate the acoustic pulse technique showed that airway size less than 0.8 to 1.0 cm2 resulted in inaccurate data downstream, possibly through viscous losses.21 However, our in-vitro nasal airway model demonstrated that MCSA (0.2 cm2) was the most accurate measure from acous-tic reflection, with 3% error in measurement. This discrepancy may be due to the fact that the earlier study used a heliox gas mixture, which is more viscous than air. Further study is needed to clarify these differences. Although the comparisons of clinical characteristics between

pilot and study groups showed no significant differences, there are trends toward older age (P = .07), higher AHI (P = .08), and bigger MCSA (P = .06). Further study to measure the nasal di-mensions before and after CPAP therapy may clarify the potential changes of nasal dimensions after use of CPAP. It is not surprising to find that MCSA (in the anterior part of the airway model, representing the nasal valve) was the most reli-able variable with regard to actual area. The underestimation of MCSA, mean area, and volume was 3%, 15%, 15%, respectively, reflecting the fact that the accuracy of the acoustic reflection di-minished with distance from source. Hence, we selected MCSA to divide patients into 2 groups for comparison and further explo-ration. AHI was not significantly different in the 2 MCSA groups (P = .2) and there was no relationship between AHI and MCSA (r = 0.08, P = .57). These results may be explained by different characteristics in the anatomy of the nose and pharynx. The nose has a close-fitting rigid framework that prevents collapse during sleep. By contrast, the pharynx, comprising a heavily muscular structure and acting as a Starling resistor, is more vulnerable to changes in airflow resistance and consequently to airway col-lapse. Thus nasal dimensions may not be a major contributor to the development of OSAHS. This was reinforced by the fact that although subjective clinical symptoms of nasal obstruction have been considered to be a risk factor for sleep-disordered breath-ing,22 objective measurements of nasal size were not related to severity of OSAHS in this study. Titration pressure was intuitively presumed to be associated with the size of the nasal cavity, since the nasal passages accounts for approximately 50% of total airway resistance.23 Our study re-vealed that titration pressure was not different in the 2 MCSA groups (P = .55). Additionally, there was no correlation between titration pressure and MCSA (r = -0.01, P = .95). This may sug-gest that the location that was determining the titration pressure during sleep was not at the nose. There are many factors affecting compliance with CPAP ther-apy. The strongest and most consistent correlates of long-term CPAP use are AHI, Epworth Sleepiness Scale score, presence of snoring, and initial use in the first 3 months.15 However, the role of nasal obstruction in contributing to CPAP compliance may be overlooked, since those patients with severe nasal obstruction might be intolerant of wearing CPAP at titration and might, there-fore, be missed by some long-term follow-up series of CPAP users. This could help explain the discrepancy between the high propor-tion of nasal symptoms (60%) occurring in new CPAP users and the 4% prevalence as a major problem in long-term users.6 In this study, CPAP use was lower in those with smaller nasal MCSA (P = .007), a positive correlation between CPAP use and MCSA (r = .34, P = .008) was observed, and MCSA explained 16% of CPAP

1557 Nasal Acoustic Reflection in OSAHS—Li et al

Table 2—Spearman Correlation Between Reflectometric and Poly-somnographic Data

AHI Titration Pressure ComplianceMCSA 0.08 (.57) -0.01 (.95) 0.34 (.008)Mean area 0.02 (.88) -0.1 (.44) 0.27 (.04)Volume 0.02 (.87) -0.12 (.38) 0.28 (.03)

Data are presented as r (P value). AHI refers to the apnea-hypopnea index, the number of apneas and hypopneas per hour of sleep; MCSA, minimal cross-sectional area.

Table 1—Anthropometric, Polysomnographic, and Reflectometric Data Between Groups With Small and Large MCSA

Small group Large group P value (n=30) (n=30)Sex, no. .02 Men 23 29 Women 7 1 Age, y 50.7 ± 11 50.3 ± 11.5 .9BMI (kg/m2) 35.3 ± 8.4 36.9 ± 10.4 .44Mask type .18 Nasal 17 22 Full face 13 8 Previous nasal stuffiness .72 Yes 25 26 No 5 4 AHI, events/h 44.8 ± 30.1 52.8 ± 29.6 .2TP, cmH2O 10.6 ± 2 10.9 ± 1.7 .55Compliance, h/night 4.1 ± 2.5 5.7 ± 1.9 .007MCSA, cm2 0.9 ± 0.1 1.3 ± 0.1 —Mean area, cm2 1.9 ± 0.4 2.7 ± 0.6 —Volume, cm3 14.7 ± 4.2 20.9 ± 4.9 —

Data are presented as mean ± standard deviation unless otherwise noted. BMI refers to body mass index; AHI, apnea-hypopnea index; TP, titration pressure; MCSA, minimal cross-sectional area.

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compliance in multivariate regression. These results suggest that, although standard CPAP can provide therapeutic levels of pres-sure to overcome upper airway resistance, the laminar airflow in smaller nasal passages might increase velocity, magnify feelings of breathing discomfort or effort, and subsequently decrease the wish to use CPAP. Our study also showed that women have smaller nasal dimen-sions than men, and there is no relationship between nasal size and OSAHS or titration pressure. This raises the question of the appropriateness of nasal surgery to treat OSAHS. Whether or not women with OSAHS can get more benefits from nasal surgery needs further investigation. Another factor that may affect compliance with CPAP is the type of mask used. We therefore compared compliance between the nasal and full-face mask groups, and the results showed no significant differences between these 2 groups (P = .18). This in-distinguishable result in compliance between 2 mask types may be due to the ordinary rule for OSAHS patients to switch to a full face mask while uncomfortable with a nasal mask before starting CPAP therapy. Subjective nasal obstruction has been identified as a risk fac-tor for sleep-disordered breathing in a population-based sample.22 The existence of nasal stuffiness might, intuitively, increase na-sal discomfort during CPAP use and result in lower compliance. However, a history of subjective nasal stuffiness was not differ-ent in the 2 MCSA groups (P = .72) and was not correlated with CPAP compliance (r = -0.15, P = .25). This indicated thus that the subjective symptom of nasal stuffiness is not equivalent to an objective measurement of acoustic reflection, and the existence of a complaint of nasal stuffiness may not necessarily lower the use of CPAP. By contrast, compliance with CPAP was different in the 2 MCSA groups (.007) and correlated positively with all acoustic-reflection parameters. These findings suggest that objective nasal acoustic reflection might be a more reliable tool than the subjec-tive symptom of nasal stuffiness in identifying patients at risk of low compliance with CPAP. Another speculation for the link between nasal dimensions and CPAP use is that severe narrowing of nasal passages during sleep may produce mouth breathing, thus resulting in air leaking

through the mouth and, subsequently, increased difficulties in us-ing CPAP.24 The value of this study was limited by its accuracy in mea-suring nasal dimensions using acoustic reflection to explain the complex respiratory physiology of obstructive sleep apnea and tolerance of CPAP and was restricted by the lack of generaliz-ability of our acoustic-reflection devices. Improvements in nasal acoustic-reflection equipment to provide more accurate param-eters of nasal area and volume for analysis could produce further future studies.

CONCLUSION

Patients with smaller nasal passages had lower CPAP use than those with larger passages. Objective measurement of nasal di-mensions may be more reliable than subjective self-report of na-sal stuffiness in identifying OSAHS patients who might struggle with CPAP therapy.

ACKNOWLEDGEMENT

The authors are grateful to Dr. Li-Ang Lee, department of oto-laryngology, Chang Gung Memorial Hospital, for sketching the airway model figure. We also thank Dr Peter Wraith, Department of Medical Physics, Royal Infirmary Edinburgh, for his technical assistance in establishing the airway model.

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Figure 5—Compliance with continuous positive airway pressure (CPAP) correlated significantly with the minimal cross-sectional area (MCSA (r=0.34, P=.008).

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